PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.

Mapping transcriptomic variations using either short- or long-read RNA sequencing is a staple of genomic research. Long reads are able to capture entire isoforms and overcome repetitive regions, whereas short reads still provide improved coverage and error rates. Yet, open questions remain, such as how to quantitatively compare the technologies, can we combine them, and what is the benefit of such a combined view? We tackle these questions by first creating a pipeline to assess matched long- and short-read data using a variety of transcriptome statistics. We find that across data sets, algorithms, and technologies, matched short-read data detects ~30% more splice junctions, such that ~10%–30% of the splice junctions included at ≥20% by short reads are missed by long reads. In contrast, long reads detect many more intron-retention events and can detect full isoforms, pointing to the benefit of combining the technologies. We introduce MAJIQ-L, an extension of the MAJIQ software, to enable a unified view of transcriptome variations from both technologies and demonstrate its benefits. Our software can be used to assess any future long-read technology or algorithm and can be combined with short-read data for improved transcriptome analysis.

The human major histocompatibility complex (MHC) is a ~4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%–99.9% with at least 30x depth) and high accuracy (99.89%–99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine.

Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.

Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer.

The Cassini mission’s samples from Saturn’s moon Enceladus have signs of various organic molecules that could be among the ingredients needed for life to get started

Complex carbon-based molecules crucial to life on Earth originated somewhere in space, but we didn't know where. Now, huge amounts of them have been spotted in a huge, cold cloud of gas

In its annual report, the Food Safety Authority of Ireland (FSAI) warned that food incidents are becoming more complex and often serious. FSAI marked its 25th anniversary in 2023. External challenges impacting food safety include the potential for supply disruption due to political unrest in the Middle East and the... Continue Reading

From assembling delicate electronics to constructing safety-critical aerospace components, the margin for error has shrunk to almost nothing. To meet these rigorous standards, the manufacturing industry increasingly relies on robotic precision. Modern robotics, equipped with advanced sensors, grippers, and AI, allow manufacturers to complete intricate tasks with extraordinary accuracy. Technological Innovations Driving Robotic Precision Today’s […]

The post Robotic Precision in Manufacturing: Achieving High Accuracy for Complex Tasks appeared first on Chart Attack.

By Ankit Mahadevia, former CEO of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC Drug development is complex. So is running a business. Sometimes, the work of doing both can make your head spin. In my

The post Boiling It Down: Conveying Complexity For Decision-makers appeared first on LifeSciVC.

This paper provides a high-level tour of five modern approaches to model building that are available in recent releases of SAS/STAT.

Complex carbon-based molecules crucial to life on Earth originated somewhere in space, but we didn't know where. Now, huge amounts of them have been spotted in a huge, cold cloud of gas

It is no secret that recent Arab uprisings have placed enormous burdens on the shoulders of BBC Arabic journalists responsible for reporting news from the region.

Covering the Arab world is not always an easy task - we need to mix sensible caution with a dose of courage in covering political issues that attract so many disputed views among Arabic-speaking audiences.

Our guiding principles are the BBC's values, its editorial guidelines, its ethical code, which are our reference points to maintain impartial, balanced and accurate reporting.

Across the Arab world - whether it's Tunisia, Yemen, Egypt or Libya, Bahrain, Syria and Iraq or the many other countries in the region - we know that audiences want access to objective and independent news, far removed from an agenda that favours one party, religion or sect against another. That is why audiences are turning to BBC Arabic.

Last year, our latest figures show that overall audiences to BBC Arabic have risen by more than 17% to a record high of 25.3 million adults weekly. That includes a big surge of 2.9 million in Saudi Arabia and 2.7 million in Egypt, where TV viewers in particular turned to the BBC to better understand the events happening in their own country. Our radio audiences are also holding up despite the reductions in transmission. Online is proving to be more of a challenge, but we are working hard to understand the needs of digital audiences and those for whom social media plays an increasingly important part in their lives.

In 2011, following the fall of the Mubarak leadership, we watched as ordinary Egyptians carried banners saying "Thank you, BBC!" But meeting the high expectation of audiences has a price and sometimes it's been a heavy one.

March 2011 brought a strong reminder of the risks that our staff face in covering the news - one of our reporters was arrested and tortured by Muammar Gaddafi's forces during the Libya uprising. In early 2012, our reporter in Yemen was beaten and received death threats from supporters of the outgoing president.

We are also challenged by those who disagree with our coverage. In countries such as Syria and Bahrain, BBC Arabic has been accused of bias.

The criticism comes from opposition and government alike. It may be a valid argument to say that getting criticism from both sides, in the case of Arab world certainly, is an indication of balanced coverage.

On Syria, for example, we had a series of documentaries looking at the civil war from a number of perspectives.

The first one, exploring what it's like to work for a Syrian television channel that's the mouthpiece of the government, was the butt of criticism and threats from Syrian opposition quarters. We followed it up with a programme charting a day in the lives of six Syrian women, five of whom were anti-government activists.

In our day-to-day news coverage, presenting a variety of voices from Syria is essential to us. And that is what distinguishes BBC Arabic from many media outlets in the Arab world which promote political views and agendas, and that is what we are determined to keep.

BBC Arabic marked its 75th anniversary in January. Arab politicians and ordinary people have expressed their appreciation of our track record of impartiality and trusted news. I am confident that the coming years will see further achievement on all our platforms - TV, radio and online.

Nature-based Solutions (NbS) are a hot topic in environment and landscape planning networks. But are they a silver bullet for solving the climate crisis?

The post Greening gray infrastructure: uncovering the complexity of Nature-based Solutions first appeared on International Water Management Institute (IWMI).

Using cryo-electron microscopy the atomic structure of the "APOBEC3G-Vif complex" has been unveiled by scientists (!--ref1--). h2 What is APOBEC3G

Patient Safety, Treatment Advances, Complex Healthcare Issues to Dominate D.C. Nursing Conference, Hosted by the America