Monthly Archives: June 2022

How Culture Went Back to the Middle Ages – ArtReview

Posted: June 24, 2022 at 9:31 pm

On Ottessa Moshfeghs Lapvona and the medieval turn

Ottessa Moshfegh is a perv. Ottessa Moshfegh is sad girl summer. Ottessa Moshfegh is on Depop. Ottessa Moshfegh is walking in New York Fashion Week. Ottessa Moshfegh isa medievalist?

For those who know Moshfegh mainly through the cultural commentary that sprung up in the wake of the mind-boggling success of her second novel, My Year of Rest and Relaxation (2018), the thought of the author as anything other than an oracle of the contemporary might seem strange. Heralded as the laureate of lockdown for her depiction of a socialite in social hibernation sleeping through a year in a narcotic-induced haze-cum-frenzy Moshfegh is often thought of spearheading the modern trend for fictions of alienation and disaffection, featuring a cast of recognisably contemporary outsiders. Alcoholic divorcees, catatonic party girls. So, despite the fact Rest and Relaxation was in fact a work of historical fiction (an eccentric yet meticulous account of New Yorks pre-9/11 culture; its downtown art scene and existential ennui), and that her debut, McGlue (2014), takes place on a nineteenth-century pirate ship, when it was announced her new novel, Lapvona, was set in a medieval fiefdom, there was an undeniable frisson of surprise.

Although, really, we should have seen this coming. Firstly, because Moshfeghs novels are abject and pervy; deviant and corporally charged. While it might be convenient to think of these qualities as unique to literature of the post-internet, and certainly the post-Reformation age, in truth they are closely aligned to many of the affective and aesthetic traditions of the Middle Ages. Indeed, the second reason why we should have expected Moshfegh to go medieval, is precisely because the contemporary popularity of grotesque, absurdist fables like hers points to a wider resurgence of medieval tropes and trends. Lapvona is landing at a time when, from the club to the catwalk, neo-medieval fashion, Catholic aesthetics, mysticism, chamber chorals, and pagan ritual are all the rage.

It feels like music is returning to some kind of medieval folk medium where we are bards again, self-promoting in the streets or taking the occasional commission from patrons, pop-cyborg Caroline Polachek said last summer. Perhaps this feeling is partly why she has, in the past, chosen chainmail, plate armour, and fantastical, elven costuming to accompany her vocals which themselves have been described as diaphanous and otherworldly, somewhere between the call of a siren and the religious arias of an eleventh-century abbess. And shes far from the only one at it. The worlds of music, fashion and visual art have been flirting with folklore and pagan iconography for some time now. Arrows raining down on models at Paris Fashion Week. Ravers dressed as medieval forest dwellers, dancing to fantasy-inspired techno. Artists merging emergent technologies such as AI and machine learning with myth and mysticism to imagine alternative worlds, which seem to hover and glitch between the ancient and the futuristic. Cinemas folk horror boom.

While all this has been seething, it might seem like literary fiction has been lagging somewhat behind its gaze resolutely set on grappling with text-speak, or, in cultural criticism, circling the unending debate over which books men and women should read. Yet, here too, a particular strain of neo-medievalism has been rising to the surface, often in the form of an ongoing obsession with female mystics. Hildegard von Bingen, Julian of Norwich and Margery Kempe keep recurring in contemporary texts, usually symbolic of an urge towards alternative female authority, power and sources of knowledge. A similar urge can be seen in the copious literary reanimations of Simone Weil, who, despite living in the twentieth century, had a curiously medieval approach to faith and spirituality one in rapture to sacrifice and suffering. Taken together, the interest in these figures suggests a growing infatuation with medieval forms of devotion, characterised by corporeal and psychic intensity.

So, Lapvona. During the pandemic, as Moshfegh was being hailed as the queen of modern malaise, she was penning a novel truly befitting an era of pestilence and plagues. On the surface, it seems purposely designed to drive her Tiktok stans into a frenzy. Where, in Rest and Relaxation, there was a beautiful blonde girl who was slim but sad in a vague, yet vaguely sexy way, in Lapvona there is Marek, a 13-year-old disabled boy, who is born of incest, beaten by his father, possibly a murderer, and, if that wasnt enough, deeply annoying. Where there were New York bodegas, now there is an unspecified hamlet in a quasi-Eastern European locale; a hut in a sheeps pasture; a manor on a hill, protected by guards. The capricious whims of a feudal lord and the obsequious enablings of a servile priest. A blind female mystic who breastfed a whole town and still allows Marek to nurse from her now empty teats. It is utterly disgusting. While Moshfegh has always been an excremental writer a devotee of shit here, the novel also features humiliation, flagellation, murder, incest, rape, a drought, dismemberment and cannibalism. Sacrifice and suffering. There is also though, a lot of shit and anal gags. Excrement, the lord Villiam wonders. Is that like sacrament? In Moshfeghs hands, it absolutely is. Lapvona is a sublime work in the truest sense mighty, irrepressible and terrifying.

Some early reviewers have already taken against it. One notably likened the setting and characters to Shrek (2001). Yet, while this may be a wry, internet-y scrap of criticism, those calling it flat, or tedious, or excessive are, to my mind, entirely missing the point. Saying Lapvona is either flat or excessive is like saying the same of Robert Eggers The Northman (2022). Lapvona should not be read as a modern narrative, but akin to a fable, allegory or epic. More than anything, perhaps, it is a kind of medieval sci-fi, and, given sci-fis long history, perhaps what I really mean is a kind of myth.

Yet, this is certainly not to say that it is untethered to the present, or that the medieval turn we are witnessing is a turning away from the specificities of modernity. And, by modernity, I of course mean capitalism. Just as Polacheks notion about returning to a bardic culture is, in fact, a biting critique of the contemporary music industry, streaming services, and the flexibility and self-reliance required of artists in the neoliberal age, so too Moshfeghs medieval fantasy is not just about shit and blood and supposedly timeless human impulses to violence. If Lapvona is a myth, it is one of exploitation, wealth hoarding, and ecological disaster at the hands of uncaring, greedy men. Indeed, the entire cultural flirtation with medieval aesthetics can be read as an attempt to grapple with the perverse conditions of today a neo-feudal billionaire class (or, as economist Yanis Varoufakis puts it, techno-feudalism); a lack of access to land ownership; a new era of pandemics; food poverty; the existential threat of climate apocalypse. Time for a peasants revolt?

Of course, the risk with any cultural or aesthetic turn to the past, is that it tips into idealisations false fetishisations that construct convenient and, often, dangerous narratives. If thinking of The Northman, for example, it would be ignorant not to also think of the way Viking mythology and attire has been adopted in the modern day by the alt-right. The myth of white racial purity; the horned helmets in the Capitol. Music, fashion, and arts shift towards the neo-medieval may not have such an explicitly racist underpinning, but we should be wary of which histories are being reclaimed as trends.

Perhaps one answer to this problem lies in resisting romanticisation in depicting the past, whether real or imagined, as a site of brutality and struggle. The historical fictions crafted by writers such as Moshfegh, AK Blakemore and Olga Tokarczuk, for example, are brutal affairs concerned with power, control, and the origins of capitalism. They wield history like a blade, cutting through the fabric of contemporary reality. Blakemores exquisite novel, The Manningtree Witches (2021) is about the witch trials of the seventeenth century, but it is also about persecution, suspicion, and how easily fear, pride and conspiracy can tip into violence. This is true of Lapvona too, which is, in a deep and essential way, about faith about truth, knowledge, scepticism, and how easily people can fall sway to the empty words of demagogues. I feel stupid when I pray, reads the epilogue a Demi Lovato lyric that proves that, while everything from that point onward may be new territory, Moshfegh still has her eye firmly trained on the details of the current moment; on contemporary blindnesses, barbarity and fears.

Read more here:

How Culture Went Back to the Middle Ages - ArtReview

Posted in Alt-right | Comments Off on How Culture Went Back to the Middle Ages – ArtReview

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes | npj Regenerative Medicine – Nature.com

Posted: at 9:31 pm

Cell culture

NCTC1469, a liver cell line established in the 1957 from a neonatal mouse36, was obtained from the FuDan IBS Cell Center (FDCC, Shanghai, China). NCTC1469 cells were cultured in Dulbeccos modified Eagles medium (DMEM) (Corning, USA) supplemented with 10% (v/v) Horse serum (Hyclone, Logan, UT, USA), 100 units/ml penicillin and 100g/ml streptomycin (Gibco, USA), at 37C in a 5% CO2 incubator. Culture medium was replaced every 23days and cells were passaged when they reached 80% confluence. Cells were mycoplasma negative through treatment with LookOut Mycoplasma Elimination Kit (Sigma-Aldrich). Gene silencing was achieved by transfecting predesigned siRNA duplexes (Supplementary Table 3) designed and synthesized by RiboBio (Guangzhou, China).

Stable knockdown of the FoxO3 gene in NCTC1469 cells was achieved by lentiviral based short-hairpin RNA delivery37. FoxO3 specific shRNA or negative control were cloned into pLOX-U6-Puro vectors for viral particle package in HEK 293T cells. Infected NCTC1469 cells were selected by puromycin and expanded to form a stable sub-line. Knockdown efficiency was confirmed at both mRNA and protein levels. The shRNA sequences are as follows: FoxO3-shRNA: 5-GGA ACT TCA CTG GTG CTA AGC-3; negative shRNA (NC): 5-ACT ACC GTT GTT ATA GGT G-3. Stable cell line generated by FoxO3-shRNA and negative shRNA were named as shFoxO3 cells and shNC cells, respectively. To establish FoxO3 overexpression stable cells, NCTC1469 cells were transfected by pLOX-FoxO3 lentiviruses19 and screened by puromycin and expanded to form a stable sub-line.

For cell proliferation assay, NCTC1469 cells were incubated for 48h in 24 well plates with different treatments. DNA synthesis was then analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) labeling, using Cell-Light EdU Apollo567 In Vitro Imaging Kit (RiboBio, Guangzhou, China) according to the manufacturers instructions. At least seven images were randomly taken per well using a Zeiss LSM 700 laser confocal microscope (Carl Zeiss). The population of EdU+ cells was determined by counting at least 500 cells per well. The EdU+ cells were quantified as the percentage of total cells. In addition, cell proliferation was also analyzed by evaluating cell count using the Enhanced Cell Counting Kit-8 (CCK-8, Beyotime Biotechnology, China) according to the manufacturers instructions.

Total RNA was isolated using RNeasy kit (Qiagen, Valencia, CA, USA) from NCTC1469 cells according to the manufactures instruction. The cDNA was transcribed from total RNA using SuperScript III Reverse Transcriptase (Roche, USA). The coding sequence (CDS) of Nox4 (NM_015760.5) was amplified by the KOD-Plus-Neo Kit (Toyobo, Japan) and cloned into the pcDNA3.1 expression vector to construct the pcDNA-Nox4 plasmid. Constructed overexpression vector pcDNA-Nox4 and control plasmid pcDNA3.1 (pcDNA) were transfected into the FoxO3-overexpressing NCTC1469 cells to explore the effect of target gene on FoxO3-mediated proliferation and apoptosis.

FoxO3-LoxP-targeted (FoxO3fl/fl) mice (C57BL/6 background) were created by Cyagen Biosciences (Suzhou, China)19. The exon 3 region of the FoxO3 gene was flanked by LoxP sites and deleted upon Cre-mediated recombination (Fig. 2a). The Albumin (Alb)-Cre transgenic line was obtained from the Jackson Laboratory (stock number 003574). Alb-Cre mice were genotyped using oIMR5374 (GAA GCA GAA GCT TAG GAA GAT GG) and 20240 (TTG GCC CCT TAC CAT AAC TG) primers and identified by a 390bp PCR product. For Alb-Cre mice, Alb promoter drive Cre recombinase expression primarily in hepatocytes with variable expression in cholangiocytes depending on the floxed gene38,39. FoxO3fl/fl mice were intercrossed with Alb-Cre mice to generate FoxO3fl/+::Alb-Cre (FoxO3+/-, heterozygote). Heterozygotes were then crossed with FoxO3fl/fl mice to generate FoxO3fl/fl::Alb-Cre mice (FoxO3-/-, hereafter termed AKO) with constitutive loss of FoxO3 in hepatocytes. The FoxO3fl/fl mice obtained from the same breeding were used as control mice (Con). Age-matched FoxO3fl/fl mice were used as control (Con). To induce conditional knockout of FoxO3 in adult liver alone, adeno-associated virus serotype 8 (AAV8) was constructed to specifically express Cre recombinase in liver. To confirm the recombination efficiency of Cre, AAV8-Tbg-Cre (AAV-Cre) virus was intravenously injected into R26-CAG-LSL-EGFP mice (Shanghai Model Organisms Center, Shanghai, China) with different concentrations. Two weeks later, the percentages of EGFP+ liver cells were then checked to evaluate Cre recombination efficiency. We found that AAV-Cre adeno-associated virus with the concentration of 51011 gc/mouse has a highest efficiency (Supplementary Fig. 11). Therefore, AAV-Cre or negative control (AAV-NC) adeno-associated virus was injected intravenously at a concentration of 51011 gc/mouse in FoxO3fl/fl mice 2weeks prior to partial hepatectomy (PH). For knockdown of Nr4a1 in adult AKO mice, AAV8-mediate shRNA targeting for Nr4a1 (AAV-shNr4a1) or negative control (AAV-shNC) adeno-associated virus was injected intravenously at a concentration of 51011 gc/mouse in AKO mice 2weeks prior to partial hepatectomy (PH). To overexpress Nox4 in AKO mice, AAV8-Tbg-Nox4 (AAV-Nox4) or negative control (AAV-NC) adenovirus was injected intravenously at a concentration of 51011 gc/mouse in FoxO3-deficient mice 2weeks prior to liver injury. For experiments using adult animals, male mice were used in this study. All animal protocols and procedures were approved by the Institutional Animal Care and Use Committee of Jinan University. Data and methods are reported here in accordance with ARRIVE guidelines40.

Male animals aged 8~9weeks were kept on a 12h-day/night cycle with free food/water access, and were used for partial hepatectomy (PH) experiments. During anesthesia induced by isoflurane, mice were subjected to 70% PH or 30% PH surgery. The surgery was performed between 8 and 12am to remove the median and left lobes and the mortality was <5%. The weight of regenerated livers as well as the whole body was measured at 07days post-PH (dpH). The ratio of wet weight of the remaining liver after PH over the weight of the whole animal was taken as the liver to body weight ratio. The 0 dpH denotes the time point in quiescent animal before PH. To induce another classic liver injury model, male adult mice were injected with CCl4 (0.6mL/kg, intraperitoneally) diluted in olive oil three times a week (every 48h) for 4weeks and euthanized 48h after the last injection as previously reported41.

Mouse livers were flushed via the portal vein using perfusion buffer containing Collagenase Type IV, followed by primary hepatocyte isolation and purification. Isolated and purified hepatocytes were fixed at 4 with 70% ethanol overnight at 4C, washed three time with PBS, and incubated with propidium iodide (PI, 50g/ml, Sigma)/RNAse A (ribonuclease, 1mg/ml, Sigma) solution for 3h at room temperature, followed by flow cytometry analysis with a FACS Aria cytometer (Becton Dickinson) to determine DNA content and ploidy distribution using ModFit LT 5.0 software (Verity Software House). Growth assay of primary hepatocytes were performed as previously report21. In brief, isolated hepatocytes were cultured in mouse hepatocyte growth medium (MHGM) with or without mitogens including EGF and HGF (Gibco, 40ng/ml for each) for 4days as described previously. DNA synthesis were then analyzed by 5-Ethynyl-2'-deoxyuridine (EdU) labeling, using Cell-Light EdU Apollo567 In Vitro Imaging Kit (RiboBio, Guangzhou, China) according to the manufacturers instructions.

Liver tissues were fixed in 4% formaldehyde and dehydrated in a series of ethanol. The fixed liver was embedded in paraffin and sectioned to 5m thickness. Sections were subjected to hematoxylin and eosin (H&E) staining for morphological and mitotic analysis. Paraffin-embedded liver sections were deparaffinized in xylene, followed by rehydration through a graded ethanol series and staining with hematoxylin and eosin stain (H&E). Mitotic activity in liver was examined and quantified as previously described2. In brief, mitotically active areas were first screened under lower magnification. For quantification, total mitotic counts in five high-magnification fields in the most mitotically active areas were considered for each mouse using a light microscope coupled with a digital image acquisition system.

Liver sections were subjected to immunofluorescence staining to analyze the expression of cell proliferating markers using a confocal fluorescence microscope42. In brief, livers were embedded in paraffin and cut in 5m sections, followed by deparaffinization and rehydration. Antigen retrieval were routinely performed using Citrate Antigen Retrieval Solution (Beyotime Biotechnology, P0081) according to the manufacturers instructions. Sections were permeabilized with 0.5% Triton X-100/PBS and then blocked with 5% goat serum (Jackson ImmunoResearch Laboratories, USA) for 1h at room temperature, and incubated with appropriate primary antibodies overnight at 4C. After washing with PBS, sections were incubated with corresponding secondary antibodies conjugated to fluorescence for 1h at room temperature, followed by counterstaining with DAPI (Sigma). Secondary antibodies used are following: Alexa Fluor 488 donkey anti-rabbit IgG (Abcam, 1:500), Alexa Fluor 405 donkey anti-goat IgG (Abcam, 1:200), and Cy3-conjugated Affinipure Goat anti-rabbit IgG (Proteintech, 1:100). For immunohistochemistry staining, sections were stained with primary antibody overnight at 4C. SignalStain Boost IHC Detection Reagents (HRP, CST) and SignalStain DAB Substrate Kit (CST) were used for amplification and development, respectively. The detailed information of primary antibodies used in this study can be found in the Supplementary Table 4. For immunostaining in liver tissues, species isotype (Santa Cruz) was used as negative control to confirm the specificity of primary antibodies. Images were captured by laser-scanning confocal microscope (LSM 700, Zeiss) and analyzed by ZEN 2012 software (Zeiss). Given that FoxO3 was predominantly expressed in nuclei of liver cells (Fig. 1a, b), FoxO3 fluorescence intensity in nuclei were normalized to nuclei size (mean fluorescence intensity, MFI) over total slides using ZEN 2012 software (Zeiss) to evaluate the total expression levels of FoxO3 protein. For the quantification of cell proliferation, the proliferation of hepatocytes (HNF4+ cells) was quantified by the percentage of proliferating hepatocytes (Ki67+ HNF4+ cells, or pH3+ HNF4+ cells) relative to total hepatocytes (HNF4+ cells). For some experiments, the proliferation of non-hepatocytes (HNF4 cells) was quantified by the percentage of proliferating non-hepatocytes (Ki67+ HNF4 cells, or pH3+ HNF4 cells) relative to total liver cells (DAPI+ cells).

Hepatocyte size was evaluated by -catenin staining. In brief, following deparaffinized, rehydrated, slides were then incubated with anti--catenin (BD, 1:500) overnight at 4C, followed by a further incubation at room temperature for 1h with goat anti-rabbit IgG H&L (Alexa Fluor 488) preadsorbed secondary antibody. Nuclear DNA was labeled in blue with DAPI. To quantify the cell size, 5 independent livers per group (at least 300 cells) were captured with laser-scanning confocal microscope (LSM 700, Zeiss). ZEN 2012 lite software (Zeiss) was used to quantify the relative size of each cell. Moreover, the relative size of primary hepatocytes was also evaluated by the forward scatter (FSC) intensity in flow cytometry.

For EdU labeling experiments, mice were intraperitoneally injected with 100l of a 1mg/ml solution of EdU (RiboBio, Guangzhou, China) dissolved in PBS. Livers were embedded in Tissue-Tek optimal cutting temperature compound (OCT) (Sakura, USA) for frozen section (4 m). Sections were rinsed three times in PBS and fixed in 4% parapormaldehyde for 30min. After rinsing three times again, citrate antigen retrieval was performed as described above. Sections were then incubated with 2mg/mL glycine solution for 10min, permeabilized with 0.5% Triton X-100 in PBS for 10min, and then rinsed with PBS once for 5min. This was followed by incubation with Apollo576 staining solution (1) at room temperature for 30min. Sections were washed three times in PBS, stained with DAPI for 10min to label nuclei, and mounted in Antifade Mounting Medium. Images were captured by a laser-scanning confocal microscope (LSM 700, Zeiss) and analyzed by ZEN 2012 software (Zeiss).

To analyze hepatocyte proliferation at the indicated time points, EdU was injected 2h prior to liver collection. For EdU pulse-chase experiments, EdU was multiply injected at indicted time points to label all proliferating hepatocytes during the whole period of liver regeneration. The last injection was performed 2h prior to liver collection. Sham-operated mice underwent the same procedure without the liver resection. For the quantification of cell proliferation, the proliferation of hepatocytes (HNF4+ cells) was quantified by the percentage of proliferating hepatocytes (EdU+ HNF4+ cells) relative to total hepatocytes (HNF4+ cells). But the proliferation of non-hepatocytes (HNF4- cells) was quantified by the percentage of proliferating non-hepatocytes (EdU+ HNF4- cells) relative to total liver cells (DAPI+ cells).

Blood was collected by shearing the right atrium and was allowed to coagulate for 2h on ice. Serum was the isolated as the supernatant fraction after centrifugation at 2000rpm for 5min. Hepatic function was analyzed using serum ALT and AST activities, which are markers of injury. Serum ALT and AST activities were determined using the Hitachi 7600 automatic biochemical analyzer (Japan) and were expressed as units per liter (U/L). In addition, enzyme activities in liver tissue were determined using commercial kits produced by Jiancheng Institute of Biotechnology (Nanjing, China). Tissue enzyme activities were normalized to total protein weight and were expressed as units per gram protein (U/g).

For total RNA isolation, liver tissues were extracted in sham and injured mice at 4days post-PH (dpH), respectively. Three mice per group were used for RNA-sequencing analysis. RNA preparation, library construction and sequencing on GBISEQ-500 platform was performed. After filtering the reads with low quality, clean reads were then obtained and mapped to the reference genome of mouse (GRCm38.p6) with the HISAT43. Gene expression level was quantified by a software package called RSEM44 and expressed as fragments per kilobase of exon per million fragments mapped (FPKM). Differential expressed (DE) genes were detected using NOISeq method45 with Probability0.8 and fold change (FC) of FPKM2. Only those genes were considered for the differential expression analysis, which displayed FPKM1 in either of the two samples under comparison. GO analysis was performed using online tool DAVID 6.8 (https://david.ncifcrf.gov/summary.jsp), and terms with p-value0.05 were included. Differentially expressed gene heat maps were clustered by hierarchical clustering using cluster software46. RNA sequencing data have been deposited in NCBI Sequence Read Archive (SRA) under the accession code SRP224045.

Total RNA was isolated using RNeasy kit (Qiagen, Valencia, CA, USA) from cells or liver tissue according to the protocol of the manufacturer, respectively. Reverse transcription to cDNA was performed with 30ng of total RNA, random primers, and SuperScript III Reverse Transcriptase (Roche, USA). The qPCR was performed using a Light Cycler 480 SYBR Green I Master (Roche, USA) and the MiniOpticon qPCR System (Bio-Rad, CA, USA). After denaturation for 10min at 95C, the reactions were subjected to 45 cycles of 95C for 30s, 60C for 30s, and 72C for 30s. GAPDH was used as the internal standard control to normalize gene expression using the 2Ct method. The sequences of the qPCR primers were listed in Supplementary Table 5.

Tissues or cells were lysed in RIPA buffer (Beyotime Biotechnology) containing protease inhibitors (Sigma) for SDS-PAGE. Protein concentrations were determined using Bio-Rad Protein Assay (Bio-Rad Laboratories). 30g of protein were separated by SDA-PAGE, proteins were transferred onto PVDF membranes (Millipore), then blocked in 5% nonfat milk/TBS-Tween 20 and incubated with primary antibodies (dilution in TBST) overnight at 4C. Membranes were then washed and incubated with corresponding second antibodies for 1h at room temperature. Bands were detected by chemiluminescence reagents (ThermoFisher Scientific). Primary antibodies can be found in the Supplementary Table 4. Secondary antibodies used are following: goat-anti-mouse horseradish peroxidase (HRP)-conjugated antibody (CST, 1:3000) and goat-anti-rabbit horseradish peroxidase (HRP)-conjugated antibody (CST, 1:2000). Regarding the visualization of housekeeping protein (-actin), the partial membrane was cropped from the same one as the target proteins of interest when their molecular weights are greatly different from each other. Otherwise, two members with same loading dose of total protein were simultaneously performed to visualize the target protein and -actin, respectively. Given that stripping and re-probing may result in errors between different bands, stripping buffer was not used in this study. Chemiluminescent signals were quantitated with Image-Pro Plus version 6.0 software (Media Cybernetics, MD, USA). The expression level of target protein was set as 100% in control group. Relative expression levels of target protein in experimental groups were expressed as the percentage of control group. All blots derive from the same experiment and were processed in parallel. The uncropped blots are listed in the Supplementary Figs. 24 and 25.

The promoter sequences (2000bp to 1bp, upstream of TSS) of the mouse Nox4 (Gene ID: 50490) and Nr4a1 (Gene ID: 15370) genes were analyzed by JASPAR 2018 online software (http://jaspar.genereg.net/)47 to determine potential FoxO3 binding sites (Supplementary Tables 1 and 2). The predicted binding site with highest score for target gene promoters were further analyzed by luciferase reporter assay, to evaluate the regulation effects of FoxO3 on the expression of mouse Nox4 and Nr4a1 genes. The pCMV-Gaussia-Dura Luc and pTK-Red Firefly Luc plasmids from ThermoFisher were used to construct the dual-luciferase reporter plasmid (pGL-RF) (Supplementary Figs. 19b and 22b), which contained both a Gaussia luciferase (GL) and a red firefly luciferase (RF). The predicted binding sites with highest score for target gene promoters were further analyzed by pGL-RF luciferase dual reporter assay, to evaluate the in vitro binding and regulating effects of FoxO3 on Nox4 and Nr4a1 genes. Briefly, promoter regions of target genes comprising predicted FoxO3 binding sites were amplified and cloned into the pGL-RF plasmid. NCTC1469 cells were co-transfected with dual reporter plasmids and pcDNA-FoxO3 plasmid (50ng for each plasmid) using LipoFiter Liposomal Transfection Reagent (Hanbio Biotechnology). Two days after transfection, luciferase reporter assay was carried out using the Pierce Gaussia-Firefly Luciferase Dual Assay Kit (ThermoFisher Scientific) according to the manufacturers protocol. Luciferase activity was measured using a BioTek SynergyTM 4 multimode microplate reader (BioTek Instruments). The relative activity of the Gaussia luciferase (GL) was normalized by the activity of red firefly luciferase (RL) and was expressed as fold change of control group. To further verify the potential binding sites, mutant luciferase reporter plasmids were generated by KOD-Plus-Mutagenesis Kit (Toyobo, Osaka, Japan), according to the manufacturers protocol.

ChIP assays were performed to evaluate the in vivo binding of FoxO3 to its consensus sequence in mouse Nr4a1 and Nox4 promoters. The assays were performed in mouse liver tissue using the SimpleChIP Plus Enzymatic Chromatin IP Kit (CST, #9004) according to the manufacturers instructions. FoxO3 antibody (CST, #2497) was used to immunoprecipitation assay. Normal goat IgG (CST, #2729) was used as a control as previously described. The DNA isolated from input chromatin fragments and from the precipitated chromatin fragments by anti-FoxO3 antibody or control IgG was subjected to PCR using primers flanking the consensus FoxO3 binding sites on Nox4 promoter. PCR products were determined on a 1.5% agarose gel. Relative binding ability of FoxO3 was expressed as the DNA signals relative to input. ChIP-PCR primers used in this study as follows: Nr4a1-ChIP-F: 5'-GGC CTC ACT TTT TCC ACC TAG T-3' and Nr4a1-ChIP-R: 5'-CCA GGG TAG GGT TGC TGT TTC-3'; Nox4-ChIP-F: 5'-TTG ACT TTG CAA TTA GCA GTA-T-3' and Nox4-ChIP-R: 5'-AGT CAG AAG CCC AAG TCT TCC T-3'.

All statistics were calculated using GraphPad Prism 8 Software. Among three or more groups, statistical analysis was performed using one-way or two-way ANOVA with Dunnetts multiple comparisons post hoc tests. Comparisons between two groups were analyzed using unpaired and 2-tailed Students t-test. All data are presented as the meanSEM. A p-value<0.05 was considered statistically significant. In this study, statistical analysis was in accordance with homogeneity of variance and normality of residuals. Homogeneity of variance was evaluated by the F-test with a p-value of >0.05. Normality of residuals was evaluated by D'AgostinoPearson test and/or ShapiroWilk test with a p-value of >0.05.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

View original post here:

FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes | npj Regenerative Medicine - Nature.com

Posted in Alt-right | Comments Off on FoxO3 restricts liver regeneration by suppressing the proliferation of hepatocytes | npj Regenerative Medicine – Nature.com

The time I studied Talmud with Uri Zohar – The Times of Israel

Posted: at 9:29 pm

Four decades ago, Israel learned that Uri Zohar, its best known comedian, was abandoning bohemia for the Haredi world. About that time, I was writing an article for The Jerusalem Post in which Zohars name came up. A private postal service was facing closure. Its head well call him Haim mentioned in passing during an interview that Zohar was one of his customers and a friend, which I noted in the article. A few weeks later Haim, himself Haredi, called me. He was exultant. The authorities had reconsidered and his service would not be shut down. The article had done it, he said. He couldnt thank me enough. Is there anything I can do for you? Anything.

I was not doing anybody a favor and in truth it was a very dull article. But as Haim talked, it occurred to me that there WAS something he might do for me. He and no other.

Could you arrange for me to study Talmud with Uri Zohar for half an hour?

He hesitated. I m not sure he would agree to that, but I can ask him.

I wont write about it, I assured him. Im just interested personally, not as a journalist.

Ill try, he said.

The news that Zohar was quitting comedy for religion had stunned me. He was, for me, a national treasure - funny, bawdy, hilarious. We seculars thirsted for wild humor like his to brighten our livesa diversion from all the bad actors strutting the political stage. It was as if Bob Hope - the American comedian who came to mind then - had abandoned his radio show and taken a vow of silence in a remote monastery, never to be heard from again.

Zohars move was a dissonance that baffled me. Was it real? A middle-aged man making a move like that? Why? Or was it a schtick, like Madonnas hyped-up flirtation with kabbalah, a pathetic lunge for publicity. If I could watch him close-up studying Talmud, I thought, it might tell me something.

Growing up on New Yorks Lower East Side, I had gone to Yeshiva Shlomo Kluger till 10th grade. Very little of my learning there stuck, but at least I could read a page of Talmud even if I didnt get the meaning unless the rabbi explained it.

Two days after my request to Haim, the phone rang at my desk. A deep, vaguely familiar voice said Mr. Rabinovich? This is Uri Zohar. I dont recall him asking any questions, although his tone seemed to carry one - is this journalist just looking for a scoop? I hastened to assure him that I would not be writing an article about him, but that I would like to share a study session with him if possible.

He agreed that I come the next morning at 10 a.m. to an address in Geula, a Haredi neighborhood in Jerusalem. Ground floor. Short flight of stairs. Door to the right. He himself responded to the doorbell. He had a beard, but the face was his. He led me into the salon where two men were sitting at a table, a Talmud tractate open before each. One was a former entertainer, born-again like Zohar, but his name was unfamiliar to me. The other was the Haredi teacher, an intelligent looking young man. Zohar gestured to a seat next to his. He didnt immediately offer me a volume, perhaps not to embarrass me if I could not follow. I asked for one and he readily took one down from a shelf, opened it to the page they were studying and placed his finger on the line they were at. That took me straight back to my yeshiva days when, it seemed, we were constantly asking each other what line we were at.

The subject, as best I recall, concerned someone finding a prayer book or another holy book on the Sabbath in a public space: can he pick it up and bring it into a private space, like his home, to save it from further desecration? Or not? Normally, it is forbidden to carry even a handkerchief in a public space on the Sabbath.

The room faced onto an inner courtyard. At one point, the rabbi placed an object on the sill of the open courtyard door to discuss the boundary between private and public spaces.

As the rabbis reading proceeded, Zohar and the other penitent offered questions and comments. I asked whether I could participate. I was urged to do so and did. The give-and-take was familiar, even fun. I could have continued, but after a while I begged leave to go. Zohar escorted me to the door. As I started down the short flight, I glanced back. He was still at the half-open door, as if poised for a question from me, so I thought, about continuing my studies. Neither of us said anything and I continued out the front door. I already had the answer to the question that had brought me there; to my dismay, Uri Zohar was not kidding about becoming a Haredi. He had passed from the public space to the private. He would remain there, except for scattered contacts with seculars, until he died this month, at age 86.

Uri Zohar (left) and Arik Einstein in Peeping Toms, Zohars 1972 film about an aging hippie. (YouTube screengrab)

ADDENDUM:

Despite my assurance to Haim and to Zohar himself that I would not write about the episode, I did write about it. I felt that the articles conclusion that Zohars conversion was sincere, was not something he could object to. The publicity might even enhance his personal agenda if it aimed at encouraging secular searchers to follow in his path.

In so deciding, I may have inadvertently stumbled on a Talmud-worthy conundrum. Although my pledge to Haim and Uri Zohar not to write about the episode ended up being false, it was not false when I made it. It became a lie only post-facto. Is that less egregious than an intentional, up-front lie? Or not?

Abraham Rabinovich is a historian and journalist who has published several books including "The Yom Kippur War," "The Boats of Cherbourg" and "The Battle For Jerusalem." As a reporter, his work has appeared in the Wall Street Journal, the New York Times, the International Herald Tribune, The New Republic, and the Christian Science Monitor. Before becoming a writer full-time, he was employed as a staff journalist for Newsday and the Jerusalem Post.

Here is the original post:

The time I studied Talmud with Uri Zohar - The Times of Israel

Posted in Talmud | Comments Off on The time I studied Talmud with Uri Zohar – The Times of Israel

Abortion access is a Jewish value: Reaction to Supreme Court overturning Roe v. Wade – Forward

Posted: at 9:29 pm

Abortion rights demonstrators outside the U.S. Supreme Court in Washington, D.C., on Friday, June 24, 2022, after it overturned Roe v. Wade, ending constitutional protections for the right to an abortion. Photo by Valerie Plesch/Bloomberg via Getty Images

By Beth HarpazJune 24, 2022

The U.S. Supreme Courton Friday overturned Roe v. Wade. The decision ended constitutional protections for the right to an abortion that had been in place for nearly 50 years. Abortion opponents have fought for decades to outlaw the procedure. Abortion will now likely be banned in about half of the states.

Here is a sampling of reaction from the Jewish community.

The Jewish Council for Public Affairs: Prohibiting abortion access is contrary to Jewish law, traditions, and our principal value of saving a life; it enshrines specific religious imperatives in American law. Judaism compels us to stand for all life, and we prioritize the life and health of a pregnant person.

Hadassah: Hadassah, The Womens Zionist Organization of America, reaffirms its unwavering support for full and complete access to reproductive health services and the right to make decisions based on each womans religious, moral and ethical values. Hadassah will continue to fight for federal and state legislation affirming and protecting reproductive rights.

U.S. Rep. Lee Zeldin (R-NY): Today is a victory for life, for family, for the constitution, and for federalism. When my daughters, Mikayla and Arianna, were born 14.5 weeks early, I had the opportunity to witness life in the second trimester and it was absolutely beautiful. In a state that has legalized late term partial birth abortion and non-doctors performing abortion, in a state that refuses to advance informed consent and parental consent, and where not enough is being done to promote adoption and support mothers, today is yet another reminder that New York clearly needs to do a much better job to promote, respect and defend life.

Keshet(LGBTQ rights): This Supreme Court decision is the culmination of a decades-long campaign by an extremist, predominantly white Christian minority to impose their religious and cultural beliefs on the majority of Americans who support abortion rights. Keshet, and the Jewish and LGBTQ+ communities, will fight to reverse this court decision and ensure abortion access for all.

Rabbinical Assembly (representing Conservative rabbis): The RA is outraged by the decision of the U.S. Supreme Court to end the Constitutional right to abortion and deny access to lifesaving medical procedures for millions of individuals in the U.S., in what will be regarded as one of the most extreme instances of governmental overreach in our lifetime.

Union of Orthodox Jewish Congregations of America: The Orthodox Union is unable to either mourn or celebrate the U.S. Supreme Courts overturning of Roe v Wade. We cannot support absolute bans on abortionat any time point in a pregnancythat would not allow access to abortion in life-saving situations. Similarly, we cannot support legislation that does not limit abortion to situations in which medical (including mental health) professionals affirm that carrying the pregnancy to term poses real risk to the life of the mother. The right to choose (as well as the right to die) are thus completely at odds with our religious and halachic values. Legislation and court rulings that enshrine such rights concern us deeply on a societal level.Yet, that same mandate to preserve life requires us to be concerned for the life of the mother.

Jewish Orthodox Feminist Alliance (Jofa): As a matter of faith, Jofa supports every womans legal right to make decisions about, and have control over, her own body, without the involvement of the government or any other entity.

Womens Rabbinic Network: The Torah, the Mishnah, and the Talmud Judaisms most sacred and authoritative texts do not view a fetus as a soul until it is born. Rather, a fetus is considered part of the parents body until delivery. Indeed, the word for soul neshama also means breath, because Judaism teaches that life begins not at conception or with a heartbeat but with the first breath. Therefore, forcing someone to carry a pregnancy that they do not want or that endangers their life is a violation of Jewish law because it prioritizes a fetus over the living adult who is pregnant. This must be understood as a violation of the United States Constitution which guarantees our freedom to practice our religion and also our freedom from the dictates of other religions.

Hillel International: Our tradition teaches that our most sacred obligation is the preservation of human life, and were dismayed that this ruling will make it more challenging to fulfill that promise for the students, professionals, and community members we serve.

Rabbi Jill Jacobs, CEO of Truah: Todays ruling ignores the First Amendment right for Jews to practice their religion without government interference, and will also have life threatening implications for millions of Americans, primarily low-income people of color, by giving states the power to revoke essential health care from nearly half the population.

Jewish Community Relations Council of Greater Washington:Even under its strictest, most traditional interpretation, Jewish law mandates the termination of a pregnancy in certain circumstances involving the life or health of the mother. While we respect other religions belief that life begins at conception, Jewish law has no such dictate. Accordingly, a ruling holding that a fetus is a person effectively elevates one religious viewpoint over others and infringes upon Jewish pregnant individuals right to follow the tenets of their faith.

Read this article:

Abortion access is a Jewish value: Reaction to Supreme Court overturning Roe v. Wade - Forward

Posted in Talmud | Comments Off on Abortion access is a Jewish value: Reaction to Supreme Court overturning Roe v. Wade – Forward

Honors, happenings, comings & goings, philanthropy June 2022 J. – The Jewish News of Northern California

Posted: at 9:29 pm

Honors

Two Bay Area natives, both students at Stanford University are among 60 students from around the world who have been selected for the 10-week Birthright Israel Excel, a business internship in Israel this summer. They are Ari Glenn, 20, of Palo Alto and Caroline Schurz, 20, of San Francisco.

Congregation Bnai Tikvah celebrated Rabbi Jennie Chabons 18th year with the Walnut Creek synagogue at its LChaim Gala in May. In an email to the community, executive director Keren Smith called the gala a wonderful community-building event, a fancy evening filled with joy and friendship and announced that, with proceeds from the event, Bnai Tikvah has exceeded its fundraising goal for the year.

Rabbi Dorothy Richman has been named rabbi emerita of Congregation Beth Sholom in San Francisco. The title rabbi emerita typically goes to a congregations retired rabbi, or an honorary rabbi. In this case, it goes to a rabbi who has been involved with Beth Sholom in many capacities over the years who will lend extra support ritual, pastoral, educational as the synagogue transitions from the leadership of Rabbi Dan Ain, who abruptly left the senior rabbi position earlier this year, to Rabbi Amanda Russell, the associate rabbi who was elevated to replace him.

Jim Heeger of Palo Alto is the new board chair of the Foundation for Jewish Camp, the national organization that supports Jewish summer camps across North America. A former Silicon Valley CEO and active Jewish community lay leader, he brings a wealth of experience in financial and administrative strategy from both the corporate and nonprofit spaces, FJC said in a press release. As a youth, Heeger spent time at Shwayder Camp in Colorado and his sons have attended URJ Camp Eisner in Massachusetts and URJ Camp Newman in Santa Rosa. Camp is the greatest vehicle for joyful engaged Judaism, and working to lead its expansion and growth is a thrill for me, he said in the press release. The world needs camp now more than ever, and I am confident that FJCs strategic plan will strengthen Jewish camps to lead the way during these uncertain times. Heeger has served on the boards of Moishe House, the S.F.-based Jewish Community Federation, the World Union for Progressive Judaism and others.

Temple Israel of Alameda has hired Rabbi Cynthia Minster as its new spiritual leader on a three-year, part-time contract. Minster will work four days a week for the Reform synagogue. I truly believe we have found what we, as a congregation, need in a Rabbi, temple president Eric Strimling wrote in an email to the congregation.

Frances Dinkelspiel, executive editor of Cityside, has stepped down from the nonprofit media organization to focus on writing her next book. She helped found Berkeleyside in 2009, concerned with the ebbing of local news. Berkeleyside has grown into a nationally recognized news provider with three editors and six reporters, 519,000 monthly readers, 70,000 Twitter followers and newsletters read by tens of thousands of people, the publication wrote in an article announcing Dinkelspiels departure. In 2019, Dinkelspiel co-founded Cityside, which launched Oaklandside in 2020.

Sarah Cohen Domont will step down after six years as executive director of Santa Cruz Hillel at the end of June. She will be moving to Chapel Hill, North Carolina to be director of lifelong learning at Kehillah Synagogue. This is a return for Cohen Domont, who previously served as associate director of North Carolina Hillel. Over the course of her tenure, Santa Cruz Hillel has become an outstanding Hillel, board president Chuck Smith said in an email to the community. Our Hillel has focused on engaging Jewish students wherever they are, through programming and engagement focused on Israel, Jewish life and learning, student leadership and community. As Sarahs time with us comes to a close, we are in a place of strength.

Rabbanit Meira Wolkenfeld is taking over the position of director of education and community engagement at Congregation Beth Israel in Berkeley. Wolkenfeld recently completed a Ph.D. in Talmud at Yeshiva University and is currently enrolled in an online ordination program at Yeshivat Maharat, which trains women as Orthodox clergy. Wolkenfeld will arrive in Berkeley in August with husband Ezra Wolkenfeld and their children, Shalev, 5, and Yakir, 3. She was born in Sacramento and spent her early years in Berkeley. Wolkenfeld is the granddaughter of longtime Beth Israel members. Throughout this process, the search committee was impressed by Rabbanit Wolkenfelds deep thoughtfulness and attentive pastoral skills, her curiosity and incisive questions, as well as by her scholarship and insightful teachings, leaders of the Modern Orthodox congregation wrote in an email to its community.

Wolkenfeld is taking over for Maharat Victoria Sutton, who is leaving at the end of July, it was previously announced. Her new position will be as a Jewish studies teacher at the Abraham Joshua Heschel School, a nursery schoolthrough12th grade Jewish day school in New York City. She and her family are moving to Brooklyn.

Congregation Beth David in Saratoga has been awarded a Scientists in the Synagogue grant from the organization Sinai and Synapses, which promotes connections between Judaism and science. The grant will fund a yearlong series of events called Judaism and Science in Conversation: Yesterday, Today and Tomorrow. Together we will explore the history of the relationship between Judaism and science and dive deeply into what Judaism and science have to say about some current issues like lab grown meat and kashrut, and what we pass on to our children biologically, socially, and spiritually, Rabbi Nathan Roller told the community in an email.

View original post here:

Honors, happenings, comings & goings, philanthropy June 2022 J. - The Jewish News of Northern California

Posted in Talmud | Comments Off on Honors, happenings, comings & goings, philanthropy June 2022 J. – The Jewish News of Northern California

Ties That Bind – The Jewish Press – JewishPress.com

Posted: at 9:29 pm

They shall make themselves tzitzis on the corners of their garments and they shall place upon the tzitzis of each corner a thread of turquoise wool. (Bamidbar 15:38)

Expounding on the intent of the mitzvah of tzitizis, our Sages say we should identify as servants of Hashem.

The Talmud (Menachos 43b) cites R Meir, who said that the punishment for not attaching white strings is greater than the punishment for not attaching techeles (blue strings). He compares it to a king of flesh and blood who ordered two of his servants to bring him a seal. Of one he requested a seal of clay, and of the other he requested a seal of gold. Both failed to bring the seals as requested. Who will have a greater punishment? R Meir says it is the one who did not bring the seal of clay.

Tosfos explains that just as a slave would have a seal on his clothing identifying him as such, the tzitzis distinguish us as servants of Hashem. When a person realizes that he is a servant of Hashem, he fulfills His mitzvos, whether he does it for love, like a faithful servant, or because he is fearful, like a servant who is not as loyal.

The Divrei Mordechai cites the Even Ezra in Bamidbar that although one prays with his tallis to fulfill the requirement in Krias Shema (they are to make themselves tzitzis on the corners of their garments ) there is a greater obligation to wear tzitzis throughout all the hours of the day so that ones servitude to Hashem should be foremost in his mind and he will not sin. During the time of prayer, there is little possibility that one will transgress.

The tzitzis alert the individual and remind him that he is a servant of Hashem who would not disobey his master. The Talmud (Menachos 44a) tells of an individual who was very conscientious about the mitzvah of tzitzis. As he readied to violate a severe Torah prohibition his tzitzis slapped him in the face and he pulled back because the four corners of tzitzis appeared to him like four witnesses.

The Sifsei Tzaddik comments that when one dons his tzitzis he should appreciate the preciousness of this mitzvah and cling to them, for they have the power to save him from sin.

The Divrei Mordechai adds here that we tie the tzitzis 39 times, equivalent to the gematria (numerical value) of the words Hashem echad Hashem is one. Thus our seal is now engraved with the name of our master, Hashem. This is an additional sign that we carry the name of Hashem with us, to maintain our Torah view and guard us from all sin.

Because of the great importance of this mitzvah, the Shulchan Aruch, Orach Chaim (24) states: Great is the punishment of a person who nullifies the mitzvah of tzitzis. Of him it is said (Iyov 38:13), To grasp the edges of the earth and shake the wicked from it.

* * *

Why the Tzaddik Fell Ill

The great tzaddik R Moshe Pardo once became ill on his travels outside Eretz Yisrael. He had a severe headache, which was then followed by overall weakness in his entire body. His host called the doctor, who requested R Moshe open his shirt so that he could listen to his heart. When the doctor saw R Moshes tallis katan, he was very moved, as it evoked forgotten childhood memories.

Are there still Jews who wear these garments? he asked emotionally.

R Moshe was momentarily distracted from his pain as he described to the physician the splendor of Eretz Yisrael, the world of Torah, and how many were returning to their Jewish roots. He also told the doctor about Ohr HaChaim the educational institutions he had established in Eretz Yisrael. He gently guided the physician to connect to his Jewish ancestry and gave him one of the very special pair of tefillin that he usually gifted to rich donors.

The doctor prescribed a protocol of treatment and medications for R Moshes recovery. He also promised that he would wear the tefillin every day and, at his first opportunity, would come to visit Eretz Yisrael. He expressed a strong interest in seeing the institutions that R Moshe Pardo had established.

R Moshe recovered and continued traveling, his meeting with the doctor soon forgotten.

Many years later, R Moshe received a phone call from an elderly man who wished to see him. When R Moshe Pardo welcomed the visitor he recognized the elderly physician, and immediately rose to happily welcome him.

The doctor related that he had kept his promise to R Moshe. He davened in shul every day and wore his tefillin, and he now wanted to support the educational institutions of R Moshe.

R Moshe gave the doctor a tour of the various buildings the school buildings, the library, the dormitory and the physician was overwhelmed. I thought you were speaking of a small school, and here I see castles. I have no family, and I want you to know that I have resolved at this moment that I am a Jew. I have accrued a large amount of money over my lifetime, and I would like to leave the sum to your institutions. R Moshe praised the doctors great zechus and observed how this one gesture was one of the greatest achievements of his life.

R Moshe would recount that when he fell ill, he was bothered slightly because our Sages tell us (Pesachim 8a), Those on the path to perform a mitzvah are not susceptible to harm. How was it possible that he fell ill? When he was able to reignite the spark of Yiddishkeit within the physician he comprehended the possible reason why he had taken ill far from home. I didnt realize at the time that this illness would later build Torah in the world. One can never predict the results of a days events.

The rest is here:

Ties That Bind - The Jewish Press - JewishPress.com

Posted in Talmud | Comments Off on Ties That Bind – The Jewish Press – JewishPress.com

The cheapening of sports – Washington Examiner

Posted: at 9:29 pm

There comes a time in every thoughtful sports fans life when he gazes at absurdly proportioned men bouncing rubber balls on wooden floors and asks himself: How much does this matter, really? These long, Talmudic inquiries into the meaning of words such as catch or throw or knee, carried live on national television before tens of millions of people, conducted amid fields of impatient millionaires dressed in body armor isnt it all a little much, if were being honest?

And if were being a little more honest, we would decide that no, it isnt all a little much.

There is a sublime unity in a Steph Curry step-back shot that exists almost nowhere else in the work of man or God. Football is its own exalted category of human affairs, the one and only plane where every phase of existence is smashed together in public, in real time. In a memorable episode of the ESPN documentary series 30 for 30, we learn that Pablo Escobar would kill anyone if it meant that the team he supported would win even a single additional soccer game, a sentiment with which even Ottawa Senators fans were once able to identify. We watch sports as a frivolous distraction and also because theyre better than everything else, profound and important unto themselves.

This idea that spectator sports have intrinsic value is under unprecedented attack, mostly from within the sports industry, which now loudly and repeatedly insists that the games dont mean much. The nationwide proliferation of app-based sports betting, a bipartisan policy innovation encouraged by every league and cheered on by ESPN and other leading broadcasters, has been a revolution in many fans relationships with the games themselves, turning them from a source of entertainment or a focus of emotional investment into a weeknight gambling opportunity.

Sports have also been vulgarized by something worse than money, as fans of the football team now called the Washington Commanders have discovered over the past couple of weeks. Look at the controversy that nearly cost defensive coordinator Jack Del Rio his job and its clear sports are now widely treated as a mere subset of the political ephemera theyd once been able to transcend.

On June 8, Del Rio responded to a question at a press conference about his reliably unhinged right-wing tweets, something that most mature adults who dont work in sports media can easily recognize as the eccentricities of a man who has spent much of his life designing blitz packages. Del Rios response was no more debatable, and no less reflective of public opinion, than, say, Golden State Warriors coach Steve Kerrs widely celebrated postgame sermons about gun control or San Antonio Spurs coach Gregg Popovichs attacks on Columbus Day. Jan. 6 had been a dust-up compared to the dozens of people killed and hundreds of businesses burned, largely in low-income areas, during the racial justice protests of 2020, Del Rio said. Why hadnt that warranted a select committee in Congress, like Jan. 6 had? the coach wondered.

The backlash was swift: Del Rios job was suddenly in danger. A Democratic state senator in Virginia used Dustupgate as a pretext for killing the latest effort to build a publicly funded stadium for the Washington areas NFL team. In a statement issued in the name of head coach Ron Rivera under the rainbow Twitter avatar of the Commanders Pentagon contractorlike logo, the team announced that words have consequences, and [Del Rios] words hurt a lot of people in our community. He was fined $100,000.

A few days later, Rivera assured everyone that he closely reviewed the text of the First Amendment before fining Del Rio, a text that Rivera said he holds sacred and thinks about constantly. This was like the patterned blinking in a hostage video. What Rivera really was saying is that owner Dan Snyder is now under investigation by Congress over claims he embezzled money meant for the other 31 NFL owners and that he was instructed that a prominent coach openly questioning the Jan. 6 committee's very existence during its opening week debut was likely to make the bosss legal situation even more difficult. At least, I think thats what Rivera meant.

NFL teams, and even entire sports leagues, now behave as if theyre in thrall to a larger apparatus, one whose demands are capricious, inconsistent, and very often partisan. Witness the MLBs cancellation of last years All-Star Game in Atlanta over Georgias election law, which was enacted prior to the states record early voting turnout this year. The episode brought on a sadness not for the fans in Atlanta but for the game of baseball itself. Once again, the people who administrate sports at the highest level had demonstrated that the game itself wasn't enough, that some higher purpose than sports needed to be served in order for the games to have any real meaning or legitimacy. Turn off this Tuesday night Pirates-Marlins matchup, the league seemed to say, and watch MSNBC instead.

Sports are political, were now often reminded to deny that sports are but an especially high-profile subsidiary in the struggle for a perfected world is to deny athletes their agency as political actors, akin to demanding that they shut up and dribble. But the sports are political formulation does not empower athletes so much as drag them down to the level of technocratic managerial policymaking types, who are the practical beneficiaries of the ascension of politics to the apex of American life. Titan-like coaches and athletes must participate in the nerdy and annoying political classs self-aggrandizement. Any deviation must be punished. The sports are politics ideology exposes a basic insecurity, a noxious idea that no life should be permitted beyond politics or lived beyond the parameters of what a Washington, D.C., consultant or a Capitol Hill legislative aide might want and care about.

Sports have always shown us that theres another, better way. They presented an image of a public life largely free of factional struggle, where everyones differences of race, of religion, of basic fundamental outlook could be subsumed into a larger goal, such as the defeat of the Philadelphia Eagles. The beliefs of Michael Jordan were famously inscrutable, and the fact that he had cooler and better things to worry about than satisfying someone elses dumb ideological test ended up being crucial to his mystique. Bear Bryant eschewed a career in politics because he knew he had a job much more important than governor of Alabama. Sports were always crucial not as a distraction from politics but as proof that society could sustain a meaningful civic existence in a space beyond politics. Of course, today, that cant be allowed to survive.

Armin Rosen is a New York-based reporter at large forTablet.

Read the original here:

The cheapening of sports - Washington Examiner

Posted in Talmud | Comments Off on The cheapening of sports – Washington Examiner

Jewish Community of Sedona and the Verde Valley: July 1-7 – Sedona.Biz – The Voice of Sedona and The Verde Valley – Sedona.biz

Posted: at 9:29 pm

By Rabbi Alicia Magal

Sedona News Shalom and greetings from the Rabbi, Board of Directors, and congregation of the Jewish Community of Sedona and the Verde Valley.

All the services, classes, and programs are listed on the synagogue website.

Come join us either in person or online. Seejcsvv.orgfor instructions to register for in-person services or online links. Visitors are welcome to attend services.

On Friday, July 1, a Friday evening Erev Shabbat service, led by Rabbi Alicia Magal, begins at 5:30 pm both in person and on Zoom, and livestreamed for members and their invitees. Congregants participate by lighting candles, doing a reading, or having an Aliyah for the Torah service. Verses from the Torah portion will be chanted:Korach (Numbers 16:1 18:32) telling of an uprising against Moses by Korach, a cousin of Moses who gathered supporters to challenge Moses leadership. The Talmud offers commentary to distinguish arguments that are for the sake of heaven vs. arguments that are NOT for the sake of heaven but are based in ego and pride, such as the manipulative words of Korach. Blessings for those who are ill and a Mazal Tov for those celebrating a birthday or anniversary will be offered. Kaddish, the Mourners prayer, will be recited in memory of those who passed away either recently or at this time in past years. Shabbat offers a time out from work and worry, an opportunity to be grateful for our lives and the bounty with which we are blessed.

Wednesday morning minyan begins at 8:30 a.m. on July 6 on zoom. Join the group to offer healing prayers, and to support those saying the mourners prayer, Kaddish, for a loved one who has passed away. Every person counts and is needed!

On Wednesday at 4:00 pm Rosalie Malter will lead a class on Jewish meditation on Zoom. Each session focuses on a different tool or aspect of Jewish meditation practices.

On Thursday, July 7, at 4:00 pm, Torah study, led by Anita Rosenfield, will be held on Zoom. The Torah portion for that week is Hukkat (Numbers 19:1 22:1) telling of the death of Miriam and Aaron, Moses sister and brother. Moses receives the answer to his plea to be able to enter the promised Land. He would not lead the people into the land, but rather Joshua would be his successor. The mysterious ceremony of the red heifer is also part of this weeks portion dealing with ritual impurity and the procedure for regaining ritual purity. Issues of leadership, patience, and faith are themes in this weeks Torah portion.

The Social Action Committee is continuing to collect food for the local Sedona food pantry. Please drop of cans or boxes of non-perishable foods in the bin outside thelower level parking lot entranceto the synagogue.

The Jewish Community of Sedona and the Verde Valley, located at 100 Meadow Lark Drive off Route 179 in Sedona, is a welcoming, egalitarian, inclusive congregation dedicated to building a link from the past to the future by providing religious, educational, social and cultural experiences. Messages to the office telephone at 928 204-1286 will be answered during the week. Updated information is available on the synagogue website http://www.jcsvv.org.

Go here to read the rest:

Jewish Community of Sedona and the Verde Valley: July 1-7 - Sedona.Biz - The Voice of Sedona and The Verde Valley - Sedona.biz

Posted in Talmud | Comments Off on Jewish Community of Sedona and the Verde Valley: July 1-7 – Sedona.Biz – The Voice of Sedona and The Verde Valley – Sedona.biz

Holding The High Line: Rapids Draw NYCFC – Last Word On Sports

Posted: at 9:29 pm

PODCAST Hello Rapids fans! This week on Holding The High Line, we catch up on last weeks news. We discuss MLS coming to Apple TV and All the Small Things that made the Denver World Cup bid fail. The guys discuss Rapids 2 player news. Matts got takes on Sam Nicholson rejoining the club. Then we do Good Thing, Bad Thing, Big Thing on the draw at New York City. We discuss how concerned you should be with Gyasi Zardes, and look ahead to Portland Timbers.

Holding The High Line is an independent soccer podcast focused on the Colorado Rapids of MLS and a member of the Beautiful Game Network. If you like the show, please consider subscribing to us on your preferred podcatcher, giving us a review, and tell other Rapids fans about us. It helps a ton. Visit bgn.fm for a bunch of other great podcasts covering soccer in North America.

We also have anewsletter. Visit ourSubstack pageto read our content and sign up for our newsletter via email.

Find us on iTunes, Google Podcasts, Stitcher, Blubrry, and many other podcatchers. See the full list of podcatchers with subscription links here. For full transcripts of every episode, check out our AudioBurst page. Our artwork was produced by CR54 Designs. Juanners does our music.

We are brought to you by Ruffneck Scarves and Icarus FC. Ruffneckscarves.com is your one-stop-shop for official MLS, USL, and U.S. Soccer scarves as well as custom scarves for your group or rec league team. Icarusfc.com is the place to go for high-quality custom soccer kits for your team or group. With an any design you want, seriously motto, they are breaking the mold of boring, expensive, template kits from the big brands.

Have your team looking fly in 2022 like Andre Shinyashiki with bleached hair with custom scarves and kits from Ruffneck Scarves and Icarus FC.

HTHL is on Patreon. If you like what we do and want to give us money, head on over to our page and become a Patreon Member.

We have partnered up with the Denver Post to sustainably grow soccer journalism in Colorado. Listeners can get a three month trial of the Denver Post digital for 99/month. Go to denverpost.com/hthl to sign up. This will give you unlimited and full access to all of the Posts online content and will support local coverage of the Rapids. Each month after the trial is $11.99/month. There is a sports-content-only option for $6.99/month.

Follow us on Twitter @rapids96podcast. You can also email the show at rapids96podcast@gmail.com. Follow our hosts individually on Twitter @LWOSMattPollard and @soccer_rabbi. Send us questions using the hashtag #AskHTHL.

Matt Pollard is the Site Manager for Last Word on Soccer and an engineer by day. A Colorado Convert, he started covering the Colorado Rapids as a credentialed member of the press in 2016, though hes watched MLS since 96. When hes not watching or writing about soccer, hes being an outdoorsman (mostly skiing and hiking) in this beautiful state or trying a new beer. For some reason, he thought that starting a podcast with Mark was a good idea and he cant figure out how to stop this madness. He also hosts Last Word SC Radio.

Mark Goodman, the artist formally known as Rapids Rabbi, moved to Colorado in 2011. Shortly thereafter he went to Dicks Sporting Goods Park, saw Lee Nguyen dribble a ball with the silky smoothness of liquid chocolate cascading into a Bar Mitzvah fountain, and promptly fell head over heels in love with domestic soccer. When not watching soccer or coaching his sons U-8 team, hes generally studying either Talmud or medieval biblical exegesis. Which explains why he watches so much MLS, probably. Having relocated to Pittsburgh in 2019, he covers the Pittsburgh Riverhounds of the USL for Pittsburgh Soccer Now.

Photo Credit: Mark Shaiken, Last Word on Soccer.

Read the original post:

Holding The High Line: Rapids Draw NYCFC - Last Word On Sports

Posted in Talmud | Comments Off on Holding The High Line: Rapids Draw NYCFC – Last Word On Sports

What the DNA of Ancient Humans Reveals About Pandemics – WIRED

Posted: at 9:28 pm

After Hunts unusual flight home, Shanidar Z made it safely to the University of Cambridge for digital scanning and will eventually be transferred back to northern Iraq to feature as the centerpiece of a new museum. The skeleton could be up to 90,000 years old, but its DNA will be used to further understanding of modern human historyby analyzing and statistically comparing the ancient DNA against the genomes of modern populations, to demonstrate when different population groups parted company, Hunt says.

Once a population splits into two or more reproductively isolated groups, the genes in each new population will evolve gradually in new directions as a result of random gene mutations as well as exposure to various environmental factors that prevent successful reproductioncoming into contact with new diseases, for instance.

Its through work like this that scientists have been able to chart the migration of different populations of humans and Neanderthal groups around the planet over the last 70,000 years, and also bust some myths about their habits and migration patterns. We now know that humans and Neanderthals interbred quite commonly, and that Neanderthal communities were likely more caring and intelligent than weve previously given them credit for. According to Hunt, evidence of burial rituals at the Shanidar Cave suggests memory, and that they looked after their injured and sick members.

Separately, analysis of ancient DNA against the modern human genome has revealed that we still carry some genetic sequences that were present in people living millennia ago. Such analysis even helped to identify a new subspecies of humans 12 years agothis discovery of Denisovans, believed to have existed across Asia around 400,000 years ago, demonstrates how much is still unknown about our human origins.

At the Francis Crick Institute in London, a major project is underway to create a reliable biobank of ancient human DNA to help build on such discoveries. Population geneticist Pontus Skoglund is leading the 1.7 million ($2.1 million) project, which will sequence 1,000 ancient British genomes by gathering data from skeletal samples from the past 5,000 years, with help from around 100 other UK institutions. From the database he hopes to determine how human genetics have changed over millennia in response to factors such as infectious diseases and changes in climate, diet, and migration.

Part of that is looking for genetic traits that may have been advantageous for past humans during earlier epidemics, he says. There is no doubt we can learn something from this in our understanding of how we manage contemporary disease and other outbreaks.

Skoglunds team sources their samples from archaeological digs around the country or from museums with existing collections. His favorite bones to sequence are the ones found in our inner ear: These are particularly good at preserving DNA, since they are the least susceptible to microbial invasion and other factors that could cause DNA to deteriorate, he explains.

The bones are ground down to be run through a sequencing machine in much the same way as any DNA sample. But the ancient DNA requires specialist protocolsmodern DNA has very long fragments that are basically intact, whereas with ancient DNA we only get on average around 35 percent of the total base pairs.

Read more:
What the DNA of Ancient Humans Reveals About Pandemics - WIRED

Posted in Human Genetics | Comments Off on What the DNA of Ancient Humans Reveals About Pandemics – WIRED