Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins

ABSTRACT The nairoviruses include assorted tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals. As negative-sense single-stranded RNA (−ssRNA) viruses, nairoviruses encode nucleoprotein (NP) that encapsidates the genomic RNA and further forms ribonucleoprotein (RNP) complex with viral RNA-dependent RNA polymerase (RdRp). We previously revealed that the monomeric NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV) presents a racket-shaped structure and shows unusual DNA-specific endonuclease activity. To examine the structural and biological variation of nairovirus-encoded NPs, here, we systematically solved the crystal structures of NPs encoded by various nairoviruses, including Hazara virus (HAZV), Kupe virus (KUPV), and Erve virus (ERVEV). Combined with biochemical analysis, our results generate a clearer picture to aid in the understanding of the functional diversity of nairovirus-encoded NPs and the formation of nairovirus RNPs. IMPORTANCE Nairoviruses comprise several tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals; however, little is known of the nairovirus genome assembly and transcription mechanisms. Based on the previous study of CCHFV NP reported by different research groups, we systematically investigate here the structural and functional diversity among three different nairoviruses. This work provides important information on nairovirus nucleoprotein function and the formation of RNPs.
Quantitative Analysis of Backchannels Uttered by an Interviewer During Neuropsychological Tests

This paper examines in detail the backchannels uttered by a French professional interviewer during a neuropsychological test of verbal memories. These backchannels are short utterances such as oui, d'accord, uhm, etc. They are mainly produced here to encourage subjects to retrieve a set of words after their controlled encoding. We show that the choice of lexical items, their production rates and their associated prosodic contours are influenced by the subject performance and conditioned by the protocol.
Mixed viral infections: detection and management

An analysis was done of the incidence and nature of mixed virus infections diagnosed in the same clinical specimen from immunocompetent patients; respiratory viruses were emphasized. Few studies have addressed mixed viral infections in any systematic fashion. The relevant studies reviewed focused on clinical relationships or diagnostic methods. Data relating to multiple infections were usually derived incidentally to the purpose of the investigations. Sixty-three percent of the reports with data on mixed infections identified them in < 5% of the total number of viral infections. Respiratory syncytial virus was the most common coinfecting virus, and respiratory syncytial virus and influenza virus were the most common virus pair identified. In considering rapid diagnostic techniques, in 87% of the reports with available data a virus was diagnosed in > 10% of specimens that were negative for the virus targeted by one method. There was no indication that mixed infections were associated with increased disease in immunocompetent patients or in certain immunocompromised patients. Immunocompromised patients, however, appeared to have a greater incidence of multiple infections. Mixed infections of single cells also occur and may have important clinical implications relative to reactivation of latent viruses and enhanced disease. The requirement for a comprehensive strategy for viral diagnosis involving multiple techniques was indicated by these findings.
Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol

To identify the genes for biosynthesis of the off-flavor terpenoid alcohol, 2-methylisoborneol (2-MIB), the key genes encoding monoterpene cyclase were located in bacterial genome databases by using a combination of hidden Markov models, protein–family search, and the sequence alignment of their gene products. Predicted terpene cyclases were classified into three groups: sesquiterpene, diterpene, and other terpene cyclases. Genes of the terpene cyclase group that form an operon with a gene encoding S-adenosyl-l-methionine (SAM)-dependent methyltransferase were found in genome data of seven microorganisms belonging to actinomycetes, Streptomyces ambofaciens ISP5053, Streptomyces coelicolor A3(2), Streptomyces griseus IFO13350, Streptomyces lasaliensis NRRL3382R, Streptomyces scabies 87.22, Saccharopolyspora erythraea NRRL2338, and Micromonospora olivasterospora KY11048. Among six microorganisms tested, S. ambofaciens, S. coelicolor A3(2), S. griseus, and S. lasaliensis produced 2-MIB but M. olivasterospora produced 2-methylenebornane (2-MB) instead. The regions containing monoterpene cyclase and methyltransferase genes were amplified by PCR from S. ambofaciens, S. lasaliensis, and Saccharopolyspora erythraea, respectively, and their genes were heterologously expressed in Streptomyces avermitilis, which was naturally deficient of 2-MIB biosynthesis by insertion and deletion. All exoconjugants of S. avermitilis produced 2-MIB. Full-length recombinant proteins, monoterpene cyclase and methyltransferase of S. lasaliensis were expressed at high level in Escherichia coli. The recombinant methyltransferase catalyzed methylation at the C2 position of geranyl diphosphate (GPP) in the presence of SAM. 2-MIB was generated by incubation with GPP, SAM, recombinant methyltransferase, and terpene cyclase. We concluded that the biosynthetic pathway involves the methylation of GPP by GPP methyltransferase and its subsequent cyclization by monoterpene cyclase to 2-MIB.
Expression of c-Jun Protein in Degenerating Retinal Ganglion Cells after Optic Nerve Lesion in the Rat

Axonal lesions to the optic nerve (ON) induce c-Jun expression in retinal ganglion cells (RGCs) of the rat in vivo. Detailed investigations using retrograde tracers, and double labeling studies for c-Jun and regeneration-associated factors, such as the growth-associated protein GAP-43, have suggested that this upregulation of c-Jun is part of a cell body response in an abortive attempt of affected RGCs to survive and regenerate an axon. On the other hand, prolonged expression of c-Jun protein has in several paradigms of neurodegeneration been linked to the induction of apoptotic cell death. In the present study, we examined the time course and subcellular localization of c-Jun protein by immunocytochemistry on retinal sections after optic nerve crush and carried out double labeling for c-Jun protein and DNA strand breaks to detect apoptosis on the same sections. Several days after ON lesion, a subpopulation of RGCs was detected in which c-Jun protein was not confined to the nucleus, but also located in the cytoplasm. In addition, RGCs were seen that displayed morphological signs of apoptosis, DNA strand breaks, and c-Jun immunoreactivity at the same time. Therefore, c-Jun expression is not confined to intact or regenerating ganglion cells, but also occurs in cells that are destined to die. Our results suggest that the decision to undergo either fate depends on additional signaling events that modulate the transcriptional actions of c-Jun.
Evaluation of lidocaine treatment and risk factors for death associated with gastric dilatation and volvulus in dogs: 112 cases (1997-2005).

OBJECTIVE To determine clinical features, outcome, risk factors for death, and efficacy of IV administration of lidocaine as a prophylactic treatment for ischemic reperfusion injury in gastric dilatation and volvulus (GDV) in dogs. DESIGN Retrospective case series. ANIMALS 112 dogs with GDV. PROCEDURES Data pertaining to breed; time lag to admission; clinical, clinicopathologic, and surgical findings; lidocaine treatment; and postoperative complications were assessed for association with outcome. RESULTS German Shepherd Dogs (28.6%) and Great Danes (17%) were significantly over-represented. Risk factors for death included time lag (> or = 5 hours vs < 5 hours) from onset of clinical signs to admission (46.0% vs 11.3%), rectal temperature (< or = 38 degrees C vs > 38 degrees C [< 100.4 degrees F vs > 100.4 degrees F]) at admission (40.0% vs 14.9%), presence or absence of ARF (67.0% vs 23.3%), presence or absence of suspected gastric wall necrosis (59.3% vs 16.0%), and untreated gastric wall necrosis, compared with treated gastric wall necrosis (100% vs 47.6%). Overall mortality rate was 26.8%; no significant differences were detected in mortality rate or postoperative complications between dogs that received lidocaine IV prior to surgical intervention (52.0%) and dogs that did not (48.0%). Mean +/- SD hospitalization time was longer in the lidocaine treatment group (3.5 +/- 1.9 days vs 2.5 +/- 1.4 days). CONCLUSIONS AND CLINICAL RELEVANCE Presence of the identified risk factors should warrant aggressive treatment. Lidocaine treatment was not associated with mortality rate or postoperative complications, but was associated with prolonged hospitalization time.
Structural Segmentation of Music Based on Repeated Harmonies

In this paper we present a simple, yet powerful method for deriving the structural segmentation of a musical piece based on repetitions in chord sequences, called FORM. Repetition in harmony is a fundamental factor in constituting musical form. However, repeated pattern discovery in music still remains an open problem, and it has not been addressed before in chord sequences. FORM relies on a suffix tree based algorithm to find repeated patterns in symbolic chord sequences that are either provided by machine transcriptions or musical experts. This novel approach complements other segmentation methods, which generally use a self-distance matrix based on other musical features describing timbre, instrumentation, rhythm, or melody. We evaluate the segmentation quality of FORM on 649 popular songs, and show that FORM outperforms two baseline approaches. With FORM we explore new ways of exploiting musical repetition for structural segmentation, yielding a flexible and practical algorithm, and a better understanding of musical repetition.
[The plasma levels of granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor in breast cancer patients].

UNLABELLED Granulocyte - colony stimulating factor (G-CSF) and granulocyte-macrophage - colony stimulating factor (GM-CSF) belong to hematopoetic growth factors (HGFs). Few clinical investigations have shown their autologous production both in vitro by human cell lines and in vivo by tumors. AIM OF THE STUDY We have investigated the plasma levels of G-CSF GM-CSF and CA 15-3 in breast cancer patients before and after surgery, and before and after chemotherapy. MATERIAL AND METHODS The plasma levels of cytokines were measured in 46 patients with breast cancer and in 30 healthy subjects. G-CSF and GM-CSF were determined using enzyme-linked immunosorbent assay (ELISA), CA 15-3 was measured by microparticle enzyme immunoassay (MEIA). RESULTS G-CSF and GM-CSF plasma levels were significantly higher in II stage breast cancer patients before surgery comparing to the control group. The plasma levels of tested cytokines were decreased after surgery, which suggested it's usefulness in evaluating breast cancer total resection. Both of tested cytokines after chemotherapy were increased, which suggested secretion from damaged breast cancer cells. Additionally we observed decreasing the plasma levels of cytokines, especially G-CSF in the 360th day after surgery. This latter result has prognostic function (no symptoms of cancer recurrence). In this study similar plasma levels of CA 15-3 were observed. CONCLUSIONS Tested cytokines, especially G-CSF, can be used in diagnostics and monitoring breast cancer therapy.
Dual Ultrastructural Localization of m-Opioid Receptors and NMDA-Type Glutamate Receptors in the Shell of the Rat Nucleus Accumbens

The effectiveness of NMDA antagonists in modulating the motor and motivational effects of opiates is attributed, in part, to functional associations involving NMDA receptors and m-opioid receptors (MORs) in the shell of the nucleus accumbens (Acb). To determine the subcellular sites for potential functional interactions between opiate ligands and NMDA receptors in this region, we examined the ultrastructural localization of antipeptide antisera against MOR and the R1 subunit of the NMDA receptor in the Acb shell of the adult rat brain. MOR-like immunoreactivity (MOR-LI) was seen primarily in dendrites, whereas NMDAR1-like immunoreactivity (NMDAR1-LI) was detected more often in axon terminals forming asymmetric synapses. In these profiles, MOR labeling was localized mainly to extrasynaptic plasma membranes, whereas NMDAR1-LI was associated with both synaptic and extrasynaptic sites. Of 307 MOR-labeled processes, 17.9% of the dendrites and 9.4% of the axon terminals also contained NMDAR1-LI. In addition, 24.7% of the dendrites containing only MOR-LI were apposed to NMDAR1-labeled axons or terminals. We conclude that in the shell of the Acb, the output of single neurons can be dually modulated by (1) activation of MOR and NMDA receptors in the same dendrites or (2) combined activation of presynaptic NMDA receptors in afferents contacting dendrites containing MOR. In addition, the colocalization of MOR and NMDAR1 in certain axon terminals in the Acb suggests their dual involvement in the presynaptic release of neurotransmitters in this region.
Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus

1 The effects of fetal intravenous treatment with phentolamine or a vasopressinergic V1‐receptor antagonist on the fetal cardiovascular responses to acute hypoxaemia in the llama were investigated. 2 Six llama fetuses were surgically prepared between 60 and 70% of gestation under general halothane anaesthesia with vascular catheters and transit‐time ultrasonic flow probes around a carotid artery and a femoral artery. At least 4 days after surgery all fetuses were subjected to a 3 h experiment: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery while on slow i.v. infusion with saline. On separate days this experiment was repeated with fetal i.v. treatment with either phentolamine or a V1‐receptor antagonist dissolved in saline. 3 During saline infusion all llama fetuses responded to acute hypoxaemia with intense femoral vasoconstriction. Phentolamine during normoxia produced hypotension, tachycardia and vasodilatation in both the carotid and the femoral circulations. During hypoxaemia, fetuses treated with phentolamine did not elicit the pronounced femoral vasoconstriction and all died within 20 min of the onset of hypoxaemia. A V1‐receptor antagonist produced a femoral vasodilatation during normoxia but did not affect the fetal cardiovascular responses to acute hypoxaemia. 4 In conclusion, α‐adrenergic and V1‐vasopressinergic mechanisms contribute to a basal vasoconstrictor tone in the femoral circulation in the llama fetus. The enhanced femoral vasoconstriction during acute hypoxaemia in the llama fetus is not mediated by stimulation of V1‐vasopressin receptors, but is dependent on α‐adrenergic receptor stimulation. Such α‐adrenergic efferent mechanisms are indispensable to fetal survival during hypoxaemia in the llama since their abolition leads to cardiovascular collapse and death.
The Neural Bases of Normal and Deviant Moral Cognition and Behavior

THE STUDY OF NORMAL AND ABNORMAL MORAL COGNITION AND BEHAVIOR Studies on normal volunteers and patients presenting with acquired or developmental antisocial behavioral disorders have begun to reveal with unprecedented clarity the neural substrates of moral cognition and behavior. This knowledge stems from 2 sources. The oldest is represented by observations on previously normal individuals who develop persistent antisocial behaviors as a result of acquired brain damage, a condition currently known as acquired sociopathy. Clinicoanatomic correlations in these cases have contributed to the development of models depicting the brain regions whose integrity is critical for moral behavior. Although most observations to date were done on adults, acquired sociopathy in children and adolescents has also shed light on the cerebral structures that are necessary for moral development. The other source of data is represented by the study of the morphological and functional abnormalities in the brains of individuals with antisocial behaviors and poor social adjustment beginning in childhood or adolescence, but without acquired brain damage. The personality and behavioral characteristics of these individuals were depicted by Cleckley, who called them psychopaths. Psychopaths began to be studied objectively thanks to the development of psychometrically sound instruments, which are known as the Psychopathy Checklists, and the development of neuroimaging gears that allow the in vivo scanning of the human brain with a high degree of spatial resolution.
Breast Cancer Heterogeneity Analysis as Index of Response to Treatment Using MRI Images: A Review

Purpose: Breast tumor structure contains a high degree of heterogeneity. This heterogeneity has been correlated with the level of tumor response to neoadjuvant chemotherapy. A significant number of studies using magnetic resonance imaging have looked into the quantification of intra tumor heterogeneity in breast cancer. Nevertheless, a limited number of these studies have specifi-cally looked at evaluating breast cancer heterogeneity as a biomarker of response to treatment. Methods: In this paper, several heterogeneity quantification methods, which have studied breast cancer response to treatment through MR images, will be presented. Important methodological and technological techniques using experimental design, such as histogram analysis, texture analysis and parametric response mapping (PRM), will be explored. Results: Data acquisition, the number of patients, the number of treatment cycles, and other analysis will be discussed for each presented research case. Furthermore, some proposed methods will be evaluated on our institution MRI dataset, collected between 2013 and 2016. Conclusion: This paper can be used as a guideline for investigators working on breast cancer het-erogeneity as a biomarker of response to treatment.
Role of Plasma, Lipopolysaccharide-Binding Protein, and CD14 in Response of Mouse Peritoneal Exudate Macrophages to Endotoxin

ABSTRACT Plasma lipopolysaccharide (LPS)-binding protein (LBP) and membrane CD14 function to enhance the responses of monocytes to low concentrations of endotoxin. Surprisingly, recent reports have suggested that LBP or CD14 may be dispensable for macrophage responses to low concentrations of LPS or may even exert an inhibitory effect in the case of LBP. We therefore investigated whether LBP and CD14 participated in the response of mouse peritoneal exudate macrophages (PEM) to LPS stimulation. In the presence of a low amount of plasma (<1%) or of recombinant mouse or human LBP, PEM were found to respond to low concentrations of LPS (<5 to 10 ng/ml) in an LBP- and CD14-dependent manner. However, tumor necrosis factor production (not interleukin-6 production) by LPS-stimulated PEM was reduced when cells were stimulated in the presence of higher concentrations of plasma or serum (5 or 10%). Yet, the inhibitory effect of plasma or serum was not mediated by LBP. Taken together with previous results obtained withLBP and CD14 knockout mice in models of experimental endotoxemia, the present data confirm a critical part for LBP and CD14 in innate immune responses of both blood monocytes and tissue macrophages to endotoxins.
Vascular endothelial growth factor expression in pediatric non-Hodgkin lymphoma: A prospective study

Serum vascular endothelial growth factor (VEGF) level is higher in children with nonHodgkin lymphoma (NHL) than healthy controls, but its prognostic significance is unknown [1]. VEGF expression has been evaluated in serum [2] and in tissue using immunohistochemistry [3] and polymerase chain reaction (PCR) [4]. After institute ethical approval, treatment-naïve patients of pediatric NHL 18 years were included from July 2012 to March 2014. Patients with early-stage nonlymphoblastic lymphomas were treated with short-course chemotherapy [5]; advanced-stage nonlymphoblastic lymphoma received NHL-BFM-90 protocol [6] and lymphoblastic lymphoma BFM-90 ALLlike protocol [7]. Survival was censored on 15 September 2015. Baseline serum VEGF-A immune reactivity was assessed using quantitative sandwich enzyme immunoassay (Quantikine Human VEGF-A Immunoassay; R&D Systems, Minneapolis, MN, USA). Cytoplasmic VEGF expression in tumor cells was assessed using immunohistochemistry with mouse monoclonal VEGF antibody (VEGF:Ab-3, Clone:JH121; Neomarkers, Fremont, CA, USA). Intensity was graded negative (0), weak, moderate, or intense. VEGF staining intensity 1+ in 10% tumor cells was considered positive. Polymerase chain reaction (PCR) was performed using gene-specific primer pair for VEGF-A and glyceraldehyde-3-phosphate dehydrogenase. There were 50 patient samples and 10 healthy ageand sex-matched controls. Median age of patients was 11 years (2–18 years). Stage III/IV disease was present in 74% patients; bone marrow was involved in 9 patients. Median VEGF level in patients was 648.2 pg/mL (16.98–3335.5 pg/mL). Median serum VEGF in patients was higher than controls (P = .03). Bone marrow involvement in lymphoma was associated with increased serum VEGF (P = .03) (Table 1). Immunohistochemistry for VEGF was performed in 27/50 tissue blocks. Positivity was observed in 17/27 (63%) patients (Supplemental Figure 1). No significant correlation was observed with VEGF positivity and baseline characteristics (Table 1). The number of patients with moderate or intense VEGF expression was 3/7 in stages I and II and 5/20 in stages III and IV (P = .37). Serum VEGF versus VEGF positivity (plotted as positive/negative) using Spearman’s correlation showed positive correlation (r = .44; P = .02).
Effects of leached components from silorane and methacrylate-based dental composites on the male mice reproductive system.

BACKGROUND This study aimed to investigate the potential toxic effects of leached components from either a methacrylate-based composite (Filtek Z250) or a silorane-based composite (Filtek P90) on the male mice reproductive system. METHODS Sixty adult Syrian male mice were divided into six groups. In test groups, leached components from composite specimens in artificial saliva or 75% aqueous ethanol solution were administered intragastrically daily for 28 days. The mice were then euthanized and the following reproductive parameters recorded: body weight changes; weight of paired testes; testis volume; Gonadosomatic Index (GSI); sperm motility; sperm viability; daily sperm production and epididymal sperm count. RESULTS There were no significant differences in body weight changes, weight of paired testes, GSI, testis volume, epididymal sperm count, and daily sperm production between groups. Sperm motility and sperm viability were significantly lower in all the test groups in comparison to the control groups. In addition, they were significantly lower in the test groups in which composite samples were immersed in aqueous ethanol solution. CONCLUSIONS Within the limitations of this study, the present data indicate that leached components from dental composites could affect sperm quality and therefore could potentially cause adverse effects on the male mice reproductive system.