N-acetyltaurine is a metabolite whose levels fluctuate with diet and exercise and that undergoes hydrolysis to form taurine and acetate. However, the enzymes that facilitate this reaction were not known. In an effort to address this, Wei et al. used liquid chromatography–mass spectrometry-based activity guided analysis of mouse tissues, detecting high N-acetyltaurine hydrolysis activity in kidney and

The formation of pathological protein aggregates occurs in many neurodegenerative diseases, such as the aggregation of the protein tau in patients with Alzheimer’s disease. Removing these aggregates offers a possible route to treat these protein misfolding diseases; however, targeting the aggregated form of a protein while sparing the monomeric form, which is required for normal cellular function,

By coupling rPAL to enzymatic glycan cleavage and sequential window acquisition of all theoretical mass spectra (SWATH-MS), the team found that acp3U was the most enriched linker (although other putative linker substrates were identified). Importantly, knocking out DTWD2, an enzyme responsible for installing acp3U in tRNAs, reduced glycoRNA levels. This study provides not only a useful tool for glycoRNA

ER-phagy, a selective form of autophagic degradation of endoplasmic reticulum (ER) fragments, plays an essential role in governing ER homeostasis. Dysregulation of ER-phagy is associated with the unfolded protein response (UPR), which is a major clue for evoking inflammatory diseases. However, the molecular mechanism underpinning the connection between ER-phagy and disease remains poorly defined. Here

Lipidated ATG8/LC3 proteins are recruited to single membrane compartments as well as autophagosomes, supporting their functions. Although recent studies have shown that Golgi-LC3 lipidation follows Golgi damage, its molecular mechanism and function under Golgi stress remain unknown. Here, by combining DLK1 overexpression as a new strategy for induction of Golgi-specific LC3 lipidation, and the application

CD8 + T cells have critical roles in tumor control, but a range of factors in their microenvironment such as low pH can suppress their function. Here, we demonstrate that acidity restricts T-cell expansion mainly through impairing IL-2 responsiveness, lowers cytokine secretion upon re-activation, and reduces the cytolytic capacity of CD8 + T cells expressing low-affinity TCR. We further find decreased

Researchers from Kenya’s Egerton University and Makerere University in Uganda begin a pilot program to mass breed desert locusts as a sustainable, protein-rich food source for animals and humans. The locusts are grown in giant domed-shaped, temperature- and humidity-controlled greenhouses equipped with wire gauze cages to stop them escaping. The Locust4Industry project aims to enable industrial exploitation

Voranigo (vorasidenib), made by French drugmaker Servier Pharmaceuticals, was approved in August by the US Food and Drug Administration. The small-molecule isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor has the go-ahead to treat patients with grade 2 astrocytoma or oligodendroglioma with IDH1 or IDH2 mutations. The approval follows a successful phase 3 trial showing

Macromolecular drugs have limited applications in the brain because they cannot cross the blood–brain barrier. A parasite that does have the natural capacity to travel to the brain is Toxoplasma gondii. In a study in Nature Microbiology, Bracha et al. make use of this feature, engineering T. gondii to deliver large proteins to the brains of mice. The authors targeted several proteins with different

Genentech, part of Roche, has signed an exclusive license with Sangamo Therapeutics to develop genomic treatments for two neurodegenerative diseases. Sangamo will receive $50 million up front and could earn up to $1.9 billion in development and commercial milestone payments plus tiered royalties for its proprietary zinc finger repressors directed to the gene encoding the tau protein, which is involved

Nearly a century later, in a bungalow three blocks from the sun-baked crowds of Rockaway Beach, New York, Karen Ingram meticulously paints portraits of flower blossoms in a Petri dish using a medium of yeast. She calls her series “Biogenetic Blooms”: blue roses, yellow and orange daffodils, red tulips, pink orchids, columbines, snapdragons, irises, black-eyed Susans. The process is surprisingly tricky

Specific microbial communities in the female genital tract are linked to health outcomes; for example, a microbiome deficient in Lactobacillus is observed in bacterial vaginosis. However, available therapies may not effectively promote the growth of beneficial bacterial species that could prevent the recurrence of disease. Writing in Cell, Zhu et al. propose that targeting unsaturated long-chain fatty

On this episode, our Associate Editor Cláudia Vilhena interviews Nicoletta Cieri, the first author of a great story on how a devised analytic framework can aid in the prevention of post-transplant disease recurrence. Join us as Nicoletta and Cláudia explore the highlights of the story, discuss the future of individualized medicine and touch base on future career opportunities following the postdoc

Recent patents relating to compositions and methods for the remediation of polluted and contaminated environments.

A historic law that negotiates price discounts for Medicare prescription drugs has led to the selection of the first ten drugs to be covered by these negotiations. From January 2026, enrollees will pay between 38% and 79% less for the ten commonly prescribed outpatient drugs. The negotiated prices are expected to save taxpayers billions of dollars. The biopharma industry, however, argues that the prices

Although stem-cell derived organoids are useful tools for studying epithelial functions in health and disease, they generally lack the immune compartment critical for modeling organ-level processes. In a paper published in Nature, Recaldin et al. now integrate tissue-resident memory T (TRM) cells into human intestinal organoids and show how this model can be used to gain insight into drug-induced intestinal

A semiannual snapshot of job expansions, reductions and availability in the biotech and pharma sectors.

Spreading powdered basalt on farmland traps CO2 from the atmosphere, a technology that is cheap, requires no huge steel reactors and, with a biotech boost, may even reduce fertilizer use.

Recent moves of note in and around the biotech and pharma industries.

Scientists are using ever more sophisticated AI algorithms trained on vast, unlabeled datasets to develop models that can ‘interpret’ biological data to help guide biomolecule design.

To maintain protein homeostasis in changing nutrient environments, cells must precisely control the amount of their proteins, despite the accompanying changes in cell growth and biosynthetic capacity. As nutrients are major regulators of cell cycle length and progression, a particular challenge arises for the nutrient-dependent regulation of 'cell cycle genes', which are periodically expressed during

Cholesterol-dependent cytolysins (CDCs) are the distinct class of β-barrel pore-forming toxins (β-PFTs) that attack eukaryotic cell membranes, and form large, oligomeric, transmembrane β-barrel pores. Listeriolysin O (LLO) is a prominent member in the CDC family. As documented for the other CDCs, membrane cholesterol is essential for the pore-forming functionality of LLO. However, it remains obscure

In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization

The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon

Despite their role as innate sentinels, macrophages can serve as cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use of viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 and E2 as critical for virion production in THP-1 derived human macrophages

Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion

Basal-like breast cancer may originate from luminal epithelial or cancerous cells. Inadequately repaired DNA damage impairs luminal differentiation and promotes aberrant luminal to basal trans-differentiation in mammary epithelial cells (MECs). Ubiquitin-specific peptidase 11 (USP11), a deubiquitinase, plays a critical role in DNA damage repair. The role of USP11 in controlling mammary cell differentiation

Dynamic ADP-ribosylation signalling is a crucial pathway that controls fundamental cellular processes, in particular, the response to cellular stresses such as DNA damage, reactive oxygen species and infection. In some pathogenic microbes the response to oxidative stress is controlled by a SirTM/zinc-containing macrodomain (Zn-Macro) pair responsible for establishment and removal of the modification

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator (PAM) of gamma-aminobutyric acid type A (GABAA) receptors. Several potential propofol binding sites that may mediate this effect have been identified using propofol-analogue photoaffinity labeling. o-PD labels β-H267, a pore-lining residue, whereas AziPm labels residues β-M286, β-M227 and α-I239 in the two

Amino acid transporters play a vital role in cellular homeostasis by maintaining protein synthesis. L-type amino acid transporter 1 (LAT1/SLC7A5/CD98lc) is a major transporter of large neutral amino acids in cancer cells because of its predominant expression. Although amino acid restriction with various amino acid analog treatments is known to induce mitotic defects, the involvement of amino acid transporters

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis

Phosphorylation is a key post-translational modification regulating protein function and biological outcomes. However, the phosphorylation dynamics orchestrating mammalian oocyte development remains poorly understood. In the present study, we apply high-resolution mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of mouse oocyte phosphorylation. Of more than

Microbes have evolved intricate communication systems that enable individual cells of a population to send and receive signals in response to changes in their immediate environment. In the fission yeast Schizosaccharomyces pombe, the oxylipin nitrogen signaling factor (NSF) is part of such communication system, which functions to regulate the usage of different nitrogen sources. Yet, the pathways and

ASAP1 and its paralog ASAP2 belong to a PI4,5P2-dependent Arf GTPase-activating protein (Arf-GAP) family capable of modulating membrane and cytoskeletal dynamics. ASAPs regulate cell adhesive structures such as invadosomes and focal adhesions during cell attachment and migration. Malfunctioning of ASAP1 has been implicated in the malignant phenotypes of various cancers. Here, we discovered that the

Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European chronic pancreatitis cohorts. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases. Proteolysis of the PNLIP variants yielded an intact

Tauopathies, including Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy, are characterised by the aggregation of tau into insoluble neurofibrillary tangles in the brain. Tau is subject to a range of post-translational modifications, including proteolysis, that can promote its aggregation. Neuroinflammation is a hallmark of tauopathies and evidence is growing for a role

The Cas3 nuclease is utilized by canonical type I CRISPR-Cas systems for processive target DNA degradation, while a newly identified type I-F CRISPR variant employs an HNH nuclease domain from the natural fusion Cas8-HNH protein for precise target cleavage both in vitro and in human cells. Here, we report multiple cryo-electron microscopy structures of the type I-F Cas8-HNH system at different functional