Miracle-dz/UniFAR-FTUs huggingface dataset:
Continuous Electroencephalographic Monitoring with Radio-Telemetry in a Rat Model of Perinatal Hypoxia–Ischemia Reveals Progressive Post-Stroke Epilepsy

The development of acquired epilepsy after a perinatal hypoxic–ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in freely behaving HI-treated and sham control rats. The hypotheses were that the acquired epilepsy is directly associated with an ischemic infarct (i.e., no lesion, no epilepsy), and the resultant epilepsy is temporally progressive. Every HI-treated rat with a cerebral infarct developed spontaneous epileptiform discharges and recurrent seizures (100%); in contrast, no spontaneous epileptiform discharges or seizures were detected with continuous monitoring in the HI-treated rats without infarcts. The initial seizures at 2 months generally showed focal onset and were nonconvulsive. Subsequent seizures had focal onsets that propagated to the homotopic contralateral cortex and were nonconvulsive or partial; later seizures often appeared to have bilateral onset and were convulsive. Spontaneous epileptiform discharges were initially lateralized to ipsilateral neocortex but became bilateral over time. The severity and frequency of the spontaneous behavioral and electrographic seizures progressively increased over time. In every epileptic rat, seizures occurred in distinct clusters with seizure-free periods as long as a few weeks. The progressive increase in seizure frequency over time was associated with increases in cluster frequency and seizures within each cluster. Thus, prolonged, continuous seizure monitoring directly demonstrated that the acquired epilepsy after perinatal HI was progressive with seizure clusters and was consistently associated with a cerebral infarct.
Ultrasound Measurement of the Median Nerve for Carpal Tunnel Syndrome of the Non-handicapped and the Handicapped

Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy and is often complicated by overuse the wrist in paraplegic and hemiplegic patients. The aim of this study was to determine the usefulness of ultrasound measurements and their best diagnostic criterion for CTS, and to reveal the feature of CTS among paraplegic and hemiplegic patients. Ninety-four patients with 132 wrists clinically and electrophysiologically diagnosed CTS, and 137 asymptomatic controls matched for age and sex were enrolled. Three ultrasound measurements were assessed: major and minor diameters, cross-sectional areas, and flattening ratios at pisiform bone and hook of hamate bone levels. Values for each of the three variables without flattening ratios of pisiform bone level were significantly different in CTS population compared to control population. Also, a strong relationship was found between the severity and the enlargement of the median nerve. Total cross sectional areas at the pisiform and hook of hamate levels larger than 16 mm2 proved to be highly predictive of CTS. The incidence of CTS among hemiplegic and paraplegic patients fully independent of ADL was 8.5%. These handicapped CTS indicated no significant ultrasound values compared to other non-handicapped CTS.
Violence among high school students in Malatya: a prevalence study

To determine the prevalence of violence-related behaviors on school property and to identify the predictors of youth violence among high school adolescents in Malatya. Materials and methods: Using a cluster sampling method, a cross-sectional descriptive study was carried out involving 1175 students. Backward logistic regression analysis was performed to evaluate the independent association existing between the potential risk factors and violence-related behaviors. Results: Of the students, 24.5% had been in a physical fight, 5.5% were injured and had to be treated by a doctor or nurse, and 4.3% had carried a weapon on school property during the 12 months preceding the survey. Of the students, 4.7% reported that they were a gang member. Conclusion: Male sex, gang membership, exposure to violence, family income, grade, and school type were predictors of violence-related behaviors. Further quantitative studies are recommended to examine the causes of and solutions for violence for students at risk.
Simvastatin Inhibits the Activation of p21ras and Prevents the Loss of Dopaminergic Neurons in a Mouse Model of Parkinson's Disease

Parkinson's disease (PD) is second only to Alzheimer's disease as the most common devastating human neurodegenerative disorder. Despite intense investigation, no interdictive therapy is available for PD. We investigated whether simvastatin, a Food and Drug Administration-approved cholesterol-lowering drug, could protect against nigrostriatal degeneration after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication to model PD in mice. First, MPP+ induced the activation of p21ras and nuclear factor-κB (NF-κB) in mouse microglial cells. Inhibition of MPP+-induced activation of NF-κB by Δp21ras, a dominant-negative mutant of p21ras, supported the involvement of p21ras in MPP+-induced microglial activation of NF-κB. Interestingly, simvastatin attenuated activation of both p21ras and NF-κB in MPP+-stimulated microglial cells. Consistently, we found a very rapid activation of p21ras in vivo in the substantia nigra pars compacta of MPTP-intoxicated mice. However, after oral administration, simvastatin entered into the nigra, reduced nigral activation of p21ras, attenuated nigral activation of NF-κB, inhibited nigral expression of proinflammatory molecules, and suppressed nigral activation of glial cells. These findings paralleled dopaminergic neuronal protection, normalized striatal neurotransmitters, and improved motor functions in MPTP-intoxicated mice. Similarly, pravastatin, another cholesterol-lowering drug, suppressed microglial inflammatory responses and protected dopaminergic neurons in MPTP-intoxicated mice, but at levels less than simvastatin. Furthermore, both the statins administered 2 d after initiation of the disease were still capable of inhibiting the demise of dopaminergic neurons and concomitant loss of neurotransmitters, suggesting that statins are capable of slowing down the progression of neuronal loss in the MPTP mouse model. Therefore, we conclude that statins may be of therapeutic benefit for PD patients.
SdiA sensing of acyl-homoserine lactones by enterohemorrhagic E. coli (EHEC) serotype O157

Chemical communication mediates signaling between cells. Bacteria also engage in chemical signaling, termed quorum sensing (QS), to coordinate population-wide behavior. The bacterial pathogen enterohemorrhagic E. coli (EHEC), responsible for outbreaks of bloody diarrhea worldwide, exploits QS to promote expression of virulence factors in humans. Although EHEC is a human pathogen, it is a member of the gastrointestinal (GI) flora in cattle, the main reservoir for this bacterium. EHEC cattle colonization requires SdiA, a QS transcription factor that uses acyl-homoserine lactones (AHLs), for proper folding and function. EHEC harbors SdiA, but does not produce AHLs, consequently having to sense AHLs produced by other bacterial species. We recently showed that SdiA is necessary for efficient EHEC passage through the bovine GI tract, and show that AHLs are prominent within cattle rumen, but absent from the other sections of the GI tract. EHEC utilizes the locus of enterocyte effacement
REST Regulates Non–Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II

RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non–cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non–cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non–cell-autonomously via SCG2. SIGNIFICANCE STATEMENT Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell-intrinsic and non–cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.
The Relationship Between Microvascular Endothelial Function and Carotid-Radial Pulse Wave Velocity in Patients with Mild Hypertension

Carotid-radial pulse wave velocity (CRPWV) can be measured rapidly using applanation tonometry and significantly higher values have been reported among patients with risk factors for vascular disease. Forearm blood flow responses to intrabrachial infusion of acetylcholine independently predict cardiovascular morbidity among hypertensive patients. We aimed to examine the relationship between CRPWV, a potentially informative, noninvasive measure and this more established parameter of arterial health. One hundred and fifteen mildly hypertensive individuals (67% men, mean (± SD) age 54 ± 8 years, mean (± SD) blood pressure (BP) 143 ± 16/83 ± 12 mmHg) were recruited from a weekly medical outpatient clinic. Each volunteer had CRPWV measured using sequential tonometry before forearm blood flow responses to intra-arterial, endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators were assessed. There was a significant negative correlation between CRPWV and maximum forearm blood flow response to acetylcholine (r = −0.225, p = 0.016). This association remained significant in a multiple regression analysis (β = −0.213, p = 0.034). Mean arterial pressure and weight were additional independent predictors of CRPWV in this model. There was no such relationship between CRPWV and response to sodium nitroprusside (r = 0.088, p = 0.349). In patients with mild hypertension, a poor forearm blood flow response to acetylcholine independently predicted faster CRPWV, thus linking an established measure of microvascular endothelial function with a noninvasive index of conduit vessel stiffness.
Impaired Path Integration and Grid Cell Spatial Periodicity in Mice Lacking GluA1-Containing AMPA Receptors

The hippocampus and the parahippocampal region have been proposed to contribute to path integration. Mice lacking GluA1-containing AMPA receptors (GluA1−/− mice) were previously shown to exhibit impaired hippocampal place cell selectivity. Here we investigated whether path integration performance and the activity of grid cells of the medial entorhinal cortex (MEC) are affected in these mice. We first tested GluA1−/− mice on a standard food-carrying homing task and found that they were impaired in processing idiothetic cues. To corroborate these findings, we developed an L-maze task that is less complex and is performed entirely in darkness, thereby reducing numerous confounding variables when testing path integration. Also in this task, the performance of GluA1−/− mice was impaired. Next, we performed in vivo recordings in the MEC of GluA1−/− mice. MEC neurons exhibited altered grid cell spatial periodicity and reduced spatial selectivity, whereas head direction tuning and speed modulation were not affected. The firing associations between pairs of neurons in GluA1−/− mice were stable, both in time and space, indicating that attractor states were still present despite the lack of grid periodicity. Together, these results support the hypothesis that spatial representations in the hippocampal–entorhinal network contribute to path integration.
Enterohemorrhagic and enteropathogenic Escherichia coli evolved different strategies to resist antimicrobial peptides

Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) are enteric human pathogens that colonize the large and small intestines, respectively. To establish infection EHEC and EPEC must overcome innate host defenses, such as antimicrobial peptides (AMPs) produced by the intestinal epithelium. Gram-negative pathogens have evolved different mechanisms to resist AMPs, including outer-membrane proteases that degrade AMPs. We showed that the protease OmpT degrades the human AMP LL-37 more rapidly in EHEC than in EPEC. Promoter-swap experiments showed that this is due to differences in the promoters of the two genes, leading to greater ompT expression and subsequently greater levels of OmpT in EHEC. Here, we propose that the different ompT expression in EHEC and EPEC reflects the varying levels of LL-37 throughout the human intestinal tract. These data suggest that EHEC and EPEC adapted to their specific niches by developing distinct AMP-specific resistance mechanisms.
Association of the Human CYP 11 B 2 Gene and Essential Hypertension in Southwest Han Chinese Population : A Haplotype-Based Case-Control Study

Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure (BP). The aldosterone-synthase gene (CYP11B2) has been regarded as a candidate gene for essential hypertension. To address this issue, we carried out a haplotype-based, case-control study to explore the association between a human CYP11B2 gene and essential hypertension (EH) in the southwest Han population of China (n = 1020 individuals). Four tag single-nucleotide polymorphisms (SNPs) (rs4536, rs4545, rs3097, and rs3802230) and the C-344T polymorphism, as well as the K173R polymorphism in the CYP11B2 gene, were genotyped using the PCR-RFLP method. Single-locus analysis showed that the C allele of rs3802230 was significantly more prevalent in the EH subjects as compared to control subjects, adjusted for covariates. Haplotype analysis showed that the haplotype AAGC constructed by the tag SNPs (rs4536, rs4545, rs3097, and rs3802230), which carried the susceptible rs3802230 C allele, significantly increased the risk of essential hypertension with an odds ratios equal to 3.56 (P = 0.0001). The present results indicated that the rs3802230 C allele might be a risk marker for essential hypertension and haplotype AAGC might confer high genetic susceptibility to essential hypertension in a southwest Han Chinese population.
Reactivation of Lysosomal Ca2+ Efflux Rescues Abnormal Lysosomal Storage in FIG4-Deficient Cells

Loss of function of FIG4 leads to Charcot-Marie-Tooth disease Type 4J, Yunis-Varon syndrome, or an epilepsy syndrome. FIG4 is a phosphatase with its catalytic specificity toward 5′-phosphate of phosphatidylinositol-3,5-diphosphate (PI3,5P2). However, the loss of FIG4 decreases PI3,5P2 levels likely due to FIG4's dominant effect in scaffolding a PI3,5P2 synthetic protein complex. At the cellular level, all these diseases share similar pathology with abnormal lysosomal storage and neuronal degeneration. Mice with no FIG4 expression (Fig4−/−) recapitulate the pathology in humans with FIG4 deficiency. Using a flow cytometry technique that rapidly quantifies lysosome sizes, we detected an impaired lysosomal fission, but normal fusion, in Fig4−/− cells. The fission defect was associated with a robust increase of intralysosomal Ca2+ in Fig4−/− cells, including FIG4-deficient neurons. This finding was consistent with a suppressed Ca2+ efflux of lysosomes because the endogenous ligand of lysosomal Ca2+ channel TRPML1 is PI3,5P2 that is deficient in Fig4−/− cells. We reactivated the TRPML1 channels by application of TRPML1 synthetic ligand, ML-SA1. This treatment reduced the intralysosomal Ca2+ level and rescued abnormal lysosomal storage in Fig4−/− culture cells and ex vivo DRGs. Furthermore, we found that the suppressed Ca2+ efflux in Fig4−/− culture cells and Fig4−/− mouse brains profoundly downregulated the expression/activity of dynamin-1, a GTPase known to scissor organelle membranes during fission. This downregulation made dynamin-1 unavailable for lysosomal fission. Together, our study revealed a novel mechanism explaining abnormal lysosomal storage in FIG4 deficiency. Synthetic ligands of the TRPML1 may become a potential therapy against diseases with FIG4 deficiency.
Linear Summation of Repulsive and Attractive Serial Dependencies: Orientation and Motion Dependencies Sum in Motion Perception

Recent work from several groups has shown that perception of various visual attributes in human observers at a given moment is biased toward what was recently seen. This positive serial dependency is a kind of temporal averaging that exploits short-term correlations in visual scenes to reduce noise and stabilize perception. To date, this stabilizing “continuity field” has been demonstrated on stable visual attributes such as orientation and face identity, yet it would be counterproductive to apply it to dynamic attributes in which change sensitivity is needed. Here, we tested this using motion direction discrimination and predict a negative perceptual dependency: a contrastive relationship that enhances sensitivity to change. Surprisingly, our data showed a cubic-like pattern of dependencies with positive and negative components. By interleaving various stimulus combinations, we separated the components and isolated a positive perceptual dependency for motion and a negative dependency for orientation. A weighted linear sum of the separate dependencies described the original cubic pattern well. The positive dependency for motion shows an integrative perceptual effect and was unexpected, although it is consistent with work on motion priming. These findings suggest that a perception-stabilizing continuity field occurs pervasively, occurring even when it obscures sensitivity to dynamic stimuli. SIGNIFICANCE STATEMENT Recent studies show that visual perception at a given moment is not entirely veridical, but rather biased toward recently seen stimuli: a positive serial dependency. This temporal smoothing process helps perceptual continuity by preserving stable aspects of the visual scene over time, yet, for dynamic stimuli, temporal smoothing would blur dynamics and reduce sensitivity to change. We tested whether this process is selective for stable attributes by examining dependencies in motion perception. We found a clear positive dependency for motion, suggesting that positive perceptual dependencies are pervasive. We also found a concurrent negative (contrastive) dependency for orientation. Both dependencies combined linearly to determine perception, showing that the brain can calculate contrastive and integrative dependencies simultaneously from recent stimulus history when making perceptual decisions.
Free-Living Pedometer Step Counts of High School Students

The purpose of this study was to examine the pedometer-measured physical activity levels of high school students (Grades 9? 12). Comparisons were made between sexes, among grades, among groups based on level of participation in sport and physical education, and among groups based on levels of self-reported physical activity (based on questions from the National Youth Risk Behavior Surveillance System). Participants wore sealed pedometers for 4 consecutive school days. Results indicated no differences among days of monitoring but did show significant differences in mean steps per day between sexes, among grades, and among activity levels. Males took more steps per day than did females, and 10th graders took more steps than did 12th graders. Teens involved in sport and physical education took more steps than did those not involved. Teens who reported meeting both moderate and vigorous activity recommendations were most active, followed by teens meeting recommendations for moderate activity
Regional Distribution of Cortical Interneurons and Development of Inhibitory Tone Are Regulated by Cxcl12/Cxcr4 Signaling

Interneurons are born in subcortical germinative zones and tangentially migrate in multiple streams above and below the developing cortex, and then, at the appropriate developmental stage, migrate radially into the cortex. The factors that control the formation of and the timing of exit from the streams remain obscure; moreover, the rationale for this complicated developmental plan is unclear. We show that a chemokine, Cxcl12, is an attractant for interneurons during the stage of stream formation and tangential migration. Furthermore, the timing of exit from the migratory streams accompanies loss of responsiveness to Cxcl12 as an attractant. Mice with mutations in Cxcr4 have disorganized migratory streams and deletion of Cxcr4 after the streams have formed precipitates premature entry into the cortical plate. In addition, constitutive deletion of Cxcr4 specifically in interneurons alters the regional distribution of interneurons within the cortex and leads to interneuron laminar positioning defects in the postnatal cortex. To examine the role of interneuron distribution on the development of cortical circuitry, we generated mice with focal defects in interneuron distribution and studied the density of postnatal inhibitory innervation in areas with too many and too few interneurons. Interestingly, alterations in IPSC frequency and amplitude in areas with excess interneurons tend toward normalization of inhibitory tone, but in areas with reduced interneuron density this system fails. Thus, the processes controlling interneuron sorting, migration, regional distribution, and laminar positioning can have significant consequences for the development of cortical circuitry and may have important implications for a range of neurodevelopmental disorders.
Vaccination against Clostridium difficile using toxin fragments

Clostridium difficile is a major cause of antibiotic associated diarrhea. Recently, we have shown that effective protection can be mediated in hamsters through the inclusion of specific recombinant fragments from toxin A and B in a systemically delivered vaccine. Interestingly while neutralizing antibodies to the binding domains of both toxin A and B are moderately protective, enhanced survival is observed when fragments from the glucosyltransferase region of toxin B replace those from the binding domain of this toxin. In this addendum, we discuss additional information that has been derived from such vaccination studies. This includes observations on efficacy and cross-protection against different ribotypes mediated by these vaccines and the challenges that remain for a vaccine which prevents clinical symptoms but not colonization. The use and value of vaccination both in the prevention of infection and for treatment of disease relapse will be discussed.