Miracle-dz/UniFAR-FTUs huggingface dataset:
Importance of the Membrane-Perturbing Properties of the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 to Viral Fusion

ABSTRACT The membrane-proximal external region (MPER; K665WASLWNWFNITNWLWYIK683) of the human immunodeficiency virus type 1 (HIV-1) gp41 ectodomain plays a critical role in envelope glycoprotein-mediated fusion. In addition, the epitopes of important neutralizing antibodies (2F5, Z13, and 4E10) and the sequence of the peptide fusion inhibitor T20 overlap this conserved region. The MPER has an unusually high percentage of tryptophan residues that likely contribute to the membrane-disrupting nature of the region, which is predicted to adopt an α-helical conformation on membrane contact. We have investigated the membrane-disruptive requirements for this region using a panel of mutants that replace most of the MPER with antibacterial, membrane-active peptides. The results demonstrate that the mutant Envs were processed, transported, and expressed on the cell surface similar to wild type. Some of the mutant Envs induced moderate levels of cell-cell fusion, demonstrating that the region can accommodate the substitution of proline-rich foreign peptides while retaining significant biological function. In contrast, the incorporation into and stability of the mutated Envs in virions was reduced, consistent with the severely impaired viral entry observed for all the mutants. These data suggest that both structural (for Env incorporation) and functional (membrane disruption) constraints may contribute to the highly conserved nature of this region.
Presence of Circulating Lactate Dehydrogenase-Immunoglobulin G (LDH-IgG) Complex in the Sera of Post-Burn Patient

Presence of Circulating Lactate Dehydrogenase-Immunoglobulin G (LDH-IgG) Complex in the Sera of Post-Burn Patient Lactate dehydrogenase (LDH) is an enzyme that belongs to the class oxidoreductase. It actively participates in the inter-conversion of lactate to pyruvate during anaerobic glycolysis in cell cytoplasm. Available literature suggests that there exist only five isoenzymes of LDH which on polyacrylamide gels (Native PAGE) resolve into five bands in normal healthy individuals. However, the presence of extra band in humans is either detected in reproductive tissues or during some pathological state. Here, we report a case in which an extra sixth band of LDH was visualized which forms a complex with IgG in the circulating sera of burn subject. The presence of LDH-IgG complex was confirmed in freshly collected sera using PAGE and immunological approaches. The complex get disappears from 2nd day onwards. The probable reason of the formation of this complex and its relation with the progression of the disease is discussed.
The “Bridge” in the Epstein-Barr Virus Alkaline Exonuclease Protein BGLF5 Contributes to Shutoff Activity during Productive Infection

ABSTRACT Replication of the human herpesvirus Epstein-Barr virus drastically impairs cellular protein synthesis. This shutoff phenotype results from mRNA degradation upon expression of the early lytic-phase protein BGLF5. Interestingly, BGLF5 is the viral DNase, or alkaline exonuclease, homologues of which are present throughout the herpesvirus family. During productive infection, this DNase is essential for processing and packaging of the viral genome. In contrast to this widely conserved DNase activity, shutoff is only mediated by the alkaline exonucleases of the subfamily of gammaherpesviruses. Here, we show that BGLF5 can degrade mRNAs of both cellular and viral origin, irrespective of polyadenylation. Furthermore, shutoff by BGLF5 induces nuclear relocalization of the cytosolic poly(A) binding protein. Guided by the recently resolved BGLF5 structure, mutants were generated and analyzed for functional consequences on DNase and shutoff activities. On the one hand, a point mutation destroying DNase activity also blocks RNase function, implying that both activities share a catalytic site. On the other hand, other mutations are more selective, having a more pronounced effect on either DNA degradation or shutoff. The latter results are indicative of an oligonucleotide-binding site that is partially shared by DNA and RNA. For this, the flexible “bridge” that crosses the active-site canyon of BGLF5 appears to contribute to the interaction with RNA substrates. These findings extend our understanding of the molecular basis for the shutoff function of BGLF5 that is conserved in gammaherpesviruses but not in alpha- and betaherpesviruses.
Formation of Guanosine(5′)Tetraphospho(5′)Adenosine Cap Structure by an Unconventional mRNA Capping Enzyme of Vesicular Stomatitis Virus

ABSTRACT The RNA-dependent RNA polymerase L protein of vesicular stomatitis virus (VSV) elicits GTPase and RNA:GDP polyribonucleotidyltransferase (PRNTase) activities to produce a 5′-cap core structure, guanosine(5′)triphospho(5′)adenosine (GpppA), on viral mRNAs. Here, we report that the L protein produces an unusual cap structure, guanosine(5′)tetraphospho(5′)adenosine (GppppA), that is formed by the transfer of the 5′-monophosphorylated viral mRNA start sequence to GTP by the PRNTase activity before the removal of the γ-phosphate from GTP by GTPase. Interestingly, GppppA-capped and polyadenylated full-length mRNAs were also found to be synthesized by an in vitro transcription system with the native VSV RNP.
Towards the implementation of ‘no evidence of disease activity’ in multiple sclerosis treatment: the multiple sclerosis decision model

Objective: The introduction of new and potent therapies for the treatment of relapsing remitting multiple sclerosis (MS) has increased the desire for therapeutic success. There is growing doubt that the mere reduction of relapse rate, Expanded Disability Status Scale (EDSS) progression and magnetic resonance imaging (MRI) markers are exclusive and appropriate factors to monitor the new aim of ‘no evidence of disease activity’ (NEDA). However, there is no generally accepted definition so far. Methods: To achieve the therapeutic aim of NEDA, a panel of MS experts searched the available literature on clinical and paraclinical outcomes to propose a test battery that is sensitive to detect disease activity in an everyday clinical setting. Results: The panel proposed to include, besides relapse rate, disability progression and MRI, neuropsychological outcome measures such as cognitive status, fatigue, depression and quality of life. To standardize the examinations in an economic and schematic way, a multifactorial model [multiple sclerosis decision model (MSDM)] that includes the domains ‘relapse’, ‘disability progression’, ‘MRI’, and ‘neuropsychology’ is proposed. The scheme reflects the complexity of the disease even in the early stages when scales such as the EDSS are not able to distinguish low levels of progression. Conclusion: The MSDM aims to support early treatment decisions and uncover timely treatment failure. Prospective investigations are required to prove that such a disease-monitoring concept leads to an early and effective silencing of disease activity.
Ultrastructural Analysis of ICP34.5− Herpes Simplex Virus 1 Replication in Mouse Brain Cells In Vivo

ABSTRACT Replication-competent forms of herpes simplex virus 1 (HSV-1) defective in the viral neurovirulence factor infected cell protein 34.5 (ICP34.5) are under investigation for use in the therapeutic treatment of cancer. In mouse models, intratumoral injection of ICP34.5-defective oncolytic HSVs (oHSVs) has resulted in the infection and lysis of tumor cells, an associated decrease in tumor size, and increased survival times. The ability of these oHSVs to infect and lyse cells is frequently characterized as exclusive to or selective for tumor cells. However, the extent to which ICP34.5-deficient HSV-1 replicates in and may be neurotoxic to normal brain cell types in vivo is poorly understood. Here we report that HSV-1 defective in ICP34.5 expression is capable of establishing a productive infection in at least one normal mouse brain cell type. We show that γ34.5 deletion viruses replicate productively in and induce cellular damage in infected ependymal cells. Further evaluation of the effects of oHSVs on normal brain cells in animal models is needed to enhance our understanding of the risks associated with the use of current and future oHSVs in the brains of clinical trial subjects and to provide information that can be used to create improved oHSVs for future use.
Design of adaptive nano/CMOS neural architectures

Memristive devices are a promising technology to implement dense learning synapse arrays emulating the high memory capacity and connectivity of biological brains. Recently, the implementation of STDP learning in memristive devices connected to spiking neurons have been demonstrated as well as the dependency of the form of the learning rule on the shape of the applied spike. In this paper, we propose a fully CMOS integrate-and-fire neuron generating a precisely shaped spike that can be tuned through programmable biases. The implementation of STDP learning is demonstrated through electrical simulations of a 4×4 array of memristors connected to 4 spiking neurons.
Web-based interventions in multiple sclerosis: the potential of tele-rehabilitation

The World Wide Web is increasingly used in therapeutic settings. In this regard, internet-based interventions have proven effective in ameliorating several health behaviors, amongst them physical activity behavior. Internet-delivered interventions have shown positive effects on physical activity and physical function in persons with MS (pwMS). In this review we give an overview on several online exercise programs for pwMS and discuss the advantages and drawbacks of web-based interventions. Although participants of online exercise programs reported a high acceptance and satisfaction with the intervention, decreasing compliance was a major issue. A possible remedy might be the implementation of game-design elements to increase compliance and long-term adherence to internet-delivered interventions. In addition we believe that the integration of social networks seems to be a promising strategy.
The immediate effects of patellar taping on balance and gait ability in individuals with chronic stroke

Objective: The aim of this study is to investigate the effect of patellar taping on balance and gait abilities in chronic stroke patients. Design: Randomized placebo-controlled trial. Methods: Thirty chronic stroke patients who have been diagnosed at least six months or before were recruited from R hospital. These study subjects were randomized to the experimental group (n=15) or placebo group (n=15). In the experimental group, patellar taping was applied while for the placebo group, placebo taping was applied. The Balance System SD was used for measuring dynamic standing balance in these two groups. In addition, the GAITRite (CIR System Inc.) system was utilized for calculating gait performance in these patients. Results: After application of taping, the patellar taping group showed a significant decrease in dynamic standing balance in their sway area ( p <0.05). However, in the placebo group, there was no significant difference in dynamic standing balance ability and gait ability before and after application of taping. Comparison of the patellar taping group and placebo group showed significant differences in dynamic standing balance ability and gait performance ( p <0.05). Conclusions: From the results of this study, it appears that application of patellar taping in chronic stroke patients significantly improved dynamic standing balance ability and gait ability in these patients. Based on these results, patellar taping is thought to be useful in real clinical settings where there are many chronic patients who are in need of improvement in their balance and gait ability.
A low-power fully differential cyclic 9-bit ADC

This paper describes a low-power fully differential cyclic ADC. It utilizes a 4-bit binary weighted capacitor array to obtain 9-bit resolution. The operational amplifier with the slew rate detection is used to increase the speed of the ADC. The simulated power consumption of the ADC is 7.4 μW@1.4 V at the sampling rate of 10 kS/s. The simulated DNL and INL are 0.1/-0.18 LSB and 0.22/-0.2 LSB respectively. The results are based on post-layout simulations.
Rotavirus Prevents the Expression of Host Responses by Blocking the Nucleocytoplasmic Transport of Polyadenylated mRNAs

ABSTRACT Rotaviruses are the most important agent of severe gastroenteritis in young children. Early in infection, these viruses take over the host translation machinery, causing a severe shutoff of cell protein synthesis while viral proteins are efficiently synthesized. In infected cells, there is an accumulation of the cytoplasmic poly(A)-binding protein in the nucleus, induced by the viral protein NSP3. Here we found that poly(A)-containing mRNAs also accumulate and become hyperadenylated in the nuclei of infected cells. Using reporter genes bearing the untranslated regions (UTRs) of cellular or viral genes, we found that the viral UTRs do not determine the efficiency of translation of mRNAs in rotavirus-infected cells. Furthermore, we showed that while a polyadenylated reporter mRNA directly delivered into the cytoplasm of infected cells was efficiently translated, the same reporter introduced as a plasmid that needs to be transcribed and exported to the cytoplasm was poorly translated. Altogether, these results suggest that nuclear retention of poly(A)-containing mRNAs is one of the main strategies of rotavirus to control cell translation and therefore the host antiviral and stress responses.
Time for a New Model of Community Involvement in Health Planning? Introducing Community Risk Group Planning

Mass public involvement in community health planning has been the dream of health planning agencies for decades. The Alma Ata Declaration announced that people have the right and duty to participate and most community health planning models agree that community involvement is essential if significant, lasting, and appropriate progress is to be made in health promotion and disease prevention. Progress toward this goal, however, has not been remarkable. This article argues that the slow progress is attributable to the way community has been defined and to deficiencies in the traditional community development models used by health planners. It advances a radical alternative to conventional methods of involving community in health planning and sets forth steps through which masses can become involved in meaningful planning.
Dimensionality reduction using asynchronous sampling of first derivative features for real-time and computationally efficient neural spike sorting

In recent years, spike sorting has become an emerging technique in multi-channel recording for neuroprosthetic applications. To achieve on-chip real-time processing, it is necessary to design reliable yet low complexity feature extraction and dimensionality reduction to suit low power hardware resources. To satisfy this criterion, this paper proposes asynchronous sampling of first derivative spike waveform features as a dimensionality reduction algorithm. The resulting accuracy of this approach enables identification of the differences temporally localized between the clusters. Directions with maximized or minimized mutual differences are chosen. The classification accuracy of this method is compared with other approaches using different datasets. Using the k-Means clustering algorithm the proposed method achieves an average classification accuracy of > 94% and has very significantly less complexity compared with techniques such as principal component analysis and discrete wavelet transform.
Effect of Preexisting Immunity on an Adenovirus Vaccine Vector: In Vitro Neutralization Assays Fail To Predict Inhibition by Antiviral Antibody In Vivo

ABSTRACT A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8+ T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8+ T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
Strength, efficacy and tolerability of morphine solution with and without added preservatives: A comparative study

Cancer patients having moderate to severe pain need immediate pain relief. Immediate release formulation of morphine is not available in Bangladesh. This open label randomised two phase crossover clinical trial was conducted to compare strength, efficacy, and tolerability of oral morphine solution prepared from morphine sulfate injectable formulation and sustained release tablet with and without added preservatives. Concentration of morphine in solutions both with and without added preservative was highest on the first day and then gradually decreased. No difference between two storage temperatures on first day, but highly significant difference afterwards. Rate of degradation of morphine in solution with added preservative was significantly slower. The present study revealed that the solutions prepared from sustained release tablets and injectable formulation with added preservative could be an option to control severe pain in cancer patients. To introduce the present research finding in clinical practice, this has to be accepted institutionally.
The Human Papillomavirus 16 E7 Oncoprotein Attenuates AKT Signaling To Promote Internal Ribosome Entry Site-Dependent Translation and Expression of c-MYC

ABSTRACT While the role of high-risk human papillomavirus (HPV) oncoproteins E6 and E7 in targeting p53 and retinoblastoma (Rb) has been intensively studied, how E6 and E7 manipulate cellular signaling cascades to promote the viral life cycle and cancer development is less understood. Keratinocytes containing the episomal HPV-16 genome had decreased activation of AKT, which was phenocopied by HPV-16 E7 expression alone. Attenuation of phosphorylated AKT (pAKT) by E7 was independent of the Rb degradation function of E7 but could be ablated by a missense mutation in the E7 carboxy terminus, H73E, thereby defining a novel structure-function phenotype for E7. Downstream of AKT, reduced phosphorylation of p70 S6K and 4E-BP1 was also observed in E7-expressing keratinocytes, which coincided with an increase in internal ribosomal entry site (IRES)-dependent translation that enhanced the expression of several cellular proteins, including MYC, Bax, and the insulin receptor. The decrease in pAKT mediated by E7 is in contrast to the widely observed increase of pAKT in invasive cervical cancers, suggesting that the activation of AKT signaling could be acquired during the progression from initial productive infections to invasive carcinomas. IMPORTANCE HPV causes invasive cervical cancers through the dysregulation of the cell cycle regulators p53 and Rb, which are degraded by the viral oncoproteins E6 and E7, respectively. Signaling cascades contribute to cancer progression and cellular differentiation, and how E6 and E7 manipulate those pathways remains unclear. The phosphoinositol 3-kinase (PI3K)/AKT pathway regulates cellular processes, including proliferation, cell survival, and cell differentiation. Surprisingly, we found that HPV-16 decreased the phosphorylation of AKT (pAKT) and that this is a function of E7 that is independent of the Rb degradation function. This is in contrast to the observed increase in AKT signaling in nearly 80% of cervical cancers, which typically show an acquired mutation within the PI3K/AKT cascade leading to constitutive activation of the pathway. Our observations suggest that multiple changes in the activation and effects of AKT signaling occur in the progression from productive HPV infections to invasive cervical cancers.
Weakly Supervised Training of a Sign Language Recognition System Using Multiple Instance Learning Density Matrices

A system for automatically training and spotting signs from continuous sign language sentences is presented. We propose a novel multiple instance learning density matrix algorithm which automatically extracts isolated signs from full sentences using the weak and noisy supervision of text translations. The automatically extracted isolated samples are then utilized to train our spatiotemporal gesture and hand posture classifiers. The experiments were carried out to evaluate the performance of the automatic sign extraction, hand posture classification, and spatiotemporal gesture spotting systems. We then carry out a full evaluation of our overall sign spotting system which was automatically trained on 30 different signs.
Diseases masking and delaying the diagnosis of urogenital tuberculosis

To the editor: We read with interest the article by Kulchavenya and Kholtobin on urogenital tuberculosis (UGTB) [Kulchavenya and Kholtobin, 2015], in which the authors provide information about unusual UGTB cases. While the authors claim that they have carried out a systematic review of the topic, we completely disagree with that statement. Systematic reviews represent the highest level of evidence available for making clinical decisions, particularly if they are based on high quality studies and a strict and accurate methodology has been followed [Akobeng, 2005]. A comprehensive and exhaustive search for primary studies that attempt to answer a clinical question is a key starting point to every systematic review; in the manuscript it is not clear what the authors want to answer. The title points towards diseases that mimic and delay diagnosis of UGTB, but the authors instead reviewed uncommon presentations of UGTB with no focus at all on diagnosis delay. Second, the search strategy included reviewing only the PubMed database, which has been considered an insufficient strategy for performing a literature search [Suarez-Almazor et al. 2000]. Other databases such as Embase should have been incorporated. In addition, most of the studies included were case reports, and guidelines for reviewing cases reports such as the CARE guidelines and the Institute of Health Economics tool for case series were not followed [Gagnier et al. 2013; Moga et al. 2012]. Third, no clear information on the selection criteria is provided; it is not clear what was considered a usual or a rare case of UGTB. Finally, the results were presented as a narrative review with no clear outcomes of their investigation. Considering that UGTB is a difficult entity to diagnose, the review of unusual UGTB presentations can be a first step to fill the lack of evidence on the topic. We suggest the authors should use the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [Moher et al. 2009]. These guidelines stand for high quality systematic reviews ensuring a transparent and thorough report of data. Authors’ endorsement of this kind of checklists warrants excellence in research and evidence-based medicine.