Mcgrathgraham4946

The gill-oxygen limitation theory (GOLT) provides mechanisms for key aspects of the biology (food conversion efficiency, growth and its response to temperature, the timing of maturation, and others) of water-breathing ectotherms (WBEs). Estradiol progestogen Receptor agonist The GOLT's basic tenet is that the surface area of the gills or other respiratory surfaces of WBE cannot, as two-dimensional structures, supply them with sufficient oxygen to keep up with the growth of their three-dimensional bodies. Thus, a lower relative oxygen supply induces sexual maturation, and later a slowing and cessation of growth, along with an increase of physiological processes relying on glycolytic enzymes and a declining role of oxidative enzymes. Because the "dimensional tension" underlying this argument is widely misunderstood, emphasis is given to a detailed refutation of objections to the GOLT. This theory still needs to be put on a solid quantitative basis, which will occur after the misconceptions surrounding it are put to rest.We present genome-wide data from 40 individuals dating to c.16,900 to 550 years ago in northeast Asia. We describe hitherto unknown gene flow and admixture events in the region, revealing a complex population history. While populations east of Lake Baikal remained relatively stable from the Mesolithic to the Bronze Age, those from Yakutia and west of Lake Baikal witnessed major population transformations, from the Late Upper Paleolithic to the Neolithic, and during the Bronze Age, respectively. We further locate the Asian ancestors of Paleo-Inuits, using direct genetic evidence. Last, we report the most northeastern ancient occurrence of the plague-related bacterium, Yersinia pestis Our findings indicate the highly connected and dynamic nature of northeast Asia populations throughout the Holocene.Equilibrium condensation of solar gas is often invoked to explain the abundance of refractory elements in planets and meteorites. This is partly motivated, by the observation that the depletions in both the least and most refractory rare earth elements (REEs) in meteoritic group II calcium-aluminum-rich inclusions (CAIs) can be reproduced by thermodynamic models of solar nebula condensation. We measured the isotopic compositions of Ce, Nd, Sm, Eu, Gd, Dy, Er, and Yb in eight CAIs to test this scenario. Contrary to expectation for equilibrium condensation, we find light isotope enrichment for the most refractory REEs and more subdued isotopic variations for the least refractory REEs. This suggests that group II CAIs formed by a two-stage process involving fast evaporation of preexisting materials, followed by near-equilibrium recondensation. The calculated time scales are consistent with heating in events akin to FU Orionis- or EX Lupi-type outbursts of eruptive pre-main-sequence stars.Alzheimer's disease (AD), the most common form of dementia, is recognized as a heterogeneous disease with diverse pathophysiologic mechanisms. In this study, we interrogate the molecular heterogeneity of AD by analyzing 1543 transcriptomes across five brain regions in two AD cohorts using an integrative network approach. We identify three major molecular subtypes of AD corresponding to different combinations of multiple dysregulated pathways, such as susceptibility to tau-mediated neurodegeneration, amyloid-β neuroinflammation, synaptic signaling, immune activity, mitochondria organization, and myelination. Multiscale network analysis reveals subtype-specific drivers such as GABRB2, LRP10, MSN, PLP1, and ATP6V1A We further demonstrate that variations between existing AD mouse models recapitulate a certain degree of subtype heterogeneity, which may partially explain why a vast majority of drugs that succeeded in specific mouse models do not align with generalized human trials across all AD subtypes. Therefore, subtyping patients with AD is a critical step toward precision medicine for this devastating disease.Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart muscle disease characterized by hypertrophy with preserved or increased ejection fraction in the absence of secondary causes. However, recent studies have demonstrated that a substantial proportion of individuals with HCM also have comorbid diabetes mellitus (~10%). Whether genetic variants may contribute a combined phenotype of HCM and diabetes mellitus is not known. Here, using next-generation sequencing methods, we identified novel and ultrarare variants in adiponectin receptor 1 (ADIPOR1) as risk factors for HCM. Biochemical studies showed that ADIPOR1 variants dysregulate glucose and lipid metabolism and cause cardiac hypertrophy through the p38/mammalian target of rapamycin and/or extracellular signal-regulated kinase pathways. A transgenic mouse model expressing an ADIPOR1 variant displayed cardiomyopathy that recapitulated the cellular findings, and these features were rescued by rapamycin. Our results provide the first evidence that ADIPOR1 variants can cause HCM and provide new insights into ADIPOR1 regulation.In cyanobacteria and red algae, the structural basis dictating efficient excitation energy transfer from the phycobilisome (PBS) antenna complex to the reaction centers remains unclear. The PBS has several peripheral rods and a central core that binds to the thylakoid membrane, allowing energy coupling with photosystem II (PSII) and PSI. Here, we have combined chemical cross-linking mass spectrometry with homology modeling to propose a tricylindrical cyanobacterial PBS core structure. Our model reveals a side-view crossover configuration of the two basal cylinders, consolidating the essential roles of the anchoring domains composed of the ApcE PB loop and ApcD, which facilitate the energy transfer to PSII and PSI, respectively. The uneven bottom surface of the PBS core contrasts with the flat reducing side of PSII. The extra space between two basal cylinders and PSII provides increased accessibility for regulatory elements, e.g., orange carotenoid protein, which are required for modulating photochemical activity.Hydrogel-polymer hybrids have been widely used for various applications such as biomedical devices and flexible electronics. However, the current technologies constrain the geometries of hydrogel-polymer hybrid to laminates consisting of hydrogel with silicone rubbers. This greatly limits functionality and performance of hydrogel-polymer-based devices and machines. Here, we report a simple yet versatile multimaterial 3D printing approach to fabricate complex hybrid 3D structures consisting of highly stretchable and high-water content acrylamide-PEGDA (AP) hydrogels covalently bonded with diverse UV curable polymers. The hybrid structures are printed on a self-built DLP-based multimaterial 3D printer. We realize covalent bonding between AP hydrogel and other polymers through incomplete polymerization of AP hydrogel initiated by the water-soluble photoinitiator TPO nanoparticles. We demonstrate a few applications taking advantage of this approach. The proposed approach paves a new way to realize multifunctional soft devices and machines by bonding hydrogel with other polymers in 3D forms.