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Nrf1-mediated proteosome activity in brown fat is required for the normal thermogenic behavior of this tissue in mice. Adipocytes possess remarkable adaptive capacity to respond to nutrient excess, fasting or cold exposure, and they are thus an important cell type for the maintenance of proper metabolic health. Although the endoplasmic reticulum (ER) is a critical organelle for cellular homeostasis, the mechanisms that mediate adaptation of the ER to metabolic challenges in adipocytes are unclear. Here we show that brown adipose tissue (BAT) thermogenic function requires an adaptive increase in proteasomal activity to secure cellular protein quality control, and we identify the ER-localized transcription factor nuclear factor erythroid 2–like 1 (Nfe2l1, also known as Nrf1) as a critical driver of this process. We show that cold adaptation induces Nrf1 in BAT to increase proteasomal activity and that this is crucial for maintaining ER homeostasis and cellular integrity, specifically when the cells are in a state of high thermogenic activity. In mice, under thermogenic conditions, brown-adipocyte-specific deletion of Nfe2l1 ( Nrf1 ) resulted in ER stress, tissue inflammation, markedly diminished mitochondrial function and whitening of the BAT. In mouse models of both genetic and dietary obesity, stimulation of proteasomal activity by exogenously expressing Nrf1 or by treatment with the proteasome activator PA28α in BAT resulted in improved insulin sensitivity. In conclusion, Nrf1 emerges as a novel guardian of brown adipocyte function, providing increased proteometabolic quality control for adapting to cold or to obesity.

Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

Microbial food spoilage is a major contributor to food waste and, hence, to the negative environmental sustainability impacts of food production and processing. Globally, it is estimated that 15–20% of food is wasted, with waste, by definition, occurring after primary production and harvesting (for example, in households and food service establishments). Although the causative agents of food spoilage are diverse, many microorganisms are major contributors across different types of foods. For example, the genus Pseudomonas causes spoilage in various raw and ready-to-eat foods. Aerobic sporeformers (for example, members of the genera Bacillus, Paenibacillus and Alicyclobacillus) cause spoilage across various foods and beverages, whereas anaerobic sporeformers (for example, Clostridiales) cause spoilage in a range of products that present low-oxygen environments. Fungi are also important spoilage microorganisms, including in products that are not susceptible to bacterial spoilage due to their low water activity or low pH. Strategies that can reduce spoilage include improved control of spoilage microorganisms in raw material and environmental sources as well as application of microbicidal or microbiostatic strategies (for example, to products and packaging). Emerging tools (for example, systems models and improved genomic tools) represent an opportunity for rational design of systems, processes and products that minimize microbial food spoilage.In this Review, Snyder et al. discuss the global impacts of food spoilage, mechanisms and causative agents, and strategies and emerging tools to control microbial food spoilage.

The timeliness, accuracy, and completeness of data for firearm injury surveillance is crucial for public health surveillance efforts and informing injury prevention measures. While emergency department (ED) visit data can provide near real-time information on firearms injuries, there are concerns surrounding the accuracy of intent coding in these data. We examined whether emergency medical service (EMS) data provide more accurate firearm injury intent coding in comparison to ED data. We applied a firearm injury definition to EMS encounter data in NC's statewide syndromic surveillance system (NC DETECT), from January 1, 2021, through December 31, 2022. We manually reviewed each record to determine intent, and the corresponding manual classifications were compared to the injury cause codes entered in the EMS data and to ED visit records where EMS-ED record linkage was possible. We then calculated the sensitivity, specificity, positive and negative predictive values for each intent classification in SAS 9.4 using the manually reviewed intent classifications as the gold standard. We identified 9557 EMS encounters from January 1, 2021, through December 31, 2022 meeting our firearm injury definition. After removing false positives and duplicates, 8584 records were available for manual injury classification. Overall, our analysis demonstrated that manual and EMS injury cause code classifications were comparable. However, for the 3401 EMS encounters that could be linked to an ED visit record, sensitivity of the ED ICD-10-CM codes was low for assault and intentional self-harm encounters at 18.2% (CI 16.5-19.9%) and 22.2% (CI 16-28.5%), respectively. This demonstrates a marked difference in the reliability of the intent coding in the two data sources. This study illustrates both the value of examining EMS encounters for firearm injury intent, and the challenges of accurate intent coding in the ED setting. EMS coding has the potential for more accurate intent coding than ED coding within the context of existing hospital-based coding guidance. This may have implications for future firearm injury research, especially for nonfatal firearm injuries.

Non-monogamous mating behaviors including polygyny or extra-pair paternity are theorized to amplify sexual selection, since some males attract multiple mates or copulate with paired females. In several well-studied songbird species, females prefer more complex songs and larger repertoires; thus, non-monogamous mating behaviors are predicted to accelerate song evolution, particularly toward increased complexity. However, studies within songbird clades have yielded mixed results, and the effect of non-monogamy on song evolution remains unclear. Here, we construct a large-scale database synthesizing mating system, extra-pair paternity, and song information and perform comparative analyses alongside songbird genetic phylogenies. Our results suggest that polygyny drives faster evolution of syllable repertoire size (measured as average number of unique syllables), but this rapid evolution does not produce larger repertoires in polygynous species. Instead, both large and small syllable repertoires quickly evolve toward moderate sizes in polygynous lineages. Contrary to expectation, high rates of extra-pair paternity coincide with smaller repertoires. Sexual selection is expected to be intensified in non-monogamous mating systems; in birds this might accelerate song evolution. Here, the authors show that across songbirds, polygyny and extra-pair paternity are associated with faster syllable repertoire size evolution and smaller repertoire size, respectively.

Staphylococcus aureus is capable of infecting nearly every organ in the human body. In order to infiltrate and thrive in such diverse host tissues, staphylococci must possess remarkable flexibility in both metabolic and virulence programs. To investigate the genetic requirements for bacterial survival during invasive infection, we performed a transposon sequencing (TnSeq) analysis of S. aureus during experimental osteomyelitis. TnSeq identified 65 genes essential for staphylococcal survival in infected bone and an additional 148 mutants with compromised fitness in vivo. Among the loci essential for in vivo survival was SrrAB, a staphylococcal two-component system previously reported to coordinate hypoxic and nitrosative stress responses in vitro. Healthy bone is intrinsically hypoxic, and intravital oxygen monitoring revealed further decreases in skeletal oxygen concentrations upon S. aureus infection. The fitness of an srrAB mutant during osteomyelitis was significantly increased by depletion of neutrophils, suggesting that neutrophils impose hypoxic and/or nitrosative stresses on invading bacteria. To more globally evaluate staphylococcal responses to changing oxygenation, we examined quorum sensing and virulence factor production in staphylococci grown under aerobic or hypoxic conditions. Hypoxic growth resulted in a profound increase in quorum sensing-dependent toxin production, and a concomitant increase in cytotoxicity toward mammalian cells. Moreover, aerobic growth limited quorum sensing and cytotoxicity in an SrrAB-dependent manner, suggesting a mechanism by which S. aureus modulates quorum sensing and toxin production in response to environmental oxygenation. Collectively, our results demonstrate that bacterial hypoxic responses are key determinants of the staphylococcal-host interaction.

In this study of injured U.S. military personnel, an advanced MRI technique found abnormalities consistent with traumatic axonal injury in some patients with mild traumatic brain injury after blasts; these abnormalities were not detected with conventional MRI. In the current wars in Iraq and Afghanistan, the number of blast-related traumatic brain injuries may be as high as 320,000. 1 Most of these injuries are categorized as uncomplicated “mild” or “concussive” traumatic brain injury on the basis of clinical criteria and the absence of intracranial abnormalities on computed tomography (CT) or conventional magnetic resonance imaging (MRI). 2 However, little is known about the nature of these “mild” injuries, and the relationship between traumatic brain injury and outcomes remains controversial. 3 , 4 No human autopsy studies conducted with the use of current immunohistochemical methods 5 , 6 have been published. 7 , 8 Computer simulations of . . .

Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans . MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids—a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging. Papsdorf et al. show that mono-unsaturated fatty acids extend lifespan of C. elegans through induction of peroxisomes and lipid droplets in fat tissues and of a lipid signature predictive of decreased lipid oxidation.

Although matriliny and matrilocality are relatively rare in contemporary human populations, these female-based descent and residence systems are present in different cultural contexts and across the globe. Previous research has generated numerous hypotheses about which cultural traits are associated with the stability or loss of matrilineal descent. In addition, several studies have examined matrilineal descent with phylogenetic analyses; however, the use of language phylogenies has restricted these analyses to comparisons within a single language family, often confined to a single continent. Cross-cultural comparisons are particularly informative when they account for the relationships between widely distributed populations, as opposed to treating each population as an independent sample or focusing on a single region. Here, we study the evolution of descent systems on a worldwide scale. First, we test for significant associations between matriliny and numerous cultural traits that have been theoretically associated with its stability or loss, such as subsistence strategy, animal domestication, mating system, residence pattern, wealth transfer and property succession. In addition, by combining genetic and linguistic information to build a global supertree that includes 16 matrilineal populations, we also perform phylogenetically controlled analyses to assess the patterns of correlated evolution between descent and other traits: for example, does a change in subsistence strategy generally predict a shift in the rules of descent, or do these transitions happen independently? These analyses enable a worldwide perspective on the pattern and process of the evolution of matriliny and matrilocality. This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals’.

The quality of a bird’s song during courtship can influence whether a male is selected as a mate. An innovative approach using machine learning offers a way to analyse the characteristics of birdsong. Innovative approach analyses birdsong characteristics.