Miracle-dz/UniFAR-FTUs huggingface dataset:
The DEAD-box RNA helicase Dhx15 controls glycolysis and arbovirus replication in Aedes aegypti mosquito cells

Aedes aegypti mosquitoes are responsible for the transmission of arthropod-borne (arbo)viruses including dengue and chikungunya virus (CHIKV), but in contrast to human hosts, arbovirus infected mosquitoes are able to efficiently control virus replication to sub-pathological levels. Yet, our knowledge about the molecular interactions of arboviruses with their mosquito hosts is largely incomplete. Here, we aimed to identify and characterize novel host genes that control arbovirus replication in Aedes mosquitoes. RNA binding proteins (RBPs) are well known to regulate immune signaling pathways in all kingdoms of life. We therefore performed a knockdown screen targeting 461 genes encoding predicted RBPs in Aedes aegypti Aag2 cells and identified 15 genes with antiviral activity against a Sindbis reporter virus. Amongst these, three DEAD-box RNA helicases, AAEL004419/Dhx15, AAEL008728 and AAEL004859 also acted as antiviral factors in dengue and CHIKV infections. Here, we explore the mechanism of Dhx15 in regulating an antiviral transcriptional response in mosquitoes by silencing Dhx15 in Aag2 cells followed by deep-sequencing of poly-A enriched RNAs. Dhx15 knockdown in uninfected or CHIKV-infected cells resulted in differential expression of 856 and 372 genes, respectively. Interestingly, amongst the consistently downregulated genes, glycolytic process was the most strongly enriched GO term as the expression of all core enzymes of the glycolytic pathway was reduced, suggesting that Dhx15 regulates glycolytic function. A decrease in lactate production supported the observation that Dhx15 silencing functionally impaired glycolysis. Modified rates of glycolytic metabolism have been implicated in controlling the replication of several classes of viruses and strikingly, infection of Aag2 cells with CHIKV by itself also resulted in the decrease of several glycolysis genes. Our data suggests that Dhx15 regulates replication of CHIKV, and possibly other arboviruses, by controlling glycolysis in mosquito cells.
Title: Evolution of Carbon Isotope Fractionation in Cyanobacteria

p WT, smaller Rubisco (17.23 vs. 25.18 ± 0.31‰, Measuring both enzymatic and biomass fractionation revealed a surprising result—ANC ε p exceeded ANC ε Rubisco in all conditions tested, violating prevailing models of cyanobacterial carbon isotope fractionation. However, these models were corrected by accounting for cyanobacterial physiology, notably the CO 2 concentrating mechanism (CCM). Our modified model indicated that powered inorganic carbon uptake systems contribute to ε p , and this effect is exacerbated in ANC. These data suggested that understanding the evolution of both the CCM and rubisco is critical for interpreting the carbon isotope record, and that large fluctuations in the record may reflect the evolving efficiency of carbon fixing metabolisms as well as changes in atmospheric CO 2 .
Evidence for the digital programming of cellular differentiation: characterization of binary switches in lineage-determining transcription factors

Previous studies of the murine Ly49 and human KIR gene clusters have revealed a role for bidirectional promoters in the control of variegated gene expression. Whether or not competing promoters control other instances of cell fate determination remains an outstanding question. Although divergent transcripts within 300 bp are found in ~6% of human genes, an analysis of human transcription factor (TF) genes (1640) revealed that 33% possess stable divergent transcripts with a transcription start site (TSS) less than 300 bp upstream, with many separated by less than 30 bp, indicating an enrichment for potential binary switches in TFs. We have performed a detailed examination of putative bidirectional promoter switches in three lineage-determining TF genes: AHR, GATA3, and RORγT. These genes also contain additional pairs of opposing promoters that would prevent simultaneous transcription of sense and antisense, and thus may represent simple on/off switches rather than probabilistic switches. In situ RNA hybridization of human tissues revealed mutually exclusive expression of sense versus antisense transcription, indicating switching between stable sense or antisense transcriptional states. Single-cell RNAseq confirmed the separate sense/antisense states, and revealed the identity of cells with active switch elements. Differential gene expression analysis of cells with antisense switch transcripts revealed an enrichment for genes found in immature/stem cells and a lack of genes associated with terminally differentiated cells. Taken together, these data indicate that there is a digital component to the differentiation program mediated by binary promoter switches in lineage-determining transcription factors.
Blocking D2/D3 dopamine receptors increases volatility of beliefs when we learn to trust others

The ability to flexibly adjust beliefs about other people is crucial for human social functioning. Dopamine has been proposed to regulate the precision of beliefs, but direct behavioural evidence of this is lacking. We investigated how a relatively high dose of the selective D2/D3 dopamine receptor antagonist sulpiride impacts learning about other people’s prosocial attitudes in a repeated trust game. Using a Bayesian model of belief updating, we show that sulpiride increased the volatility of beliefs, which led to higher precision-weights on prediction errors. This effect was entirely driven by participants with genetically conferring higher dopamine availability (Taq1a polymorphism). Higher precision weights were reflected in higher reciprocal behaviour in the repeated trust game but not in single-round trust games. This finding suggests that antipsychotic medication might acutely reduce rigidity of pathological beliefs.
Partial reuse of circadian clock genes along parallel clines of diapause in two moth species

Understanding the molecular basis of repeated evolution is essential for improving our ability to predict evolution. Genes repeatedly used in independent cases of adaptation to similar environments are strong candidates for predicting adaptation across phylogeny. The Asian corn borer (Ostrinia furnacalis; ACB) and the European corn borer (Ostrinia nubilalis; ECB) are two closely related moths that display remarkable adaptability to a wide range of climate on two separate continents, largely manifesting as changes in the timing of diapause (dormancy), but the genetic basis of parallel clinal responses remains to be characterized. We extensively sampled the ACB cline in China in a genome-wide association study (GWAS) using pooled sequencing data (Pool-seq). We characterized the genetic basis of clinal diapause response in ACB and showed that genes involved in circadian rhythm were over-represented among the candidate genes under spatially varying selection. Comparing with previous results from ECB, we found that the circadian clock gene period (per), but not pigment-dispersing factor receptor (Pdfr), was repeatedly used, but the alleles were not shared between the species. The corn borers’ shared adaptability is likely based in per but seemingly through independent mutational paths.
Ralstonia solanacearum alters root developmental programs in auxin-dependent and independent manners

Microbial pathogens and other parasites can modify the development of their hosts, either as a target or a side effect of their virulence activities. The plant pathogenic bacterium Ralstonia solanacearum, causal agent of the devastating bacterial wilt disease, is a soil-borne microbe that invades host plants through their roots, and later proliferates in xylem vessels. In this work, we studied the early stages of R. solanacearum infection in the model plant Arabidopsis thaliana, using an in vitro infection system. In addition to the previously reported inhibition of primary root length and increase in root hair formation at the root tip, we observed an earlier xylem differentiation during R. solanacearum infection that occurs in a HrpG-dependent manner, suggesting that the pathogen actively promotes the development of the vascular system upon invasion of the root. Moreover, we found that the phytohormone auxin, of which the accumulation is promoted by the bacterial infection, is required for the R. solanacearum-triggered induction of root hair formation, but not earlier xylem differentiation. Altogether, our results shed light on the capacity of R. solanacearum to induce alterations of root developmental pathways and on the role of auxin in this process.
The Functional Landscape of SARS-CoV-2 3CL Protease

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as the etiologic agent of COVID-19 (coronavirus disease 2019) has drastically altered life globally. Numerous efforts have been placed on the development of therapeutics to treat SARS-CoV-2 infection. One particular target is the 3CL protease (3CLpro), which holds promise as it is essential to the virus and highly conserved among coronaviruses, suggesting that it may be possible to find broad inhibitors that treat not just SARS-CoV-2 but other coronavirus infections as well. While the 3CL protease has been studied by many groups for SARS-CoV-2 and other coronaviruses, our understanding of its tolerance to mutations is limited, knowledge which is particularly important as 3CL protease inhibitors become utilized clinically. Here, we develop a yeast-based deep mutational scanning approach to systematically profile the activity of all possible single mutants of the SARS-CoV-2 3CLpro, and validate our results both in yeast and in authentic viruses. We reveal that the 3CLpro is highly malleable and is capable of tolerating mutations throughout the protein, including within the substrate binding pocket. Yet, we also identify specific residues that appear immutable for function of the protease, suggesting that these interactions may be novel targets for the design of future 3CLpro inhibitors. Finally, we utilize our screening results as a basis to identify E166V as a resistance-conferring mutation against the therapeutic 3CLpro inhibitor, nirmatrelvir, in clinical use. Collectively, the functional map presented herein may serve as a guide for further understanding of the biological properties of the 3CL protease and for drug development for current and future coronavirus pandemics.
RAD18 opposes transcription-associated genome instability through FANCD2 recruitment

DNA replication is a vulnerable time for genome stability maintenance. Intrinsic stressors, as well as oncogenic stress, can challenge replication by fostering conflicts with transcription and stabilizing DNA:RNA hybrids. RAD18 is an E3 ubiquitin ligase for PCNA that is involved in coordinating DNA damage tolerance pathways to preserve genome stability during replication. In this study, we show that RAD18 deficient cells have higher levels of transcription-replication conflicts and accumulate DNA:RNA hybrids that induce DNA double strand breaks and replication stress. We find that these effects are driven in part by failure to recruit the Fanconi Anemia protein FANCD2 at difficult to replicate and R-loop prone genomic sites. While RAD18 is important for FANCD2 localization after splicing inhibition or aphidicolin treatment, it is comparatively less important during interstrand crosslink repair. Thus, we highlight a RAD18 dependent pathway promoting FANCD2-mediated suppression of R-loops and transcription-replication conflicts. AUTHOR SUMMARY Genome instability, a state in which cells acquire mutations more quickly, drives cancer initiation and progression. DNA is normally protected from such mutations by a host of specialized factors that recognize and repair potentially damaging circumstances. Here we describe under-appreciated links between a protein called RAD18, which recognizes potentially damaging stress, and a phenomenon called a transcription-replication conflict. If not repaired such conflicts can lead to DNA breaks. We find that RAD18 plays an important role in recruiting another repair protein called FANCD2 to sites of transcription-replication conflicts. By doing so, RAD18 protects the human genome from damage when it is faced with stresses such as those seen in cancer cells. This work provides new insight to how the FANCD2 protein is brought to potentially damaging sites in our genomes.
Determining optimal combination of RCCP mixture containing RAP and crumb rubber using hybrid ANN-GA method considering energy absorbency approach

The present study investigates the effectiveness of evolutionary algorithms such as genetic algorithm (GA) evolved neural network in estimating Roller Compacted Concrete Pavement (RCCP) characteristics including flexural and compressive strength of RCC and also energy absorbency of mixes with different compositions. A real coded GA algorithm was implemented as training algorithm of feed forward neural network to simulate the models. The genetic operators were carefully selected to optimize the neural network, avoiding premature convergence and permutation problems. To evaluate the performance of the genetic algorithm neural network model, Nash-Sutcliffe efficiency (NSE) criterion was employed and also utilized as fitness function for genetic algorithm which is a different approach for fitting in this area. The results showed that the GA-based neural network model gives a superior modeling. The well-trained neural network can be used as a useful tool for modeling RCC specifications.
Effect of Deficit Irrigation Regimes on Yield and Fruit Quality of Olive Trees (cv. Memecik) on the Aegean Coast of Turkey

In this study, six different irrigation treatments were applied to an olive orchard using the drip irrigation method. Five of these were arranged according to 25% (S0.25), 50% (S0.50), 75% (S0.75), 100% (S1.00) and 125% (S1.25) of the evaporation in 5 days of a class ‘A’ evaporation pan, and one control (SC) was arranged so as to bring the reducing moisture at a soil depth of 0–90 cm to field capacity. Yield values were not affected by the irrigation treatment (p > 0.05). In contrast, 100‐fruit weight, pulp ratio, hardness moisture, oil, reducing sugar content and bitterness were affected by irrigation (p < 0.05). Generally, an increase in the amount of irrigation water given in the study was accompanied by a fall in ripeness index values, a rise in moisture content, and a reduction in the oil content of fruit. The highest content of reducing sugar was obtained from S0.25, generally being lower with increase in the water applied. The findings show that application of 25% of the evaporation of a class ‘A’ evaporation pan (treatment S0.25) can be recommended for cv. Memecik. Application of this recommendation can achieve a 72% saving in water and make a significant contribution to the conservation of limited water resources. Copyright © 2017 John Wiley & Sons, Ltd.
Assessing the Infrastructure Performance of Indian States: A Normalized Approach

Infrastructure provides the necessary services that support economic growth by increasing the productivity of labours and capital, thereby reducing the costs of production and raising profitability, production, income and employment. Extensive and efficient infrastructure is critical for ensuring the effective functioning of any economy. However, the development of infrastructure and its growth may depend upon the peculiar priorities and performance of the State governments in a federal structure of government such as that of India. Some states have grown very fast while some have been sluggish in their infrastructure development, due to various reasons. In this context this study made an attempt to assess the performance of Indian States on infrastructure using the framework of inter-State analysis. The infrastructure performance of these States has been analysed using infrastructure density data i.e., service capacity created per unit service area or population and the growth performance through ‘quadrant analysis’. The assessment of Infrastructure performance of States has been done with reference to each infrastructure categories through the ranking of States in terms of levels over two time periods and growth. The States that have performed on both counts have further been categorised into top and bottom performers. The overall assessment of infrastructure density performance of States has been done subsequently by aggregating sector ranks and then categorising into top and bottom overall performers. These scores are also normalised within and across sectors to get indexed performance.
Ratings Lead you to the Product, Reviews Help you Clinch it? The Dynamics and Impact of Online Review Sentiments on Products Sales

It is generally assumed that ratings are a numeric representation of text sentiments and their valences are consistent. This however may not always be true. Using a panel of data on over 4,000 books from Amazon.com, we develop a multiple equation model to examine the inter-relationships between ratings, sentiments, and sales. We find that ratings do not have a significant direct impact on sales but have an indirect impact through sentiments. Sentiments, however, have a direct significant impact on sales. Our findings also indicate that the two most accessible types of reviews – most helpful and most recent play a significant role in determining sales. This suggests that information that is easily accessible and cognitive effort-reducing heuristics play a role in online purchase decisions. This study advances our understanding on the inter-relationship between ratings, sentiments, and sales and sheds insight on the relevance of ratings and sentiments over a sequential decision making process.
Discrete event approach to network fault management

Failure diagnosis in large and complex systems such as a communication network is a critical task. An important aspect of network management is fault management ,i.e.,determining, locating, isolating, and correcting faults in the network. In the realm of discrete event systems Sampath et al proposed a failure diagnosis approach, and ~Tiang et al proposed an efficient algorithm for testing diagnosability. In this work, we adopt the framework of the communicating finite state machine (CFSM)of Miller et al for modeling networks and to investigate fault detection, fault identification and fault location using Sam~ath et al and Jiang et al methods. Our approach provides a systematic way of performing fault diagnosis aspects of network fault management.
Edinburgh Research Explorer Patients' experiences and views of cascade screening for familial hypercholesterolemia (FH)

Familial DNA cascade screening for familial hypercholesterolemia (FH) has recently been introduced in Scotland. This study investigated index patients' experiences of DNA testing and mediating cascade screening. Thirty-eight patients with a clinical diagnosis of definite or possible FH who had undergone DNA testing in the lipid clinic took part in semi-structured qualitative interviews. All patients were positive about DNA screening being undertaken by familiar and trusted clinicians within the lipid clinic. Most patients had already cascaded close relatives for serum cholesterol testing following their attendance at the lipid clinic. Identified mutation carriers who had attended the genetics clinic ( n =15) for a cascading appointment described finding this consultation helpful because it identified other at-risk family members and provided them with tailored information for their relatives. Participants who expressed a preference said they favoured indirect (patient-mediated) methods of cascading as they considered indirect approaches to be less threatening to family members than direct clinical contact. We conclude that DNA screening and indirect familial cascading is perceived as highly acceptable to index patients with FH. However, while indirect cascading methods may be more acceptable to patients, they do not yield the same numbers as more direct methods. There is, therefore, a need for further systematic research to investigate patients', family members' and staff views of the acceptability of direct versus indirect methods of cascade screening.
Institutional Knowledge at Singapore Management University Institutional Knowledge at Singapore Management University On Leverage in a Stochastic Volatility Model On Leverage in a Stochastic Volatility Model

This paper is concerned with speciﬁcation for modelling ﬁnancial leverage eﬀect in the context of stochastic volatility (SV) models. Two alternative speciﬁcations co-exist in the literature. One is the Euler approximation to the well known continuous time SV model with leverage eﬀect and the other is the discrete time SV model of Jacquier, Polson and Rossi (2004, Journal of Econometrics, forthcoming). Using a Gaussian nonlinear state space form with uncorrelated measurement and transition errors, I show that it is easy to interpret the leverage eﬀect in the conventional model whereas it is not clear how to obtain the leverage eﬀect in the model of Jacquier et al. Empirical comparisons of these two models via Bayesian Markov chain Monte Carlo (MCMC) methods reveal that the speciﬁcation of Jacquier et al is inferior. Simulation experiments are conducted to study the sampling properties of the Bayes MCMC for the conventional model.
Glycaemic Evaluation of Murraya koenigii in Alloxan-induced Diabetic Rabbits

Background: Study was aimed to evaluate the antidiabetic activity of Murraya koenigii, a traditional medicinal plant (Curry leaf) in normoglycemic and alloxan-induced diabetes rabbits. Methods: Antidiabetic activity of aqueous extract of M. koenigii in 100, 200 300 mg/k doses was determined by estimating blood glucose before and at 1, 2, 4, 8, 24, and 72 hours post treatment intervals in treated rabbits. Results: Aqueous extract of Murraya koenigii showed a dose dependent antidiabetic activity with maximum effect established at 300 mg/kg. The extract also exhibited a significant (p<0.05) dose-dependent hypoglycemic effect on normal and alloxan-induced diabetic rabbits. Conclusion: Murraya koenigii causes a reduction in blood glucose. This hypoglycemic property supports-its usein folkloric medicine as an antidiabetic agent and thus suggests a place for it in nutritional therapy in the management of diabetes mellitus and thus as an oral hypoglycaemic agent.
Relationship Dynamics and Sexual Risk Reduction Strategies Among Heterosexual Young Adults: A Qualitative Study of Sexually Transmitted Infection Clinic Attendees at an Urban Chicago Health Center

Abstract Few studies have examined risk-reduction alternatives to consistent condom use for HIV prevention among heterosexual young adults. We used qualitative methodology to explore risk reduction strategies and contextual factors influencing attempts to reduce risk in an urban, high morbidity sexually transmitted infection (STI) clinic. Focus groups were conducted October–December 2014 with heterosexually identified men (n = 13) and women (n = 20) aged 18–29 seeking STI screening at an urban clinic. Groups were audio recorded, transcribed verbatim, and analyzed for thematic content using Atlas.ti software. Quantitative information included sociodemographics, HIV/STI testing history, and 6-month sexual behaviors. Among 33 predominantly African-American participants with a median age of 22, risk-reduction strategies included monogamy agreements, selective condom use with casual and high-risk partners, and frequent HIV/STI testing, though testing was commonly used as a post-hoc reassurance after risk expos.