Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Autophagy by α-Herpesviruses in Myeloid Cells Is Mediated by Cytoplasmic Viral DNA through a Mechanism Dependent on Stimulator of IFN Genes

Autophagy has been established as a player in host defense against viruses. The mechanisms by which the host induces autophagy during infection are diverse. In the case of HSV type 1 (HSV-1), dsRNA-dependent protein kinase is essential for induction of autophagy in fibroblasts through phosphorylation of eukaryotic initiation factor 2α (eIF2α). HSV-1 counteracts autophagy via ICP34.5, which dephosphorylates eIF2α and inhibits Beclin 1. Investigation of autophagy during HSV-1 infection has largely been conducted in permissive cells, but recent work suggests the existence of a eIF2α-independent autophagy-inducing pathway in nonpermissive cells. To clarify and further characterize the existence of a novel autophagy-inducing pathway in nonpermissive cells, we examined different HSV and cellular components in murine myeloid cells for their role in autophagy. We demonstrate that HSV-1–induced autophagy does not correlate with phosphorylation of eIF2α, is independent of functional dsRNA-dependent protein kinase, and is not antagonized by ICP34.5. Autophagy was activated independent of viral gene expression, but required viral entry. Importantly, we found that the presence of genomic DNA in the virion was essential for induction of autophagy and, conversely, that transfection of HSV-derived DNA induced microtubule-associated protein 1 L chain II formation, a marker of autophagy. This occurred through a mechanism dependent on stimulator of IFN genes, an essential component for the IFN response to intracellular DNA. Finally, we observed that HSV-1 DNA was present in the cytosol devoid of capsid material following HSV-1 infection of dendritic cells. Thus, our data suggest that HSV-1 genomic DNA induces autophagy in nonpermissive cells in a stimulator of IFN gene-dependent manner.
Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells

The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created “sialic acid low” tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing “sialic acid low” tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack.
The Role of Late Complement Components and the Alternate Complement Pathway in Experimental Cryptococcosis

Summary Duration of survival was comparable in normal and C4D guinea pigs infected iv with cryptococci. Survival was shortened in animals depleted of late complement components by treatment with CVF. Some animals received a single treatment with CVF to allow recovery of complement components after challenge with cryptococci. This resulted in lower counts of fungi in peripheral blood, lung, and liver, but no improvement in levels of fungi in brain, or in survival when compared with animals continuously depleted of C3–9. Late complement components were therefore important in clearance of cryptococci from extraneural sites. However, once infection was established in brain, complement levels in the central nervous system may have been too low to aid in destruction or organisms. The authors wish to thank Miss Margret Huber for expert technical assistance and Dr. David Alling for help with statistical evaluation.
Psychological, Academic, and Work Functioning in College Students with Childhood-Onset Asthma

This study investigated differences in psychological, academic, and work functioning between college students with and without asthma and identified predictors of functioning. Both participants with asthma (n = 121) and age-and gender-matched healthy control subjects (n = 121) completed measures of psychological distress, provided information on missed school and work days, and consented to have their grade point averages released from the registrar. College students with asthma also completed measures of illness uncertainty and illness intrusiveness. Participants with asthma reported greater anxiety, general psychological distress, and more missed school and work days compared to healthy control subjects. Within the asthma group, both illness uncertainty and illness intrusiveness independently predicted anxious and depressive symptoms and general psychological distress; illness intrusiveness also predicted missed school days. Although enrollment in college implies resilient functioning, college students with asthma remain at risk for problems with psychological and academic functioning.
Title Refining orthologue groups at the transcript level

Background: Orthologues are genes in different species that are related through divergent evolution from a common ancestor and are expected to have similar functions. Many databases have been created to describe orthologous genes based on existing sequence data. However, alternative splicing (in eukaryotes) is usually disregarded in the determination of orthologue groups and the functional consequences of alternative splicing have not been considered. Most multi-exon genes can encode multiple protein isoforms which often have different functions and can be disease-related. Extending the definition of orthologue groups to take account of alternate splicing and the functional differences it causes requires further examination. Results: A subset of the orthologous gene groups between human and mouse was selected from the InParanoid database for this study. Each orthologue group was divided into sub-clusters, at the transcript level, using a method based on the sequence similarity of the isoforms. Transcript based sub-clusters were verified by functional signatures of the cluster members in the InterPro database. Functional similarity was higher within than between transcript-based sub-clusters of a defined orthologous group. In certain cases, cancer-related isoforms of a gene could be distinguished from other isoforms of the gene. Predictions of intrinsic disorder in protein regions were also correlated with the isoform sub-clusters within an orthologue group. Conclusions: Sub-clustering of orthologue groups at the transcript level is an important step to more accurately define functionally equivalent orthologue groups. This work appears to be the first effort to refine orthologous groupings of genes based on the consequences of alternative splicing on function. Further investigation and refinement of the methodology to classify and verify isoform sub-clusters is needed, particularly to extend the technique to more distantly related species.
Informational Di erences and Performance : Experimental Evidence ∗

This paper provides a theoretical framework and experimental evidence on how informational di erences may translate into performance di erences in competitive environments. In a laboratory tournament setting, we manipulate beliefs about the e ortreward relationship by varying how well people are informed on the role of luck for pay outcomes. We employ binary information conditions with one group having a smaller sample of information available than the other. Depending on the information condition, subjects are either well or poorly informed on the potential impact of luck on tournament outcomes, and compete either with equally or di erentially informed counterparts. We nd that an informational disadvantage leads to a less clear understanding of how e ort impacts tournament outcomes, and signi cantly lowers performance, particularly when informational di erences are public information. Our study is inspired by informational di erences in the labor market where some individuals have less data on the determinants of economic success than others due to social networks or the availability of similar others to learn from. (JEL C91, D81, M50) ∗We wish to thank David Cesarini, Armin Falk, Guillaume Fréchette, Xavier Gabaix, Andy Schotter, and Richard Zeckhauser, along with seminar audiences at Universitat Autònoma de Barcelona (MOVEWorkshop) and Harvard Kennedy School, for helpful comments. Financial support from the Women and Public Policy Program and the Women's Leadership Board at Harvard Kennedy School is gratefully acknowledged. †Harvard University, Kennedy School of Government, 79 John F. Kennedy Street, Cambridge, MA 02138. iris_bohnet@harvard.edu. ‡New York University, Department of Economics, 19 W. 4 Street, New York, NY 10012. saidi@nyu.edu.
Activation of NTS A 2 a adenosine receptors differentially resets baroreflex control of renal vs . adrenal sympathetic nerve activity

Ichinose TK, O’Leary DS, Scislo TJ. Activation of NTS A2a adenosine receptors differentially resets baroreflex control of renal vs. adrenal sympathetic nerve activity. Am J Physiol Heart Circ Physiol 296: H1058 –H1068, 2009. First published February 6, 2009; doi:10.1152/ajpheart.00906. 2008. —The role of nucleus of solitary tract (NTS) A2a adenosine receptors in baroreflex mechanisms is controversial. Stimulation of these receptors releases glutamate within the NTS and elicits baroreflex-like decreases in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), whereas inhibition of these receptors attenuates HR baroreflex responses. In contrast, stimulation of NTS A2a adenosine receptors increases preganglionic adrenal sympathetic nerve activity (preASNA), and the depressor and sympathoinhibitory responses are not markedly affected by sinoaortic denervation and blockade of NTS glutamatergic transmission. To elucidate the role of NTS A2a adenosine receptors in baroreflex function, we compared full baroreflex stimulus-response curves for HR, RSNA, and pre-ASNA (intravenous nitroprusside/phenylephrine) before and after bilateral NTS microinjections of selective adenosine A2a receptor agonist (CGS-21680; 2.0, 20 pmol/50 nl), selective A2a receptor antagonist (ZM-241385; 40 pmol/100 nl), and nonselective A1 A2a receptor antagonist (8-SPT; 1 nmol/100 nl) in urethane/ -chloralose anesthetized rats. Activation of A2a receptors decreased the range, upper plateau, and gain of baroreflex-response curves for RSNA, whereas these parameters all increased for pre-ASNA, consistent with direct effects of the agonist on regional sympathetic activity. However, no resetting of baroreflexresponse curves along the MAP axis occurred despite the marked decreases in baseline MAP. The antagonists had no marked effects on baseline variables or baroreflex-response functions. We conclude that the activation of NTS A2a adenosine receptors differentially alters baroreflex control of HR, RSNA, and pre-ASNA mostly via nonbaroreflex mechanism(s), and these receptors have virtually no tonic action on baroreflex control of these sympathetic outputs.
Receptive fields in cat superior colliculus after visual cortex lesions.

1. The superior colliculus has been studied in intact cats and in cats with visual cortex lexions by recording the responses of single tectal units to visual stimuli. 2. Three classes of units have been identified in the superficial layers of the colliculus in these visually decorticate cats. 3. One class, comprising 5% of the units studied, has receptive fields organized concentrically in a manner similar to retinal ganglion cells. 4. The second class, comprising 12% of the units studied, responds to stimulus velocities over 300/sec, responds well to both small and large stimuli, and can be driven by strobe flashes at frequencies up to 35‐‐40/sec. These units are termed ‘flicker’ cells. 5. The third class comprising 83% of the units studied, responds best to stimuli which are not larger than the activating region of the receptive field, moving at relatively low velocities. These units show strong suppressive surrounds which are sensitive to higher velocities of stimulus movement than the central activating region. Responses from the activating region in these units are dramatically inhibited by flickering dhanges in the level of background illumination. 6. In intact cats few units are found which are strongly inhibited by background flicker. 7. It is suggested that a high‐velocity sensitive element such as the ‘flicker’ cell or phasic retinal ganglion cell is responsible for the flicker‐induced inhibition of collicular units in the visually decorticate cat.
Stable W-length

We study stable W-length in groups, especially for W equal to the n-fold commutator γ_n := [x_1, [x_2,. [x_(n−1), x_n]]. We prove that in any perfect group, for any n ≥ 2 and any element g, the stable commutator length of g is at least as big as 2^(2−n) times the stable γ_n-length of g. We also establish analogues of Bavard duality for words γn and for β_2 := [[x, y], [z,w]]. Our proofs make use of geometric properties of the asymptotic cones of verbal subgroups with respect to bi-invariant metrics. In particular, we show that for suitable W, these asymptotic cones contain certain subgroups that are normed vector spaces.
Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Ultrashort echo time (550 μs) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2* , were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation. Five mice instilled with saline served as controls. At week 8, the mean normalized signal intensity ± SD was 0.89 ± 0.20 for healthy controls and 0.64 ± 0.10 for animals with emphysema. Similarly, a reduced value of T 2* (1.27 ± 0.35 ms vs 0.96 ± 0.18 ms) was found in the emphysema group. The mean signal intensity drop and the reduction of T 2* were prominent at 3 weeks following elastase instillation and stabilized between 3 and 8 weeks. The results indicated an excellent agreement between MR findings and histological morphometry (signal intensity, r = −0.78, P = 0.004; T 2* , r = −0.78, P = 0.001). This result shows that proton MRI allows structural changes at alveolar level to be monitored longitudinally. This technique, applied routinely in preclinical trials will represent a valuable tool for assessment of drug therapy efficacy. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Altered Receptor Specificity and Cell Tropism of D222G Hemagglutinin Mutants Isolated from Fatal Cases of Pandemic A(H1N1) 2009 Influenza Virus

ABSTRACT Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of α2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease.
Modeling and predicting transcriptional units of <$O_SSF>Escherichia coli<$C_SSF>genes using hidden Markov models

Motivation: The hidden Markov model (HMM) is a valuable technique for gene-finding, especially because its flexibility enables the inclusion of various sequence features. Recent programs for bacterial gene-finding include the information of ribosomal binding site (RBS) to improve the recognition accuracy of the start codon, using this feature. We report here our attempt to extend the model into the total transcriptional unit, enabling the prediction of operon structures. Results: First, we improved the prediction accuracy of coding sequences (CDSs) by employing the models of ‘typical’, ‘atypical’ and ‘negative (false-positive)’ classes as well as the models of RBS and its downstream spacer. The sensitivity of exactly predicting the 204 experimentally confirmed CDSs reached 90.2% in an objective test. Based on the prediction result of CDSs, the positions of the promoters and terminators were predicted. Our model could exactly recognize 60% of 390 known transcriptional units. Thus, the accuracy and significance of this prediction problem is far from trivial. We would like to propose this problem as an open theme in bioinformatics because the ongoing or planned postsequencing projects will produce much data for future improvements. Availability: The table of predicted transcriptional units of Escherichia coli will be distributed upon request.
Development of Tumors in Hamsters Inoculated in the Neonatal Period with Vacuolating Virus, SV40 ∗

Summary Intracerebral and subcutaneous injection into newborn hamsters of vacuolating virus, SV40, grown in renal cell cultures of grivet monkey resulted in single or multiple fibrosarcomas at site of injection which were histologically of varying degree of malignancy. These occurred 3 1/2 to 8 months post-inoculation and in both sexes. Animals injected with appropriate control materials or held uninoculated failed to develop tumors. Tests to exclude mouse polyoma virus as a factor were clearly negative. Evidence for the role of SV40 virus as a primary oncogenic agent was provided by recovery of the virus from the tumor and by demonstration of SV40 antigen in tumors by fluorescent antibody staining. The agent appeared to be localized in the tumors since the virus was not detected in blood or excretions, since antibody response was minimal or lacking, and since gross metastases were lacking. Transplantation and serial passage of SV40-induced tumors were accomplished with ease. The data represent the first definitive evidence implicating a virus of primate origin as a malignant oncogenic agent in experimental animals. The findings relate to observations of oncogenesis in hamsters and do not warrant extrapolation to oncogenesis in other mammalian species.
Bathing Water Quality and Health Implications

Considerable controversy exists with respect to water quality at bathing beaches. In the UK, South Wales beaches appear to be at the forefront regarding these views. An exhaustive study investigating water quality and health was carried out at Barry Island, Wales during the summer tourist season. The beach is a very popular holiday resort and attracts some 850,000 during the summer months. It is composed of fine grained sand backed by a sea wall. Water samples were taken at two hourly intervals between 1 1:00 and 15:00 hours over a 6 day period during a hot August period in 1995. Testing was carried out for faecal colifonns and faecal streptococci. Simultaneously, a very detailed questionnaire (n=1276) was distributed to beach users. The questions related to health, food consumed, family history, entry to the water or not, etc. Ten days later a follow up telephone questionnaire was carried out specifically to find if any person had contacted for example, ear problems, gastrointestinal symptoms etc. Twenty four percent of swimmers had illnesses compared to 5% for non-swimmers. Levels of faecal colifonns and faecal streptococci were found to be significantly high (45,000 and 16,000 respectively per 100ml). The survey was continued in 1996 at three South Wales beaches. Emphasis was placed on public perception of beaches and attitudes to seaside award schemes such as the European Blue Flag, investigating the legislative framework through which water quality is controlled and impact on the beach consumer.
Self‐reported traffic density and atopic disease in children. Results of the ISAAC Phase III survey in Muenster, Germany

Positive associations between traffic exposure and atopic respiratory disorders in children have been described in several studies. We analyzed data related to self‐reported truck traffic density and several symptoms and diagnoses of asthma and hay fever (12‐month wheezing and rhinitis symptoms, diagnoses of asthma and hay fever) from the ISAAC Phase III survey in Muenster, Germany, using core written and video questionnaires. Data were collected from representative school‐based samples (n = 7345) of 6–7‐ and 13–14‐yr‐olds. In 13–14‐yr‐olds, according to exposure levels categorized into rare, frequent, and constant, with the ‘never’‐category used as reference, the sex‐adjusted prevalence ratios were 1.29 (95% CI = 1.08–1.53), 1.58 (1.29–1.94), and 1.57 (1.18–2.10) for wheeze in the past 12 months, and 1.20 (1.06–1.34), 1.35 (1.17–1.55), and 1.69 (1.42–2.0) for rhinitis symptoms in the past 12 months. Prevalence ratios in 6–7‐yr‐olds and results for a diagnosis of asthma were less consistent while no positive association was detected between hay fever and truck traffic in both age groups. When analyses were based on a more general traffic indicator (self‐reported traffic noise), no consistent associations were observed. Our data provide support for the hypothesis that residential exposure to truck traffic may adversely affect the health of children.
Patient Safety Culture in Jordanian Hospitals

Background: A good safety system depends on having a culture that supports and encourages employees to report their errors and near misses. Since there has been no previous literature or current research studies in Jordanian hospitals that measure an organization's safety culture, the purpose of this study is to validate an Arabic version of the Hospital Survey on Patient Safety Culture (HSOPSC; 2009 version) and to measure health-staff perceptions of the safety culture in Jordanian Ministry of Health (MoH) hospitals. Methodology: A cross-sectional design using multistage stratified random sampling technique was selected. Results: A total of 287 respondents completed and returned the survey, representing a response rate of nearly 60%. Internal consistency of the instrument was measured by calculating Cronbach's coefficient alpha. A good overall score of 0.797 (range 0.12 to 0.85) was obtained. The highest positive participant response came from 'Teamwork within units' (average of 68%), although overall perception of patient safety was only 42%. Conclusion: The Arabic translation of the HSOPSC was found to be valid and reliable. Application of this tool and support for the patient safety culture should be priorities within the provision of health services in Jordan.