Unlocking the Genetic Puzzle of Obesity Across Sexes and Ages – SciTechDaily

A study has identified genes that influence obesity risk differently across sexes and age groups, offering new insights into the biological pathways of obesity. These discoveries underscore the importance of considering sex and age in obesity research and could lead to new treatments.

Researchers have discovered genes that impact obesity risk differently in men and women and across various ages, revealing potential new pathways for understanding and treating obesity.

From influencing how our body stores fat to how our brain regulates appetite, hundreds of genes, along with environmental factors, collectively determine our weight and body size. Now, researchers add several genes, that appear to affect obesity risk in certain sexes and ages, to that list. The study, published in the journal Cell Genomics, may shed light on new biological pathways that underlie obesity and highlight how sex and age contribute to health and disease.

There are a million and one reasons why we should be thinking about sex, age, and other specific mechanisms rather than just lumping everyone together and assuming that disease mechanism works the same way for everyone, says senior author John Perry, a geneticist and professor at the Wellcome-MRC Institute of Metabolic Science, University of Cambridge, U.K. Were not expecting people to have completely different biology, but you can imagine things like hormones and physiology can contribute to specific risks.

To untangle sexs role in obesity risk, the research team sequenced the exomethe protein-coding part of the genomeof 414,032 adults from the UK Biobank study. They looked at variants, or mutations, within genes associated with body mass index (BMI) in men and women, respectively. Based on height and weight, BMI is an estimated measurement of obesity. The search turned up five genes influencing BMI in women and two in men.

Researchers identified age-specific and sex-specific obesity genes by looking into the genome of 414,032 people from the UK. Credit: Cell Genomics/Kaisinger et al.

Among them, faulty variants of three genesDIDO1, PTPRG, and SLC12A5are linked to higher BMI in women, up to nearly 8 kg/m more, while having no effect on men. Over 80% of the women with DIDO1 and SLC12A5 variants had obesity, as approximated by their BMI. Individuals carrying DIDO1 variants had stronger associations with higher testosterone levels and increased waist-to-hip ratio, both risk indicators for obesity-related complications like diabetes and heart disease. Others with SLC12A5 variants had higher odds of having type 2 diabetes compared with non-carriers. These findings highlight previously unexplored genes that are implicated in the development of obesity in women but not men.

Perry and his colleague then repeated their method to look for age-specific factors by searching for gene variants associated with childhood body size based on participants recollections. They identified two genes, OBSCN and MADD, that were not previously linked to childhood body size and fat. While carriers of OBSCN variants had higher odds of having higher weight as a child, MADD variant carriers were associated with smaller body sizes. In addition, the genetic variants acting on MADD had no association with adult obesity risk, highlighting age-specific effects on body size.

Whats quite surprising is that if you look at the function of some of these genes that we identified, several are clearly involved in DNA damage response and cell death, says Perry. Obesity is a brain-related disorder, whereas biological and environmental factors act to influence appetite. Theres currently no well-understood biological paradigm for how DNA damage response would influence body size. These findings have given us a signpost to suggest variation in this important biological process may play a role in the etiology of obesity.

Next, the research team hopes to replicate the study in a larger and more diverse population. They also plan to study the genes in animals to peer into their function and relationship with obesity.

Were at the very earliest stages of identifying interesting biology, says Perry. We hope the study can reveal new biological pathways that may one day pave the way to new drug discovery for obesity.

Reference: Large-scale exome sequence analysis identifies sex- and age-specific determinants of obesity by Lena R. Kaisinger, Katherine A. Kentistou, Stasa Stankovic, Eugene J. Gardner, Felix R. Day, Yajie Zhao, Alexander Mrseburg, Christopher J. Carnie, Guido Zagnoli-Vieira, Fabio Puddu, Stephen P. Jackson, Stephen ORahilly, I. Sadaf Farooqi, Laura Dearden, Lucas C. Pantaleo, Susan E. Ozanne, Ken K. Ong and John R.B. Perry, 2 August 2023, Cell Genomics. DOI: 10.1016/j.xgen.2023.100362

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Unlocking the Genetic Puzzle of Obesity Across Sexes and Ages - SciTechDaily

Futures Fall; Elon Musk Makes This Tesla Threat – Investor’s Business Daily

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Infestation 88 Has Already Changed Its Name Due To Nazi Connotations – TheGamer

Earlier this week, indie developer Nightmare Forge Games announced its new title Infestation 88, wasting no time capitalizing on Steamboat Willie becoming public domain. The game blew up on social media for its use of Disney's beloved mascot as a huge hulking monster players have to avoid, but people began to raise eyebrows over the game's name.

According to the Anti-Defamation League, the number 88 is a "white supremacist numerical code" used by neo-Nazis to symbolize the phrase "Heil Hitler". The letter "H" is the eighth letter of the alphabet, which stands to reason that 88 equals "HH". After basking in its newfound attention, Nightmare Forge Games quickly addressed the Nazi connotations of its game's name, and has changed the game's name to Infestation: Origins.

In a statement to Inverse, Nightmare Forge Games claimed that it was "unaware" of the implications that the number 88 would give off, and that the game was previously titled Infestation 88 in reference to the year the game is set. When asked whether the team behind the game are neo-Nazis themselves, it simply claimed "No, we are not."

Unfortunately, when announcing the game, we were unaware of the additional implications associated with the number 88. Our game is set in the 1980s, with the year 1988 being chosen simply for its symmetrical design in our game's artwork.

That would usually be enough to put the situation to bed, but mysteries still surround the project regarding who is actually behind development. Nightmare Forge Games is supposedly made up of a team of "industry veterans" who have been making horror games for over a decade, but none of the staff is disclosed on the studio's website. When asked about this, Nightmare Forge Games said it was to "maintain privacy" due to the large amount of social media attention.

There are also claims on Twitter that the game's official Discord has "out/proud neo-Nazis" on its mod team, though there's little in the way of proof besides some tasteless "edgy" jokes. Others have pointed out that the number 14 (also considered a neo-Nazi hate symbol) appears a lot in the game's marketing, with the title "Infestation 88" being made up of 14 characters and the studio being made up of industry veterans that supposedly have 14 years of experience.

Another example that people have raised concerns over is the game's description, which claimed that the game is a 1-4 player co-op title (another reference to the number 14) that has you exterminating an "outbreak of vermin". It seems as though this description has since been changed, though another reference to the number 14 can be seen in the found footage section of the game's trailer, which was captured on October 13, 1988, meaning the game likely takes place on October 14.

It gets to the point where you need to start busting out the red string, but it's worth noting that potential Nazi dog whistles like these are usually deliberately obscure and confusing so those behind them can feign ignorance. It's entirely possible that people are seeing something that isn't there and that it's all just a huge misunderstanding, but the general feeling is that there are too many coincidences piling up for it to be just one minor mistake.

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Infestation 88 Has Already Changed Its Name Due To Nazi Connotations - TheGamer

NASA Laser Reflecting Instruments to Help Pinpoint Earth Measurements – NASA

The best known use of GPS satellites is to help people know their location whether driving a car, navigating a ship or plane, or trekking across remote territory. Another important, but lesser-known, use is to distribute information to other Earth-viewing satellites to help them pinpoint measurements of our planet.

NASA and several other federal agencies, including the U.S. Space Force, U.S. Space Command,the U.S. Naval Research Laboratory, and the National Geospatial-Intelligence Agency are improving the location accuracy of these measurements down to the millimeter with a new set of laser retroreflector arrays, or LRAs.

The primary benefit of laser ranging and LRAs is to improve the geolocation of all of our Earth observations, said Stephen Merkowitz, project manager for NASAs Space Geodesy Project at NASAs Goddard Space Flight Center in Greenbelt, Maryland.

A team of scientists and engineers with the project tested these arrays earlier this year to ensure they were up to their task and they could withstand the harsh environment of space. Recently the first set of these new laser retroreflector arrays was shipped to the U.S. Space Force and Lockheed Martin in Littleton, Colorado, to be added to the next generation of GPS satellites.

How do Laser Retroreflector Arrays Work?

Laser retroreflector arrays make it possible to do laser ranging using small bursts of laser light to detect distances between objects. Pulses of laser light from a ground station are directed toward an orbiting satellite, which then reflect off the array and return to the station. The time it takes for the light to travel from the ground to the satellite and back again can be used to calculate the distance between the satellite and the ground.

Laser ranging and laser retroreflector arrays have been part of space missions for decades, and they are currently mounted on and essential to the operation of Earth-viewing satellites like ICESat-2 (Ice, Cloud, and land Elevation satellite 2), SWOT (Surface Water and Ocean Topography), and GRACE-FO (Gravity Recovery and Climate Experiment Follow On). LRAs for laser ranging were even deployed on the surface of the Moon during the Apollo missions.

The LRAs are special mirrors, said Merkowitz. Theyre different from a normal mirror because they bounce back light directly towards its original source.

For laser ranging, scientists want to direct light beams back to the original source. They do this by placing three mirrors at right angles, essentially forming an inside corner of a cube. The laser retroreflector arrays are made up of an array of 48 of these mirrored corners.

When light enters the array, due to those 90-degree angles, the light will bounce and take a series of reflections, but the output angle will always come out at the same angle as the one that came in, said Zach Denny, optical engineer for the Space Geodesy Project at Goddard.

What Will Laser Retroreflector Arrays Help?

Geodesy is the study of Earths shape, as well as its gravity and rotation, and how they all change over time. Laser ranging to laser retroreflector arrays is a key technique in this study.

The surface of Earth is constantly changing in small ways due to shifting tectonic plates, melting ice, and other natural phenomena. With these constant shifts and the fact that Earth is not a perfect sphere there must be a way to define the measurements on Earths surface. Scientists call this a reference frame.

Not only do these arrays and laser ranging help to precisely locate the satellites in orbit, but they also provide accurate positioning information for the ground stations back on Earth. With this information, scientists can even go so far as to find the center of the mass of Earth, which is the origin, or zero point, of the reference frame.

Geodetic measurements laser ranging to reference satellites like LAGEOS (Laser Geodynamic Satellites) are used to constantly determine the location of Earths center of mass down to a millimeter. These measurements are critical for enabling scientists to assign a longitude and latitude to satellite measurements and put them on a map.

Significant events like tsunamis and earthquakes can cause small changes to the Earths center of mass. Scientists need accurate laser ranging measurements to quantify and understand those changes, said Linda Thomas, a research engineer at the U.S. Naval Research Laboratory in Washington.

Satellite measurements of subtle but important Earth phenomena, such as sea level rise, rely on an accurate reference frame. The long-term global trend of sea level rise, as well as its seasonal and regional variations, occur at rates of just a few millimeters a year. The reference frame needs to be more accurate than such changes if scientists want to accurately measure them.

Geodesy is a fundamental part of our daily lives because it tells us where we are and it tells us how the world is changing, said Frank Lemoine, project scientist for NASAs Space Geodesy Project.

ByErica McNameeNASAs Goddard Space Flight Center, Greenbelt, Md.

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NASA Laser Reflecting Instruments to Help Pinpoint Earth Measurements - NASA