bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of intracytoplasmic membranes in alphaproteobacteria involves the conserved mitochondrial crista-developing protein Mic60
Authors: Muñoz-Gómez Sergio A. , Cadena Lawrence Rudy , Gardiner Alastair T. , Leger Michelle M. , Sheikh Shaghayegh , Connell Louise , Bilý Tomáš , Kopejtka Karel , Beatty J. Thomas , Koblížek Michal , Roger Andrew J. , Slamovits Claudio H. , Lukeš Julius , Hashimi Hassan 
Published: June 2022

AbstractMitochondrial cristae expand the surface area of respiratory membranes and ultimately allow for the evolutionary scaling of respiration with cell volume across eukaryotes. The discovery of Mic60 homologs among alphaproteobacteria, the closest extant relatives of mitochondria, suggested that cristae might have evolved from bacterial intracytoplasmic membranes (ICMs). Here, we investigated the predicted structure and function of alphaproteobacterial Mic60, and a protein encoded by an adjacent gene Orf52, in two distantly related purple alphaproteobacteria,Rhodobacter sphaeroidesandRhodopseudomonas palustris. In addition, we assessed the potential physical interactors of Mic60 and Orf52 inR. sphaeroides. We show that the three α-helices of mitochondrial Mic60’s mitofilin domain, as well as its adjacent membrane-binding amphipathic helix, are present in alphaproteobacterial Mic60. The disruption of Mic60 and Orf52 caused photoheterotrophic growth defects, which are most severe under low light conditions, and both their disruption and overexpression led to enlarged ICMs in both studied alphaproteobacteria. We also found that alphaproteobacterial Mic60 physically interacts with BamA, the homolog of Sam50, one of the main physical interactors of eukaryotic Mic60. This interaction, responsible for making contact sites at mitochondrial envelopes, has been conserved in modern alphaproteobacteria despite more than a billion years of evolutionary divergence. Our results suggest a role for Mic60 in photosynthetic ICM development and contact site formation at alphaproteobacterial envelopes. Overall, we provide support for the hypothesis that mitochondrial cristae evolved from alphaproteobacterial ICMs, and therefore have improved our understanding of the nature of the mitochondrial ancestor.
Identifying cortical areas that underlie the transformation from retinal to world motion signals
Authors: Wen Puti , Landy Michael S. , Rokers Bas 
Published: June 2022

AbstractAccurate motion perception requires that the visual system integrate the retinal motion signals received by the two eyes into a single representation of 3D (i.e., world) motion. However, most experimental paradigms limit the motion stimuli to the fronto-parallel plane (i.e., 2D motion) and are thus unable to dissociate retinal and world motion signals. Here, we used stereoscopic displays to present separate motion signals to the two eyes and examined their representation in visual cortex using fMRI. Specifically, we presented random-dot motion stimuli that produced percepts of various 3D motion trajectories. We also presented control stimuli that contained the same retinal motion energy in the two eyes but were inconsistent with any 3D motion trajectory. We decoded the stimuli from BOLD activity using a probabilistic decoding algorithm. We found that 3D motion direction can be reliably decoded in three major clusters in the human visual system. In early visual cortex (V1-V3), we found no significant difference in decoding performance between the 3D motion and control stimuli, suggesting that these areas represent retinal motion rather than world motion signals. In voxels in and surrounding hMT and IPS0 however, decoding performance was consistently superior for 3D motion compared to control stimuli. Our results reveal the parts of the visual processing hierarchy that are critical for the transformation of retinal into world motion signals and suggest a role for IPS0 in the representation of 3D motion signals, in addition to its sensitivity to 3D object structure and static depth.
Conservation at the uterine-placental interface
Authors: Scott Regan L. , Vu Ha T. H. , Jain Ashish , Iqbal Khursheed , Tuteja Geetu , Soares Michael J. 
Published: June 2022

ABSTRACTThe hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus. This is not a consistent feature of hemochorial placentation and has hindered the establishment of suitable animal models. The rat represents an intriguing model for investigating hemochorial placentation with deep trophoblast cell invasion. In this study, we used single cell RNA sequencing to characterize the transcriptome of the invasive trophoblast cell lineage, as well as other cell populations within the rat uterine-placental interface during early (gestation day, gd, 15.5) and late (gd 19.5) stages of intrauterine trophoblast cell invasion. We identified a robust set of transcripts that define invasive trophoblast cells, as well as transcripts that distinguished endothelial, smooth muscle, natural killer, and macrophage cells. Invasive trophoblast, immune, and endothelial cell populations exhibited distinct spatial relationships within the uterine-placental interface. Furthermore, the maturation stage of invasive trophoblast cell development could be determined by assessing gestation-stage dependent changes in transcript expression. Finally, and most importantly, expression of a prominent subset of rat invasive trophoblast cell transcripts is conserved in the invasive extravillous trophoblast cell lineage of the human placenta. These findings provide foundational data to identify and interrogate key conserved regulatory mechanisms essential for development and function of an important compartment within the hemochorial placentation site that is essential for a healthy pregnancy.SIGNIFICANCETrophoblast cell-guided restructuring of the uterus is an essential event in the establishment of the hemochorial placenta. Establishment of a suitable animal model for investigating regulatory mechanisms in this critical developmental process is a key to better understanding the etiology of diseases of placentation, such as early pregnancy loss, preeclampsia, intrauterine growth restriction, and preterm birth. The rat exhibits deep trophoblast cell invasion, as seen in human hemochorial placentation. Similarities are identified in the transcriptomes of rat and human invasive trophoblast cells, leading to the discovery of conserved candidate regulators of the invasive trophoblast cell lineage. This creates opportunities to test hypotheses underlying the pathophysiologic basis of trophoblast cell-guided uterine transformation and new insights into the etiology of diseases of placentation.
Protein Function Prediction from Three-Dimensional Feature Representations Using Space-Filling Curves
Authors: Rappoport Dmitrij , Jinich Adrian 
Published: June 2022

AbstractCompact and interpretable structural feature representations are required for accurately predicting properties and the function of proteins. In this work, we construct and evaluate three-dimensional feature representations of protein structures based on space-filling curves. We focus on the problem of enzyme substrate prediction, using two ubiquitous enzyme families as case studies: the short-chain dehydrogenase/reductases (SDRs) and the S-adenosylmethionine dependent methyltransferases (SAM-MTases). Space-filling curves such as Hilbert curve and the Morton curve generate a reversible mapping from discretized three-dimensional to one-dimensional representations and thus help to encode three-dimensional molecular structures in a system-independent way and with a minimal number of parameters. Using three-dimensional structures of SDRs and SAM-MTases generated using AlphaFold2, we assess the performance of the SFC-based feature representations in predictions on a new benchmark database of enzyme classification tasks including their cofactor and substrate selectivity. Gradient-boosted tree classifiers yield binary prediction accuracy of 0.766–0.906 and AUC (area under curve) parameters of 0.828–0.922 for the classification tasks. We investigate the effects of amino acid encoding, spatial orientation, and (the few) parameters of SFC-based encodings on the accuracy of the predictions. Our results suggest that geometry-based approaches such as SFCs are promising for generating protein structural representations and are complementary to the highly parametric methods, for example, convolutional neural networks (CNNs).
Phytochemical and antibacterial analyses of Onychium japonicum (Thunb.) Kunze
Authors: Shah Syed AHsan , Shah Ghulam Mujtaba , Hassan Mohamed M. , Alsanie Walaa F. , Nawazish Shamyla , Ali Waqar , Basit Abdul , Shafqath DR. Nosheen , Jabeen Nadia , Shah Syed Abdul Majid , Shah Zarbad , Ishtiaq Muhammad , Gul DR. Alia , alam jan , Islam Muhammad , Faheem Asma ,   Experts from Microbiology and Biichemistry as well participated in the current work
Published: June 2022

AbstractIn clinical practice bacterial resistance against antibiotics has become a serious health problem, thus using alternative approaches such as natural products as the supplementary drug could solve it. Therefore, the current study was conducted to thoroughly investigate the enrichment of phytochemicals and antibacterial potential of O. japonicum. The fronds samples of O. japonicum prepared in different solvents were used against MDR bacterial strains and phytochemical analyses.The analyses of data revealed that O. japonicum was enriched with flavonoids, alkaloids, saponins, tannins, glycosides, carotenoids, terpenoids, phlobatanins, phenols, and coumarins while quantitatively this plant has a significantly higher content of phenols(1100.91µM/g) followed by sugar contents (748.67µM/ml), ascorbic acid (426.12mM/g), flavonoids (160.65mg/g), anthocyanin (101.06µM/g) and proline (80.58µM/g). On the other hand, the organic extracts of O. japonicum were highly active against all bacterial strains while hydric extract was inactive against selected bacteria. Specifically, O. japonicum was highly active against S. aureus in all organic extracts (chloroform=16.66±0.33, ethyl acetate=15±0.57, methyl alcohol= 14±0.57, N-hexane=20.33±0.33) followed by K. pneumonia (chloroform=14.33±0.33, ethyl acetate=4.33±4.33, methyl alcohol=3.66±3.66, N-hexane=16.66±0.33) and P. aeruginosa (chloroform= 8.33±4.17, ethyl acetate=8.33±4.17, methyl alcohol=6±3.00, N-hexane=9.33±4.66), while E. coli (chloroform=0±0.00, ethyl acetate=7±3.51, methyl alcohol=3.33±3.33, N-hexane=4±4.00).Based on current findings it is concluded that O. japonicum is enriched in many useful phytochemicals that could be use as a supplement with other traditionally used antibiotics.
SOX10 Expression Levels may be a Critical Mediator of White Matter Dysfunction in Schizophrenia
Authors: McPhie Donna L , Ren Boyu , Garcıa-Leon Juan Antonio , Verfaillie Catherine M , Cohen Bruce M 
Published: June 2022

AbstractAbnormalities of brain connectivity are consistently observed in individuals with schizophrenias (SZ). Underlying these anomalies, convergent in vivo, post-mortem, and genomic evidence suggest abnormal oligodendrocyte (OL) development and function, including lower in vivo myelination in SZ. Using patient derived induced pluripotent stem cells (IPSCs), we previously observed a significant and substantial reduction in the number of OLs produced in cells from the SZ group compared to the healthy control (HC) group. We a lso observed a correlation between white matter (WM) estimated in brain in vivo and the number of OLs produced in vitro.We have now characterized potential mediators that may contribute to the SZ-associated deficit in OL production. We ran qRT-PCRs to detect group-specific differences in key myelin pathway proteins. Significant reductions of PAX6 and SOX10 expression were seen in the SZ group. We focused on SOX10 since one of its functions is the commitment of precursor cells to an oligodendrocyte fate. Using an inducible lentiviral system, we expressed SOX10 in patterned neural stem cells (NSCs) and quantified the number of OLs produced. Expression of SOX10 rescued the SZ-associated deficit in OL production, indicating that reduced SOX10 may be a critical mediator of OL dysfunction in SZ. We then ran qRT-PCRs to screen mRNAs for three proteins (SOX9, QK1 and FEZ1) whose expression was directly influenced by SOX10 or directly influenced the expression of SOX10. We saw significant reductions of SOX9 expression and a reduction in QK1 expression in the SZ group. RNAseq analysis confirmed these gene expression changes.
Dietary polyphenols drive alterations in behavior, transcriptional regulation, and commensal microbiota in models of opioid use
Authors: Osman Aya , Hofford Rebecca S. , Meckel Katherine R. , Dave Yesha A. , Zeldin Sharon M. , Shipman Ava L. , Lucerne Kelsey E. , Trageser Kyle J , Oguchi Tatsunori , Pasinetti Giulio M. , Kiraly Drew D. 
Published: June 2022

AbstractOpioid Use Disorder (OUD) is a neuropsychiatric condition associated with tremendous medical and social consequences. Despite this burden, current pharmacotherapies for OUD are ineffective or intolerable for many patients. As such, interventions aimed at promoting overall health and resilience against OUD are of immense clinical and societal interest. Recently, treatment with a Bioactive Dietary Polyphenol Preparation (BDPP) was shown to promote behavioral resilience and adaptive neuroplasticity in multiple models of neuropsychiatric disease. Here, we assessed effects of BDPP treatment on behavioral and molecular responses to repeated morphine treatment. We find that BDPP pre-treatment alters responses across the dose range for both locomotor sensitization and conditioned place preference. Most notably, polyphenol treatment consistently reduced formation of preference at low dose (5mg/kg) morphine but enhanced it at high dose (15mg/kg). In parallel, we performed transcriptomic profiling of the nucleus accumbens, which again showed a dose x polyphenol interaction. At high dose morphine, BDPP pre-treatment potentiated gene expression changes induced by morphine particularly for genes related to synaptic function. We also profiled microbiome composition and function, as polyphenols are metabolized by the microbiome and can act as prebiotics. The profile revealed polyphenol treatment markedly altered microbiome composition and function, particularly in the low dose morphine group. Finally, we investigated involvement of the SIRT1 histone deacetylase, and the role of specific polyphenol metabolites in these behavioral phenotypes. Taken together, these results demonstrate that polyphenols have robust dose-dependent effects on behavioral and physiological responses to morphine and lay the foundation for future translational work.
Draft genome of the lowland anoa (Bubalus depressicornis) and comparison with buffalo genome assemblies (Bovidae, Bubalina)
Authors: Porrelli Stefano , Gerbault-Seureau Michèle , Rozzi Roberto , Chikhi Rayan , Curaudeau Manon , Ropiquet Anne , Hassanin Alexandre 
Published: June 2022

AbstractGenomic data for wild species of the genus Bubalus (Asian buffaloes) are still lacking while several whole genomes are currently available for domestic water buffaloes. To address this, we sequenced the genome of a wild endangered dwarf buffalo, the lowland anoa (Bubalus depressicornis), produced a draft genome assembly, and made comparison to published buffalo genomes.The lowland anoa genome assembly was 2.56 Gbp long and contained 103,135 contigs, the longest contig being 337.39 kbp long. N50 and L50 values were 38.73 kbp and 19.83 kbp, respectively, mean coverage was 44x and GC content was 41.74%. Two strategies were adopted to evaluate genome completeness: (i) determination of genomic features with de novo and homology-based predictions using annotations of chromosome-level genome assembly of the river buffalo, and (ii) employment of benchmarking against universal single-copy orthologs (BUSCO). Homology-based predictions identified 94.51% complete and 3.65% partial genomic features. De novo gene predictions identified 32,393 genes, representing 97.14% of the reference’s annotated genes, whilst BUSCO search against the mammalian orthologues database identified 71.1% complete, 11.7% fragmented and 17.2% missing orthologues, indicating a good level of completeness for downstream analyses. Repeat analyses indicated that the lowland anoa genome contains 42.12% of repetitive regions. The genome assembly of the lowland anoa is expected to contribute to comparative genome analyses among bovid species.
Void volume fraction of granular scaffolds
Authors: Riley Lindsay , Wei Grace , Bao Yijun , Cheng Peter , Wilson Katrina L. , Liu Yining , Gong Yiyang , Segura Tatiana 
Published: June 2022

AbstractVoid volume fraction (VVF) of granular biomaterials is a global measurement frequently used to characterize void space. There is currently no gold standard for measuring the VVF of granular scaffolds made in lab. To help the biomaterials field, we provide a library of different simulated scaffolds with known VVF for easy look-up. We use our simulated data to explore the relationship between microscope magnification and VVF, and we study the accuracy of approximating VVF using 2-D z-slice images, which is the most common approach for computing VVF of real scaffolds. Lastly, we test four different approaches for computing VVF using microscope images of real granular scaffolds and reveal that VVF may be an unreliable descriptor.
The transition zone in Hirschsprung’s bowel contains abnormal hybrid ganglia with characteristics of extrinsic nerves
Authors: Smith Megan , Chhabra Sumita , Shukla Rajeev , Kenny Simon , Almond Sarah , Edgar David , Wilm Bettina 
Published: June 2022

AbstractThe aganglionic bowel in short segment Hirschsprung’s disease is characterised both by the absence of enteric ganglia and the presence of extrinsic thickened nerve bundles (TNBs). The relationship between the TNBs and the loss of enteric ganglia is unknown. Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between ganglionic and aganglionic gut, and there is some evidence of spatial contact between them in this region. To determine the cellular interactions involved, we have analysed the expression of perineurial markers of TNBs and enteric ganglionic markers for both neural cells and their ensheathing telocytes across four cranio-caudal segments consisting of most proximal ganglionic to most distal aganglionic from pull-through resected colon. We show that in the TZ, enteric ganglia are abnormal, being surrounded by perineurium cells characteristic of TNBs. Furthermore, short processes of ganglionic neurons extend caudally towards the aganglionic region, where telocytes in the TNB are located between the perineurium and nerve fibres into which they project telopodes. Thus, enteric ganglia within the TZ have abnormal structural characteristics, the cellular relationships of which are shared by the TNBs. These findings will help towards elucidation of the cellular mechanisms involved in the aetiology of Hirschsprung’s disease.
Prevalence and severity of symptoms 3 months after infection with SARS-CoV-2 compared to test-negative and population controls in the Netherlands
Authors: van der Maaden Tessa , Mutubuki Elizabeth N. , de Bruijn Siméon , Leung Ka Yin , Knoop Hans , Slootweg Jaap , Tulen Anna D. , Wong Albert , van Hoek Albert Jan , Franz Eelco , Van den Wijngaard Cees C. 
Published: June 2022

ABSTRACTBackgroundMore information is needed on prevalence of long-term symptoms after SARS-CoV-2-infection. This prospective study assesses symptoms three months after SARS-CoV-2-infection compared to test-negative and population controls, and the effect of vaccination prior to infection.MethodsParticipants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2-test, or after invitation from the general population (population controls). After three months, participants indicated presence of 41 symptoms, and severity of four symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection.FindingsBetween May 19th and December 13th 2021 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At three months, 13 symptoms, and severity of fatigue, cognitive impairment and dyspnoea, were significantly elevated between cases and controls. Of cases, 48.5% reported ≥1 significantly elevated symptom, compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could only be determined for cases <65yrs, and was found to be significantly protective for loss of smell and taste but not for other symptoms.InterpretationThree months after SARS-CoV-2 infection, almost half of the cases still report symptoms, which is higher than the background prevalence and prevalence in test-negative controls. Vaccination prior to infection was protective against loss of smell and taste as assessed in cases aged <65.
Daily administration of low-dose daunorubicin or doxorubicin inhibits hypoxia-inducible factor 1 and tumor vascularization
Authors: Yang Yongkang , Qian David Z. , Rey Sergio , Liu Jun O. , Semenza Gregg L. 
Published: June 2022

AbstractUsing a hypoxia-inducible factor 1 (HIF-1)-dependent luciferase reporter in Hep3B human hepatocellular carcinoma cells, we screened over 3,000 drugs that have been used in clinical trials and identified multiple anthracyclines as inhibitors of HIF-1 activity. Anthracyclines interfered with the ability of HIF-1 to bind to DNA. Daily injection of tumor-bearing mice with anthracyclines at low dose inhibited expression of the luciferase reporter and HIF-1 target genes that encode vascular endothelial growth factor A (VEGFA; ligand of VEGFR2), stromal-derived factor 1 (SDF-1; ligand of CXCR4), and stem cell factor (SCF; ligand of CD117) in tumor tissue. Increased numbers of circulating CXCR4+/Sca1+, VEGFR2+/CD34+, and VEGFR2+/CD117+ cells were demonstrated in immunodeficient mice bearing prostate cancer xenografts but not in tumor-bearing mice treated with anthracyclines, which also significantly inhibited angiogenesis in tumor tissue. Our findings indicate that HIF-1 inhibition underlies the anti-angiogenic effect associated with daunorubicin or doxorubicin metronomic therapy and suggest that these drugs may be particularly effective in patients with high levels of HIF-1α in their diagnostic tumor biopsy.