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Lilly buys Verve and its in vivo gene editors for up to US$1.3 billion

Acetylation of microtubule-binding PinX1 orchestrates ribosome biogenesis to nutrient starvation via the RNA polymerase I preinitiation complex

Long lasting effects of perinatal exposure to the Chlorpyrifos pesticide on sleep, breathing, and neuroinflammation in adult mice

Early-life exposure to environmental stressors may increase the risk of disease later in life. Chlorpyrifos (CPF), a widely used pesticide and acetylcholinesterase inhibitor, can cross the placental barrier and can be found in breast milk, leading to excessive cholinergic stimulation. Acetylcholine is involved in sleep and respiratory regulation. The main objective of this study was to investigate whether perinatal CPF exposure affects sleep-related breathing together with promotion of neuroinflammatory processes in adulthood. To explore these effects, CPF (5 mg/kg/day) or vehicle was administered orally to dams from mating to weaning. The offspring were not directly treated. At 17–18 weeks of age, male and female offspring underwent electroencephalographic and electromyographic electrode implantation to monitor sleep-wake cycles. Recordings were conducted over 48 hours in home cages, and for 7 hours in a plethysmographic chamber to assess sleep-related breathing pattern. At the end of recordings, hippocampal tissues were collected for gene expression analysis via real-time PCR. Results revealed that CPF perinatal exposure increased sighs and apneas during sleep in adult mice, especially in female. Additionally, expression of pro-inflammatory cytokines was upregulated while expression of peroxisome proliferator-activated receptor genes was downregulated in the hippocampus of female mice born to CPF-treated dams. These findings suggest that perinatal CPF exposure can induce long-lasting alterations in sleep-related respiratory patterns and hippocampal inflammatory responses, with a sex-specific susceptibility—females being more affected. This highlights the perinatal period as a critical window of vulnerability to environmental toxicants such as pesticides. The results support the hypothesis that adult sleep and brain inflammation phenotypes may be modulated by early-life chemical exposures during pregnancy and lactation.

The US biosimilars market after one decade

O-GlcNAcylation of fatty acid synthase is required for its proper subcellular localization, expression level, and activity

Mental and physical health of US rural/urban caregivers of persons with dementia

Purpose Increased dependence on caregiving and limited access to healthcare services in rural US communities may contribute to worse mental and physical health in rural caregivers of persons with dementia (PWD) relative to their urban counterparts. We assessed the association between rural/urban residence and mental and physical health among US caregivers of PWD. Methods Using 2020–2022 Behavioral Risk Factor Surveillance System data, we identified caregivers of PWD from rural (n = 2311) and urban (n = 15094) areas. Mental health outcome was operationalized as poor mental health days (PMHD); categorized as 0, 1–13, and ≥14 PMHD in previous month. Poor physical health (PPHD) was operationalized in the same manner. Covariates included socio-demographic and caregiving factors. Four sets of unadjusted and adjusted survey-weighted multinomial logistic models (reference: 0 days) were created for PMHD and PPHD. Results Approximately, 25.7% of rural and 20.8% of urban caregivers reported ≥14 PMHD while 25% of rural and 10% of urban caregivers reported ≥14 PPHD. Prior to adjustment, rural caregivers had lower odds (0.59, 95% CI: 0.34–1.05) of 1–13 vs. 0 PMHD but higher odds (1.13, 95% CI: 0.55–2.30) of 14 + vs 0 PMHD compared to urban caregivers with neither association being statistically significant. In adjusted models, the association for 1–13 vs 0 PMHD became significant, while rural residence became associated with lower, non-significant odds of 14 + vs. 0 PMHD. For physical health, rural caregivers had lower odds (0.86, 95% CI: 0.53–1.41) of 1–13 vs 0 PPHD but higher odds (2.57, 95% CI: 1.00–6.63) of 14 + vs 0 PPHD in unadjusted models with neither result being significant. After adjustment, the associations for 1–13 vs. 0 PPHD were attenuated and remained non-significant, while rural caregivers had significantly higher odds of 14 + vs 0 PPHD, consistent with unadjusted results. Conclusions Rural caregivers of PWD are less likely to experience short-term mental health problems compared to their urban counterparts. However, they face similar levels of experiencing PMHD. Additionally, rural caregivers of PWD are more likely to endure more PPHD than urban caregivers. Considering the extensive day-to-day responsibilities that caregivers of PWD carry and the ongoing need for their support, it is crucial to enhance long-term mental health resources for both rural and urban caregivers. Furthermore, targeted initiatives to support the long-term physical health of rural caregivers are equally essential.

FDA approves twice-yearly capsid inhibitor for HIV prevention

An anti-CD47 antibody binds to a distinct epitope in a novel metal ion-dependent manner to minimize cross-linking of red blood cells

“Sun brings all things”: Sun and moon lore as biocultural knowledge on Aneityum island, Vanuatu

Across the Pacific, traditional myths and contemporary narratives describe the origins, animacy, and importance to daily human activities of the Sun and Moon. In Vanuatu, Indigenous local knowledge systems interpret ways that the Sun and Moon interact with humans and plants to achieve productive and sustainable lifeways. In this ethnographic study, we explore how residents of Aneityum Island perceive and narrate the Sun and Moon’s interactions with animals, humans, and plants. We consider the influence of the Sun and Moon on domains of daily life on Aneityum, including agriculture, architecture, fishing, health care, navigation, time-reckoning, and diverse ritual activities. Aneityum islanders possess generationally accumulated understandings of their relationship to the environment, framed within the local cosmology and communicated orally. Sun and Moon lore—as expressed through myths and stories—directly informs Aneityumese people’s actions and efforts at sustainable living, survival technologies, and biodiversity conservation on land and sea. This body of knowledge reveals the causes and manifestations of natural phenomena, and strategies for responding to their impacts. Due to the influences of globalization, many biocultural tools that focus on Sun and Moon lore are at risk of being forgotten. The Aneityumese people—aided by outside experts—are undertaking efforts to document and revitalize this knowledge to ensure the continuity of their resilient and sustainable lifeways.

Dual-payload ADCs move into first oncology clinical trials

A key loop in the catalytic pocket of the PL17 family of alginate lyases determines minimal substrate recognition

Cognitive impairment in Sjogren’s syndrome: Interplay between BACE1 activity, inflammatory blood biomarkers and neurocognitive testing

Background Sjogren’s syndrome (SS) is considered as a chronic, autoimmune disorder, that can present with various manifestations both intra and extra-glandular. Cognitive dysfunction is pivotal in recognizing neurological complications in SS. Methods A study involving 44 SS cases and 37 controls was conducted to evaluate cognitive dysfunction further. Participants underwent multiple cognitive tests and blood tests for evaluation. Also, the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), Interleukin 6 (IL-6), total antioxidant capacity (TAC), nitric oxide (NO), and malondialdehyde (MDA) serum levels were measured. Multiple analyses were done by PRISM 10 and SPSS 22. Results The MoCA and SDLT scores were lower in Sjogren patients (P < 0.001). Serum BACE1, IL-6, NO, TAC, and MDA did not statistically vary in the SS patients. The only variables varied by medication therapy with methotrexate (MTX), hydroxychloroquine (HCQ), and prednisone were WBC count (P = 0.03) and triglyceride levels (in MTX and HCQ, P = 0.04), with no effect on neurocognitive factors. IL-6 was strongly correlated with the duration of symptoms (r = 0.99, P-value < 0.001). BACE1 had a positive correlation with IL-6 level (r = 0.4, P-value = 0.027). Conclusion SS patients demonstrated significantly lower performance in neurocognitive tests, while BACE1 and inflammatory markers were not altered. This indicates that cognitive decline in SS is present but the mechanism still requires further evaluation. MTX, HCQ, and Prednisone use did not alter neurocognitive factors. Important correlations were found between hematological and cognitive tests in this study which provides new insights in the field of SS.

Subcellular determinants of orthoflavivirus protease activity

Effects of a non-standard information leaflet on patient recruitment in acute care: Embedded cluster-randomised controlled trial

Background Recruiting study participants is a key component and major challenge in clinical research. Evidence shows that the design of written study information can influence recruitment success. However, there is a lack of research on the effectiveness and acceptability of different written study information. Objective We aimed to investigate the effectiveness and acceptability of an information leaflet including an information video compared to a formal information letter in patient recruitment in acute care. Design We conducted a cluster-randomised controlled trial embedded in a cross-sectional study (“Sleep Acute host study”) addressing patients’ sleep in hospitals. Methods In a stratified random sample of hospitals, we allocated selected wards either to the intervention group (information leaflet including a link to an information video) or the control group (formal information letter) using external concealed randomisation. Adult patients hospitalised for at least 48 hours were eligible for participation. Our primary endpoint was recruitment success measured by the participation rate in the Sleep Acute host study. The secondary endpoint was acceptability of the written study information. Persons involved in the analyses were blinded concerning group allocation. Results In total, 53 wards with 498 patients were cluster-randomised, 28 wards with 262 patients were allocated to the intervention group and 25 wards with 236 patients to the control group. The participation rate in the Sleep Acute host study was 51.1% (134 of 262) for the intervention and 47.5% (112 of 236) for the control group (OR 1.186 (0.698 to 2.013), p = 0.528). There were no significant differences concerning the acceptability of the written study information between both groups. Conclusions More patients who received an information leaflet including a link to an information video participated in the host study, although the difference is not statistically significant. Study registration DRKS-ID: DRKS00029707. Registered on 30. August 2022

Stealthy polymer attacks Gram-negative bacteria

Functional investigation of the RNA helicase MOV10 with respect to its interplay with factors involved in nonsense-mediated mRNA decay

Static strengths of circular hollow section stub column strengthened with carbon fiber reinforced polymer

In previous studies, the strengthening effectiveness and feasibility of carbon fiber reinforced polymer (CFRP) were mainly evaluated through experimental research or numerical analysis. Although these methods can accurately provide estimates, both experimental and numerical assessment processes are costly in terms of time and cost. There is a need for reliable calculation formulae that can predict the static strengths of circular hollow section (CHS) stub columns in a more convenient and cost-saving manner. Therefore, this paper mainly conducted theoretical analysis and derived the calculation formulae. Furthermore, finite element (FE) analysis of CHS stub columns strengthened with CFRP was also conducted, and FE simulations were obtained. The accuracy of these formulae was validated by comparing the theoretical predictions with both FE simulations conducted by the authors and experimental results derived from previous studies. The maximum error was found to be no more than 10%. The cost-effective number of CFRP laminates bonded on the steel tube surface can be determined using the CFRP confinement coefficient λ, where λ balances the construction cost and the strengthening efficiency. A parametric study was also conducted to investigate the impact of steel strength, the number of CFRP laminates, and the bonding configuration of CFRP on the strengthening efficiency.

Improvement in the potency of a N1-methylpseudouridine-modified self-amplifying RNA through mutations in the RNA-dependent RNA polymerase

Analysis and comparison of the bacterial σ54 regulon: Evidence of phylogenetic trends in gene regulation

While the role of σ54 in regulating genes involved in nitrogen metabolism, flagellar biosynthesis, and stress responses in Pseudomonadota is well established, its involvement in regulating alternative metabolic pathways and cellular processes in other phyla has been less explored. By employing position-specific scoring matrices (PSSMs) to identify promoter sequences regulated by the σ54 factor, we successfully predicted genes under its control across 33 taxonomic classes spanning 16 distinct phyla. For the first time, we conducted a comprehensive statistical assessment of σ54 regulation across major bacterial phylogenetic groups. Our findings provide an extensive perspective on the regulatory role of σ54 beyond nitrogen metabolism and reveal the different trends in which metabolic and biological processes can be regulated by this sigma factor depending on the phylogenetic group. The main findings of our study are available on the aRpoNDB webpage (https://biocomputo.ibt.unam.mx/arpondb/).

FDA approves first factor XIIa inhibitor, for hereditary angioedema