Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia

Background: Despite decades of research, little clarity exists regarding pathogenic mechanisms related to schizophrenia. Investigations on the disease biology of schizophrenia have primarily focused on neuronal alterations. However, there is substantial evidence pointing to a significant role for the brain’s microvasculature in mediating neuroinflammation in schizophrenia. Summary: Brain microvascular endothelial cells (BMEC) are a central element of the microvasculature that forms the blood-brain barrier (BBB) and shields the brain against toxins and immune cells via paracellular, transcellular, transporter, and extracellular matrix proteins. While evidence for BBB dysfunction exists in brain disorders, including schizophrenia, it is not known if BMEC themselves are functionally compromised and lead to BBB dysfunction. Key Messages: Genome-wide association studies, postmortem investigations, and gene expression analyses have provided some insights into the role of the BBB in schizophrenia pathophysiology. However, there is a significant gap in our understanding of the role that BMEC play in BBB dysfunction. Recent advances differentiating human BMEC from induced pluripotent stem cells (iPSC) provide new avenues to examine the role of BMEC in BBB dysfunction in schizophrenia.
Coding-Complete Genome Sequences of 23 SARS-CoV-2 Samples from the Philippines

Here, we report the coding-complete genome sequences of 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples from the Philippines. Sequences were obtained from nasopharyngeal and oropharyngeal swabs from COVID-19-positive patients. Mutation analysis showed the presence of the D614G mutation in the spike protein in 22 of 23 genomes. ABSTRACT Here, we report the coding-complete genome sequences of 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples from the Philippines. Sequences were obtained from nasopharyngeal and oropharyngeal swabs from coronavirus disease 2019 (COVID-19)-positive patients. Mutation analysis showed the presence of the D614G mutation in the spike protein in 22 of 23 genomes.
Making Sense of Infants’ Differential Responses to Incongruity

Infants show strikingly different reactions to incongruity: looking or smiling. The former occurs in response to magical events and the latter to humorous events. We argue that these reactions depend largely on the respective experimental methodologies employed, including the popular violation of expectation (VOE) paradigm. Although both types of studies involve infants’ reactions to incongruity, their literatures have yet to confront each other, and researchers in each domain are drawing strikingly different conclusions regarding infants’ understanding of the world. Here, we argue that infants are sensitive to and constrained by several contextual differences in the methodologies employed by incongruity researchers that afford one or the other reaction. We apply De Jaegher and Di Paolo’s participatory sense-making framework to further understand what infants are sensitive to in these paradigms. Understanding infants’ reactions to incongruity (i.e., VOE) is necessary to clear up claims regarding the sophistication of their knowledge of physical and social phenomena. Attention to several simple methodological details is recommended.
Who will win the electric vehicle race? The role of place-based assets and policy

Regional economies are shaped by their economic histories and existing endowments. This paper explores the question: how do a region’s economic history and institutional endowments affect its success and trajectory in an emerging industry? Our case, electric vehicle development and production, is an industry which combines more traditional skilled manufacturing with knowledge-driven innovation activities. We present deep qualitative case studies of two regions, focusing on one firm in each. The case of Tesla in the San Francisco Bay Area examines an electric vehicle firm in a region with a strong tech innovation system, while the case of Maserati in Emilia-Romagna, Italy, examines a firm that builds on a regional history of automotive manufacturing. Across cases, we compare regional skill endowments, institutional coordination, and place-based policymaking. We conclude that, as an emerging industry under a new economic paradigm, electric vehicle manufacturing by Tesla and Maserati represents two different conceptions of the industry and consequently two different location strategies. Yet these two strategies remain rooted in regional contexts, owing both their success to successful exploitations of these, and their struggles to their failure to compensate for regional gaps. This presents a clear opportunity for place-based industrial strategy to evolve and intervene.
Evolutionary recent dual obligatory symbiosis among adelgids indicates a transition between fungus and insect associated lifestyles

Adelgids (Insecta: Hemiptera: Adelgidae) form a small group of insects but harbor a surprisingly diverse set of bacteriocyte-associated endosymbionts, which suggest multiple replacement and acquisition of symbionts over evolutionary time. Specific pairs of symbionts have been associated with adelgid lineages specialized on different secondary host conifers. Using a metagenomic approach, we investigated the symbiosis of the Adelges laricis/tardus species complex containing betaproteobacterial (‘ Candidatus Vallotia tarda’) and gammaproteobacterial (‘Candidatus Profftia tarda’) symbionts. Genomic characteristics and metabolic pathway reconstructions revealed that Vallotia and Profftia are evolutionary young endosymbionts, which complement each other’s role in essential amino acid production. Phylogenomic analyses and a high level of genomic synteny indicate an origin of the betaproteobacterial symbiont from endosymbionts of Rhizopus fungi. This evolutionary transition was accompanied with substantial loss of functions related to transcription regulation, secondary metabolite production, bacterial defense mechanisms, host infection and manipulation. The transition from fungus to insect endosymbionts extends our current framework about evolutionary trajectories of host-associated microbes.
Anticipation of temporally structured events in the brain

Learning about temporal structure is adaptive because it enables the generation of expectations. We examined how the brain uses experience in structured environments to anticipate upcoming events. During fMRI, individuals watched a 90-second movie clip six times. To uncover neural anticipation, we used a Hidden Markov Model applied to searchlights across the whole brain. This allowed us to identify temporal shifts between activity patterns evoked by the first vs. repeated viewings of the movie clip. In multiple regions throughout the cortex, neural activity patterns for repeated viewings shifted to preceded those of initial viewing. This anticipation varied hierarchically in a posterior (less anticipation) to anterior (more anticipation) fashion. In a subset of these regions, neural event boundaries shifted with repeated viewing to precede subjective event boundaries by 6-7 seconds. Together, these results demonstrate a hierarchy of anticipatory signals in the human brain and link them to subjective experiences of events.
Structural studies on M. tuberculosis decaprenyl phosphoryl-β-D-ribose epimerase-2 enzyme involved in cell wall biogenesis

The Mycobacterium DprE2 is a NADH-dependent enzyme and converts the decaprenylphosphoryl-β-D-ribose (DPX) to decaprenylphosphoryl-β-D-arabinofuranose (DPA). The FAD-containing oxidoreductase MtbDprE1 and NADH-dependent reductase MtbDprE2 enzymes catalyses together the epimerization reaction, which coverts DPR to DPA. Here, MtbDprE2 enzyme was purified and structurally characterized using circular dichroism, molecular modelling and dynamics simulation techniques. The MtbDprE2 was purified, which eluted as oligomer from size exclusion column. The circular dichroism analysis yielded ~ 47.6% α-helix, ~ 19.8% β-sheet and ~ 32.6% random coil structures in MtbDprE2 enzyme and showed highly thermostability. The molecular modelling of MtbDprE2 and its complex with NADH showed that it contains two domains (i) the large domain consists of central twisted seven β-sheets decorated by eight α-helices and (ii) a small domain contains two short α-helices connect by loop. Overall, the MtbDprE2 adopts a typical short-chain dehydrogenase rossmann fold and NADH binds to Asp69, Ser147, Tyr160, Lys164 of catalytic triad and Gly16, Ser19, Glu20, Ile21 of Gly-rich motif of MtbDprE2. 1 ns dynamics simulation was performed on apo and NADH bound MtbDprE2, which indicated the small conformational change in ligand binding site, which resulted more closed pocket than open pocket observed in apo enzyme. Small conformational changes were observed in active site residues and orientation between large and small domains of MtbDprE2 upon NADH binding. Current knowledge of MtbDprE2 structure and its NADH binding mechanism will contribute significantly in development of specific inhibitors against M. tuberculosis.
Ecological and Nutritional Functions of Agroecosystems as Indicators of Smallholder Resilience

Smallholder agriculture is the foundation of global food systems, yet smallholders face severe socio-economic and environmental challenges that can destabilize livelihoods and threaten their resilience. Given that smallholder farmers rely on household production to meet their nutritional needs, management of soil fertility, biodiversity, and other ecological characteristics of agroecosystems directly affects smallholders' capacity to produce sufficient crop nutrients for their diets. However, we lack explicit frameworks linking ecological and nutritional functions of agroecosystems, as well as research exploring farmers' adaptive capacity and agency in mediating these functions, and ultimately, agroecosystem resilience. To address these gaps, we developed an indicator framework to evaluate the complementary roles of ecological and nutritional functions of agroecosystems for smallholder resilience. Paired ecological and nutritional indicators were aggregated into an index representing four agroecosystem functions: (1) Productivity, (2) Diversity, (3) Quality, and (4) Functional Diversity. We then applied this framework and index to a case study of Q'eqchi' Maya smallholders in eastern Guatemala, using farm management and crop quality data from 60 households to determine the status of agroecosystem functions and assess coping and adaptive capacities in response to shocks. More than three-quarters of farms in the sample relied solely on household production of staples to meet their nutritional demands. Across farms, ecological and nutritional indicators were significantly related (Kendall's tau = 0.58, z = 5.7, p < 0.0001), and we found both synergistic (Quality, Functional Diversity) and tradeoff (Productivity) relationships between indicator pairs. We found that farmers using ecological adaptation strategies such as cover cropping and agroforestry had significantly higher levels of agroecosystem functioning and resilience than farmers who were coping with shocks by working off-farm or renting land from plantations. Our findings demonstrate the importance of linking ecological and nutritional functions of agroecosystems through diversified management practices to leverage their synergies. Because smallholder agroecosystems underlie a third of the food system, understanding and promoting their resilience is critical for the social, ecological, and nutritional well-being of global populations.
Robotic multi-probe single-actuator inchworm neural microdrive

Electrophysiology is one of the major experimental techniques used in neuroscience. The favorable spatial and temporal resolution as well as the increasingly larger site counts of brain recording electrodes contribute to the popularity and importance of electrophysiology in neuroscience. Such electrodes are typically mechanically placed in the brain to perform acute or chronic freely moving animal measurements. The micro positioners currently used for such tasks employ a single translator per independent probe being placed into the targeted brain region, leading to significant size and weight restrictions. To overcome this limitation, we have developed a miniature robotic multi-probe neural microdrive that utilizes novel phase-change-material-filled resistive heater micro-grippers. The microscopic dimensions, gentle gripping action, independent electronic actuation control, and high packing density of the grippers allow for micrometer-precision independent positioning of multiple arbitrarily shaped parallel neural electrodes with only a single piezo actuator in an inchworm motor configuration. This multi-probe-single-actuator design allows for significant size and weight reduction, as well as remote control and potential automation of the microdrive. We demonstrate accurate placement of multiple independent recording electrodes into the CA1 region of the rat hippocampus in vivo in acute and chronic settings. Thus, our robotic neural microdrive technology is applicable towards basic neuroscience and clinical studies, as well as other multi-probe or multi-sensor micro-positioning applications. One Sentence Summary Miniature robotic multi-probe single-actuator microdrive utilizing phase change material based micro-grippers.
Synthesis and biological evaluation of novel neoflavonoid derivatives as potential antidiabetic agents

Various substituted neoflavonoid derivatives were synthesized using sulfated montmorillonite K-10 as a catalyst. This method is environmental friendly, sustainable and economical, convenient in isolation and purification processes, with little byproducts, using earth-abundant catalysts and has relatively high yield. Those neoflavonoid derivatives were screened for antioxidant, a-glucosidase inhibitory, aldose reductase 2 (ALR2) inhibitory and advanced glycation end-product formation inhibitory effects. Most compounds exhibited significant antioxidant and advanced glycation end-product (AGE) formation inhibitory activities. It was interesting to note that out of thirty compounds, 8k and 8l were found to have greater ALR2 inhibitory activity than the standard drug quercetin. The pharmacological studies suggested neoflavonoid with adjacent 7,8-dihydroxy groups were more effective in inhibiting ALR2. Antidiabetic activity studies had shown that compounds 8l and 8m were equipotent to the standard drug glibenclamide in vivo. In summary, the target compound 8l provided a potential drug design concept for the development of therapeutic or prophylactic agents of diabetes and diabetes complications.
Replicability of spatial gene expression atlas data from the adult mouse brain

Background Spatial gene expression is particularly interesting in the mammalian brain, with the potential to serve as a link between many data types. However, as with any type of expression data, cross-dataset benchmarking of spatial data is a crucial first step. Here, we assess the replicability, with reference to canonical brain sub-divisions, between the Allen Institute’s in situ hybridization data from the adult mouse brain (ABA) and a similar dataset collected using Spatial Transcriptomics (ST). With the advent of tractable spatial techniques, for the first time we are able to benchmark the Allen Institute’s whole-brain, whole-transcriptome spatial expression dataset with a second independent dataset that similarly spans the whole brain and transcriptome. Results We use LASSO, linear regression, and correlation-based feature selection in a supervised learning framework to classify expression samples relative to their assayed location. We show that Allen reference atlas labels are classifiable using transcription, but that performance is higher in the ABA than ST. Further, models trained in one dataset and tested in the opposite dataset do not reproduce classification performance bi-directionally. Finally, while an identifying expression profile can be found for a given brain area, it does not generalize to the opposite dataset. Conclusions In general, we found that canonical brain area labels are classifiable in gene expression space within dataset and that our observed performance is not merely reflecting physical distance in the brain. However, we also show that cross-platform classification is not robust. Emerging spatial datasets from the mouse brain will allow further characterization of cross-dataset replicability.
The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder

The effectiveness of selection varies among species. It is often estimated by means of an “effective population size” based on neutral polymorphism, but this is confounded in complex ways with demography. The strength of codon bias more directly pertains to how well adaptation at many sites can be maintained in the face of deleterious mutations, but past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS) that corrects for both confounders. Unlike previous metrics, CAIS yields the expected relationship with adult vertebrate body mass. As an example of the use of CAIS, we ask whether protein domains evolve lower intrinsic structural disorder (ISD) when present in more exquisitely adapted species, as expected given that ISD is higher in eukaryotic proteomes than prokaryotic proteomes. Using phylogenetically corrected linear models, we find, contrary to expectations, that the ISD of a given protein domain evolves to be higher when in well-adapted species. This effect is stronger in young protein domains but is also present in ancient domains.
The Adaptor Protein Complex 1 limits E-cadherin endocytosis during epithelial morphogenesis

Intracellular trafficking regulates the distribution of transmembrane proteins including the key determinants of epithelial polarity and adhesion. The Adaptor Protein 1 (AP-1) complex is the key regulator of vesicle sorting, which binds a large number of specific cargos. We examined roles of the AP-1 complex in epithelial morphogenesis, using the Drosophila wing as a paradigm. We found that AP-1 knockdown leads to ectopic folds caused by trafficking defects of integrins. This occurs concurrently with an increase in the apical cell area and induction of cell death due to defects in E-cadherin trafficking. We discovered a distinct pool of AP-1 localizes at the apical Adherens Junctions, where it limits internalization of E-cadherin from the cell surface. Upon AP-1 knockdown, the accompanying hyperinternalization of E-cadherin induces cell death by an uncharacterised mechanism with a potential tumour-suppressive role. Simultaneously, cells increase expression of E-cadherin in a compensatory mechanism to maintain cell-cell adhesion.
Identification of Differential Gene Groups From Single-Cell Transcriptomes Using Network Entropy

A complex tissue contains a variety of cells with distinct molecular signatures. Single-cell RNA sequencing has characterized the transcriptomes of different cell types and enables researchers to discover the underlying mechanisms of cellular heterogeneity. A critical task in single-cell transcriptome studies is to uncover transcriptional differences among specific cell types. However, the intercellular transcriptional variation is usually confounded with high level of technical noise, which masks the important biological signals. Here, we propose a new computational method DiffGE for differential analysis, adopting network entropy to measure the expression dynamics of gene groups among different cell types and to identify the highly differential gene groups. To evaluate the effectiveness of our proposed method, DiffGE is applied to three independent single-cell RNA-seq datasets and to identify the highly dynamic gene groups that exhibit distinctive expression patterns in different cell types. We compare the results of our method with those of three widely applied algorithms. Further, the gene function analysis indicates that these detected differential gene groups are significantly related to cellular regulation processes. The results demonstrate the power of our method in evaluating the transcriptional dynamics and identifying highly differential gene groups among different cell types.
A wild Cucurbita genome reveals the role of structural variants and introgression in domestication

Despite their economic importance and well-characterized domestication syndrome, the genomic impact of domestication and the identification of variants underlying the domestication traits in Cucurbita species (pumpkins and squashes) is currently lacking. Cucurbita argyrosperma, also known as cushaw pumpkin or silver-seed gourd, is a Mexican crop consumed primarily for its seeds rather than fruit flesh. This makes it a good model to study Cucurbita domestication, as seeds were an essential component of early Mesoamerican diet and likely the first targets of human-guided selection in pumpkins and squashes. We obtained population-level data using tunable Genotype by Sequencing libraries for 192 individuals of the wild and domesticated subspecies of C. argyrosperma across Mexico. We also assembled the first wild Cucurbita genome at a chromosome level. Comparative genomic analyses revealed several structural variants and presence/absence of genes related to domestication. Our results indicate a monophyletic origin of this domesticated crop in the lowlands of Jalisco. We uncovered candidate domestication genes that are involved in the synthesis and regulation of growth hormones, plant defense mechanisms, flowering time and seed development. The presence of shared selected alleles with the closely related species Cucurbita moschata suggests domestication-related introgression between both taxa.
A Comparative Study of Nanohydroxyapetite Obtained from Natural Shells and Wet Chemical Process

In this study, a simple, economic and successful synthesis of nanohydroxyapatite powders was carried out from naturally available bio-waste resources; more specifically crabs shells and eggshells. At first, calcium oxide powders were obtained from crab shells and eggshells via calcination at 800 °C and 1000 °C for 3 hours under ambient air atmosphere. These powders were used as precursor materials for the preparation of the hydroxyapatite samples, which were then compared with the hydroxyapatite obtained from wet chemical process. Structure, morphology and chemical composition of the hydroxyapatite samples were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, scanning electron microscopy, Energy dispersive X-ray spectroscopy, transmission electron microscopy and selected area electron diffraction. Presence of good quality crystals of hydroxyapatite was confirmed and the measured average size of the hydroxyapatite prepared from crab shells, eggshells and wet chemical process were 293 nm, 182 nm and 106 nm respectively. ARTICLE HISTORY Received 20-05-2020 Revised 27-05-2020 Accepted 02-06-2020 Published 10-06-2020