Miracle-dz/UniFAR-FTUs huggingface dataset:
The Novel Dominant Mutation Dspd Leads to a Severe Spermiogenesis Defect in Mice1

Abstract Spermiogenesis is a complex process that is regulated by a plethora of genes and interactions between germ and somatic cells. Here we report a novel mutant mouse strain that carries a transgene insertional/translocational mutation and exhibits dominant male sterility. We named the mutation dominant spermiogenesis defect (Dspd). In the testes of Dspd mutant mice, spermatids detached from the seminiferous epithelium at different steps of the differentiation process before the completion of spermiogenesis. Microinsemination using spermatids collected from the mutant testes resulted in the birth of normal offspring. These observations indicate that the major cause of Dspd infertility is (are) a defect(s) in the Sertoli cell-spermatid interaction or communication in the seminiferous tubules. Fluorescent in situ hybridization (FISH) analysis revealed a translocation between chromosomes 7F and 14C at the transgene insertion site. The deletion of a genomic region of chromosome 7F greater than 1 megabase and containing at least six genes (Cttn, Fadd, Fgf3, Fgf4, Fgf15, and Ccnd1) was associated with the translocation. Cttn encodes the actin-binding protein cortactin. Immunohistochemical analysis revealed localization of cortactin beside elongated spermatids in wild-type testes; abnormality of cortactin localization was found in mutant testes. These data suggest an important role of cortactin in Sertoli cell-spermatid interactions and in the Dspd phenotype.
Why Social Relationships Are Important for Physical Health: A Systems Approach to Understanding and Modifying Risk and Protection

&NA; Social relationships are adaptive and crucial for survival. This review presents existing evidence indicating that our social connections to others have powerful influences on health and longevity and that lacking social connection qualifies as a risk factor for premature mortality. A systems perspective is presented as a framework by which to move social connection into the realm of public health. Individuals, and health‐relevant biological processes, exist within larger social contexts including the family, neighborhood and community, and society and culture. Applying the social ecological model, this review highlights the interrelationships of individuals within groups in terms of understanding both the causal mechanisms by which social connection influences physical health and the ways in which this influence can inform potential intervention strategies. A systems approach also helps identify gaps in our current understanding that may guide future research.
Calcium-Induced Virulence Factors Associated with the Extracellular Matrix of Mucoid Pseudomonas aeruginosa Biofilms

ABSTRACT Pseudomonas aeruginosa colonizes the pulmonary tissue of patients with cystic fibrosis (CF), leading to biofilm-associated infections. The pulmonary fluid of CF patients usually contains elevated concentrations of cations and may contain the P. aeruginosa redox-active pigment pyocyanin, which is known to disrupt calcium homeostasis of host cells. Since divalent cations are important bridging ions for bacterial polysaccharides and since they may play regulatory roles in bacterial gene expression, we investigated the effect of calcium ions on the extracellular matrix constituents of P. aeruginosa biofilms. For mucoid strain P. aeruginosa FRD1, calcium addition (1.0 and 10 mM as CaCl2) resulted in biofilms that were at least 10-fold thicker than biofilms without added calcium. Scanning confocal laser microscopy showed increased spacing between cells for the thick biofilms, and Fourier transform infrared spectroscopy revealed that the material between cells is primarily alginate. An algD transcriptional reporter demonstrated that calcium addition caused an eightfold increase in alg gene expression in FRD1 biofilms. Calcium addition also resulted in increased amounts of three extracellular proteases (AprA, LasB, and PrpL). Immunoblots of the biofilm extracellular material established that AprA was harbored within the biofilm extracellular matrix. An aprA deletion mutation and a mutation in gene for a putative P. aeruginosa calmodulin-like protein did not significantly affect calcium-induced biofilm structure. Two-dimensional gel electrophoresis showed increased amounts of phenazine biosynthetic proteins in FRD1 biofilms and in calcium-amended planktonic cultures. Spectrochemical analyses showed that the calcium addition causes a three- to fivefold increase in pyocyanin production. These results demonstrate that calcium addition affects the structure and extracellular matrix composition of mucoid P. aeruginosa biofilms, through increased expression and stability of bacterial extracellular products. The calcium-induced extracellular matrix of mucoid P. aeruginosa consists primarily of the virulence factor alginate and also harbors extracellular proteases and perhaps pyocyanin, a biomolecule that may further disrupt cellular calcium levels.
Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEX™ bDNA, MONITOR AMPLICOR™ and SUPERQUANT™ assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO‐LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0.456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut‐offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.
[Traumatic diaphragmatic rupture: analysis of 48 cases].

BACKGROUND Our aim is to investigate treatment modalities and the results of traumatic diaphragmatic rupture in our trauma patients. METHODS In this retrospective study, 48 patients admitted to our hospital between 1997-2000 with diaphragmatic injury were evaluated according to the type of injury, diagnostic methods, associated organ injury, treatment modality, morbidity and mortality. Injury severity score (ISS) was used in patients with associated organ injury to assess the effect on mortality. RESULTS There was penetrating injury in 69% and blunt injury in 31% of patients. Physical examination and X-ray films were enough in the diagnosis of 66.6% of patients. There was associated organ injury in 83.3% and isolated diaphragm injury in 16.6% of patients. The morbidity and mortality ratio were 8.3% and 10.4% respectively. There was no difference between mortality ratio of penetrating and blunt trauma statistically (p > 0.05). On the other hand, in regard with morbidity and mortality; the injury severity score was higher in patients with associated organ injury (p < 0.0001). CONCLUSION Traumatic diaphragmatic rupture is usually seen with associated organ injury and mortality and morbidity are higher in this case.
Capacitive coupled TLP (CC-TLP) and the correlation with the CDM

Capacitive Coupled Transmission Line Pulsing (CC-TLP) has successfully identified a known CDM weakness at the RF inputs of two different 90 nm CMOS RF products. The presented study compares electrical and physical failure signatures for packaged devices and even for devices stressed at wafer level. The peak stress currents resulting in a failure as well as the failure signatures correlate very well for CDM and CC-TLP. The results also support the application of a single stress per pin with the potential to save many hours of test time without loosing confidence.
Continuous Estimation of Human Multi-Joint Angles From sEMG Using a State-Space Model

Due to the couplings among joint-relative muscles, it is a challenge to accurately estimate continuous multi-joint movements from multi-channel sEMG signals. Traditional approaches always build a nonlinear regression model, such as artificial neural network, to predict the multi-joint movement variables using sEMG as inputs. However, the redundant sEMG-data are always not distinguished; the prediction errors cannot be evaluated and corrected online as well. In this work, a correlation-based redundancy-segmentation method is proposed to segment the sEMG-vector including redundancy into irredundant and redundant subvectors. Then, a general state-space framework is developed to build the motion model by regarding the irredundant subvector as input and the redundant one as measurement output. With the built state-space motion model, a closed-loop prediction-correction algorithm, i.e., the unscented Kalman filter (UKF), can be employed to estimate the multi-joint angles from sEMG, where the redundant sEMG-data are used to reject model uncertainties. After having fully employed the redundancy, the proposed method can provide accurate and smooth estimation results. Comprehensive experiments are conducted on the multi-joint movements of the upper limb. The maximum RMSE of the estimations obtained by the proposed method is 0.16±0.03, which is significantly less than 0.25±0.06 and 0.27±0.07 (p < 0.05) obtained by common neural networks.
Long Polar Fimbriae of Enterohemorrhagic Escherichia coli O157:H7 Bind to Extracellular Matrix Proteins

ABSTRACT Adherence to intestinal cells is a key process in infection caused by enterohemorrhagic Escherichia coli (EHEC). Several adhesion factors that mediate the binding of EHEC to intestinal cells have been described, but the receptors involved in their recognition are not fully characterized. Extracellular matrix (ECM) proteins might act as receptors involved in the recognition of enteric pathogens, including EHEC. In this study, we sought to characterize the binding of EHEC O157:H7 to ECM proteins commonly present in the intestine. We found that EHEC prototype strains as well as other clinical isolates adhered more abundantly to surfaces coated with fibronectin, laminin, and collagen IV. Further characterization of this phenotype, by using antiserum raised against the LpfA1 putative major fimbrial subunit and by addition of mannose, showed that a reduced binding of EHEC to ECM proteins was observed in a long polar fimbria (lpf) mutant. We also found that the two regulators, H-NS and Ler, had an effect in EHEC Lpf-mediated binding to ECM, supporting the roles of these tightly regulated fimbriae as adherence factors. Purified Lpf major subunit bound to all of the ECM proteins tested. Finally, increased bacterial adherence was observed when T84 cells, preincubated with ECM proteins, were infected with EHEC. Taken together, these findings suggest that the interaction of Lpf and ECM proteins contributes to the EHEC colonization of the gastrointestinal tract.
Cell cycle inhibition attenuates microglial proliferation and production of IL‐1β, MIP‐1α, and NO after focal cerebral ischemia in the rat

We recently showed that suppressing cell cycle progression inhibited reactive astrogliosis and promoted neuronal survival in an acute focal cerebral ischemia rat model. However, it remains unclear whether and to what extent the beneficial effects of cell cycle inhibition might also be attributed to the inhibition of microglial proliferation and cytokine/chemokine production. In this study, we showed that application of the cell cycle inhibitor roscovitine before middle carotid artery occlusion (MCAO) in the rat inhibited microglial proliferation and cytokine/chemokine production, and reduced the number of cell‐cycle‐related proteins including cyclin A, cyclin B, and cyclin E. All of these microglia‐related changes may contribute to roscovitine's effect on reducing neuronal apoptosis and infarct volume, thus improving neurological scores. Using the BV‐2 microglia cell line, we showed that roscovitine not only inhibited oxygen‐glucose deprivation (OGD) induced cell cycle activation by arresting the cells at G1/S and G2/M in a dose‐dependent manner, but it also inhibited interleukin‐1 beta (IL‐1β), macrophage inflammatory protein‐1α (MIP‐1α), and nitric oxide (NO) production. These results suggest that cell cycle modulation results in neuroprotection in ischemia, mediated at least in part through inhibition of microglia proliferation and production of inflammatory cytokines such as IL‐1β, MIP‐1α, and NO. © 2008 Wiley‐Liss, Inc.
Time course of cocaine‐induced behavioral and neurochemical plasticity

Factors that result in augmented reinstatement, including increased withdrawal period duration and high levels of cocaine consumption, may provide insight into relapse vulnerability. The neural basis of augmented reinstatement may arise from more pronounced changes in plasticity required for reinstatement and/or the emergence of plasticity expressed only during a specific withdrawal period or under specific intake conditions. In this study, we examined the impact of withdrawal period duration and cocaine intake on the magnitude of cocaine‐primed reinstatement and extracellular glutamate in the nucleus accumbens, which has been shown to be required for cocaine‐primed reinstatement. Rats were assigned to self‐administer under conditions resulting in low (2 hours/day; 0.5 mg/kg/infusion, IV) or high (6 hours/day; 1.0 mg/kg/infusion, IV) levels of cocaine intake. After 1, 21 or 60 days of withdrawal, drug seeking and extracellular glutamate levels in the nucleus accumbens were measured before and after a cocaine injection. Cocaine‐reinstated lever pressing and elevated extracellular glutamate at every withdrawal time point tested, which is consistent with the conclusion that increased glutamatergic signaling in the nucleus accumbens, is required for cocaine‐induced reinstatement. Interestingly, high‐intake rats exhibited augmented reinstatement at every time point tested, yet failed to exhibit higher levels of cocaine‐induced increases in extracellular glutamate relative to low‐intake rats. Our current data indicate that augmented reinstatement in high‐intake rats is not due to relative differences in extracellular levels of glutamate in the nucleus accumbens, but rather may stem from intake‐dependent plasticity.
Mutations in Sialidosis Impair Sialidase Binding to the Lysosomal Multienzyme Complex*

Sialidosis is an autosomal recessive disease caused by the genetic deficiency of lysosomal sialidase, which catalyzes the catabolism of sialoglycoconjugates. The disease is associated with progressive impaired vision, macular cherry-red spots, and myoclonus (sialidosis type I) or with skeletal dysplasia, Hurler-like phenotype, dysostosis multiplex, mental retardation, and hepatosplenomegaly (sialidosis type II). We analyzed the effect of the missense mutations G68V, S182G, G227R, F260Y, L270F, A298V, G328S, and L363P, which are identified in the sialidosis type I and sialidosis type II patients, on the activity, stability, and intracellular distribution of sialidase. We found that three mutations, F260Y, L270F, and A298V, which are clustered in the same region on the surface of the sialidase molecule, dramatically reduced the enzyme activity and caused a rapid intralysosomal degradation of the expressed protein. We suggested that this region might be involved in sialidase binding with lysosomal cathepsin A and/or β-galactosidase in the multienzyme lysosomal complex required for the expression of sialidase activity. Transgenic expression of mutants followed by density gradient centrifugation of cellular extracts confirmed this hypothesis and showed that sialidase deficiency in some sialidosis patients results from disruption of the lysosomal multienzyme complex.
Detection of colorectal liver metastases: comparison of laparotomy, CT, US, and Doppler perfusion index and evaluation of postoperative follow-up results.

PURPOSE To assess the value of the Doppler perfusion index (DPI = the ratio of hepatic arterial to total liver blood flow) as measured with duplex and color Doppler sonography (DCDS) in comparison with computed tomography (CT), conventional ultrasound (US), and laparotomy for the detection of liver metastases in patients with colorectal cancer. MATERIALS AND METHODS DCDS measurement of the DPI and CT, US, and laparotomy were performed in 161 consecutive colorectal cancer patients. Patients who underwent an apparently curative resection were followed up at 3-month intervals with US and at annual CT. RESULTS Fifty-six patients had histologically proved liver metastases at initial examination. Liver metastases were detected with DPI, CT, US, and laparotomy in 56, 45, 27, and 36 patients, respectively. After a 1-year follow-up, 23 patients had developed liver metastases, all of which were predicted on the basis of an abnormal DPI value. CONCLUSION Results suggest that DCDS measurement of the DPI is the most sensitive technique in detection of colorectal liver metastases. All studies should attempt to define normal liver on the basis of follow-up results rather than those of laparotomy.
Does Proximity to Clinic Affect Immunization Rates and Blood Pressure?

Objective: Primary care clinics are frequently placed in neighborhoods to improve access. Little is known whether or not this improves outcomes. We sought to determine if childhood immunization rates and adult blood pressure (BP) levels are related to proximity of home to clinic. Method: We conducted a retrospective chart review in a community family medicine clinic in a neighborhood grocery store (CC) and a hospital-based family medicine residency clinic (HC) in Milwaukee, Wisconsin. Randomly selected subjects included children aged 2–5 years (n = 151 CC; 241 HC) and adult continuity patients (n = 197 CC; 242 HC). ARC-GIS was used to geocode patient home addresses, and distances were analyzed using Kruskal-Wallis, Spearman's rank correlation, or Mann-Whitney test. Proportion of primary immunization by age 2 and age at completion, numerical BP, and proportion abnormal BP were each correlated to distance and driving distance to clinic. Results: Median driving distance of patient to clinic was significantly less for CC than HC (children = 1.47 versus 2.35 miles, p < 0.0001; adults = 1.53 versus 3.12, p < 0.001). For each clinic, and for all subjects combined, and for subsets by gender, ethnicity and insurance status, there was no significant correlation between proportion immunized by age 2 or age at completion and linear or categorical driving distance (or linear distance) to clinic (p = 0.12–0.99), or between BP values or proportion abnormal and distances to clinic (p = 0.44–0.97). Conclusions: In this urban area, proximity of home to clinic did not correlate with primary immunization completion or blood pressure in either a hospital-based or a community clinic.
The Use of Neurodiagnostic Technologies in the 21st Century Neuroscientific Revolution

ABSTRACT Neuroscience is fascinating, mysterious, and truly medicine’s “final frontier,” but deciphering its marvels has historically been inhibited by its sheer complexity. The recent escalation of global neuroscientific endeavors and vast financial backing from governments, foundations, and industries, however, are changing this perspective. The sequencing of the human genome, development of innovative tools for mapping neuronal connectivities, and enhanced resolution capabilities of imaging techniques have made landmark contributions toward advancing neurotechnologies. Nations all around the world have initiated and launched brain mapping projects on such a profound and financially immense scale that research in 2015 and beyond are highly anticipated to revolutionize medicine and our interaction with the technological world. Although neurodiagnostic technology is not the vanguard of research interest in the scientific community, it will certainly ride the coattails of these new neuroscientific endeavors. And, in turn, these advancements will greatly impact how we diagnose, treat, and care for our patients in the future. Therefore, the purpose of this article is not only to introduce current neuroscientific enterprises, but to also explore some of the most interesting and instrumental findings using neurodiagnostic technology over the past year.
Discriminating translation of insulin‐like growth factor‐II (IGF‐II) during mouse embryogenesis

The problem is to discover which of the promoters of the insulin‐like growth factor‐II gene stimulate the transcription of mRNA which is translated into protein. Three alternative leader exons are attached to the coding sequences in RNA transcribed from this gene in other systems, and it is mainly the paternal allele which is expressed in mouse development. Transcripts bearing each of the three leader exons were found in the RNA from the chorio‐allantoic placenta, visceral yolk sac, and embryo, starting at 9.5 days. A varying proportion of one abundant transcript was disengaged from the polysomes at different days of development. This transcript was prefixed by the longest of the three alternative untranslated 5′ leader exons (exon 2), and it was consistently associated with polysomes in the choroid plexus and leptomeninges of the brain. Many exon 2 transcripts were abbreviated by endonucleolytic cleavage and lacked a poly(A) tail. In contrast, the transcripts with the shortest leader (exon 3) were mainly displayed on polysomes at all the stages of development which were examined. During mouse development, the production of IGF‐II protein must be partly controlled by the mechanisms which regulate translation. © 1994 Wiley‐Liss, Inc.
Examining brain structures associated with the motive to achieve success and the motive to avoid failure: A voxel-based morphometry study

The motive to achieve success (MAS) and motive to avoid failure (MAF) are two different but classical kinds of achievement motivation. Though many functional magnetic resonance imaging studies have explored functional activation in motivation-related conditions, research has been silent as to the brain structures associated with individual differences in achievement motivation, especially with respect to MAS and MAF. In this study, the voxel-based morphometry method was used to uncover focal differences in brain structures related to MAS and MAF measured by the Mehrabian Achieving Tendency Scale in 353 healthy young Chinese adults. The results showed that the brain structures associated with individual differences in MAS and MAF were distinct. MAS was negatively correlated with regional gray matter volume (rGMV) in the medial prefrontal cortex (mPFC)/orbitofrontal cortex while MAF was negatively correlated with rGMV in the mPFC/subgenual cingulate gyrus. After controlling for mutual influences of MAS and MAF scores, MAS scores were found to be related to rGMV in the mPFC/orbitofrontal cortex and another cluster containing the parahippocampal gyrus and precuneus. These results may predict that compared with MAF, the generation process of MAS may be more complex and rational, thus in the real world, perhaps MAS is more beneficial to personal growth and guaranteeing the quality of task performance.