Miracle-dz/UniFAR-FTUs huggingface dataset:
Captivity Influences Gut Microbiota in Crocodile Lizards (Shinisaurus crocodilurus)

Captivity is an important measure for conservation of an endangered species, and it is becoming a hot topic in conservation biology, which integrates gut microbiota and endangered species management in captivity. As an ancient reptile, the crocodile lizard (Shinisaurus crocodilurus) is facing extreme danger of extinction, resulting in great significance to species conservation in the reserve. Thus, it is critical to understand the differences in gut microbiota composition between captive and wild populations, as it could provide fundamental information for conservative management of crocodile lizards. Here, fecal samples of crocodile lizards were collected from two wild and one captive populations with different ages (i.e., juveniles and adults) and were analyzed for microbiota composition by 16S ribosomal RNA (rRNA) gene amplicon sequencing. This study showed that the lizard gut microbiota was mainly composed of Firmicutes and Proteobacteria. The gut microbiota composition of crocodile lizard did not differ between juveniles and adults, as well as between two wild populations. Interestingly, captivity increased community richness and influenced community structures of gut microbiota in crocodile lizards, compared with wild congeners. This was indicated by higher abundances of the genera Epulopiscium and Glutamicibacter. These increases might be induced by complex integration of simple food resources or human contact in captivity. The gut microbiota functions of crocodile lizards are primarily enriched in metabolism, environmental information processing, genetic information processing, and cellular processes based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. This study provides fundamental information about the gut microbiota of crocodile lizards in wild and captive populations. In the future, exploring the relationship among diet, gut microbiota, and host health is necessary for providing animal conservation strategies.
Assessment of a Potential Role of Dickeya dadantii DSM 18020 as a Pectinase Producer for Utilization in Poultry Diets Based on in silico Analyses

Currently, the poultry industry has been faced with consumer pressure to utilize only vegetable feedstuffs in poultry diets, eliminate antibiotics from poultry production, and rear poultry in free range systems. To maintain current production standards, the industry must determine ways to enhance nutrient uptake and utilization further. One possible solution is the supplementation of pectinase, an enzyme that degrades pectin within the cell walls of plants, in poultry diets. Therefore, the objective of the current study was to determine the potential role of a pectinase producer, Dickeya dadantii DSM 18020, as a commercially utilized pectinase producer in poultry diets against other known pectinase producers, in silico. In the current study, whole genomes of Dickeya dadantii DSM 18020 (Dd18020), D. dadantii 3937 (Dd3937), D. solani IPO 2222 (Ds2222), Bacillus halodurans C-125 (BhC125), and B. subtilis subsp. subtilis str. 168 (Bs168) were compared using bioinformatic approaches to compare the chromosomal genome size, GC content, protein coding genes (CDS), total genes, average protein length (a.a.) and determine the predicted metabolic pathways, predicted pectin degrading enzymes, and pectin-degradation pathways across pectinase producers. Due to insufficient information surrounding the genome of Dd18020 (lack of annotation), the genome of Dd3937, a 99% identical genome to Dd18020, was utilized to compare pectinase-associated enzymes and pathways. The results from the current study demonstrated that Dd3937 possessed the most significant proportion of pathways presented and the highest number of pathways related to degradation, assimilation, and utilization of pectin. Also, Dd18020 exhibited a high number of pectinase-related enzymes. Both Dd3937 and Dd2222 shared the pectin degradation I pathway via the EC 3.1. 1.11, EC 3.2. 1.82, and EC 4.2. 2. - enzymes, but did not share this pathway with either Bacillus species. In conclusion, Dd18020 demonstrated the genetic potential to produce multiple pectinase enzymes that could be beneficial to the degradation of pectin in poultry diets. However, for Dd18020 to become a commercially viable enzyme producer for the poultry industry, further research quantifying the pectinase production in vitro and determining the stability of the produced pectinases during feed manufacturing are necessary.
Laser-induced cell injury in closed micro physiological systems: a novel method to study regeneration processes in vitro

Closed micro-physiological systems (MPS) are miniaturized, chip-sized platforms that can be used as cellularized organoid systems to study cellular processes like migration, regeneration or proliferation in vitro. Due to the limited accessibility of the cells inside of closed MPS, the establishment of a well-defined mechanism to induce specific cell damage is difficult. Here we present a novel laser based method to induce well-defined lesions in closed cell layers. This could be a novel tool to study cellular mechanisms of different cell types after injury. The present project aimed to establish well-defined lesion in cellular layers without removing the dead cells and the molecular signaling that is caused by apoptosis. Considering that, we constructed a MPS that was produced by layer laminate manufacturing. According to the experimental needs, the MPS contains two fluidic circuits which include reservoirs, channels, and an integrated micro pump. To establish the method, blood endothelial outgrowth cells (BOEC) were seeded into the MPS previously coated with collagen (5μg/cm2) at a density of approximately 7,5×104 cells/cm2. After 3 hours of attachment, a pulsatile flow was applied to the channels. When the whole channel was covered with a BOEC monolayer, laser ablation took place between day 3 and 6 after seeding. To induce the selective cell injury we used a JenLas D2.mini laser that was optically integrated into an inverted microscope. The irradiation took several seconds with a wavelength of 532 nm. The damage and the following regeneration processes were observed by fluorescence microscopy using LIVE/DEAD Viability/Cytotoxicity Kit and Time Lapse recording
Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine

Schizophrenia is a chronic and severe mental disorder characterized by positive, negative, and cognitive symptoms. Negative symptoms are usually present from the prodromal phase; early diagnosis and management of negative symptoms is a major health concern since an insidious onset dominated by negative symptoms is associated with a worse outcome. Antipsychotic medications, which are effective for treating positive symptoms, are generally ineffective for treating negative or cognitive symptoms. We present a 23-year-old woman showing severe symptoms at her first visit to our department. The patient’s parents reported that their daughter had experienced several years of psychosocial decline and putative psychiatric symptoms, but no medical attention had been previously sought; as such, the diagnosis of schizophrenia with predominantly negative symptoms was very much delayed. Early onset of schizophrenia, longer duration of untreated psychosis, and severe negative symptoms, which have limited treatment options, suggested a poor prognosis. We initiated monotherapy with cariprazine, a novel antipsychotic that has recently been proven efficacious in treating schizophrenia with predominantly negative symptoms. This report describes a 52-week cariprazine treatment regimen and follows the patient’s impressive clinical improvement confirmed by PANSS and CGI scores, and psychological tests.
Intrinsic Genetic and Transcriptomic Patterns Reflect Tumor Immune Subtypes Facilitating Exploring Possible Combinatory Therapy

The classification of immune subtypes was based on immune signatures highlighting the tumor immuno-microenvironment. It was found that immune subtypes associated with mutation and expression patterns in the tumor. How the intrinsic genetic and transcriptomic alterations contribute to the immune subtypes and how to select drug combinations from both targeted drugs and immune therapeutic drugs according to different immune subtypes are still not clear. Through statistical analysis of genetic alterations and transcriptional profiles of breast invasive carcinoma (BRCA) samples, we found significant differences in the number of somatic missense mutations and frameshift deletions among the different immune subtypes. The high mutation load for somatic missense mutations and frameshift deletions may be explained by the high frequency of mutations and high expression of DNA double-strand break repair pathway genes. Extensive analysis of signaling pathways in both the genetic and transcriptomic levels reveals significantly altered pathways such as tumor protein Tumor Protein P53 (TP53) and receptor tyrosine kinase (RTK)/RAS signaling pathways among different subtypes. Drug targets in the signaling pathways such as mitogen-activated protein kinase kinase kinase 1 (MAP3K1) and Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) show genetic alteration in specific subtypes, which may be potential targets for patients of a specific subtype. More drug targets which show transcriptional difference among immune subtypes were discovered, such as cyclin-dependent kinase (CDK)4, CDK6, Erb-B2 receptor tyrosine kinase 2 (ERBB2), etc. Moreover, differences in functional activity between tumor growth and immune-related pathways also elucidate the extrinsic factors of differences in prognosis and suggest potential drug combinations for different immune subtypes. These results help to explain how intrinsic alterations are associated with the immune subtypes and provide clues for possible combination therapy for different immune subtypes.
Abundance, Functional, and Evolutionary Analysis of Oxalyl-Coenzyme A Decarboxylase in Human Microbiota

Oxalic acid and its oxalate salts have been linked to kidney stones and other health problems and about 80% kidney stones are made up of calcium oxalate. Oxalyl coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of oxalate. In this study, we performed bioinformatic and biochemical analysis of OXC. First, we mined the OXC sequences from a public protein database and collected 1396 putative OXC sequences. These sequences were widely spread and mainly distributed in Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, and Betaproteobacteria and classified into seven clusters. The phylogenetic relationship and evolutionary rate of the 7 clusters showed that OXC are highly conserved. Second, the abundance of the different clusters of OXC was explored in 380 human microbiome datasets, which showed that OXCs in Cluster 1 were relatively high in the gut while OXCs in Clusters 2–4 were relatively enriched in the vagina. Third, we measured the activity of one OXC from Mycobacterium mageritense (OXCmm) in Cluster 3, in which there was no experimentally characterized enzymes. Mutation analysis showed that OXCmm shared the same active sites with the OXC from Oxalobacter formigenes. Taken together, this analysis provides a better insight into the distribution and catalysis of OXC and further potential alternative application of OXC active bacteria as probiotics in the management of kidney stone disease.
Environment-dependent behavioral traits and experiential factors shape addiction vulnerability

The transition from controlled drug use to drug addiction depends on an interaction between a vulnerable individual, their environment and a drug. Here we tested the hypothesis that conditions under which individuals live influence behavioral vulnerability traits and experiential factors operating in the drug taking environment to determine the vulnerability to addiction. The role of behavioural vulnerability traits in mediating the influence of housing conditions on the tendency to acquire cocaine self-administration was characterised in 48 rats housed in either an enriched (EE) or a standard (SE) environment. Then, the influence of these housing conditions on the individual vulnerability to develop addiction-like behaviour for cocaine or alcohol was measured in 72 EE or SE rats after several months of cocaine self-administration or intermittent alcohol drinking, respectively. The determining role of negative experiential factors in the drug taking context was further investigated in 48 SE rats that acquired alcohol drinking as a self-medication strategy. The environment influenced the acquisition of drug intake through its effect on behavioral markers of resilience to addiction. In contrast, the initiation of drug taking as a coping strategy or in a negative state occasioned by the contrast between enriched housing conditions and a relatively impoverished drug taking setting, facilitated the development of compulsive cocaine and alcohol intake. These data demonstrate that addiction vulnerability depends on environmentally determined experiential factors, suggesting that initiating drug use through negative reinforcement-based self-medication facilitates the development of addiction in vulnerable individuals. Significance Statement The factors that underlie an individual’s vulnerability to switch from controlled, recreational drug use to addiction are not well understood. We showed that in individuals housed in enriched conditions, the experience of drugs in the relative social and sensory impoverishment of the drug taking context, and the associated change in behavioural traits of resilience to addiction, exacerbate the vulnerability to develop compulsive drug intake. We further demonstrated that the acquisition of alcohol drinking as a mechanism to cope with distress increases the vulnerability to develop compulsive alcohol intake. Together these results demonstrate that experiential factors in the drug taking context shape the vulnerability to addiction.
Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design

Novel coronavirus has wrecked medical and health care facilities claiming ~5% death tolls globally. All efforts to contain the pathogenesis either using inhibitory drugs or vaccines largely remained futile due to a lack of better understanding of the genomic feature of this virus. In the present study, we compared the 2019-nCoV with other coronaviruses, which indicated that bat-SARS like coronavirus could be a probable ancestor of the novel coronavirus. The protein sequence similarity of pangolin-hCoV and bat-hCoV with human coronavirus was higher as compared to their nucleotide similarity denoting the occurrence of more synonymous mutations in the genome. Phylogenetic and alignment analysis of 591 novel coronaviruses of different clades from Group I to Group V revealed several mutations and concomitant amino acid changes. Detailed investigation on nucleotide substitution unfolded 100 substitutions in the coding region of which 43 were synonymous and 57 were of non-synonymous type. The non-synonymous substitutions resulting into 57 amino acid changes were found to be distributed over different hCoV proteins with maximum on spike protein. An important diamino acid change RG to KR was observed in ORF9 protein. Additionally, several interesting features of the novel coronavirus genome have been highlighted in respect to various other human infecting viruses which may explain extreme pathogenicity, infectivity and simultaneously the reason behind failure of the antiviral therapies. Summary This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. This analysis will provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.
Existing actin filaments orient new filament growth to provide structural memory of filament alignment during cytokinesis

During cytokinesis, animal cells rapidly remodel the equatorial cortex to build an aligned array of actin filaments called the contractile ring. Local reorientation of filaments by equatorial contraction is thought to underlie the emergence of filament alignment during ring assembly. Here, combining single molecule analysis and modeling in one-cell C. elegans embryos, we show that filaments turnover is far too fast for reorientation of single filaments by equatorial contraction/cortex compression to explain the observed alignment, even if favorably oriented filaments are selectively stabilized. Instead, by tracking single Formin/CYK-1::GFP speckles to monitor local filament assembly, we identify a mechanism that we call filament-guided filament assembly (FGFA), in which existing filaments serve as templates to guide/orient the growth of new filaments. We show that FGFA sharply increases the effective lifetime of filament orientation, providing structural memory that allows slow equatorial contraction to build and maintain highly aligned filament arrays, despite rapid turnover of individual filaments.
Investigating the origin and consequences of endogenous default options in repeated economic choices

Classical value-based decision theories state that economic choices are solely based on the value of available options. Experimental evidence suggests, however, that individuals’ choices are biased towards default options, prompted by the framing of decisions. Although the effects of default options created by exogenous framing – such as how choice options are displayed – are well-documented, little is known about the potential effects and properties of endogenous framing, that is, originating from an individual’s internal state. In this study, we investigated the existence and properties of endogenous default options in a task involving choices between risky lotteries. By manipulating and examining the effects of three experimental features – time pressure, time spent on task and relative choice proportion towards a specific option –, we reveal and dissociate two features of endogenous default options which bias individuals’ choices: a natural tendency to prefer certain types of options (natural default), and the tendency to implicitly learn a default option from past choices (learned default). Additional analyses suggest that while the natural default may bias the standard choice process towards an option category, the learned default effects may be attributable to a second independent choice process. Overall, these investigations provide a first experimental evidence of how individuals build and apply diverse endogenous default options in economic decision-making and how this biases their choices.
The IDR-containing protein PID-2 affects Z granules and is required for piRNA-induced silencing in the embryo

In Caenorhabditis elegans, the piRNA (21U RNA) pathway is required to establish proper gene regulation and an immortal germline. To achieve this, PRG-1-bound 21U RNAs trigger silencing mechanisms mediated by RNA-dependent RNA polymerase (RdRP)-synthetized 22G RNAs. This silencing can become PRG-1-independent, and heritable over many generations. This state is named RNAe. It is unknown how and when RNAe is established, and how it is maintained. We show that maternally provided 21U RNAs can be sufficient to trigger RNAe in embryos. Additionally, we identify the IDR-containing protein PID-2, as a factor required to establish and maintain RNAe. PID-2 interacts with two novel, partially redundant, eTudor domain proteins, PID-4 and PID-5. Additionally, PID-5 has a domain related to the X-prolyl aminopeptidase protein APP-1, and binds APP-1, implicating N-terminal proteolysis in RNAe. All three proteins are required for germline immortality, localize to perinuclear foci, affect Z granules, and are required for balancing of 22G RNA populations. Overall, our study identifies three new proteins with crucial functions in the C. elegans small RNA silencing network.
A Drosophila natural variation screen identifies NKCC1 as a substrate of NGLY1 deglycosylation and a modifier of NGLY1 deficiency

N-Glycanase 1 (NGLY1) is a cytoplasmic deglycosylating enzyme. Loss-of-function mutations in the NGLY1 gene cause NGLY1 deficiency, which is characterized by developmental delay, seizures, and a lack of sweat and tears. To model the phenotypic variability observed among patients, we crossed a Drosophila model of NGLY1 deficiency onto a panel of genetically diverse strains. The resulting progeny showed a phenotypic spectrum from 0-100% lethality. Association analysis on the lethality phenotype as well as an evolutionary rate covariation analysis generated lists of modifying genes, providing insight into NGLY1 function and disease. The top association hit was Ncc69 (human NKCC1/2), a conserved ion transporter. Analyses in NGLY1 -/- mouse cells demonstrated that NKCC1 is misglycosylated and has reduced function, making it only the second confirmed NGLY1 enzymatic substrate. The misregulation of this ion transporter may explain the observed defects in secretory epithelium function in NGLY1 deficiency patients.
Invasion of homogeneous and polyploid populations in nutrient-limiting environments

Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Progression is accompanied by a switch to an invasive cell phenotype. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how co-existing cells differ in their response to nutrient limitations and how this impacts invasion of the metapopulation as a whole. We integrate mathematical modeling with microenvironmental perturbation-data to investigate invasion in nutrient-limiting environments inhabited by one or two cancer cell subpopulations. Hereby, subpopulations are defined by their energy efficiency and chemotactic ability. We estimate the invasion-distance traveled by a homogeneous population. For heterogeneous populations, our results suggest that an imbalance between nutrient efficacy and chemotactic superiority accelerates invasion. Such imbalance will spatially segregate the two populations and only one type will dominate at the invasion front. Only if these two phenotypes are balanced do the two subpopulations compete for the same space, which decelerates invasion. We investigate ploidy as a candidate biomarker of this phenotypic heterogeneity to discern circumstances when inhibiting chemotaxis amplifies internal competition and decelerates tumor progression, from circumstances that render clinical consequences of chemotactic inhibition unfavorable. Significance A better understanding of the nature of the double-edged sword of high ploidy is a prerequisite to personalize combination-therapies with cytotoxic drugs and inhibitors of signal transduction pathways such as MTOR-Is.