Miracle-dz/UniFAR-FTUs huggingface dataset:
The inner rod protein controls substrate switching and needle length in a Salmonella type III secretion system

Significance Type III secretion systems are multiprotein nanomachines with the capacity to inject bacterial proteins into eukaryotic cells that are used by bacterial symbionts or pathogens to interact with their hosts. The main component of these machines is the needle complex, a multiprotein organelle composed of a bacterial envelope-associated multiring base and a filament-like structure, the needle, that projects from the bacterial surface and is linked to the base by an inner rod. Here we have studied the inner rod in detail and provided important insight into the mechanism of assembly and function of type III secretion machines. Understanding the function of type III secretion machines could lead to the development of novel antimicrobials. Type III secretion machines are essential for the biology of many bacteria that are pathogenic or symbiotic for animals, plants, or insects. They exert their function by delivering bacterial effector proteins into target eukaryotic cells. The core component of these machines is the needle complex, a multiprotein structure that spans the bacterial envelope and serves as a conduit for proteins that transit this secretion pathway. The needle complex is composed of a multiring base embedded in the bacterial envelope and a filament-like structure, the needle, that projects from the bacterial surface and is linked to the base by the inner rod. Assembly of the needle complex proceeds in a step-wise fashion that is initiated by the assembly of the base and is followed by the export of the building subunits for the needle and inner rod substructures. Once assembled, the needle complex reprograms its specificity and becomes competent for the secretion of effector proteins. Here through genetic, biochemical, and electron microscopy analyses of the Salmonella inner rod protein subunit PrgJ we present evidence that the assembly of the inner rod dictates the timing of substrate switching and needle length. Furthermore, the identification of mutations in PrgJ that specifically alter the hierarchy of protein secretion provides additional support for a complex role of the inner rod substructure in type III secretion.
Role of factor VIII on activated protein C resistance ratio in inflammatory diseases

Activated protein C resistance ratio (APC‐Rr), factor VIIIC (FVIIIC) and plasma fibrinogen levels were studied in patients with inflammatory disease. The patient mean APC‐Rr was significantly lower than in the control group. This decreased ratio in inflammatory diseases appeared to be connected with increased FVIIIC. Moreover, supplementation of plasmas with purified factor VIII decreased the APC‐Rr in plasma from both groups, and suppressed the difference between groups. These data suggest that factor VIIIa and factor Va compete for protein C‐catalysed cleavage. Ratios were identical in both groups when FVIIIC level was lowered by dilution in factor V deficient plasma.
Role of MicroRNA-93 I in Pathogenesis of Left Ventricular Remodeling via Targeting Cyclin-D1

Background The objective of this study was to identify the pathway responsible for ventricular remodeling. Material/Methods We collected remodeling myocardium tissue (n=18) and control myocardium tissue (n=22), and detected the expression of 4 miRNAs in these 2 groups using real-time PCR. We then searched the miRNA database online to find the candidate genes of miR-93. Real-time PCR and Western blot analysis were used to confirm the regulatory relationship. Results We found that only miR-93 was decreased in remodeling myocardium tissue, and validated CCND1 to be the direct target gene of miR-93, with the “seed sequence” located within the 3′-UTR of the target gene via luciferase reporter assay system. Furthermore, we established the negative regulatory relationship between miR-93 and CCND1 by determining the relative luciferase activity of cells transfected with wild-type or mutant 3′-UTR of CCND1. We also found that The CCND1 protein and mRNA expression level of HL-1 cells treated with 50 nM miR-93 mimics were apparently lower than the scramble control, and those of the cells treated with 100 nM miR-93 mimics and CCND1 siRNA (100 nM) were even lower than those in the 50 nM treatment group. Meanwhile, cells transfected with miR-93 mimics (50 nM) showed evidently downregulated viability when compared with the scramble controls, while cells transfected with (100 nM) and CCND1 siRNA (100nM) showed even lower viability. Conclusions We showed that CCND1 is a direct target of miR-93, and the dysregulation of the miR-93/CCND1 signaling pathway is responsible for the development of ventricular remodeling.
Arx homeobox gene is essential for development of mouse olfactory system

The olfactory system provides an excellent model in which to study cell proliferation, migration, differentiation, axon guidance, dendritic morphogenesis, and synapse formation. We report here crucial roles of the Arx homeobox gene in the developing olfactory system by analyzing its mutant phenotypes. Arx protein was expressed strongly in the interneurons and weakly in the radial glia of the olfactory bulb, but in neither the olfactory sensory neurons nor bulbar projection neurons. Arx-deficient mice showed severe anatomical abnormalities in the developing olfactory system: (1) size reduction of the olfactory bulb, (2) reduced proliferation and impaired entry into the olfactory bulb of interneuron progenitors, (3) loss of tyrosine hydroxylase-positive periglomerular cells, (4) disorganization of the layer structure of the olfactory bulb, and (5) abnormal axonal termination of olfactory sensory neurons in an unusual axon-tangled structure, the fibrocellular mass. Thus, Arx is required for not only the proper developmental processes of Arx-expressing interneurons, but also the establishment of functional olfactory neural circuitry by affecting Arx-non-expressing sensory neurons and projection neurons. These findings suggest a likely role of Arx in regulating the expression of putative instructive signals produced in the olfactory bulb for the proper innervation of olfactory sensory axons.
OPTIMIZATION OF EXTRACTION CONDITIONS AND ANTIMICROBIAL POTENTIAL OF A BIOACTIVE METABOLITE, CORDYCEPIN FROM CORDYCEPS MILITARIS 3936

Cordycepin, a nucleoside derivative, is an active component of parasitic fungus, Cordyceps militaris which has been known for many pharmacological activities. The present study was carried out to develop an extraction strategy for cordycepin and to evaluate its antimicrobial potential. Solvent- solvent extraction method was used to extract cordycepin from liquid culture of C. militaris. Crude concentrated extract of fermented broth was sequentially partitioned with hexane, chloroform and n-butanol. Further we assessed the effect of solvent-solvent ratio, extraction time and temperature on cordycepin extraction Antimicrobial properties of various Cordyceps militris derived fractions such as hexane; chloroform and n-butanol were investigated against human pathogenic microorganisms using the disc diffusion. Maximum yield of cordycepin was achieved at a solvent ratio of 1:2 (v/v) with extraction time of 90 minutes at 40°C. Final purity of the cordycepin was recorded up to 95% based on high performance liquid chromatography. Butanolic fractions, demonstrated the highest antimicrobial activity, due to the presence of cordycepin as an active component. The minimum inhibition concentration (MIC) of cordycepin was found to be 25-40 µg/disc for all the microorganisms tested. Hence Cordyceps militaris derived cordycepin could potentially be used in the treatment of infectious diseases caused by pathogenic microorganisms.
Global Functional Connectivity Deficits in Schizophrenia Depend on Behavioral State

Schizophrenia is a devastating psychiatric illness characterized by deterioration of cognitive and emotional processing. It has been hypothesized that aberrant cortical connectivity is implicated in the disease (Friston, 1998), yet previous studies of functional connectivity (FC) in schizophrenia have shown mixed results (Garrity et al., 2007; Jafri et al., 2008; Lynall et al., 2010). We measured FC using fMRI in human schizophrenia patients and healthy controls during two different tasks and a rest condition, and constructed a voxel-based global FC index. We found a striking FC decrease in patients compared with controls. In the task conditions, relatively weaker FC was specific to regions of cortex not active during the task. In the rest condition, the FC difference between patients and controls was larger and allowed a case-by-case separation between individuals of the two groups. The results suggest that the relative reduction of FC in schizophrenia is dependent on the state of cortical activity, with voxels not activated by the task showing higher levels of FC deficiency. This novel finding may shed light on previous reports of FC in schizophrenia. Whether this neural characteristic is related to the development of the disorder remains to be established.
Hardware implementation of FIR/IIR digital filters using integral stochastic computation

Stochastic computing (SC) has received much recent attention due to its inherent fault-tolerance and low implementation cost compared to binary radix representations. SC has been proposed for various signal processing applications such as digital filters. The prior art in stochastic FIR filters can accurately implement the desired filtering function for low-order filters, however, their accuracy degrades as the filter order increases. Moreover, stochastic IIR filters demonstrate high hardware complexity and degraded accuracy. In this paper, we propose an architecture for high-order FIR filters with negligible accuracy loss compared to fixed-point implementation. The proposed architecture requires fewer random number generators. We also describe a novel cascaded second-order direct-form II structure for IIR filters. The implementation results of the proposed design show an improvement in latency and hardware complexity compared to the stochastic architectures reported to date.
Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse: A finite element study

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions – compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.
Further Evaluation of the Children's Hope Scale

Two studies addressed the psychometric properties of the Children's Hope Scale (CHS; Snyder et al., 1997). A sample of 460 high school students was administered the CHS along with measures of life satisfaction, extraversion, neuroticism, social support, and externalizing and internalizing behaviors. The results revealed adequate internal consistency for the CHS for research purposes. Furthermore, confirmatory factor analysis procedures supported the correlated, two-factor conceptual model underlying the CHS. Finally, evidence of criterion-related validity was provided. The findings were replicated with a sample of 531 middle school students. Taken together, the studies extend support for the reliability and validity of the CHS with adolescents.
Savoring Beliefs Inventory (SBI): A scale for measuring beliefs about savouring

Background : Research has shown that beliefs about one's capacity to savour positive outcomes, a form of perceived control over positive emotions, are largely independent of beliefs about coping, a form of perceived control over negative emotions. Aim : To describe a new measure of savouring beliefs, the Savoring Beliefs Inventory (SBI). Method : Six studies validating the SBI that is designed to assess individuals' perceptions of their ability to derive pleasure through anticipating upcoming positive events, savouring positive moments, and reminiscing about past positive experiences. Results : SBI scores were found to be: (a) positively correlated with affect intensity, extraversion, optimism, internal locus of control, reported self-control behaviours, life satisfaction, value fulfilment, self-esteem, and intensity and frequency of happiness; (b) negatively correlated with neuroticism, guilt, physical and social anhedonia, hopelessness, depression, and the frequency of unhappy and neutral affect; and (c) uncorrelated with socially desirable responding. SBI was validated prospectively by first measuring college students' savouring beliefs and then later assessing their behaviours and affects in looking forward to, enjoying the actual experience of, and looking back on their Christmas vacation. Within each of the three time frames, the relevant SBI subscale generally predicted behaviours and affects more strongly than did the subscales associated with the other two temporal orientations. Finally, SBI was cross-validated in a sample of older adults. Conclusion : These results provide strong evidence that the SBI is a valid and reliable measure of individuals' beliefs about their capacity to savour positive experiences through anticipation, present enjoyment, and reminiscence.
Role of fungus in eosinophilic sinusitis

Purpose of review Chronic rhinosinusitis is characterized by a broad diagnostic and etiologic spectrum. It has been postulated that fungal organisms might represent the immunologic target initiating and maintaining the disease process in patients with chronic rhinosinusitis as a common denominator. This review analyzes the available data to describe the current understanding of the role of fungus in the pathophysiology of chronic rhinosinusitis. Recent findings Recent findings have demonstrated that using highly sensitive methods, the detection rate of fungi in nasal mucin can be increased to approximately 100% in patients and in healthy controls. If this ubiquitous fungal contamination were to be related to a causative mechanism in chronic rhinosinusitis, there would have to be an immunologic sensitization in patients in contrast with healthy individuals, which is yet not fully understood. However, studies were able to demonstrate cytokine production in blood-derived lymphocytes in the presence of fungi in patients, but not in healthy controls. Several questions arise. If this is a relevant finding, in what percentage of chronic rhinosinusitis patients could it be causative? Is chronic rhinosinusitis, then, a systemic disease? How is the extramucosal target in the mucin presented to the immune system? Is intranasal, topical antifungal treatment a successful option? Summary The role of fungal organisms in the etiology of eosinophilic rhinosinusitis is reviewed with respect to novel findings, and arising questions are discussed in the light of recent investigations.
MF59- and Al(OH)3-Adjuvanted Staphylococcus aureus (4C-Staph) Vaccines Induce Sustained Protective Humoral and Cellular Immune Responses, with a Critical Role for Effector CD4 T Cells at Low Antibody Titers

Staphylococcus aureus (S. aureus) is an important opportunistic pathogen that may cause invasive life-threatening infections, like sepsis and pneumonia. Due to the increasing antibiotic resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T-cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T-cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell-deficient mice, we demonstrated that both T and B-cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low-antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.
Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a phosphatidylinositol 3‐kinase (PI3) kinase‐dependent manner in Neuro2a cells

Insulin signalling is well studied in peripheral tissue, but not in neuronal tissue. To gain more insight into neuronal insulin signalling we examined protein kinase B (PKB) and extracellular regulated kinase 1 and 2 (ERK1/2) regulation in serum‐deprived Neuro2a cells. Insulin phosphorylated PKB in a dose‐dependent manner but reduced phosphorylation of ERK1/2. Both processes were phosphatidylinositol 3‐kinase (PI3K) dependent. Interestingly, blockade of PI3K in combination with insulin induced phosphorylation of ERK1/2. The phosphorylation of ERK1/2 could be blocked with a specific inhibitor of mitogen‐activated protein/ERK kinase (MEK), suggesting that it was mediated through the highly conserved Ras–Raf–MEK–ERK1/2 pathway. Prolonged exposure to high concentrations of insulin resulted in a desensitized PI3K–PKB route. The insulin‐induced inhibition of ERK1/2 phosphorylation was also diminished when the PI3K–PKB route was desensitized. Blockade of PI3K in combination with insulin, however, still resulted in an unaltered MEK‐dependent phosphorylation of ERK1/2. We conclude that PI3K is an important integrator of insulin signalling in Neuro2a cells as it regulates activation of PKB and inhibition of ERK1/2, and is sensitive to the duration of the insulin stimulus.
Temperature, Cultural Masculinity, and Domestic Political Violence

Cross-national data sets were used to examine the association between ambient temperature and internal political violence in 136 countries between 1948 and 1977. Political riots and armed attacks occur more frequently in warm countries than in both cold and hot countries, after controlling for effects of population size and density and levels of socioeconomic development and democracy. National differences on the cultural masculinity dimension, however, do account for this curvilinear temperature-violence association, in a subsample of 53 countries, suggesting that culture mediates the association. An explanation for this mediation in terms of Paternal Investment Theory is proposed.
Genome-wide profiles of H2AX and γ-H2AX differentiate endogenous and exogenous DNA damage hotspots in human cells

Phosphorylation of the histone variant H2AX forms γ-H2AX that marks DNA double-strand break (DSB). Here, we generated the sequencing-based maps of H2AX and γ-H2AX positioning in resting and proliferating cells before and after ionizing irradiation. Genome-wide locations of possible endogenous and exogenous DSBs were identified based on γ-H2AX distribution in dividing cancer cells without irradiation and that in resting cells upon irradiation, respectively. γ-H2AX-enriched regions of endogenous origin in replicating cells included sub-telomeres and active transcription start sites, apparently reflecting replication- and transcription-mediated stress during rapid cell division. Surprisingly, H2AX itself, prior to phosphorylation, was specifically located at these endogenous hotspots. This phenomenon was only observed in dividing cancer cells but not in resting cells. Endogenous H2AX was concentrated on the transcription start site of actively transcribed genes but was irrelevant to pausing of RNA polymerase II (pol II), which precisely coincided with γ-H2AX of endogenous origin. γ-H2AX enrichment upon irradiation also coincided with actively transcribed regions, but unlike endogenous γ-H2AX, it extended into the gene body and was not specifically concentrated on the pausing site of pol II. Sub-telomeres were less responsive to external DNA damage than to endogenous stress. Our findings provide insight into DNA repair programs of cancer and may have implications for cancer therapy.
The relationship between music preferences of different mode and tempo and personality traits – implications for music pedagogy

The aim of this research was to examine the relationship between music preferences of different mode and tempo and personality traits. The survey included 323 students who had to fill out the following tests: questionnaire of music preferences, scale of optimism and pessimism and International Personality Item Pool for measuring Big Five personality traits. Results showed that female in comparison to male students reported a higher degree of music preferences, regardless of tempo and mode, while the male and female showed a higher degree of preference for musical fragments in the fast tempo and major key. Results of hierarchical regression analysis showed that emotional stability and optimism were significant predictors of preferences for music in fast tempo and major key, while openness to experiences, introversion and gender were significant predictors of preferences for the slow tempo and music in minor key. The authors suggest the importance of applying these results in creating the curriculum of music teaching.