Miracle-dz/UniFAR-FTUs huggingface dataset:
p53 Controls Murine Gammaherpesvirus Latency and Prevents Infection-Associated IgH/c-Myc Translocations

Gammaherpesviruses (GHVs) establish life-long infections and cause cancer in humans and other animals. To facilitate chronic infection, GHV oncoproteins promote cellular proliferation and differentiation. Aberrant cell-cycle progression driven by viral oncogenes should trigger activation of tumor suppressor p53, unless p53 is functionally deactivated during GHV latency establishment. However, interactions of GHVs with the p53 pathway during the establishment and maintenance of latent infection are poorly defined. Here we demonstrate in vivo that p53 is induced specifically in infected cells during latency establishment by murine gammaherpesvirus 68 (MHV68). In the absence of p53, MHV68 latency establishment was significantly increased, especially in germinal center B cells, and correlated with enhanced cellular proliferation. However, enhanced latency was not sustainable, and MHV68 exhibited a defect in long-term latency maintenance in p53-deficient mice. Moreover, IgH/c-Myc translocations were readily detected in B cells from infected p53-null mice indicating virus-driven genomic instability. These data demonstrate that p53 intrinsically restricts MHV68 latency establishment and reveal a paradigm in which a host restriction factor provides a long-term benefit to a chronic pathogen by limiting infection-associated damage.
Optimal seasonal routines across animals and latitudes

Most animals face seasonal fluctuations in food availability and need to develop an annual routine that maximizes their lifetime reproductive success. Two particularly common strategies are reducing energy expenditure and building storage to sustain the animal in meager periods (winters). Here, we pose a simple and generic model for an animal that can decide, at each time during the season, on its level of foraging effort and on building energy stores. Using dynamic optimization, we identify the optimal annual routines that maximize the trade-off between energy and mortality over a life-long horizon. We investigate how the optimal strategies depend on the body size and longevity of the animal, and upon the seasonal variability in the environment. We find that with large fluctuations, the optimal annual routine for small animals is to develop a surviving egg/spore stage rather than to attempt to survive the winter. Medium sized animals invest heavily in reserves to allow long hibernation, while larger animals only need smaller reserves and a shorter hibernation period. In environments with smaller fluctuations, organisms do not need energy stores or hibernation but reduce foraging activities during spring and summer where their fitness is highest. Our optimization model can be used as a null hypothesis to explain the annual routines of animals of all body sizes across the globe.
Sweet anticipation: Predictability of familiar music in autism

Autism has been characterised by different behavioural and cognitive profiles compared to typically developing (TD) individuals, and increasingly these differences have been associated with differences in structural and functional brain connectivity. It is currently unknown as to whether autistic and TD listeners process music in the same way: emotionally, mnemonically, and perceptually. The present study explores the brain’s dynamical landscape linked to music familiarity in an fMRI dataset from autistic and TD individuals. Group analysis using leading eigenvector dynamics analysis (LEiDA) revealed significantly higher probability of occurrence of a brain network in TD compared to autistic individuals during listening to familiar music. This network includes limbic and paralimbic areas (amygdala, hippocampus, parahippocampal gyrus, and temporal pole). No significant differences were found between autistic and TD individuals while listening to a scrambled, i.e. unfamiliar and more unpredictable, version of the same music track. These findings provide novel neuroimaging insights into how autistic prediction monitoring may shape brain networks during listening to familiar musical excerpts.
Postoperative Ultrasound in Kidney Transplant Recipients: Association Between Intrarenal Resistance Index and Cardiovascular Events

Background. Doppler ultrasound, including intrarenal resistance index (RI) measurement, is a widely used modality to assess kidney transplantation (KTx) vascularization. The aim of this study is to gain insight in the associations between early postoperative RI measurements and cardiovascular events (CVEs), all-cause mortality, and death-censored graft survival. Methods. From 2015 to 2017, a prospective cohort study was conducted in patients in which RI measurement was performed immediately after KTx. The RI was calculated as (peak systolic velocity—end-diastolic velocity)/peak systolic velocity. End points were CVEs, all-cause mortality, and graft failure. Kaplan-Meier analyses (logrank test) were used for differences in end points. Univariate and multivariate associations were investigated by means of Cox regression analyses. Results. RI cutoff of 0.70 was used. We included 339 recipients, of which 271 (80%) had an RI ≤ 0.70 and 68 (20%) had an RI > 0.70. CVEs were observed in 27 (8%) patients, 27 (8%) patients died, and 17 (5%) patients had graft failure during a median follow-up of 37 months (interquartile range, 33–43). Kaplan-Meier analyses and univariate Cox regression indicated a significant association with overall CVE-free survival (hazard ratios [HR], 2.79; P = 0.011; logrank test, P = 0.008) and all-cause mortality (HR, 2.59; P = 0.017; logrank test, P = 0.013) for patients with an RI above and below 0.70. An independent association was shown between an RI > 0.70 and CVE-free survival (HR, 2.48; P = 0.042) when deceased donation was not included in the model. Conclusions. In the early postoperative period, a high RI showed to be associated with CVEs after adjustment for cardiovascular risk factors, whereas no independent association was found with overall survival and graft failure. For the interpretation of RI measurements after KTx surgery, patients’ cardiovascular state should be taken into consideration.
SET Domain Containing 2 Deficiency in Myelodysplastic Syndrome

Recent studies have shown that myelodysplastic syndrome’s (MDS) progression to acute myeloid leukemia (AML) is associated with gene mutations. SET domain containing 2 (SETD2) variants were reported as a risk factor of poor prognosis in patients with AML. However, little is known about the potential contribution of the SETD2 gene in MDS. In this study, we investigated the roles of SETD2 gene mutations/variants on clinical features and prognosis in patients with MDS. A 43-gene panel was used for next-generation sequencing in 203 patients with primary MDS, and then the effects of SETD2 mutation on Wnt/β-catenin signaling was investigated during the different stages of MDS. At a median follow up of 33 months, 65 (32.0%) deaths and 94 (46.3%) leukemic transformations were recorded. The most frequent mutations/variants included TET2, DNMT3A, and ASXL1 mutations/variants. 37 patients had SETD2 gene mutations/variants, and these patients exhibited a significantly increased frequency of TP53 mutations. Multivariate survival analyses indicated that SETD2 mutations/variants were closely associated with overall survival (OS), and they were identified as risk factors for progression-free survival (PFS), especially with low expression of SETD2 gene. Further, we found that SETD2 loss could promote MDS progression via upregulation DVL3 mRNA level in BM cells and it could also cause genomic instability. Secondary mutations, such as TP53 and FLT3 mutations, were acquired at the time of progression to AML. In conclusion, we showed that SETD2 deficiency was associated with poor outcomes in patients with MDS. Moreover, SETD2 deficiency may upregulate DVL3 expression and modulate genomic stability that caused AML transformation.
Triploidy affects standard and postprandial metabolism in brook charr, Salvelinus fontinalis

The use of sterile triploids in aquaculture is currently limited because of reduced performance in situations of aerobic stress such as high temperature, hypoxia, and exhaustive exercise. Many studies have therefore attempted to find underlying metabolic differences between triploids and their diploid counterparts to improve triploid rearing protocols. This study investigated the effects of triploidy on postprandial metabolism (and therefore also pre-feeding standard metabolic rate; SMR) by measuring oxygen uptake and total ammonia nitrogen (TAN) excretion at 14-15°C of previously fasted (for eight days) diploid and triploid brook charr, Salvelinus fontinalis, from 48h before to 48h after being fed a single ration of 0.4% body mass. Triploids had significantly lower SMRs and higher postprandial metabolic rates (i.e., specific dynamic action) and net TAN excretion than diploids. While this greater cost of processing a meal may not represent a major diversion of metabolic reserves for triploids, it could affect their growth and survival when simultaneously faced with oxygen-limiting conditions.
Insight Into the Role of Ferroptosis in Non-neoplastic Neurological Diseases

Ferroptosis is an iron-dependent form of cell death characterized by the accumulation of intracellular lipid reactive oxygen species (ROS). Ferroptosis is significantly different from other types of cell death including apoptosis, autophagy, and necrosis, both in morphology and biochemical characteristics. The mechanisms that are associated with ferroptosis include iron metabolism, lipid oxidation, and other pathophysiological changes. Ferroptosis inducers or inhibitors can influence its occurrence through different pathways. Ferroptosis was initially discovered in tumors, though recent studies have confirmed that it is also closely related to a variety of neurological diseases including neurodegenerative disease [Alzheimer’s disease (AD), Parkinson’s disease (PD), etc.] and stroke. This article reviews the definition and characteristics of ferroptosis, the potential mechanisms associated with its development, inducers/inhibitors, and its role in non-neoplastic neurological diseases. We hope to provide a theoretical basis and novel treatment strategies for the treatment of central nervous system diseases by targeting ferroptosis.
Positively and negatively autocorrelated environmental fluctuations have opposing effects on species coexistence

Environmental fluctuations can mediate coexistence between competing species via the storage effect. This fluctuation-dependent coexistence mechanism requires three conditions: (i) a positive covariance between environment conditions and the strength of competition, (ii) species-specific environmental responses, and (iii) species are less sensitive to competition in environmentally unfavorable years. In serially uncorrelated environments, condition (i) only occurs if favorable environmental conditions immediately and directly increase the strength of competition. For many demographic parameters, this direct link between favorable years and competition may not exist. Moreover, many environmental variables are temporal autocorrelated, but theory has largely focused on serially uncorrelated environments. To address this gap, a model of competing species in autocorrelated environments is analyzed. This analysis shows that positive autocorrelations in demographic rates that increase fitness (e.g. maximal fecundity or adult survival) produce the positive environment-competition covariance. Hence, when these demographic rates contribute to buffered population growth, positive temporal autocorrelations generate a storage effect, otherwise they destabilize competitive interactions. For negatively autocorrelated environments, this theory highlights an alternative stabilizing mechanism that requires three conditions: (i’) a negative environmental-competition covariance, (ii) species-specific environmental responses, and (iii’) species are less sensitive to competition in more favorable years. When the conditions for either of these stabilizing mechanisms are violated, temporal autocorrelations can generate stochastic priority effects or hasten competitive exclusion. Collectively, these results highlight that temporal autocorrelations in environmental conditions can play a fundamental role in determining ecological outcomes of competing species.
DLDTI: A learning-based framework for identification of drug-target interaction using neural networks and network representation

To elucidate novel molecular mechanisms of known drugs, efficient and feasible computational methods for predicting potential drug-target interactions (DTI) would be of great importance. A novel calculation model called DLDTI was generated for predicting DTI based on network representation learning and convolutional neural networks. The proposed approach simultaneously fuses the topology of complex networks and diverse information from heterogeneous data sources and copes with the noisy, incomplete, and high-dimensional nature of large-scale biological data by learning low-dimensional and rich depth features of drugs and proteins. Low-dimensional feature vectors were used to train DLDTI to obtain optimal mapping space and infer new DTIs by ranking DTI candidates based on their proximity to optimal mapping space. DLDTI achieves promising performance under 5-fold cross-validation with AUC values of 0.9172, which was higher than that of the method based on different classifiers or different feature combination technique. Moreover, biomedical experiments were also completed to validate DLDTI’s performance. Consistent with the predicted result, tetramethylpyrazine, a member of pyrazines, reduced atherosclerosis progression and inhibited signal transduction in platelets, via PI3K/Akt, cAMP and calcium signaling pathways. The source code and datasets explored in this work are available at https://github.com/CUMTzackGit/DLDTI
Genome Fractionation and Loss of Heterozygosity in Hybrids and Polyploids: Mechanisms, Consequences for Selection, and Link to Gene Function

Hybridization and genome duplication have played crucial roles in the evolution of many animal and plant taxa. During their evolution, the subgenomes of parental species undergo considerable changes in hybrids and polyploids, which often selectively eliminate segments of one subgenome. However, the mechanisms underlying these changes are not well understood, particularly when the hybridization is linked with asexual reproduction that may enforce specific evolutionary pathways. We studied the genome evolution in asexual diploid and polyploid hybrids between fish from the genus Cobitis. Comparing exome sequencing with published cytogenetic and RNAseq data revealed that clonal genomes remain static on chromosome-scale levels but undergo considerable small-scale restructurations owing to two major processes; hemizygous deletions and gene conversions. Interestingly, polyploids were much more tolerant to accumulating deletions than diploid asexuals where gene conversions prevailed. The genomic restructurations accumulated preferentially in genes characterized by high transcription levels, relatively strong purifying selection and some specific functions such as interacting with intracellular membranes. The likelihood of an ortholog’s retention or loss correlated with its parental-species ancestry, GC content, and expression. Furthermore, all hybrids showed a strong bias towards the retention of one parental subgenome. Contrary to expectations, however, the preferentially retained subgenome was not transcriptionally dominant as all hybrids were phenotypically more similar to the other parent. The present study demonstrated that the fate of subgenomes in asexual hybrids and polyploids depends on the complex interplay of selection and several molecular mechanisms whose impact depends on ploidy, sequence composition, gene expression as well as parental ancestry.
Exploration of the Neisseria Resistome Reveals Resistance Mechanisms in Commensals That May Be Acquired by N. gonorrhoeae through Horizontal Gene Transfer

Non-pathogenic Neisseria have repeatedly been demonstrated to transfer antibiotic resistance genes to their pathogenic relative, Neisseria gonorrhoeae. However, the resistance genotypes and subsequent phenotypes of non-pathogens within the genus have been studied and described less frequently. Here, we use Etests to characterize the minimum inhibitory concentrations (MICs) of a panel of Neisseria (n=26) – including several commensal species – acquired from the CDC & FDA’s Antibiotic Resistance (AR) Isolate Bank to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database (CARD) Resistance Gene Identifier (RGI) platform to predict possible causal resistance-encoding mutations. Within this panel, resistant isolates to all tested antimicrobials including penicillin (n=5/26), ceftriaxone (n=2/26), cefixime (n=3/26), tetracycline (n=10/26), azithromycin (n=11/26), and ciprofloxacin (n=4/26) were found. In total we identify 63 distinct mutations predicted by RGI to be involved in resistance. The presence of several of these mutations had clear associations with increases in MIC such as: DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type β-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by non-pathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.
Hardware- and Software-in-the-loop Simulation for Parameterizing the Model and Control of Synchronous Condenser

The rapid increase of converter-based generation in the grid causes significant changes in the system dynamic characteristics. These changes require verification and testing of the reliability, optimization, and functionality of power system elements and controllers, which become more important for guaranteeing a secure operation. This paper first introduces a hardware-in-the-loop (HiL) setup of an automatic voltage regulator (AVR) control system and then proposes a softwarein-the-loop (SiL) setup for the parameterization of an IEEE standard AVR/excitation system model and a power oscillation damping (POD) controller of synchronous condenser. The AVR hardware is interfaced with a simulated grid in real-time digital simulator (RTDS) using EMT simulation to evaluate its control functions. Parameter optimization for the POD and the AVR simulation model by SiL simulation is implemented in a closed loop between RTDS and Matlab/Simulink interfaced through OPC to satisfy the optimization objectives. By tests executed on the future Western Danish power system, parameter optimization of the POD and IEEE standard AVR model, and the function of AVR hardware are successfully implemented and verified.
Mergers of agrifood cooperatives and their effects: from expectations to results. An empirical study in four Spanish Autonomous Regions.

Mergers have become the most widely accepted formula for business growth among many different sectors. However, these processes do not always contribute to obtaining the expected results, particularly from an economic viewpoint. In light of these reflections, this study attempts to establish whether mergers carried out between Spanish agrifood cooperatives during the period 1995-2005 have contributed to reaching some of the objectives they were set out to achieve: improving the economic-financial situation of the companies involved, increasing income and reducing costs. To do so, mergers that took place during this period were analyzed in four autonomous communities (Andalusia, Navarra, La Rioja and the Basque Country). Despite the considerable variability observed following the time-based analysis of the economic-financial situation of cooperatives prior to and after merger, statistically significant differences were only found in four of the fifteen variables studied. These were operating profit (a 99% reduction), financial income (an increase of 240%), extraordinary income (400% increase) and cost of goods sold (16% reduction), of all of which are calculated with respect to production value. The results obtained generally indicate that the objectives that were originally the motivation for initiating the merger processes have not been reached, as the financial situation of the cooperatives has not, by and large, undergone any significant improvement, nor have average unit costs been reduced. Performance and profitability have not improved either and the firms involved have found themselves at lower levels than the average for the sector.
Occurrence and functioning of phosphate solubilizing microorganisms from oil palm tree (Elaeis guineensis) rhizosphere in Cameroon

Phosphorus replenishment, particularly in smallholder agriculture, remains a challenge as it is mainly fertilizer dependent. While the use of soluble mineral phosphate fertilizers is the obvious best means to combat phosphate deficiency in Cameroon, their use is limited by their high cost and availability at farmer’s level. This study was aimed at maintaining the fertility of Cameroon soils by biological means, in order to improve agricultural production, using low inputs technology. Isolates were obtained from oil palm tree (Elaeis guineensis) root fragments and rhizospheric soils and their activity in mobilizing phosphate from insoluble sources was evaluated on agar plates and liquid culture media containing sparingly soluble phosphates. At the end of incubation time, it appeared that, phosphate solubilization resulted from a combined effect of pH decrease of the media and organic acids production. Furthermore, each of the tested isolates was able to produce at least one of the most important organic acids such as citrate, malate and tartrate. Among the ten isolates tested, three were identified as Pseudomonas fluorescens and would be considered as potential biofertilizers.
A LHFPL3-AS1/miR-580-3p/STAT3 Feedback Loop Promotes the Malignancy in Melanoma via Activation of JAK2/STAT3 Signaling

Melanoma is one of the severe skin cancers, accounting for three fourths of all deaths caused by skin cancers and gathering attention from researchers. Previous studies have elucidated that long noncoding RNAs (lncRNA) engage actively in tissue physiology and disease development, especially in tumorigenesis. LncRNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) has rarely been mentioned in researches regarding cancers; therefore, the underlying role and function of LHFPL3-AS1 in melanoma arouse our interest. Data from our work suggested that LHFPL3-AS1 expression was markedly elevated in melanoma tissues and cells. Of note, patients with melanoma with high level of LHFPL3-AS1 were burdened with unfavorable prognosis. Functionally, it has been revealed that LHFPL3-AS1 exerted pro-growth, pro-invasion, and pro-EMT functions in melanoma. Mechanistically, it was figured out that LHFPL3-AS1 could be transcriptionally activated by STAT3. In turn, LHFPL3-AS1 served as a sponge of miR-580-3p to augment STAT3 expression, resulting in activated JAK2/STAT3 signaling pathway in melanoma. Implications: Our study revealed a novel positive feedback loop LHFPL3-AS1/miR-580-3p/STAT3 in melanoma, which might contribute to finding potential therapeutic targets for melanoma.