Injured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.
Malabsorption syndromes are common in family medicine but may be overlooked because of a wide variation in presentation. Classic symptoms include diarrhea, steatorrhea, weight loss, flatulence, and postprandial abdominal pain. Nongastrointestinal manifestations can include elevated levels of liver function markers, anemia, skin conditions, infertility, and bone disease. Associated conditions include lactose intolerance, celiac disease, and exocrine pancreatic insufficiency. Testing should include screening for anemia. A standard test for lactose intolerance is the hydrogen breath test; however, formal testing typically is not required for diagnosis. The diagnosis of celiac disease depends on serologic testing, histologic findings on duodenal biopsy, or both. Patients should not restrict their diets before testing for malabsorption syndromes. If the initial evaluation is negative for celiac disease, other conditions should be considered, including nonceliac gluten sensitivity, irritable bowel syndrome, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) intolerance. Therapies for patients with malabsorption syndromes involve dietary modification. A lactose-restricted diet and use of dairy substitutes are recommended for lactose intolerance. A gluten-free diet is the primary intervention for celiac disease. Pancreatic enzyme replacement therapy and replacement of fat-soluble vitamins are the primary therapies for management of exocrine pancreatic insufficiency.
Our aim was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies and physical health outcomes associated with human immunodeficiency virus (HIV) but not acquired immunodeficiency syndrome.
Evidence for the efficacy of low-volume high-intensity interval training (HIIT) for the modulation of body composition is unclear.
The study aimed (1) to assess the prognostic value of three-dimensional echocardiography (3DE) derived right ventricular (RV) ejection fraction (EF) and (2) to evaluate relative prognostic importance of reduced and preserved left ventricular (LV) EF and RVEF to predict all-cause mortality and cardiac death in a large cohort of patients with cardiac diseases.
It is uncertain whether mechanical thrombectomy (MT) increases the probability of a good outcome (modified Rankin Scale (mRS) 0-2) in patients with Alberta Stroke Program Early CT Score (ASPECTS) 0-6.
Professional paediatrics associations play an important role in promoting the highest standard of care for women and children. Education and guidelines must be made in the best interests of patients. Given the importance of breastfeeding for the health, development and survival of infants, children and mothers, paediatric associations have a particular responsibility to avoid conflicts of interest with companies that manufacture breast-milk substitutes (BMSs). The objective of this study was to investigate the extent to which national and regional paediatric associations are sponsored by BMS companies.
The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of substrate ssDNA from non-substrate. Using 2'-deoxy-2'-fluorine substituted cytidines, we show that a 2'-endo sugar conformation of the target deoxycytidine is favored for substrate binding and deamination. Trajectories of the MD simulation indicate that a ribose 2'-hydroxyl group destabilizes the π-π stacking of the target cytosine and H257, resulting in dislocation of the target cytosine base from the catalytic position. Interestingly, APOBEC3A, which can deaminate ribocytidines, retains the ribocytidine in the catalytic position throughout the MD simulation. Our results indicate that A3Gctd catalytic selectivity against RNA is dictated by both the sugar conformation and 2'-hydroxyl group.
Since the Late Paleozoic, forests have become distributed worldwide and significantly changed the Earth’s climate and landscapes, but the record of forests is rare in the Devonian (419-359 Ma in age) when they first appeared. From the Upper Devonian (Famennian with the age of 372-359 Ma) of Xinhang, Anhui, China, we report a very large in situ forest, which includes locally dense stands of lycopsid plants. The Xinhang forest is monospecific with a small tree lycopsid Guangdedendron gen. nov., probably dioecious with monocarpic reproduction. The plant shows the earliest stigmarian rooting system typical of giant tree lycopsids dominating Carboniferous forests. It colonizes coastal clastic wetlands that were influenced by floods. This significantly increases the paleogeographical coverage of in situ Devonian forests, and contributes to our understanding of atmospheric CO2 decline and coastal consolidation.
Severe marine heatwaves have recently become a common feature of global ocean conditions due to a rapidly changing climate [1, 2]. These increasingly severe thermal conditions are causing an unprecedented increase in the frequency and severity of mortality events in marine ecosystems, including on coral reefs . The degradation of coral reefs will result in the collapse of ecosystem services that sustain over half a billion people globally [4, 5]. Here, we show that marine heatwave events on coral reefs are biologically distinct to how coral bleaching has been understood to date, in that heatwave conditions result in an immediate heat-induced mortality of the coral colony, rapid coral skeletal dissolution, and the loss of the three-dimensional reef structure. During heatwave-induced mortality, the coral skeletons exposed by tissue loss are, within days, encased by a complex biofilm of phototrophic microbes, whose metabolic activity accelerates calcium carbonate dissolution to rates exceeding accretion by healthy corals and far greater than has been documented on reefs under normal seawater conditions. This dissolution reduces the skeletal density and hardness and increases porosity. These results demonstrate that severe-heatwave-induced mortality events should be considered as a distinct biological phenomenon from bleaching events on coral reefs. We also suggest that such heatwave mortality events, and rapid reef decay, will become more frequent as the intensity of marine heatwaves increases and provides further compelling evidence for the need to mitigate climate change and instigate actions to reduce marine heatwaves.