Genome-wide association of the metabolic shifts underpinning dark-induced senescence in Arabidopsis.

Dark-induced senescence provokes profound metabolic shifts to recycle nutrients and to guarantee plant survival. To date, research on these processes has largely focused on characterizing mutants deficient in individual pathways. Here, we adopted a time-resolved genome-wide association-based approach to characterize dark-induced senescence by evaluating the photochemical efficiency and content of primary and lipid metabolites at the beginning, or after 3 or 6 days in darkness. We discovered six patterns of metabolic shifts and identified 215 associations with 81 candidate genes being involved in this process. Among these associations, we validated the roles of four genes associated with glycine, galactinol, threonine, and ornithine levels. We also demonstrated the function of threonine and galactinol catabolism during dark-induced senescence. Intriguingly, we determined that the association between tyrosine contents and TYROSINE AMINOTRANSFERASE 1 influences enzyme activity of the encoded protein and transcriptional activity of the gene under normal and dark conditions, respectively. Moreover, the single-nucleotide polymorphisms affecting the expression of THREONINE ALDOLASE 1 and the amino acid transporter gene AVT1B, respectively, only underlie the variation in threonine and glycine levels in the dark. Taken together, these results allow us to present a very detailed model of the metabolic aspects of dark-induced senescence, as well as the process itself.

An Opportunity for Change: Principles for Reforming Internal Medicine Inpatient Conferences.

Inpatient educational conferences are a key part of internal medicine residency training. Many residencies made conferences virtual during the COVID-19 pandemic, and are now returning to in-person sessions. As we navigate this change, we can seize this opportunity to re-evaluate the role that inpatient conferences serve in resident education. In this paper, we briefly review the history of inpatient educational conferences before offering five recommendations for improvement. Our recommendations include grounding conference formats in educational theory, leveraging the expertise of all potential educators, broadening content to include health equity and justice throughout all curricula, and explicitly focusing on cultivating community among participants. Recognizing that each residency program is different, we anticipate that these recommendations may be implemented differently based on program size, available resources, and current institutional practices. We also include examples of prior successful curricular reforms aligned with our principles. We hope these recommendations ensure inpatient conferences continue to be a central part of residency education for future generations of internal medicine residents.

Harnessing Ion-Dipole Interactions for Water-Lean Solvation Chemistry: Achieving High-Stability Zn Anodes in Aqueous Zinc-Ion Batteries.

The reversibility and stability of aqueous zinc-ion batteries (AZIBs) are largely limited by water-induced interfacial parasitic reactions. Here, dimethyl(3,3-difluoro-2-oxoheptyl)phosphonate (DP) is introduced to tailor primary solvation sheath and inner-Helmholtz configurations for robust zinc anode. Informed by theoretical guidance on solvation process, DP with high permanent dipole moments can effectively substitute the coordination of H2O with charge carriers through relatively strong ion-dipolar interactions, resulting in a water-lean environment of solvated Zn2+. Thus, interfacial side reactions can be suppressed through a shielding effect. Meanwhile, lone-pair electrons of oxygen and fluorinated features of DP also reinforce the interfacial affinity of metallic zinc, associated with exclusion of neighboring water to facilitate reversible zinc planarized deposition. Thus, these merits endow the Zn anode with a high-stability performance exceeds 3800 hours at 0.5 mA cm-2 and 0.5 mAh cm-2 for Zn||Zn batteries and a high average Coulombic efficiency of 99.8% at 4 mA cm-2 and 1 mAh cm-2 for Zn||Cu batteries. Benefiting from the stable zinc anode, the Zn||NH4V4O10 cell maintains 80.3% of initial discharge capacity after 3000 cycles at 5 A g-1 and exhibits a high retention rate of 99.4% against to the initial capacity during the self-discharge characterizations.

Opening and Constructing Stable Lithium-ion Channels within Polymer Electrolytes.

Lithium-ion batteries play an integral role in various aspects of daily life, yet there is a pressing need to enhance their safety and cycling stability. In this study, we have successfully developed a highly secure and flexible solid-state polymer electrolyte (SPE) through the in situ polymerization of allyl acetoacetate (AAA) monomers. This SPE constructed an efficient Li+ transport channel inside and effectively improved the solid-solid interface contact of solid-state batteries to reduce interfacial impedance. Furthermore, it exhibited excellent thermal stability, an ionic conductivity of 3.82×10-4 S cm-1 at room temperature (RT), and a Li+ transport number (tLi+) of 0.66. The numerous oxygen vacancies on layered inorganic SiO2 created an excellent environment for TFSI- immobilization. Free Li+ migrated rapidly at the C=O equivalence site with the poly(allyl acetoacetate) (PAAA) matrix. Consequently, when cycled at 0.5C and RT, it displayed an initial discharge specific capacity of 140.6 mAh g-1 with a discharge specific capacity retention rate of 70 % even after 500 cycles. Similarly, when cycled at a higher rate of 5C, it demonstrated an initial discharge specific capacity of 132.3 mAh g-1 while maintaining excellent cycling stability.

Predicting plasticity of rosette growth and metabolic fluxes in Arabidopsis thaliana.

Plants can rapidly mitigate the effects of suboptimal growth environments by phenotypic plasticity of fitness-traits. While genetic variation for phenotypic plasticity offers the means for breeding climate-resilient crop lines, accurate genomic prediction models for plasticity of fitness-related traits are still lacking. Here, we employed condition- and accession-specific metabolic models for 67 Arabidopsis thaliana accessions to dissect and predict plasticity of rosette growth to changes in nitrogen availability. We showed that specific reactions in photorespiration, linking carbon and nitrogen metabolism, as well as key pathways of central carbon metabolism exhibited substantial genetic variation for flux plasticity. We also demonstrated that, in comparison with a genomic prediction model for fresh weight (FW), genomic prediction of growth plasticity improves the predictability of FW under low nitrogen by 58.9% and by additional 15.4% when further integrating data on plasticity of metabolic fluxes. Therefore, the combination of metabolic and statistical modeling provides a stepping stone in understanding the molecular mechanisms and improving the predictability of plasticity for fitness-related traits.

Rapid shifts in thermal reaction norms and tolerance of brooded coral larvae following parental heat acclimation.

Thermal priming of reef corals can enhance their heat tolerance; however, the legacy effects of heat stress during parental brooding on larval resilience remain understudied. This study investigated whether preconditioning adult coral Pocillopora damicornis to high temperatures (29°C and 32°C) could better prepare their larvae for heat stress. Results showed that heat-acclimated adults brooded larvae with reduced symbiont density and shifted thermal performance curves. Reciprocal transplant experiments demonstrated higher bleaching resistance and better photosynthetic and autotrophic performance in heat-exposed larvae from acclimated adults compared to unacclimated adults. RNA-seq revealed strong cellular stress responses in larvae from heat-acclimated adults that could have been effective in rescuing host cells from stress, as evidenced by the widespread upregulation of genes involved in cell cycle and mitosis. For symbionts, a molecular coordination between light harvesting, photoprotection and carbon fixation was detected in larvae from heat-acclimated adults, which may help optimize photosynthetic activity and yield under high temperature. Furthermore, heat acclimation led to opposing regulations of symbiont catabolic and anabolic pathways and favoured nutrient translocation to the host and thus a functional symbiosis. Notwithstanding, the improved heat tolerance was paralleled by reduced light-enhanced dark respiration, indicating metabolic depression for energy saving. Our findings suggest that adult heat acclimation can rapidly shift thermal tolerance of brooded coral larvae and provide integrated physiological and molecular evidence for this adaptive plasticity, which could increase climate resilience. However, the metabolic depression may be maladaptive for long-term organismal performance, highlighting the importance of curbing carbon emissions to better protect corals.

Enhanced stretchability towards a flexible and wearable reflective display coating using chalcogenide phase change materials.

Reflective color switching coatings based on chalcogenide phase change material (PCM) is becoming one of the most promising display technologies in the future. However, it is still a challenge to kindly control the stress and enhance the stretchability for flexible display coatings. Here, we report crack-reduced reflective color coatings on a flexible substrate by using buckling structure to regulate the distribution of vacancies in PCM. It significantly suppresses the formation of cracks and improves the robustness of optical and electrical properties during stretching of the display device, which opens the doors of opportunity for phase change display applications in a wide range of flexible and wearable display fields.

L2,1-norm regularized multivariate regression model with applications to genomic prediction.

MOTIVATION: Genomic selection (GS) is currently deemed the most effective approach to speed up breeding of agricultural varieties. It has been recognized that consideration of multiple traits in GS can improve accuracy of prediction for traits of low heritability. However, since GS forgoes statistical testing with the idea of improving predictions, it does not facilitate mechanistic understanding of the contribution of particular single nucleotide polymorphisms (SNP). RESULTS: Here, we propose a L2,1-norm regularized multivariate regression model and devise a fast and efficient iterative optimization algorithm, called L2,1-joint, applicable in multi-trait GS. The usage of the L2,1-norm facilitates variable selection in a penalized multivariate regression that considers the relation between individuals, when the number of SNPs is much larger than the number of individuals. The capacity for variable selection allows us to define master regulators that can be used in a multi-trait GS setting to dissect the genetic architecture of the analyzed traits. Our comparative analyses demonstrate that the proposed model is a favorable candidate compared to existing state-of-the-art approaches. Prediction and variable selection with datasets from Brassica napus, wheat and Arabidopsis thaliana diversity panels are conducted to further showcase the performance of the proposed model. AVAILABILITY AND IMPLEMENTATION: : The model is implemented using R programming language and the code is freely available from https://github.com/alainmbebi/L21-norm-GS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Fabrication of a Tool Electrode with Hydrophobic Features and Its Stray-Corrosion Suppression Performance for Micro-electrochemical Machining.

Micro-electrochemical machining (micro-ECM) can machine microstructures with excellent surface integrity on difficult-to-cut alloys. During micro-ECM, stray corrosion results in tapered sidewalls of machined structures. To suppress the stray corrosion, a novel tool electrode with the sidewall insulation of a gas film is proposed by fabricating the metal tool sidewall into a hydrophobic surface. The sidewall surface is designed to be characterized with spherical array cavities (radius of 500 nm) acting as the hydrophobic features, enhancing the gas-shielding effect of the gas film under electrolysis. The fabrication process of the hydrophobic sidewall is described in detail, including the self-assembly procedure of a monolayer template of Φ1 µm polystyrene microspheres, the copper-electroforming procedure for filling the microspheres' gaps, and the removal procedure for forming spherical array cavities. The fabricated tool electrode (Φ500 µm) obtains the hydrophobic features of a contact angle of up to 138°. As a result, bubbles generated on the tool surface can form an air-electrolyte interface instead of a dispersed bubble cluster. Micro-ECM experiments of microstructures verify that the novel tool electrode can improve machining accuracy by suppressing sidewall stray corrosion.

Enantioselective synthesis of isoxazole-containing spirooxindole tetrahydroquinolines via squaramide-catalysed cascade reactions.

A class of o-sulfonylaminostyryl isoxazole synthons were designed and demonstrated to be useful building blocks in asymmetric cascade aza-Michael/Michael reaction with 3-olefinic oxindoles. This squaramide-catalysed cascade reaction afforded structurally complex isoxazole-containing spirooxindole tetrahydroquinolines bearing three contiguous stereocenters in good to excellent yields (up to 99%) with high diastereoselectivities (up to >20 : 1 dr) and enantioselectivities (up to 88% ee). Moreover, the gram-scale synthesis and synthetic transformations were also demonstrated.

Asymmetric synthesis of isoxazole and trifluoromethyl-containing 3,2'-pyrrolidinyl dispirooxindoles via squaramide-catalysed [3 + 2] cycloaddition reactions.

A highly efficient squaramide-catalysed asymmetric domino Michael/Mannich [3 + 2] cycloaddition of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles and N-2,2,2-trifluoroethylisatin ketimines was developed. A new class of complex and diverse-skeleton isoxazole and trifluoromethyl-containing 3,2'-pyrrolidinyl dispirooxindoles bearing four contiguous stereogenic centers including two adjacent spiro quaternary stereocentres were obtained in good to excellent yields (up to 99%) with excellent diastereoselectivities (>20 : 1 dr, in all cases) and enantioselectivities (up to 96% ee). Moreover, the potential utilities of the protocol have been demonstrated by gram-scale synthesis and further transformation experiments.

Characterization of effects of genetic variants via genome-scale metabolic modelling.

Genome-scale metabolic networks for model plants and crops in combination with approaches from the constraint-based modelling framework have been used to predict metabolic traits and design metabolic engineering strategies for their manipulation. With the advances in technologies to generate large-scale genotyping data from natural diversity panels and other populations, genome-wide association and genomic selection have emerged as statistical approaches to determine genetic variants associated with and predictive of traits. Here, we review recent advances in constraint-based approaches that integrate genetic variants in genome-scale metabolic models to characterize their effects on reaction fluxes. Since some of these approaches have been applied in organisms other than plants, we provide a critical assessment of their applicability particularly in crops. In addition, we further dissect the inferred effects of genetic variants with respect to reaction rate constants, abundances of enzymes, and concentrations of metabolites, as main determinants of reaction fluxes and relate them with their combined effects on complex traits, like growth. Through this systematic review, we also provide a roadmap for future research to increase the predictive power of statistical approaches by coupling them with mechanistic models of metabolism.

Archaic human remains from Hualongdong, China, and Middle Pleistocene human continuity and variation.

Middle to Late Pleistocene human evolution in East Asia has remained controversial regarding the extent of morphological continuity through archaic humans and to modern humans. Newly found ∼300,000-y-old human remains from Hualongdong (HLD), China, including a largely complete skull (HLD 6), share East Asian Middle Pleistocene (MPl) human traits of a low vault with a frontal keel (but no parietal sagittal keel or angular torus), a low and wide nasal aperture, a pronounced supraorbital torus (especially medially), a nonlevel nasal floor, and small or absent third molars. It lacks a malar incisure but has a large superior medial pterygoid tubercle. HLD 6 also exhibits a relatively flat superior face, a more vertical mandibular symphysis, a pronounced mental trigone, and simple occlusal morphology, foreshadowing modern human morphology. The HLD human fossils thus variably resemble other later MPl East Asian remains, but add to the overall variation in the sample. Their configurations, with those of other Middle and early Late Pleistocene East Asian remains, support archaic human regional continuity and provide a background to the subsequent archaic-to-modern human transition in the region.

Ancient horse genomes reveal the timing and extent of dispersals across the Bering Land Bridge.

The Bering Land Bridge (BLB) last connected Eurasia and North America during the Late Pleistocene. Although the BLB would have enabled transfers of terrestrial biota in both directions, it also acted as an ecological filter whose permeability varied considerably over time. Here we explore the possible impacts of this ecological corridor on genetic diversity within, and connectivity among, populations of a once wide-ranging group, the caballine horses (Equus spp.). Using a panel of 187 mitochondrial and eight nuclear genomes recovered from present-day and extinct caballine horses sampled across the Holarctic, we found that Eurasian horse populations initially diverged from those in North America, their ancestral continent, around 1.0-0.8 million years ago. Subsequent to this split our mitochondrial DNA analysis identified two bidirectional long-range dispersals across the BLB ~875-625 and ~200-50 thousand years ago, during the Middle and Late Pleistocene. Whole genome analysis indicated low levels of gene flow between North American and Eurasian horse populations, which probably occurred as a result of these inferred dispersals. Nonetheless, mitochondrial and nuclear diversity of caballine horse populations retained strong phylogeographical structuring. Our results suggest that barriers to gene flow, currently unidentified but possibly related to habitat distribution across Beringia or ongoing evolutionary divergence, played an important role in shaping the early genetic history of caballine horses, including the ancestors of living horses within Equus ferus.

Ns-pulsewidth pulsed power supply by regulating electrical parameters for AFM nano EDM of nm-removal-resolution.

Nano electro discharge machining (nano EDM), as a frontier processing method in the research stage of exploration, has an important application prospect in the machining of metal and alloy materials for achieving nanoscale removal resolution. A pulsed power supply used in nano EDM is expected to limit a single pulse energy to nJ order of magnitude for improving the removal resolution of single pulsed discharge even to nanoscale. One developing direction is to decrease pulsewidth of the pulsed power supply. Conventional pulsed power supplies hardly output a single pulse and continuous pulses with nanosecond (ns) pulsewidth, resulting in too large single pulsed energy ofµJ order of magnitude usually. In this research, a novel pulsed power supply is designed for realizing the ns-pulsewidth with controllable pulsewidth and peak voltage. The key novelty lies in a cascaded circuit with two triodes working in the state of ultra-fast avalanche conduction, where pF capacitors are applied to adjust the pulsewidth and pulsed energy precisely. Performance tests verified that a single pulse of 5 ns pulsewidth or continuous pulses up to 9 MHz can be outputted. Furthermore, nano EDM experiments of single pulsed discharge are carried out under the conditions of nanometer (nm) discharge gap and nm-tip tool electrode based on an atomic force microscope (AFM) system. The special results are achieved: a single pulsed energy can reach down to 1.75 nJ by outputting a pulsewidth of 10 ns, and a nano-EDM crater is only about 182 nm in diameter with regular shape and little recasting. Those results verify the possibility of AFM-tip-based nano EDM for machining nanostructures.

The earliest unequivocally modern humans in southern China.

The hominin record from southern Asia for the early Late Pleistocene epoch is scarce. Well-dated and well-preserved fossils older than ∼45,000 years that can be unequivocally attributed to Homo sapiens are lacking. Here we present evidence from the newly excavated Fuyan Cave in Daoxian (southern China). This site has provided 47 human teeth dated to more than 80,000 years old, and with an inferred maximum age of 120,000 years. The morphological and metric assessment of this sample supports its unequivocal assignment to H. sapiens. The Daoxian sample is more derived than any other anatomically modern humans, resembling middle-to-late Late Pleistocene specimens and even contemporary humans. Our study shows that fully modern morphologies were present in southern China 30,000-70,000 years earlier than in the Levant and Europe. Our data fill a chronological and geographical gap that is relevant for understanding when H. sapiens first appeared in southern Asia. The Daoxian teeth also support the hypothesis that during the same period, southern China was inhabited by more derived populations than central and northern China. This evidence is important for the study of dispersal routes of modern humans. Finally, our results are relevant to exploring the reasons for the relatively late entry of H. sapiens into Europe. Some studies have investigated how the competition with H. sapiens may have caused Neanderthals' extinction (see ref. 8 and references therein). Notably, although fully modern humans were already present in southern China at least as early as ∼80,000 years ago, there is no evidence that they entered Europe before ∼45,000 years ago. This could indicate that H. neanderthalensis was indeed an additional ecological barrier for modern humans, who could only enter Europe when the demise of Neanderthals had already started.

Middle Pleistocene human femoral diaphyses from Hualongdong, Anhui Province, China.

OBJECTIVES: The paleontological description and comparative analysis using discrete morphology, morphometrics (linear and geometric) and cross-sectional geometry of three femoral diaphyseal sections from the Middle Pleistocene site of Hualongdong, China. MATERIALS AND METHODS: The material consists of the original Hualongdong femoral fossils and available data on femoral diaphyses from Middle and Late Pleistocene archaic humans and Middle and earlier Upper Paleolithic modern humans. The methods include visual observation, diaphyseal diameters, cross-sectional parameters (transverse areas and second moments of area derived from micro-CT scans), and geometric morphometrics using semilandmark data. RESULTS: The Hualong 11 midshaft section is similar to other Middle and Late Pleistocene archaic humans in being transversely broad and lacking a pilaster despite a prominent linea aspera. It clusters principally with archaic human femora in all measured parameters. The Hualong 15 and 16 subtrochanteric pieces are similar to many Middle Pleistocene and early modern human femora in being transversely broad. In particular, Hualong 15 exhibits a prominent lateral (gluteal) buttress, similar to many Upper Paleolithic femora but also the Lazaret and Krapina archaic ones. In addition, Hualong 15 has a small third trochanter, a common Upper Paleolithic but rare earlier feature. DISCUSSION: The Hualong 11 femoral piece reinforces the general Middle Pleistocene pattern, especially for eastern Eurasia from which archaic human femora are rare. The subtrochanteric proportions of Hualong 15 and 16 reinforce the Early Pleistocene and (generally) Middle Pleistocene pattern of bone distributions, but their subperiosteal contours align them (along with those of the Lazaret and Krapina femora) with Upper Paleolithic ones. It is difficult to account for these proportions from the generally broad pelves of Pleistocene archaic humans.

Removal of antibiotic resistance genes from secondary effluent by processes combining nano-iron, ultrasound-activated persulfate, and ultrafiltration.

Antibiotic resistance genes (ARGs), as a new type of environmental pollutant that threaten human health, have been detected in the effluent of sewage treatment systems. In this study, the removal from water of ARGs, 16S rRNA, class 1 integron (intI1), and dissolved organic carbon (DOC) were investigated using processes combining nano-iron (nFe), ultrasound (US), activated persulfate (PS) and ultrafiltration (UF). The oxidation mechanism was also studied. The results showed that both nFe and US activation could improve the oxidative effect of PS, and the effect of nFe was better than that of US. Compared with PS-UF, nFe/PS-UF and US/PS-UF significantly enhanced the removal of various ARGs and DOC. nFe/PS-UF was the most effective treatment, reducing cell-associated and cell-free ARGs by 1.74-3.14-log and 1.00-2.61-log, respectively, while removing 30% of DOC. Pre-oxidation methods using PS, nFe/PS, and US/PS significantly enhanced the efficacy of UF for removing DOC with molecular weights above 50 kDa and below 10 kDa, but the removal of DOC between 10 and 50 kDa decreased. The free radicals SO4·- and ·OH were shown to participate in the process of ARGs oxidation.

Canalization of Tomato Fruit Metabolism.

To explore the genetic robustness (canalization) of metabolism, we examined the levels of fruit metabolites in multiple harvests of a tomato introgression line (IL) population. The IL partitions the whole genome of the wild species Solanum pennellii in the background of the cultivated tomato (Solanum lycopersicum). We identified several metabolite quantitative trait loci that reduce variability for both primary and secondary metabolites, which we named canalization metabolite quantitative trait loci (cmQTL). We validated nine cmQTL using an independent population of backcross inbred lines, derived from the same parents, which allows increased resolution in mapping the QTL previously identified in the ILs. These cmQTL showed little overlap with QTL for the metabolite levels themselves. Moreover, the intervals they mapped to harbored few metabolism-associated genes, suggesting that the canalization of metabolism is largely controlled by regulatory genes.

An Interpenetrating Alginate/Gelatin Network for Three-Dimensional (3D) Cell Cultures and Organ Bioprinting.

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca2+ to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca2+) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses.