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Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking
Abstract Alcohol use disorder is marked by disrupted behavioral and emotional states which persist into abstinence. The enduring synaptic alterations that remain despite the absence of alcohol are of interest for interventions to prevent relapse. Here, 28 male rhesus macaques underwent over 20 months of alcohol drinking interspersed with three 30-day forced abstinence periods. After the last abstinence period, we paired direct sub-second dopamine monitoring via ex vivo voltammetry in nucleus accumbens core with RNA-sequencing of the ventral tegmental area. We found persistent augmentation of dopamine transporter function, kappa opioid receptor sensitivity, and putative dynorphin release – all inhibitory regulators which act to decrease extracellular dopamine. Surprisingly, though transcript expression was not altered, the relationship between gene expression and functional readouts of these encoded proteins was highly dynamic and altered by drinking history. These results outline the long-lasting synaptic impact of alcohol use and suggest that assessment of transcript-function relationships is critical for the rational design of precision therapeutics.
RH3 enhances antiviral defense by facilitating small RNA loading into Argonaute 2 at endoplasmic reticulum–chloroplast membrane contact sites
KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan
Abstract Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene results in distinct, severe phenotypic consequences. Here we show that, surprisingly, 4-fold overexpression of Kat6b rescues all previously described developmental defects in Kat6a mutant mice, including rescuing the absence of hematopoietic stem cells. Kat6b restores acetylation at histone H3 lysines 9 and 23 and reverses critical gene expression anomalies in Kat6a mutant mice. Our data suggest that the target gene specificity of KAT6A can be substituted by the related paralogue KAT6B, despite differences in amino acid sequence, if KAT6B is expressed at sufficiently high levels.
Broad-spectrum capture of hundreds of per- and polyfluoroalkyl substances from fluorochemical wastewater
Abstract Hundreds of per- and polyfluoroalkyl substances (PFAS) are present in fluorochemical production effluents, and existing adsorption devices are inadequate to address this PFAS challenge given their extreme structural diversity. Here, we achieve the broad-spectrum capture of 107 PFAS from fluorochemical effluents using a treatment-train strategy that combines Zn-based electrocoagulation (EC) with anion-exchange resin (AER) beds. The “zero-carbon” adsorbent, zinc hydroxide flocs generated insitu by Zn-based EC, bulk removes PFAS with log K ow > 4 through a semi-micellar adsorption mechanism similar to mineral flotation and achieves adsorption capacities at the optimal level of all reported adsorbents. Technical-economic analysis and life-cycle environmental impact show that coupling Zn-based EC reduces the cost by an order-of-magnitude and the carbon-footprint by 70% compared to AER beds alone. It is also observed that iodinated PFAS, with some fluorine atoms are replaced by iodine atoms, exhibit significantly improved adsorption selectivity, which may shed light on designing environmentally-friendly fluorochemicals.
Electronic metal-support interaction modulates Cu electronic structures for CO2 electroreduction to desired products
Prevention of tuberculosis in cynomolgus macaques by an attenuated Mycobacterium tuberculosis vaccine candidate
Ultra-wideband unidirectional pseudospin-polarized waveguide with dual boundary conditions
Th1-poised naive CD4 T cell subpopulation reflects anti-tumor immunity and autoimmune disease
Author Correction: Association of higher potency statin use with risk of osteoporosis and fractures in patients with stroke in a Korean nationwide cohort study
Effect of substituting Al with Zn on the microstructure and mechanical properties of the as-cast Mg–4Y–4Al alloy
Sex-specific variation in breeding-ground departure decisions and detection rates during southbound migration in West Atlantic Flyway Whimbrels (Numenius phaeopus)
An improved salp swarm algorithm for permutation flow shop vehicle routing problem
Risk-benefits assessment of tamoxifen or raloxifene as chemoprevention for risk reduction of breast cancer among BRCA1 and BRCA2 carriers: a meta-analysis
Machine learning for early diagnosis of Kawasaki disease in acute febrile children: retrospective cross-sectional study in China
CC-chemokine ligand 18, CXC motif chemokine 13 and osteopontin as biomarkers of silicosis and asbestosis: a prospective observational study
Paleoenvironmental and paleobiogeographical significance of Paleocene – early Eocene ostracods in Wadi Tarfa, North Eastern Desert, Egypt
Abstract This study investigates ostracod faunas from the well-preserved Paleocene to lower Eocene sedimentary succession at Wadi Tarfa, North Eastern Desert, Egypt. A total of 22 species and subspecies across 16 genera and 8 families were identified across 57 samples. Three zones were identified: Doricythereis jordanica jordanica Zone, Cytheropteron toshkaensis Zone, and Phalcocythere horraensis Zone, based on the stratigraphic distribution of ostracod fauna. However, correlations with other sections revealed inconsistencies in the first and last occurrences of ostracod species, indicating complexities in regional biostratigraphic correlation by ostracod fauna and the influence of localized depositional factors. Both R-mode and Q-mode clustering analyses were applied to ostracod assemblages, identifying four distinct faunal clusters and five biofacies, reflecting depositional changes from outer neritic to upper bathyal environments. The late Paleocene revealed reduced ostracod diversity, correlating with a deepening marine environment, particularly in the Tarawan Formation. Non-Metric Multidimensional Scaling (NMDS) analyses indicated significant paleobiogeographic connections between North African and Levantine sites, while faunal differentiation was greater in West African and Middle Eastern regions due to marine barriers.