Miracle-dz/UniFAR-FTUs huggingface dataset:
(p)ppGpp is required for virulence of Shigella flexneri

ABSTRACT Infection by the enteric pathogen Shigella flexneri requires transit through the gastrointestinal tract and invasion of and replication within the cells of the host colonic epithelium. This process exposes the pathogen to a range of diverse microenvironments. Furthermore, the unique composition and physical environment of the eukaryotic cell cytosol represents a stressful environment for S. flexneri, and extensive physiological adaptations are needed for the bacterium to thrive. In this work, we show that disrupting synthesis of the stringent response alarmone (p)ppGpp in S. flexneri diminished expression of key virulence genes, including ipaA, ipaB, ipaC, and icsA, and it reduced bacterial invasion and intercellular spread. Deletion of the (p)ppGpp synthase gene relA alone had no effect on S. flexneri virulence, but disruption of both relA and the (p)ppGpp synthase/hydrolase gene spoT resulted in loss of (p)ppGpp synthesis and virulence. While the relA spoT deletion mutant was able to invade a cultured human epithelial cell monolayer, albeit at reduced levels, it was unable to maintain the infection and spread to adjacent cells, as indicated by loss of plaque formation. Complementation with spoT on a plasmid vector restored plaque formation. Thus, SpoT alone is sufficient to provide the necessary level of (p)ppGpp for virulence. These results indicate that (p)ppGpp is required for S. flexneri virulence and adaptation to the intracellular environment, adding to the repertoire of signaling pathways that affect Shigella pathogenesis.
AKT2 Loss Impairs BRAF-Mutant Melanoma Metastasis

Simple Summary Skin cancer, such as melanoma, is often treatable but becomes deadly when it expands to other places in the body, a process called metastasis. While many current drugs target melanoma tumor growth, no drugs yet exist to specifically prevent metastasis. Improving treatment outcomes, therefore, will require an understanding of the molecular mechanisms leading to metastasis. The AKT family of proteins are important regulators of cellular growth and signaling, which play differing roles in cancer. This work sought to study each of the AKT isoforms and their contributions to melanoma cell migration and metastasis. We found that AKT2 specifically regulates melanoma cell metastasis through effects on metabolism and melanoma cell properties, while AKT1 is involved in cellular proliferation and growth. This study suggests that specifically targeting AKT2 and AKT1 represents novel therapeutic strategies for different-stage melanoma patients. Abstract Despite recent advances in treatment, melanoma remains the deadliest form of skin cancer due to its highly metastatic nature. Melanomas harboring oncogenic BRAFV600E mutations combined with PTEN loss exhibit unrestrained PI3K/AKT signaling and increased invasiveness. However, the contribution of different AKT isoforms to melanoma initiation, progression, and metastasis has not been comprehensively explored, and questions remain about whether individual isoforms play distinct or redundant roles in each step. We investigate the contribution of individual AKT isoforms to melanoma initiation using a novel mouse model of AKT isoform-specific loss in a murine melanoma model, and we investigate tumor progression, maintenance, and metastasis among a panel of human metastatic melanoma cell lines using AKT isoform-specific knockdown studies. We elucidate that AKT2 is dispensable for primary tumor formation but promotes migration and invasion in vitro and metastatic seeding in vivo, whereas AKT1 is uniquely important for melanoma initiation and cell proliferation. We propose a mechanism whereby the inhibition of AKT2 impairs glycolysis and reduces an EMT-related gene expression signature in PTEN-null BRAF-mutant human melanoma cells to limit metastatic spread. Our data suggest that the elucidation of AKT2-specific functions in metastasis might inform therapeutic strategies to improve treatment options for melanoma patients.
Seroprevalence study of Feline Coronavirus in owned and feral cats in Sydney, Australia

Objectives i) To establish the seroprevalence of Feline Coronavirus (FCoV) infection in two defined groups of cats in Sydney: owned and feral cats; ii) to identify factors associated with an increased risk of infection with FCoV; and iii) to establish the seroprevalence and FCoV antibody titres of owned cats with immunohistochemically confirmed feline infectious peritonitis (FIP). Design Prospective multi-institutional cross sectional study. Procedure
Epidural anesthesia with bupivacaine, bupivacaine and fentanyl, or bupivacaine and sufentanil during intravenous administration of propofol for ovariohysterectomy in dogs.

OBJECTIVE To compare cardiovascular and systemic effects and analgesia during the postoperative period of epidural anesthesia performed with bupivacaine alone or with fentanyl or sufentanil in bitches maintained at a light plane of anesthesia with continuous infusion of propofol. STUDY DESIGN Prospective randomized masked clinical trial. ANIMALS 30 female dogs of various breeds. PROCEDURES Dogs were allocated into 3 groups of 10 each. One group received fentanyl (2 microg/kg [0.91 microg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1 group received sufentanil (1 microg/kg) and bupivacaine (1 mg/kg), and 1 group received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) and continuous infusion of propofol for sedation. The agents were administered into the lumbosacral space and diluted in saline (0.9% NaCl) solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia, sedation level, serum cortisol concentrations, and plasma catecholamine concentrations were measured regularly for 6 hours. RESULTS No important changes in cardiovascular, respiratory, or sedation variables were observed. Degree of analgesia in the postoperative period was higher in the sufentanil group, although use of fentanyl and bupivacaine also resulted in a sufficient level of analgesia. CONCLUSIONS AND CLINICAL RELEVANCE Use of the 3 anesthetic techniques permitted ovariohysterectomy with sufficient analgesia and acceptable neuroendocrine modulation of pain with minimal adverse effects.
Gender and relationship differences in condom use among 15-24-year-olds in Angola.

CONTEXT The sexual behavior of young people in Angola will play a major role in the future spread of HIV, yet few young people use condoms consistently, and reported rates of condom use are low. It is important to identify determinants of condom use among Angolan adolescents and young adults. METHODS Data for analysis came from 1,995 sexually experienced youth aged 15-24 who participated in a 2001 knowledge, attitudes and practices survey in Luanda, Angola. Logistic regression analysis was performed to identify predictors of consistent condom use by gender and determinants of condom use at last intercourse by type of relationship. RESULTS For both males and females, consistent condom use was positively associated with higher levels of education (odds ratios, 1.7-2.6) and believing that condoms did not diminish sexual pleasure (1.8 for both genders). It was negatively associated with being married or in a cohabiting relationship (0.1-0.5). Females who equated condom use with lack of trust were less likely to use condoms consistently (0.5), and males who believed that condoms were safe and those who had multiple partners were more likely to be consistent users (1.6 and 1.7, respectively). Urban residence, higher education, being in school and not equating condom use with lack of trust were important predictors of use at last intercourse in regular and casual relationships, whereas access to condoms was the most important factor in spousal relationships (4.5). CONCLUSIONS Intervention programs aimed at less educated, periurban and unemployed young people should be part of an effective HIV-prevention strategy. Such programs must address misperceptions among youth about condom use and the need for protection from HIV and other STIs.
Physiological predictors Of peak inspiratory flow using Observed lung function resultS (POrOs): evaluation at discharge among patients hospitalized for a COPD exacerbation

Background: Peak inspiratory flow (PIF) as generated through the resistance of a dry powder inhaler (DPI) device is a critical patient-dependent maneuver impacting the success of DPI medication delivery. Despite its importance, it is not routinely measured in clinical practice. Little is currently known about the relationship, if any, between PIF through DPI devices, routine spirometry and disease outcomes. Aim: to identify potential predictors of PIF for different DPIs from spirometric parameters and patient characteristics and explore the association between PIF and follow-up events. methods: A retrospective observational study at among patients for a COPD exacerbation Spirometry was performed using an Easy on-PC™ spirometer. PIF was measured through four DPI resistances using the In-Check™ DIAL. Regression analyses were used to investigate the association between PIF through resistances and spirometric parameters obtained at discharge, comorbidities and demographic parameters. However, R -squared values for all three devices were weak ( , 0.4). Conclusion: The study did not provide evidence to support the use of surrogate measurements for PIF through device resistance, which could assist in determining the appropriateness of inhaler device type. Although PIF measurement is feasible in patients at discharge and could be a valuable addition to the standard of care in COPD management, it needs to be measured directly.
The influence of vegetation, microbial inoculation, and aging of pesticide residues on the degradation of atrazine and metolachlor in soils

The abilities of native prairie grasses, big bluestem (Andropogon gerardii), Indian grass (Sorghastrum nutans L.), and switch grass (Panicum virgatum L.) and two soil bacteria, Agrobacterium radiobacter J14a and Pseudomonasfluorescens UA5-40, to degrade the herbicides atrazine and metoiachlor were evaluated in soils taken from two pesticidecontaminated sites in Iowa (Alpha and Bravo). J 14a and vegetation significantly decreased the concentration of atrazine in Alpha soil when the initial concentration of atrazine was 93.3 |ig g*1. However, they had no effect on the degradation of atrazine when the initial concentration of atrazine was 4.9 ng g"1. The effect of Jl4a on the degradation of atrazine was not enhanced by the presence of the plants. Inoculation with J 14a and addition of the plants did not increase the atrazine degradation in the Bravo soil. The degradation of atrazine by J 14a and the indigenous atrazine-degrading microbial population in Bravo soil was not affected by the presence of exogenous nitrogen. Vegetation significantly increased the number of atrazine-mineralizing microorganisms in J14a-inoculated Bravo soil, and exogenous N significantly increased the number of the atrazine-mineralizing microorganisms. In the Bravo soil without vegetation and N amendment, atrazinemineralizing microorganisms were significantly more numerous in the uninoculated soil than in the J14a-inoculated soil. Inoculation of UA5-40 did not enhance the transformation of metoiachlor in either soil. The native prairie grasses significantly decreased the metoiachlor residues in both soils. Aging metolachlor-treated soils did not influence the degrading capability of the plants. Our results indicate that the degradative ability of J 14a and the native prairie grasses on atrazine is affected by the bioavailability of the compound and the presence of indigenous atrazine-mineralizing microorganisms. KeywordsAgrobacterium radiobacter J14a Pseudomonas fluorescens UA5-40 Atrazine Metoiachlor Bioavailability Vegetation N Amendment
Beyond microRNAs: Analysis of chimeric reads characterises the diverse targetome of AGO2-mediated regulation

Argonaute proteins are instrumental in regulating RNA stability and translation. AGO2, the major mammalian Argonaute protein, is known to primarily associate with microRNAs, a family of small RNA ‘driver’ sequences, and identifies its targets primarily via a ‘seed’ mediated partial complementarity process Despite numerous studies, a definitive experimental dataset of AGO2 ‘driver’-’target’ interactions remains elusive. Our study employs two experimental methods - AGO2 CLASH and AGO2 eCLIP, to generate thousands of AGO2 target sites verified by chimeric reads. These chimeric reads contain both the AGO2 loaded small RNA ‘driver’ and the target sequence, providing a robust resource for modeling AGO2 binding preferences. Our novel analysis pipeline reveals thousands of AGO2 target sites driven by microRNAs and a significant number of AGO2 ‘drivers’ derived from fragments of other small RNAs such as tRNAs, YRNAs, snoRNAs, rRNAs, and more. We utilize convolutional neural networks to train machine learning models that accurately predict the binding potential for each ‘driver’ class and experimentally validate several interactions. In conclusion, our comprehensive analysis of the AGO2 targetome broadens our understanding of its ‘driver’ repertoire and potential function in development and disease. Moreover, we offer practical bioinformatic tools for future experiments and the prediction of AGO2 targets. All data and code from this study are freely available at https://github.com/ML-Bioinfo-CEITEC/HybriDetector/ Contact panagiotis.alexiou@um.edu. mt, stepanka.vanacova@ceitec.muni. cz
Clinical outcomes using standard phacoemulsification and femtosecond laser-assisted surgery with toric intraocular lenses

Purpose: To compare the 1-month and 1-year results of toric intraocular lens (IOL) implantation with standard (manual) phacoemulsification vs femtosecond laser-assisted surgery. Patients and methods: Refractive data, visual acuity data, and ocular aberration measured with a wavefront aberrometer were collected for two groups of patients from one site. The first group had standard phacoemulsification, while the second group had femtosecond laser-assisted surgery, and both groups were implanted with toric IOLs, either monofocal or multifocal. Differences in visual acuity, refractive outcomes, and higher order aberrations – total, corneal, and internal – were evaluated at 1 month and 1 year postoperatively. Results: Toric IOLs were implanted in 62 eyes using standard phacoemulsification and 53 eyes using femtosecond laser-assisted surgery. Uncorrected visual acuity and best-spectacle-corrected visual acuity at 1 month and 1 year were not statistically significantly different between the groups ( P . 0.05) nor was the mean cylinder or mean spherical equivalent refraction ( P . 0.12). Total ocular higher order aberrations were significantly different between the groups ( P , 0.05), but absolute differences appeared to be the same. Internal vertical coma was significantly lower in the femto group at 1 year ( P = 0.03). Differences in aberrations did not correlate with corrected or uncorrected visual acuity. Conclusion: Patients who underwent uncomplicated lens surgery with toric IOLs in both the groups had comparable refractive outcomes in terms of visual acuity and residual refraction at 1 year. The femto group had significantly lower internal vertical coma at 1 year. Optometry; Visual science; Pharmacology and drug therapy in eye diseases; Basic Sciences; Primary and eye care; Patient and of
New Phenomena in Large-Scale Internet Traffic

The Internet is transforming our society, necessitating a quantitative understanding of Internet traffic. Our team collects and curates the largest publicly available Internet traffic data sets. An analysis of 50 billion packets using 10,000 processors in the MIT SuperCloud reveals a new phenomenon: the importance of otherwise unseen leaf nodes and isolated links in Internet traffic. Our analysis further shows that a two-parameter modified Zipf-Mandelbrot distribution accurately describes a wide variety of source/destination statistics on moving sample windows ranging from 100{,}000 to 100{,}000{,}000 packets over collections that span years and continents. The measured model parameters distinguish different network streams, and the model leaf parameter strongly correlates with the fraction of the traffic in different underlying network topologies.
Out of Eden

In a brilliant synthesis of genetic, archaeological, linguistic and climatic data, Oppenheimer challenges current thinking with his claim that there was only one successful migration out of Africa. In 1988 Newsweek headlined the startling discovery that everyone alive on the earth today can trace their maternal DNA back to one woman who lived in Africa 150,000 years ago. It was thought that modern humans populated the world through a series of migratory waves from their African homeland. Now an even more radical view has emerged, that the members of just one group are the ancestors of all non-Africans now alive, and that this group crossed the mouth of the Red Sea a mere 85,000 years ago. It means that not only is every person on the planet descended from one African 'Eve' but every non-African is related to a more recent Eve, from that original migratory group. This is a revolutionary new theory about our origins that is both scholarly and entertaining, a remarkable account of the kinship of all humans. Further details of the findings in this book are presented at www.bradshawfoundation. com/stephenoppenheimer/
Chaining Meets Chain Rule: Multilevel Entropic Regularization and Training of Neural Networks

We derive generalization and excess risk bounds for neural networks using a family of complexity measures based on a multilevel relative entropy. The bounds are obtained by introducing the notion of generated hierarchical coverings of neural networks and by using the technique of chaining mutual information introduced by Asadi et al. ’18. The resulting bounds are algorithm-dependent and multiscale: they exploit the multilevel structure of neural networks. This, in turn, leads to an empirical risk minimization problem with a multilevel entropic regularization. The minimization problem is resolved by introducing a multiscale extension of the celebrated Gibbs posterior distribution, proving that the derived distribution achieves the unique minimum. This leads to a new training procedure for neural networks with performance guarantees, which exploits the chain rule of relative entropy rather than the chain rule of derivatives (as in backpropagation), and which takes into account the interactions between diﬀerent scales of the hypothesis sets of neural networks corresponding to diﬀerent depths of the hidden layers. To obtain an eﬃcient implementation of the latter, we further develop a multilevel Metropolis algorithm simulating the multiscale Gibbs distribution, with an experiment for a two-layer neural network on the MNIST data set.
Age-dependent differences in myelin basic protein expression the hippocampus of young , adult and aged gerbils

Ji Hyeon Ahn"#, Tae-Kyeong Lee2,#, Joon Ha Park', Jeong Hwi Ch02, In Hye Kim 2, Jae Chul Lee2, Seongkweon Hont, Yong Hwan Jeon4, II Jun Kang5, Young Joo Lee6, Moo-Ho Won2,*, Choong-Hyun Lee7,* 1 Department of Biomedical Science and Research Institute for Bioscience and Biotechnolo~ Hallym Universit)iJ Chuncheon, Korea 2Department of Neurobiolo~ School of Medicine, Kangwon National Universit)/J Chuncheon, Korea 3Department of Surger)iJ School of Medicine, Kangwon National Universit)/J Kangwon National University Hospital, Chuncheon, Korea 4Department of Radiolo~ School of Medicine, Kangwon National Universit)iJ Kangwon National University Hospital, Chuncheon, Korea 5Department of Food Science and Nutrition, Hallym Universit)iJ Chuncheon, Korea GDepartment of Emergency Medicine, Seoul Hospital, College of Medicine, Sooncheonhyang Universit)iJ Seoul, Korea 7Department of PharmaC)iJ College of PharmaC)iJ Dankook Universit)iJ Cheonan, Korea
Quality of life and coping strategies of outpatients with a depressive disorder in maintenance therapy – a cross-sectional study

Background: The quality of life (QoL) is a multidimensional view that represents all aspects of patient well-being in various areas of patient life. Specific coping strategies may be connected to both the QoL and the severity of mental disorder. The aim of this investigation was to examine the relationship between the QoL and the coping strategies of outpatients with a depressive disorder. Methods: Eighty-two outpatients, who met the criteria of the International Classification of Diseases, Tenth Revision, for a depressive disorder, were enrolled in the cross-sectional study. Data on sociodemographic and clinical variables were obtained from the medical records. Individuals filled the following standardized questionnaires: Quality of Life Satisfaction and Enjoyment Questionnaire, Stress Coping Style Questionnaire, and Clinical Global Impression. Multiple regression analyses with backward elimination were performed to discover the most influential factors contributing to QoL. Results: The participants with a depressive disorder showed an overuse of negative coping strategies, especially escape tendency and resignation. A positive self-instruction strategy was used by the patients less often. The coping strategies were significantly associated with the QoL. A more frequent use of positive coping strategies had a positive association with the QoL. The main factors related to QoL were the subjective severity of the disorder, employment, and positive coping strategies. Conclusion: The study confirmed the relationship between QoL and the coping strategies of outpatients with a depressive disorder.
Micronucleus Frequency in Peripheral Blood Lymphocytes and Cancer Risk with Methyl Isocyanate-Exposure in Bhopal

Methyl isocyanate (CH3N=C=O) (MIC; CAS No. 624-83-9) is a common monoisocyanate that is widely used as a precursor in carbamate pesticide production (Bucher, 1987; ATSDR, 2002). Humans exposed to MIC occupationally or accidently may run an elevated risk of developing respiratory disorders including asthma-like allergy and inflammation, airway hyper responsiveness, reactive airway dysfunction syndrome (RADS) (HSFS, 2002; Dhara and Dhara, 2002; Bessac et al., 2009) and
Farmers' participation in European agri-environmental policies /доклад на 10 конгрессе ЕААЕ, Exploring Diversity in the European Agri-Food System, Zaragoza, Spain, 28-31 August 2002

This paper examines the factors influencing farmers' participation in several agri-environmental schemes. A multinominal logit model is used to separate between participating and nonparticipating farmers. In addition this model allows to predict farmers participation in one measure as well as in different measures simultaneously. Data stems from a survey conducted in eight European countries and includes a description of both farmer and farm characteristics. Three categories of schemes have been analysed: landscape maintenance, biodiversity protection and restriction of intensive farming practices. The combination of these three types of schemes provides eight possible packages which can be selected by eligible farmers. The multinominal logit model shows the importance of both farm and farmer as well as attitudinal characteristics on the participation in different combinations of schemes. For instance, the environmental concern favours landscape maintenance and biodiversity protection as well as their combinations with schemes requiring restrictions of intensive practices. However, it has a negative effect on the single participation in schemes requiring restrictions of intensive practices only. Our analysis confirms a number of previous findings. In addition, it shows the importance for policy makers to take into account that farmers have the opportunity to enter several schemes simultaneously. Indeed, due to cost complementarities, joint participation provides both private and public benefits.