Miracle-dz/UniFAR-FTUs huggingface dataset:
IGF2BP2 is Induced by Stress in the Heart and Mediates Dilated Cardiomyopathy

The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results raise the possibility that IGF2BP2 might play an adaptive role during cardiac stress and recovery. Using a conditional, inducible transgenic mouse line, we found that enhanced expression of an IGF2BP2 transgene in newborn or adult hearts leads to dilated cardiomyopathy (DCM) and death within 3-4 weeks. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Hearts overexpressing IGF2BP2 downregulate sarcomeric and mitochondrial proteins and have fragmented mitochondria and elongated, thinner sarcomeres. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results suggest that IGF2BP2 may be an attractive target for therapeutic intervention in DCM.
Glutathione induces Arabidopsis PHT1;5 gene via WRKY75 transcription factor to regulate phosphate homeostasis

Phosphorus is a macronutrient that regulates a wide range of physiological processes, including plant growth and development. The scarcity of bioavailable phosphate is often a constraint for plant growth in most agricultural ecosystems. Under phosphate limited conditions, plants increase phosphate acquisition or alter its distribution within tissues by activating different phosphate transporters and phosphate starvation-induced genes. Glutathione (GSH), on the other hand, is known to play a critical role in regulating iron and zinc homeostasis in Arabidopsis. However, how it regulates phosphate homeostasis under phosphate limited conditions remains unexplored. We found that the two GSH-deficient mutants, cad2-1, and pad2-1, were hypersensitive to phosphate starvation. Under phosphate-sufficient condition, the root phosphate content was lower in the mutants but significantly higher in the shoot over the Col-0 plants. The pattern was reversed under phosphate-deficient condition. Interestingly, among the different phosphate transporters analyzed, the AtPHT1;5 was significantly down-regulated in the two GSH-deficient mutants. Treatment with exogenous GSH could alter phosphate accumulation in Col-0 and the pht1;5 complementation lines but not in the pht1;5 mutant. This observation confirmed the role of GSH in phosphate reallocation during phosphate starvation via the AtPHT1;5 transporter. Further, promoter analysis demonstrated that GSH regulates the transcription of the AtPHT1;5 gene. The phosphate-responsive transcription factor (TF), AtWRKY75 was identified to interact with the AtPHT1;5 promoter, and phosphate deficiency or GSH treatment enhanced its binding affinity. Together our investigation delineates that GSH regulates the AtPHT1;5 transporter via the AtWRKY75 TF to modulate phosphate distribution under altered phosphate conditions. Summary statement Glutathione regulates phosphate translocation in Arabidopsis under altered phosphate condition via transcriptional activation of AtPHT1;5 gene by AtWRKY75 transcription factor.
Positive selection drives cis- regulatory evolution across the threespine stickleback Y

Allele-specific gene expression evolves rapidly across gametologs on heteromorphic sex chromosomes 15 (X and Y or Z and W). Current models of sex chromosome evolution suggest this occurs through the 16 rapid accumulation of mutations within regulatory regions. However, these patterns have not been 17 demonstrated empirically due to the limited number of Y chromosome assemblies available to survey 18 sequence evolution outside of coding regions. The threespine stickleback ( Gasterosteus aculeatus ) Y 19 chromosome is an ideal model to test hypotheses of rapid regulatory evolution due to its intermediate 20 state of divergence from the X chromosome. A large number of Y-linked gametologs still exist across 21 three differently aged evolutionary strata to test these hypotheses. We found that putative enhancer 22 regions (accessible chromatin regions defined through ATAC-seq) on the Y chromosome exhibited 23 elevated substitution rates when compared to intergenic regions and synonymous sites within coding 24 regions. This strongly suggests that many regulatory regions are under positive selection on the Y 25 chromosome. This divergence was correlated with X-biased gametolog expression, indicating the loss of 26 expression from the Y chromosome may be favored by selection. Our findings provide evidence that Y- 27 linked regulatory regions exhibit signs of positive selection quickly after the suppression of 28 recombination, supporting recent theoretical models that show the rapid divergence of regulatory regions 29 may be favored to mask deleterious mutations on the Y chromosome.
Phosphoproteomic profiling highlights CDC42 and CDK2 as key players in the regulation of the TGF-β pathway in ALMS1 and BBS1 knockout models

BACKGROUND The primary cilium is a sensory organelle that extends from the plasma membrane. It plays a vital role in physiological and developmental processes by controlling different signalling pathways such as WNT, Sonic hedgehog (SHh), and transforming growth factor β (TGF-β). Ciliary dysfunction has been related to different pathologies such as Alström (ALMS) or Bardet-Biedl (BBS) syndrome. The leading cause of death in adults with these syndromes is chronic kidney disease (CKD), which is characterised by fibrotic and inflammatory processes often involving the TGF-β pathway. METHODS Using genomic editing with CRISPR-CAS9 and phosphoproteomics we have studied the TGF-β signalling pathway in knockout (KO) models for ALMS1 and BBS1 genes. We have developed a network diffusion-based analysis pipeline to expand the data initially obtained and to be able to determine which processes were deregulated in TGF-β pathway. Finally, we have analysed protein-protein and kinase-substrate interactions to prioritise candidate genes in the regulation of the TGF-β pathway in ALMS and BBS. RESULTS Analysis of differentially phosphorylated proteins identified 10 candidate proteins in the ALMS1 KO model and 41 in the BBS1 KO model. After network expansion using a random walk with a restart algorithm, we were able to identify the TGF-β signalling pathway together with other related processes such as endocytosis in the case of ALMS1 or the regulation of the extracellular matrix in BBS1. Protein interaction analyses demonstrated the involvement of CDC42 as a central protein in the interactome in ALMS1 and CDK2 in the case of BBS1. CONCLUSION In conclusion, the depletion of ALMS1 and BBS1 affects the TGF-β signalling pathway, conditioning the phosphorylation and activation of several proteins, including CDC42 in the case of ALMS1 and CDK2 in the case of BBS1.
Islet-on-a-chip device reveals first phase glucose-stimulated respiration is substrate limited by glycolysis independent of Ca2+ activity

Pancreatic islets respond metabolically to glucose by closing KATP channels resulting in Ca2+-influx and insulin secretion. Previous work has revealed the importance of glycolytic flux in triggering insulin secretion. However, it is unclear whether the triggered (‘first phase’) secretion is further amplified by Ca2+-stimulation of mitochondrial NADH production and/or oxidative phosphorylation (OxPhos). Although commercially available tools have been developed to explore islet metabolism, these methods often overlook islet variability and have poor spatiotemporal resolution. To tease apart first phase glucose-stimulated respiration, we designed an islet-on-a-chip microfluidic device to simultaneously measure O2-consumption rate (OCR) and Ca2+-activity of individual islets with high temporal resolution. We used finite element analysis to optimize placement of sensor in optically clear microwells on a thin glass coverslip. The microfluidic channels were subsequently fabricated using O2-impermeable plastic to limit outside-in diffusion and push islets against the microsensor. We validated our device using living mouse islets and well-established modulators of respiration. By inhibiting glycolysis and mitochondrial pyruvate transport, we show that islet OxPhos is limited by NADH-substrate rather than ADP in low and high glucose. We subsequently imaged glucose-stimulated OCR and Ca2+-influx simultaneously to reveal a biphasic respiratory response that is determined by glycolytic flux through pyruvate kinase (PKM2) and independent of Ca2+. These data demonstrate the unique utility of our modular and optically clear O2-sensor to simultaneously measure glucose-stimulated OCR and Ca2+ activity of multiple individual islets.
Cross correlation of cosmic shear and extragalactic gamma-ray background: Constraints on the dark matter annihilation cross section

We present the first measurement of the cross-correlation of weak gravitational lensing and the extragalactic gamma-ray background emission using data from the Canada-France-Hawaii Lensing Survey and the Fermi Large Area Telescope. The cross-correlation is a powerful probe of signatures of dark matter annihilation, because both cosmic shear and gamma-ray emission originate directly from the same DM distribution in the universe, and it can be used to derive constraints on dark matter annihilation cross-section. We show that the measured lensing-gamma correlation is consistent with a null signal. Comparing the result to theoretical predictions, we exclude dark matter annihilation cross sections of =10^{-24}-10^{-25} cm^3 s^-1 for a 100 GeV dark matter. If dark matter halos exist down to the mass scale of 10^-6 M_sun, we are able to place constraints on the thermal cross sections ~ 3 x 10^{-26} cm^3 s^-1 for a 10 GeV dark matter annihilation into tau^{+} tau^{-}. Future gravitational lensing surveys will increase sensitivity to probe annihilation cross sections of ~ 5 x 10^{-26} cm^3 s^-1 even for a 100 GeV dark matter. Detailed modeling of the contributions from astrophysical sources to the cross correlation signal could further improve the constraints by ~ 40-70 %.
Probing the magnetic field of the nearby galaxy pair Arp 269

We present a multiwavelength radio study of the nearby galaxy pair Arp 269 (NGC 4490/85). High sensitivity to extended structures gained by using the merged interferometric and single- dish maps allowed us to reveal a previously undiscovered extension of the radio continuum emission. Its direction is significantly different from that of the neutral gas tail, suggesting that different physical processes might be involved in their creation. The population of radio- emitting electrons is generally young, signifying an ongoing, vigorous star formation -- this claim is supported by strong magnetic fields (over 20 {\mu}G), similar to the ones found in much larger spiral galaxies. From the study of the spectral energy distribution, we conclude that the electron population in the intergalactic bridge between member galaxies originates from the disc areas, and therefore its age (approximately 3.7--16.9 Myr, depending on the model used) reflects the time-scale of the interaction. We have also discovered an angularly near compact steep source -- which is a member of a different galaxy pair -- at a redshift of approximately 0.125.
Eastern king prawn Penaeus plebejus stock enhancement—Genetic evidence that hatchery bred prawns have survived in the wild after release

Eastern king prawn (Penaeus plebejus) is endemic to eastern Australia and is of high commercial and recreational value. As part of a recreational fisheries enhancement initiative, hatchery reared juveniles from Queensland were released into two, more Southern New South Wales (NSW) estuaries between 2014 and 2015. Responsible stock enhancement programs rely on knowledge of the population structure of the released species. Previously, in consideration of fisheries data, it was assumed the king prawn populations in Australia are one single breeding stock. In the present study, our first aim was to test this posit of no genetic differentiation using mtDNA control region (mtCR) sequences from the wild samples collected from four estuaries ranging from Queensland/NSW border (source of the stocked animals) to Southern NSW. The second objective was to test for signals of hatchery-released animals in the two stocked estuaries. All four surveyed populations had an extremely high level of haplotype diversity (average h = 99.8%) and low level of haplotype sharing between populations. Estimates of PhiPT values were <0.01 or close to zero and AMOVA test did not indicate any significant differences among populations. Further, phylogenetic analysis and principal coordinate analysis did not support division of samples by population. Collectively these results suggest that eastern king prawn populations along the NSW coast can be considered as a single stock and stocking from the Queensland samples will not necessarily impact the genetic composition of the overall stock. After stocking of two estuaries, sharing of haplotypes was moderate to very high in the stocked sites (>80% in some collections) but negligible in the two unstocked estuaries (≤2%, which is assumed to be background coancestry unrelated to the hatchery). Moreover, some haplotypes present in the hatchery broodstock were detected in stocked sites, but not in unstocked sites. The highest stocking signal was detected in the estuary which becomes isolated from the sea by sand barrier suggesting such “lakes” maybe more favourable for stocking than estuaries directly open to the sea. Findings in the current study should assist in designing and implementation of future prawn stocking programs.
TMT proteomics analysis of a pseudocereal crop, quinoa (Chenopodium quinoa Willd.), during seed maturation

Quinoa (Chenopodium quinoa Willd.), an Andean native crop, is increasingly popular around the world due to its high nutritional content and stress tolerance. The production and the popularity of this strategic global food are greatly restricted by many limiting factors, such as seed pre-harvest sprouting, bitter saponin, etc. To solve these problems, the underlying mechanism of seed maturation in quinoa needs to be investigated. In this study, based on the investigation of morphological characteristics, a quantitative analysis of its global proteome was conducted using the combinational proteomics of tandem mass tag (TMT) labeling and parallel reaction monitoring (PRM). The proteome changes related to quinoa seed maturation conversion were monitored to aid its genetic improvement. Typical changes of morphological characteristics were discovered during seed maturation, including mean grain diameter, mean grain thickness, mean hundred-grain weight, palea, episperm color, etc. With TMT proteomics analysis, 581 differentially accumulated proteins (DAPs) were identified. Functional classification analysis and Gene Ontology enrichment analysis showed that most DAPs involved in photosynthesis were downregulated, indicating low levels of photosynthesis. DAPs that participated in glycolysis, such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase, were upregulated to fulfill the increasing requirement of energy consumption during maturation conversion. The storage proteins, such as globulins, legumins, vicilins, and oleosin, were also increased significantly during maturation conversion. Protein–protein interaction analysis and function annotation revealed that the upregulation of oleosin, oil body-associated proteins, and acyl-coenzyme A oxidase 2 resulted in the accumulation of oil in quinoa seeds. The downregulation of β-amyrin 28-oxidase was observed, indicating the decreasing saponin content, during maturation, which makes the quinoa “sweet”. By the PRM and qRT-PCR analysis, the expression patterns of most selected DAPs were consistent with the result of TMT proteomics. Our study enhanced the understanding of the maturation conversion in quinoa. This might be the first and most important step toward the genetic improvement of quinoa.
Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions

Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower depth of coverage (DOC) was evaluated by subsampling and HLA typing 230 WES samples at DOC ranging from 1X to 100X. The HLA typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions (P group and pseudo-sequence), which specifically focus on the peptide binding region. On average, across the five HLA loci examined, HLA*LA was found to have the highest typing accuracy. For the individual loci, HLA-A, -B and -C, Optitype’s typing accuracy was the highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1. The tools’ robustness to lower DOC data varied widely and further depended on the specific HLA locus. For all Class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the HLA molecule) at 50X, but increasing the DOC beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA loci as well as HLA*LA’s typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which is often based on sequencing data with lower quality and DOC. Interestingly, we found that Optitype’s typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the DOC is sufficiently high.
Aberrant expression of FBXO22 is associated with propofol-induced synaptic plasticity and cognitive dysfunction in adult mice

Recent observation demonstrated that prolonged anesthesia modifies brain synaptic architecture in all ages, including adult. Propofol is the most commonly utilized anesthetics at clinic. Whether repeated administration of propofol modulates cognitive impairment in adults and changes synaptic plasticity remains, however, to be explored. In this study, we first discovered that repeated and prolonged exposure to propofol-induced cognitive impairment in adult rodents. Then, we examined the property of hippocampal primary neurons and slices after propofol treatment in mice, including synaptic protein profile, dendritic spine density, as well as synaptic transmission. We found the distinctive change of the F-box only protein 22 (FBXO22), an F-box E3 ligase, during this process and further explored its role. Knockdown experiments showed the downregulation of FBXO22 restored the changes by propofol treatment on hippocampal primary neurons and attenuated propofol-induced hippocampal dependent cognitive dysfunction. Our results showed that FBXO22 is involved in the regulation of repeated propofol treatment induced changes of synaptic plasticity and cognitive dysfunction in adult mice. Repeated propofol treatment leads to cognitive dysfunction by regulating FBXO22 in adult rodents.
The inhibitory effect of human umbilical cord mesenchymal stem cells expressing anti-HAAH scFv-sTRAIL fusion protein on glioma

Glioma is the most common malignant intracranial tumor with low 5-year survival rate. In this study, we constructed a plasmid expressing anti-HAAH single-chain antibody and sTRAIL fusion protein (scFv-sTRAIL), and explored the effects of the double gene modified human umbilical cord mesenchyreal stem cells (hucMSCs) on the growth of glioma in vitro and in vivo. The isolated hucMSCs were identified by detecting the adipogenic differentiation ability and the osteogenic differentiation ability. The phenotypes of hucMSCs were determined by the flow cytometry. The hucMSCs were infected with lentivirus expression scFv-sTRAIL fusion protein. The expression of sTRAIL in hucMSCs were detected by immunofluorescence staining, western blot and ELISA. The tropism of hucMSCs toward U87G cells was assessed by transwell assay. The inhibitory effect of hucMSCs on U87G cells were explored by CCK8 and apoptosis assay. The xenograft tumor was established by subcutaneously injection of U87G cells into the back of mice. The hucMSCs were injected via tail veins. The inhibitory effect of hucMSCs on glioma in vivo was assessed by TUNEL assay. The hucMSCs migrated into the xenograft tumor were revealed by detecting the green fluorescent. The results showed that the scFv-sTRAIL expression did not affect the phenotypes of hucMSCs. The scFv-sTRAIL expression promoted the tropism of hucMSCs toward U87G cells, enhanced the inhibitory effect and tumor killing effect of hucMSCs on U87G cells. The in vivo study showed that hucMSCs expressing scFv-sTRAIL demonstrated significantly higher inhibitory effect and tumor killing effect than hucMSCs expressing sTRAIL. The green fluorescence intensity in the mice injected with hucMSCs expressing scFv-sTRAIL was significantly higher than that injected with hucMSCs expressing sTRAIL. These data suggested that the scFv conferred the targeting effect of hucMSCs tropism towards the xenograft tumor. In conclusion, the hucMSCs expressing scFv-sTRAIL fusion protein gained the capability to target and kill gliomas cells in vitro and in vivo. These findings shed light on a potential therapy for glioma treatment.
Numerical Study on the performance of a heat pump-driven-DCMD for sustainable desalination

The study presents an energy-efficient desalination system that combines direct contact membrane distillation (DCMD) and a heat pump to improve thermal efficiency and integrate with photovoltaics. DCMD is a sort of thermal desalination process, and it requires a lot of thermal energy. A heat pump is a device that produces both hot and cold energy simultaneously with less electrical energy input compared to other heating devices, such as a boiler and an electrical heater. A hollow-fiber DCMD and a 10-kW water-to-water heat pump were considered for a numerical simulation in this study. Numerical models were established for each device and validated against the results obtained from the literature. The simulation was first carried out to identify the performance of the system based on the baseline. After that, a series of simulations were carried out in order to investigate the performance of the proposed system in terms of specific energy consumption (SEC), gained output ratio (GOR), and the coefficient of performance (COP) under various operating conditions. Results showed that the minimum SEC and the maximum GOR were achieved at the inlet feed water temperature of 66.5°C with a mass flow rate of 20 kg/min and the inlet permeate temperature of 19.8°C with a mass flow rate of 10 lpm. On the other hand, it was found that the maximum COP can be observed at the inlet feed water temperature of 23.6°C with a mass flow rate of 10 lpm and at the inlet permeate temperature of 8.9°C with a mass flow rate of 20 lpm.