Miracle-dz/UniFAR-FTUs huggingface dataset:
De Novo Assembly of Transcriptome Sequencing in Caragana korshinskii Kom. and Characterization of EST-SSR Markers

Caragana korshinskii Kom. is widely distributed in various habitats, including gravel desert, clay desert, fixed and semi-fixed sand, and saline land in the Asian and African deserts. To date, no previous genomic information or EST-SSR marker has been reported in Caragana Fabr. genus. In this study, more than two billion bases of high-quality sequence of C. korshinskii were generated by using illumina sequencing technology and demonstrated the de novo assembly and annotation of genes without prior genome information. These reads were assembled into 86,265 unigenes (mean length = 709 bp). The similarity search indicated that 33,955 and 21,978 unigenes showed significant similarities to known proteins from NCBI non-redundant and Swissprot protein databases, respectively. Among these annotated unigenes, 26,232 a unigenes were separately assigned to Gene Ontology (GO) database. When 22,756 unigenes searched against the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) database, 5,598 unigenes were assigned to 5 main categories including 32 KEGG pathways. Among the main KEGG categories, metabolism was the biggest category (2,862, 43.7%), suggesting the active metabolic processes in the desert tree. In addition, a total of 19,150 EST-SSRs were identified from 15,484 unigenes, and the characterizations of EST-SSRs were further compared with other four species in Fabraceae. 126 potential marker sites were randomly selected to validate the assembly quality and develop EST-SSR markers. Among the 9 germplasms in Caranaga Fabr. genus, PCR success rate were 93.7% and the phylogenic tree was constructed based on the genotypic data. This research generated a substantial fraction of transcriptome sequences, which were very useful resources for gene annotation and discovery, molecular markers development, genome assembly and annotation. The EST-SSR markers identified and developed in this study will facilitate marker-assisted selection breeding.
Pi at School

In this paper, an attempt has been made to define π by using the greatest lower bound and the least upper bound properties of the real number system. Using this definition, the usual formulas for the perimeter and area of a circle are proved. Though the formulas are well-known, their proofs are not found in text books. This paper tries to fill that gap.
GPCRs: Lipid-Dependent Membrane Receptors That Act as Drug Targets

G protein-coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across cell membranes and represent major targets in the development of novel drug candidates in all clinical areas. Although there have been some recent leads, structural information on GPCRs is relatively rare due to the difficulty associated with crystallization. A specific reason for this is the intrinsic flexibility displayed by GPCRs, which is necessary for their functional diversity. Since GPCRs are integral membrane proteins, interaction of membrane lipids with them constitutes an important area of research in GPCR biology. In particular, membrane cholesterol has been reported to have a modulatory role in the function of a number of GPCRs. The role of membrane cholesterol in GPCR function is discussed with specific example of the receptor. Recent results show that GPCRs are characterized with structural motifs that preferentially associate with cholesterol. An emerging and important concept is oligomerization of GPCRs and its role in GPCR function and signaling. The role of membrane cholesterol in GPCR oligomerization is highlighted. Future research in GPCR biology would offer novel insight in basic biology and provide new avenues for drug discovery.
Comprehensive analysis of PD-L1 expression in glioblastoma multiforme

Glioblastoma multiforme are highly malignant brain tumours with frequent genetic and epigenetic alterations. The poor clinical outcome of these tumours necessitates the development of new treatment options. Immunotherapies for glioblastoma multiforme including PD1/PD-L1 inhibition are currently tested in ongoing clinical trials. The purpose of this study was to investigate the molecular background of PD-L1 expression in glioblastoma multiforme and to find associated pathway activation and genetic alterations. We show that PD-L1 is up-regulated in IDH1/2 wildtype glioblastoma multiforme compared to lower-grade gliomas. In addition, a strong association of PD-L1 with the mesenchymal expression subgroup was observed. Consistent with that, NF1 mutation and corresponding activation of the MAPK pathway was strongly connected to PD-L1 expression. Our findings may explain different response to PD-L1 inhibition of patients in ongoing trials and may help to select patients that may profit of immunotherapy in the future.
Effects of Bile Acids and the Bile Acid Receptor FXR Agonist on the Respiratory Rhythm in the In Vitro Brainstem Medulla Slice of Neonatal Sprague-Dawley Rats

Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR) plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR) and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA) was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1–6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), cholic acid (CA) as well as ursodeoxycholic acid (UDCA) at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO) as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC), Inspiratory time (TI), Expiratory Time (TE) and Integral Amplitude (IA) were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.
QuantifyMe: An Open-Source Automated Single-Case Experimental Design Platform †

Smartphones and wearable sensors have enabled unprecedented data collection, with many products now providing feedback to users about recommended step counts or sleep durations. However, these recommendations do not provide personalized insights that have been shown to be best suited for a specific individual. A scientific way to find individualized recommendations and causal links is to conduct experiments using single-case experimental design; however, properly designed single-case experiments are not easy to conduct on oneself. We designed, developed, and evaluated a novel platform, QuantifyMe, for novice self-experimenters to conduct proper-methodology single-case self-experiments in an automated and scientific manner using their smartphones. We provide software for the platform that we used (available for free on GitHub), which provides the methodological elements to run many kinds of customized studies. In this work, we evaluate its use with four different kinds of personalized investigations, examining how variables such as sleep duration and regularity, activity, and leisure time affect personal happiness, stress, productivity, and sleep efficiency. We conducted a six-week pilot study (N = 13) to evaluate QuantifyMe. We describe the lessons learned developing the platform and recommendations for its improvement, as well as its potential for enabling personalized insights to be scientifically evaluated in many individuals, reducing the high administrative cost for advancing human health and wellbeing.
Microbial Stimulation and Succession following a Test Well Injection Simulating CO₂ Leakage into a Shallow Newark Basin Aquifer

In addition to efforts aimed at reducing anthropogenic production of greenhouse gases, geological storage of CO2 is being explored as a strategy to reduce atmospheric greenhouse gas emission and mitigate climate change. Previous studies of the deep subsurface in North America have not fully considered the potential negative effects of CO2 leakage into shallow drinking water aquifers, especially from a microbiological perspective. A test well in the Newark Rift Basin was utilized in two field experiments to investigate patterns of microbial succession following injection of CO2-saturated water into an isolated aquifer interval, simulating a CO2 leakage scenario. A decrease in pH following injection of CO2 saturated aquifer water was accompanied by mobilization of trace elements (e.g. Fe and Mn), and increased bacterial cell concentrations in the recovered water. 16S ribosomal RNA gene sequence libraries from samples collected before and after the test well injection were compared to link variability in geochemistry to changes in aquifer microbiology. Significant changes in microbial composition, compared to background conditions, were found following the test well injections, including a decrease in Proteobacteria, and an increased presence of Firmicutes, Verrucomicrobia and microbial taxa often noted to be associated with iron and sulfate reduction. The concurrence of increased microbial cell concentrations and rapid microbial community succession indicate significant changes in aquifer microbial communities immediately following the experimental CO2 leakage event. Samples collected one year post-injection were similar in cell number to the original background condition and community composition, although not identical, began to revert toward the pre-injection condition, indicating microbial resilience following a leakage disturbance. This study provides a first glimpse into the in situ successional response of microbial communities to CO2 leakage after subsurface injection in the Newark Basin and the potential microbiological impact of CO2 leakage on drinking water resources.
Neural sensitivity to eudaimonic and hedonic rewards differentially predict adolescent depressive symptoms over time

Significance Although optimal well-being may be achieved through eudaimonic activities (meaning and purpose), individuals tend to orient toward hedonic activities (pleasure seeking), potentially placing them at risk for ill-being. We find that reward-related neural activation during eudaimonic decisions predicts longitudinal declines in depressive symptoms, whereas reward-related neural activation to hedonic decisions predicts longitudinal increases in depressive symptoms. We identified a potential neural mechanism by which adolescents may develop or be protected from developing ill-being. These findings underscore how the motivational context underlying neural sensitivity to rewards can differentially predict changes in well-being over time. To our knowledge, this is the first study to show that reward-related neural activation within an individual can be both a source of risk and protection. The pursuit of happiness and reward is an impetus for everyday human behavior and the basis of well-being. Although optimal well-being may be achieved through eudaimonic activities (e.g., meaning and purpose), individuals tend to orient toward hedonic activities (e.g., pleasure seeking), potentially placing them at risk for ill-being. We implemented a longitudinal study and followed adolescents over 1 y to examine whether neural sensitivity to eudaimonic (e.g., prosocial decisions) and hedonic (e.g., selfish rewards and risky decisions) rewards differentially predicts longitudinal changes in depressive symptoms. Ventral striatum activation during eudaimonic decisions predicted longitudinal declines in depressive symptoms, whereas ventral striatum activation to hedonic decisions related to longitudinal increases in depressive symptoms. These findings underscore how the motivational context underlying neural sensitivity to rewards can differentially predict changes in well-being over time. Importantly, to our knowledge, this is the first study to show that striatal activation within an individual can be both a source of risk and protection.
Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date.
MODIFIED MODEL FOR SHEAR CARRYING CAPACITY OF SEGMENTAL CONCRETE BEAMS WITH EXTERNAL TENDONS

The study presents an investigation of the shear behavior of segmental concrete beams with external tendons considering the effect of joint opening. Joint position and prestressing force that affect the joint opening have been examined based on the results of experimental procedure and FEM. The simplified truss model with the small number of degree of freedom has been modified for segmental concrete beams with external tendons. The formulations to predict the variable angle and the thickness of struts are suggested with considering the effect of joint opening. A satisfactory prediction for the shear carrying capacity and the failure mechanism of segmental concrete beams with external tendons has been obtained.
Tensor Canonical Correlation Analysis for Action Classification

We introduce a new framework, namely tensor canonical correlation analysis (TCCA) which is an extension of classical canonical correlation analysis (CCA) to multidimensional data arrays (or tensors) and apply this for action/gesture classification in videos. By tensor CCA, joint space-time linear relationships of two video volumes are inspected to yield flexible and descriptive similarity features of the two videos. The TCCA features are combined with a discriminative feature selection scheme and a nearest neighbor classifier for action classification. In addition, we propose a time-efficient action detection method based on dynamic learning of subspaces for tensor CCA for the case that actions are not aligned in the space-time domain. The proposed method delivered significantly better accuracy and comparable detection speed over state-of-the-art methods on the KTH action data set as well as self-recorded hand gesture data sets.
Distribution of Mammalian-Like Melanopsin in Cyclostome Retinas Exhibiting a Different Extent of Visual Functions

Mammals contain 1 melanopsin (Opn4) gene that is expressed in a subset of retinal ganglion cells to serve as a photopigment involved in non-image-forming vision such as photoentrainment of circadian rhythms. In contrast, most nonmammalian vertebrates possess multiple melanopsins that are distributed in various types of retinal cells; however, their functions remain unclear. We previously found that the lamprey has only 1 type of mammalian-like melanopsin gene, which is similar to that observed in mammals. Here we investigated the molecular properties and localization of melanopsin in the lamprey and other cyclostome hagfish retinas, which contribute to visual functions including image-forming vision and mainly to non-image-forming vision, respectively. We isolated 1 type of mammalian-like melanopsin cDNA from the eyes of each species. We showed that the recombinant lamprey melanopsin was a blue light-sensitive pigment and that both the lamprey and hagfish melanopsins caused light-dependent increases in calcium ion concentration in cultured cells in a manner that was similar to that observed for mammalian melanopsins. We observed that melanopsin was distributed in several types of retinal cells, including horizontal cells and ganglion cells, in the lamprey retina, despite the existence of only 1 melanopsin gene in the lamprey. In contrast, melanopsin was almost specifically distributed to retinal ganglion cells in the hagfish retina. Furthermore, we found that the melanopsin-expressing horizontal cells connected to the rhodopsin-containing short photoreceptor cells in the lamprey. Taken together, our findings suggest that in cyclostomes, the global distribution of melanopsin in retinal cells might not be related to the melanopsin gene number but to the extent of retinal contribution to visual function.
Poverty and blindness in Pakistan: results from the Pakistan national blindness and visual impairment survey

Objective To explore the association between blindness and deprivation in a nationally representative sample of adults in Pakistan. Design Cross sectional population based survey. Setting 221 rural and urban clusters selected randomly throughout Pakistan. Participants Nationally representative sample of 16 507 adults aged 30 or above (95.3% response rate). Main outcome measures Associations between visual impairment and poverty assessed by a cluster level deprivation index and a household level poverty indicator; prevalence and causes of blindness; measures of the rate of uptake and quality of eye care services. Results 561 blind participants (<3/60 in the better eye) were identified during the survey. Clusters in urban Sindh province were the most affluent, whereas rural areas in Balochistan were the poorest. The prevalence of blindness in adults living in affluent clusters was 2.2%, compared with 3.7% in medium clusters and 3.9% in poor clusters (P<0.001 for affluent v poor). The highest prevalence of blindness was found in rural Balochistan (5.2%). The prevalence of total blindness (bilateral no light perception) was more than three times higher in poor clusters than in affluent clusters (0.24% v 0.07%, P<0.001). The prevalences of blindness caused by cataract, glaucoma, and corneal opacity were lower in affluent clusters and households. Reflecting access to eye care services, cataract surgical coverage was higher in affluent clusters (80.6%) than in medium (76.8%) and poor areas (75.1%). Intraocular lens implantation rates were significantly lower in participants from poorer households. 10.2% of adults living in affluent clusters presented to the examination station wearing spectacles, compared with 6.7% in medium clusters and 4.4% in poor cluster areas. Spectacle coverage in affluent areas was more than double that in poor clusters (23.5% v 11.1%, P<0.001). Conclusion Blindness is associated with poverty in Pakistan; lower access to eye care services was one contributory factor. To reduce blindness, strategies targeting poor people will be needed. These interventions may have an impact on deprivation in Pakistan.
Promiscuous Speciation with Gene Flow in Silverside Fish Genus Odontesthes (Atheriniformes, Atherinopsidae) from South Western Atlantic Ocean Basins

The present paper integrates phylogenetic and population genetics analyses based on mitochondrial and nuclear molecular markers in silversides, genus Odontesthes, from a non-sampled area in the SW Atlantic Ocean to address species discrimination and to define Managements Units for sustainable conservation. All phylogenetic analyses based on the COI mitochondrial gene were consistent to support the monophyly of the genus Odontesthes and to include O. argentinensis, O. perugiae-humensis and some O. bonariensis haplotypes in a basal polytomy conforming a major derivative clade. Microsatellites data revealed somewhat higher genetic variability values in the O. argentinensis-perugia populations than in O. bonariensis and O. perugia-humensis taxa. Contrasting population genetics structuring emerged from mitochondrial and microsatellites analyses in these taxa. Whereas mitochondrial data supported two major groups (O. argentinensis-perugia-humensis vs. O. bonariensis-perugiae-humensis populations), microsatellite data detected three major genetic entities represented by O. bonariensis, O. perugiae-humensis and an admixture of populations belonging to O. argentinensis-perugiae respectively. Therefore, the star COI polytomy in the tree topology involving these taxa could be interpreted by several hypothetic scenarios such as the existence of shared ancestral polymorphisms, incomplete lineage sorting in a radiating speciation process and/or reticulation events. Present findings support that promiscuous and recent contact between incipient species sharing asymmetric gene flow exchanges, blurs taxa boundaries yielding complicated taxonomy and Management Units delimitation in silverside genus Odontesthes from SW Atlantic Ocean basins.
Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of severe aortic stenosis: a meta-analysis of randomized trials.

AIMS In view of the currently available evidence from randomized trials, we aimed to compare the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the spectrum of risk and in important subgroups. METHODS AND RESULTS Trials comparing TAVI vs. SAVR were identified through Medline, Embase, and Cochrane databases. The primary outcome was death from any cause at 2 years. We performed random-effects meta-analyses to combine the available evidence and to evaluate the effect in different subgroups. This systematic review and meta-analysis is registered with PROSPERO (CRD42016037273). We identified four eligible trials including 3806 participants, who were randomly assigned to undergo TAVI (n = 1898) or SAVR (n = 1908). For the primary outcome of death from any cause, TAVI when compared with SAVR was associated with a significant 13% relative risk reduction [hazard ratio (95% CI): 0.87 (0.76-0.99); P = 0.038] with homogeneity across all trials irrespective of TAVI device (Pinteraction = 0.306) and baseline risk (Pinteraction = 0.610). In subgroup analyses, TAVI showed a robust survival benefit over SAVR for patients undergoing transfemoral access [0.80 (0.69-0.93); P = 0.004], but not transthoracic access [1.17 (0.88-1.56); P = 0.293] (Pinteraction = 0.024) and in female [0.68 (0.50-0.91); P = 0.010], but not male patients [0.99 (0.77-1.28); P = 0.952] (Pinteraction = 0.050). Secondary outcomes of kidney injury, new-onset atrial fibrillation, and major bleeding favoured TAVI, while major vascular complications, incidence of permanent pacemaker implantation, and paravalvular regurgitation favoured SAVR. CONCLUSION Compared with SAVR, TAVI is associated with a significant survival benefit throughout 2 years of follow-up. Importantly, this superiority is observed irrespective of the TAVI device across the spectrum of intermediate and high-risk patients, and is particularly pronounced among patients undergoing transfemoral TAVI and in females.