Miracle-dz/UniFAR-FTUs huggingface dataset:
Overlapping Local and Long-Range RNA-RNA Interactions Modulate Dengue Virus Genome Cyclization and Replication

ABSTRACT The dengue virus genome is a dynamic molecule that adopts different conformations in the infected cell. Here, using RNA folding predictions, chemical probing analysis, RNA binding assays, and functional studies, we identified new cis-acting elements present in the capsid coding sequence that facilitate cyclization of the viral RNA by hybridization with a sequence involved in a local dumbbell structure at the viral 3′ untranslated region (UTR). The identified interaction differentially enhances viral replication in mosquito and mammalian cells.
Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer's disease

Correspondence: Stefano Dall’Acqua Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5 35100, Padova, Italy Email stefano.dallacqua@unipd.it Abstract: The inhibition of acetylcholinesterase (AChE) has been one of the most used strategies for the treatment of Alzheimer’s disease (AD). The AChE inhibitors (AChE-I) produce not only short-term symptomatic effects, but can also play a role in other pathological mechanisms of the disease (eg, formation of amyloid-β plaques), which has renewed interest in the discovery of such inhibitors. Four of the five currently prescribed treatments for AD are AChE-I. Natural alkaloids such as galantamine or alkaloid-related synthetic compounds (such as rivastigmine) are considered beneficial for patients with mild-to-moderate AD. However, there is a need for the discovery of more effective compounds and for this reason, plants can still be a potential source of new AChE-I. Findings and advances in knowledge about natural alkaloids as potential new drugs acting as AChE-I will be summarized in this paper.
Subtemporal transparahippocampal amygdalohippocampectomy for surgical treatment of mesial temporal lobe epilepsy: Technical note

Amygdalohippocampectomy (AH) is an accepted surgical option for treatment of medically refractory mesial temporal lobe epilepsy. Operative approaches to the amygdala and hippocampus that previously have been reported include: the sylvian fissure, the superior temporal sulcus, the middle temporal gyrus, and the fusiform gyrus. Regardless of the approach, AH permits not only extirpation of an epileptogenic focus in the amygdala and anterior hippocampus, but interruption of pathways of seizure spread via the entorhinal cortex and the parahippocampal gyrus. The authors report a modification of a surgical technique for AH via the parahippocampal gyrus, in which excision is limited to the anterior hippocampus, amygdala and parahippocampal gyrus while preserving the fusiform gyrus and the rest of the temporal lobe. Because transparahippocampal AH avoids injury to the fusiform gyrus and the lateral temporal lobe, it can be performed without intracarotid sodium amobarbital testing of language dominance and language mapping. Thus the operation would be particularly suitable for pediatric patients in whom intraoperative language mapping before resection is difficult.
Methadone Treatment and Acquired Immunodeficiency Syndrome

To the Editor. — The use of the term "innocent victims" to refer to some of those who have contracted human immunodeficiency virus 1 is inappropriate to a major medical journal and should not be tolerated. Since early in the epidemic, those infected have commonly been divided into "innocent victims" and—who are the others? Guilty victims? I have worked in acquired immunodeficiency syndrome policy, prevention, and education at the epicenter for several years and have yet to meet anyone who either deserved or wanted to contract human immunodeficiency virus. Health professionals must reject this discriminatory terminology once and for all, for it is neither descriptive nor scientific and reveals only the author's prejudice.
Synergistic Interaction of Interferon-β and Interferon-γ in Coxsackievirus B3-Infected Carrier Cultures of Human Myocardial Fibroblasts

The antiviral effects of human interferon-beta (IFN-beta) and human recombinant interferon-gamma (rIFN-gamma) were studied in persistently coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts over a period of 21 days. Synergism was observed with concentrations as low as 30 IU of IFN-beta plus 10 IU of rIFN-gamma/mL, reducing mean viral titers from 6.0 x 10(7) to 1.3 x 10(4) pfu/mL and number of infected cells from 14.4% to 0.1% as determined by quantitative in situ hybridization. Higher concentrations of IFNs (both > or = 30 IU/mL) were associated with transient antagonism followed by antiviral synergism. With 100 IU of IFN-beta plus 30 IU of rIFN-gamma/mL, elimination of infectious virus was consistently achieved and sustained for 6 weeks after cessation of IFN application, whereas at least threefold higher concentrations were required with single drugs. In summary, our data support a concept of low-dose IFN combination schedules that might become useful in the treatment of enteroviral heart disease.
Usefulness of quantitative peritumoural perfusion and proton spectroscopic magnetic resonance imaging evaluation in differentiating brain gliomas from solitary brain metastases

Objectives The purpose of our study was to evaluate whether peritumoural perfusion weighted and proton spectroscopic magnetic resonance imaging can be used in differentiating between primary gliomas and solitary metastases. Methods Ten low-grade gliomas, eight high-grade gliomas and 10 metastases were prospectively evaluated with magnetic resonance imaging, dynamic susceptibility contrast enhanced perfusion imaging and single-voxel proton magnetic resonance spectroscopy before surgical resection or stereotactic biopsy. Maximal relative cerebral blood volume values were calculated drawing three regions of interest of 2 cm2 in the non-enhancing peritumoural areas. Maximal relative cerebral blood volume values were normalised to that of contralateral normal-appearing white matter. Maximal choline/creatine ratios were calculated from three voxels of 10 cm3 placed in the peritumoural areas defined as non-enhancing peritumoural white matter surrounding the tumour. The tumour grade presumed with these values was compared to histopathological grading. Differences in the study parameters between groups were assessed using the Mann–Whitney test. A receiver operating characteristic analysis was performed to determine cut-off values. Results A clear relative cerebral blood volume cut-off value of 1.88 was detected for differentiating low-grade gliomas from high-grade gliomas. A clear relative cerebral blood volume cut-off value of 1.20 was detected for differentiation of metastases from gliomas. The differences in the choline/creatine ratios in the peritumoural regions of high-grade gliomas and of solitary metastasis were statistically significant (P < 0.001) but a clear cut-off value was not found. Conclusion Our preliminary data support the hypothesis that peritumoural perfusion-weighted imaging can assist in preoperative differentiation between a glioma and a solitary metastasis.
Correction to "Downlink Scheduling via Genetic Algorithms for Multiuser Single-Carrier and Multicarrier MIMO Systems With Dirty Paper Coding" [Sep 09 3247-3262]

An equation in the Appendix of a previous paper (IEEE Trans. Veh. Technol ., vol. 58, no. 7, pp. 3247-3262, Sep. 2009) contains an error, which propagates to a few more equations in the Appendix. This error does not affect the main body of the text or results presented in that paper, apart from a change to one equation. In this correspondence, we correct the error and provide a revised Appendix.
Expression of Gamma Interferon-Dependent Genes Is Blocked Independently by Virion Host Shutoff RNase and by US3 Protein Kinase

ABSTRACT Gamma interferon receptor α (IFN-γRα) is stable but posttranslationally modified in herpes simplex virus 1(F) [HSV-1(F)]-infected cells. Studies with antibody directed to the phosphorylation site indicate that IFN-γRα is phosphorylated by the US3 kinase. The modification is abolished in cells infected with ΔUS3, ΔUL13, or Δ(US3/UL13) mutant virus. Transcripts of the IFN-γ-dependent genes do not accumulate in cells transduced with the US3 protein kinase and treated with IFN-γ. In contrast, the accumulation of IFN-γ-dependent gene transcripts is suppressed in cells infected with the wild-type virus, in cells infected with the ΔUS3 mutant virus, and to a lesser extent in the ΔUL41 virus-infected cells. The accumulation of IFN-γ-dependent gene transcripts in ΔUL41-infected cells could be due at least in part to a significant delay and reduction in the accumulation of the US3 protein. The results suggest that the expression of IFN-γ-dependent genes is blocked independently by the degradation of IFN-γ-dependent gene transcripts—a function of the virion host shutoff RNase—and by posttranslational modification of the IFN-γRα protein.
Role of Viral RNA and Co-opted Cellular ESCRT-I and ESCRT-III Factors in Formation of Tombusvirus Spherules Harboring the Tombusvirus Replicase

ABSTRACT Plus-stranded RNA viruses induce membrane deformations in infected cells in order to build viral replication complexes (VRCs). Tomato bushy stunt virus (TBSV) co-opts cellular ESCRT (endosomal sorting complexes required for transport) proteins to induce the formation of vesicle (spherule)-like structures in the peroxisomal membrane with tight openings toward the cytosol. In this study, using a yeast (Saccharomyces cerevisiae) vps23Δ bro1Δ double-deletion mutant, we showed that the Vps23p ESCRT-I protein (Tsg101 in mammals) and Bro1p (ALIX) ESCRT-associated protein, both of which bind to the viral p33 replication protein, play partially complementary roles in TBSV replication in cells and in cell extracts. Dual expression of dominant-negative versions of Arabidopsis homologs of Vps23p and Bro1p inhibited tombusvirus replication to greater extent than individual expression in Nicotiana benthamiana leaves. We also demonstrated the critical role of Snf7p (CHMP4), Vps20p, and Vps24p ESCRT-III proteins in tombusvirus replication in yeast and in vitro. Electron microscopic imaging of vps23Δ yeast revealed the lack of tombusvirus-induced spherule-like structures, while crescent-like structures are formed in ESCRT-III deletion yeasts replicating TBSV RNA. In addition, we also showed that the length of the viral RNA affects the sizes of spherules formed in N. benthamiana cells. The 4.8-kb genomic RNA is needed for the formation of spherules 66 nm in diameter, while spherules formed during the replication of the ∼600-nucleotide (nt)-long defective interfering RNA in the presence of p33 and p92 replication proteins are 42 nm. We propose that the viral RNA serves as a “measuring string” during VRC assembly and spherule formation. IMPORTANCE Plant positive-strand RNA viruses, similarly to animal positive-strand RNA viruses, replicate in membrane-bound viral replicase complexes in the cytoplasm of infected cells. Identification of cellular and viral factors affecting the formation of the membrane-bound viral replication complex is a major frontier in current virology research. In this study, we dissected the functions of co-opted cellular ESCRT-I (endosomal sorting complexes required for transport I) and ESCRT-III proteins and the viral RNA in tombusvirus replicase complex formation using in vitro, yeast-based, and plant-based approaches. Electron microscopic imaging revealed the lack of tombusvirus-induced spherule-like structures in ESCRT-I or ESCRT-III deletion yeasts replicating TBSV RNA, demonstrating the requirement for these co-opted cellular factors in tombusvirus replicase formation. The work could be of broad interest in virology and beyond.
Actividad de picadura de Culex quinquefasciatus (SAY, 1863) en Bogotá, Colombia

Antecedentes. La presencia de mosquitos en el sur de Bogota se constituye en una molestia sanitaria debido a sus altas densidades. Objetivo. Caracterizar la abundancia mensual y la actividad de picadura de los mosquitos. Materiales y metodos. Se recolectaron mosquitos utilizando trampas Shannon, durante una noche por mes y por un periodo de seis meses, en dos sitios aledanos a fosos de excavacion minera, inundadas por el rio Tunjuelito. Resultados. Se recolectaron un total de 18891 mosquitos. 99,93% se determinaron como culex quinquefasciatus. Los meses de mayor abundancia de mosquitos fueron marzo y abril, los cuales presentan mayor precipitacion. Se encontraron dos patrones de actividad nocturna, uno con un solo pico hacia la media noche en el sitio mas cercano a las minas de excavacion y otro con dos picos definidos en el sitio mas cercano a las viviendas. La tasa de paridad fue de 64,4%. Conclusion. Este comportamiento diferente posiblemente este asociado a las condiciones microambientales, como luz y actividad minera de la zona durante las 24 horas del dia, pero no se encontro que estuviera relacionado con la presencia o ausencia de lluvia
The Stress Granule Protein G3BP1 Recruits Protein Kinase R To Promote Multiple Innate Immune Antiviral Responses

ABSTRACT Stress granules (SGs) are cytoplasmic storage sites containing translationally silenced mRNPs that can be released to resume translation after stress subsides. We previously showed that poliovirus 3C proteinase cleaves the SG-nucleating protein G3BP1, blocking the ability of cells to form SGs late in infection. Many other viruses also target G3BP1 and inhibit SG formation, but the reasons why these functions evolved are unclear. Previously, we also showed a link between G3BP1-induced SGs and protein kinase R (PKR)-mediated translational control, but the mechanism of PKR interplay with SG and the antiviral consequences are unknown. Here, we show that G3BP1 exhibits antiviral activity against several enteroviruses, whereas truncated G3BP1 that cannot form SGs does not. G3BP1-induced SGs are linked to activation of innate immune transcriptional responses through NF-κB and JNK. The G3BP1-induced SGs also recruit PKR and other antiviral proteins. We show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to SGs, for eIF2α phosphorylation driven by PKR, and for nucleating SGs of normal composition. We also show that deletion of the PXXP domain in G3BP1 compromises its antiviral activity. These findings tie PKR activation to its recruitment to SGs by G3BP1 and indicate that G3BP1 promotes innate immune responses at both the transcriptional and translational levels and integrates cellular stress responses and innate immunity. IMPORTANCE Stress granules appear during virus infection, and their importance is not well understood. Previously, it was assumed that they were nonfunctional artifacts associated with cellular stress. PKR is a well-known antiviral protein; however, its regulation in cells is not well understood. Our work links cellular stress granules with activation of PKR and other innate immune pathways through the activity of G3BP1, a critical stress granule component. The ability of stress granules and G3BP1 to activate PKR and other innate immune transcriptional responses indicates that G3BP1 is an antiviral protein. This work helps to refine a longstanding paradigm indicating stress granules are inert structures and explains why G3BP1 is subverted by many viruses to promote a productive infection.
Outage Analysis of Decode-and-Forward Cognitive Dual-Hop Systems With the Interference Constraint in Nakagami-$m$ Fading Channels

This paper studies the outage probability performance of decode-and-forward (DF) cognitive dual-hop systems for Nakagami-m fading channels, with consideration of an interference temperature limit. An exact outage probability expression is derived, and the impact of various key system parameters, such as interference temperature and fading severity, is investigated. Our results show that the interference temperature constraint causes the outage saturation phenomenon, but the outage performance gets better when the channel quality of the secondary transmission links improves. However, how the channel quality of the interfering links affects the outage performance depends on the channel quality of the secondary transmission links, as well as the interference temperature constraint and maximum transmit power.
Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

ABSTRACT RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCE Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection. Moreover, we have found that CNV co-opts HSP70 family homologs to facilitate several aspects of the infection process such as viral RNA, coat protein and virus accumulation. Chloroplast targeting of the CNV CP is also facilitated, which may aid in CNV suppression of host defense responses. Several viruses have been shown to induce HSP70 during infection and others to utilize HSP70 for specific aspects of infection such as replication, assembly, and disassembly. We speculate that HSP70 may play multiple roles in the infection processes of many viruses.
A Comprehensive Review on Dry Eye Disease: Diagnosis, Medical Management, Recent Developments, and Future Challenges

Dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS) is a common disorder of the tear film caused by decreased tear production or increased evaporation and manifests with a wide variety of signs and symptoms. The present review from interpretation of the literature gives detailed information on the prevalence, definition, causes, diagnostic tests, and medical management of dry eye disease. A number of systems contribute to the physiological integrity of the ocular surface and disruption of system may or may not produce symptoms. Therefore accurate diagnosis of dry eyes with no or minimal disruption of physiological function is necessary. The paper also discusses different colloidal drug delivery systems and current challenges in the development of topical ophthalmic drug delivery systems for treatment of KCS. Due to the wide prevalence and number of factors involved, newer, more sensitive diagnostic techniques and novel therapeutic agents have been developed to provide ocular delivery systems with high therapeutic efficacy. The aim of this review is to provide awareness among the patients, health care professionals, and researchers about diagnosis and treatment of KCS and recent developments and future challenges in management of dry eye disease.
Effectiveness of commercially available gaming devices in upper limb stroke rehabilitation

Abstract Background: Hemiparesis of the upper extremity is estimated to affect 50–75% of individuals who experience a stroke. Recently the use of commercially available off-the-shelf (COTS) gaming technology has shown promise for providing interactive rehabilitation. The existing evidence however, has not yet been reviewed systematically to determine the effectiveness of such gaming devices in upper limb (UL) rehabilitation post-stroke. Objectives: To determine the effectiveness of COTS gaming technology for UL rehabilitation in post-stroke patients and to assess the feasibility, and effect on quality of life (QoL). Methods: A systematic search of the databases CINAHL, MEDLINE, PsycINFO, Pubmed, SPORTDiscus, and SCOPUS was conducted. Quality scoring of the included articles was based on the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies. Results: In total, eight studies were included for review. The commercial gaming devices were found to be feasible for use among post-stroke individuals. The devices were found to be effective as an adjunct to conventional stroke rehabilitation, and were feasible in relation to time taken, cost-effectiveness, safety, and the positive effect on the QoL of the stroke population. Conclusions: As the findings of the current review are primarily based on lower levels of research, it is not possible to make recommendations regarding the use of these devices in clinical practice. However, findings of the included studies did indicate that rehabilitation including gaming technology had a positive effect on the UL rehabilitation of stroke patients.