Miracle-dz/UniFAR-FTUs huggingface dataset:
The removal of myoplasmic free calcium following calcium release in frog skeletal muscle.

Transient changes in intracellular free calcium concentration (delta [Ca2+]) in response to pulse depolarizations were monitored in isolated segments of single frog skeletal muscle fibres cut at both ends and voltage clamped at a holding potential of ‐90 mV in a double‐Vaseline‐gap chamber. Calcium transients were monitored optically using the metallochromic indicator dye Antipyrylazo III (APIII), which entered the fibre by diffusion from the solution applied to the cut ends. Optical artifacts due to fibre movement were minimized or eliminated by stretching the fibres to sarcomere lengths at which there was little or no overlap of thick and thin contractile filaments. Remaining movement‐independent optical changes intrinsic to the fibre and unrelated to the dye were monitored at 850 nm, where free and dye‐bound APIII have no absorbance. These 850 nm signals scaled by lambda ‐1.2 were used to remove intrinsic components from the signals at 700 or 720 nm, wave‐lengths at which the APIII absorbance increases when calcium is bound. The corrected 700 or 720 nm signals were used to calculate delta [Ca2+]. The decay of delta [Ca2+] following fibre repolarization at the termination of a depolarizing pulse was well described by a single exponential plus a constant. The exponential rate constant for the decay of delta [Ca2+] decreased and the final 'steady' level that delta [Ca2+] appeared to be approaching increased with increasing amplitude and/or duration of the depolarizing pulse. Both the decreasing decay rate and the build up of the 'steady' level can be accounted for using a two‐component model for the removal of free calcium from the myoplasm. One component consists of a set number of a single type of saturable calcium binding site in the myoplasm. The second component is a non‐saturable, first‐order uptake mechanism operating in parallel with the saturable binding sites. The removal model parameter values were adjusted to fit simultaneously the decay of delta [Ca2+] after pulses of various amplitudes and durations in a given fibre. The basic procedure was to track delta [Ca2+] during each pulse when an undetermined calcium release was occurring, but to calculate the decay of delta [Ca2+] starting 14 ms after repolarization when release was assumed to be negligible. After appropriate selection of parameter values, the model reproduced most aspects of the decay of delta [Ca2+]. (ABSTRACT TRUNCATED AT 400 WORDS)
Long non-coding RNA HULC promotes tumor angiogenesis in liver cancer by up-regulating sphingosine kinase 1 (SPHK1)

Highly up-regulated in liver cancer (HULC) is a long non-coding RNA (lncRNA). We found that HULC up-regulated sphingosine kinase 1 (SPHK1), which is involved in tumor angiogenesis. Levels of HULC were positively correlated with levels of SPHK1 and its product, sphingosine-1-phosphate (S1P), in patients HCC samples. HULC increased SPHK1 in hepatoma cells. Chicken chorioallantoic membrane (CAM) assays revealed that si-SPHK1 remarkably blocked the HULC-enhanced angiogenesis. Mechanistically, HULC activated the promoter of SPHK1 in hepatoma cells through the transcription factor E2F1. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) further showed that E2F1 was capable of binding to the E2F1 element in the SPHK1 promoter. HULC increased the expression of E2F1 in hepatoma cells and levels of HULC were positively correlated with those of E2F1 in HCC tissues. Intriguingly, HULC sequestered miR-107, which targeted E2F1 mRNA 3′UTR, by complementary base pairing. Functionally, si-SPHK1 remarkably abolished the HULC-enhanced tumor angiogenesis in vitro and in vivo. Taken together, we conclude that HULC promotes tumor angiogenesis in liver cancer through miR-107/E2F1/SPHK1 signaling. Our finding provides new insights into the mechanism of tumor angiogenesis.
Downstream structure and evolution of a simulated CME-driven sheath in the solar corona

Context. The transition of the magnetic field from the ambient magnetic field to the ejecta in the sheath downstream of a coronal mass ejection (CME) driven shock is analyzed in detail. The field rotation in the sheath occurs in a two-layer structure. In the first layer, layer 1, the magnetic field rotates in the coplanarity plane (plane of shock normal and the upstream magnetic field), and in layer 2 rotates off this plane. We investigate the evolution of the two layers as the sheath evolves away from the Sun. Aims. In situ observations have shown that the magnetic field in the sheath region in front of an interplanetary coronal mass ejection (ICME) form a planar magnetic structure, and the magnetic field lines drape around the flux tube. Our objective is to investigate the magnetic configuration of the CME near the sun. Methods. We used the space weather modeling framework (SWMF), a 3D magnetohydrodynamics (MHD) simulation code, to simulate the propagation of CMEs and the shock driven by it. Results. We find that close to the Sun, layer 2 dominates the width of the sheath, diminishing its importance as the sheath evolves away from the Sun, in agreement with observations at 1 AU.
Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter

Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors’ knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.
Identification of nitrated proteins in the normal rat brain using a proteomics approach

Abstract Background: The nitration of tyrosine has been suggested to play a role in the pathogenesis of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD). Methods: In the present study, we identified four targets of protein nitration, T-complex polypeptide 1α subunit (TCP-1), neurofilament L (NFL), glial fibrillary acidic protein (GFAP) and clathrin heavy chain (CHC), in the normal rat cortex using a proteomics approach. Conclusions: There have been no reports on these proteins being identified by proteomics as nitrated forms in the brain. For further study, we have to investigate alterations in these nitrated proteins during aging and in neurodegenerative disorders.
High prevalence of Neisseria gonorrhoeae in a remote, undertreated population of Namibian pastoralists

SUMMARY The highly remote pastoralist communities in Kaokoland, Namibia, have long been presumed to have high gonorrhoea prevalence. To estimate gonorrhoea prevalence and correlates of infection, we conducted a cross-sectional study of 446 adults across 28 rural villages. Gonorrhoea status was determined from urethral and vaginal swabs via qPCR assay. All participants answered a closed-ended interview about demographics, sexual behaviour and symptom history. Sixteen per cent of participants had high-level infections (⩾ID50 dose) and 48% had low-level infections (<ID50 dose). Women had higher prevalence than men of both high- and low-level infections. High-level infections were regionally and seasonally clustered, occurring in young adults in the Ehama region during the winter. Low-level infections were distributed homogenously across demographic characteristics, season, and region. All low-level infections and most high-level infections (men 78%, women 95%) were asymptomatic and left untreated. The epidemic-like nature of high-level gonorrhoea cases suggests that intervention efforts can be focused on seasons of high social activity.
Oxytocin in animal models of autism spectrum disorder

Autism spectrum disorder is a behavioral disorder characterized by impairments in social interaction and communication together with the presence of stereotyped behaviors and restricted interests. Although highly genetic, its etiology is complex which correlates with the extensive heterogeneity found in its clinical manifestation, adding to the challenge of understanding its pathophysiology and develop targeted pharmacotherapies. The neuropeptide oxytocin is part of a highly conserved system involved in the regulation of social behavior, and both animal and human research have shown that variation in the oxytocin system accounts for interindividual differences in the expression of social behaviors in mammals. In autism, recent studies in human patients and animal models are starting to reveal that alterations in the oxytocin system are more common than previously anticipated. Genetic variation in the key players involved in the system (i.e., oxytocin receptor, oxytocin, and CD38) has been found associated with autism in humans, and animal models of the disorder converge in an altered oxytocin system and/or dysfunction in oxytocin related biological processes. Furthermore, oxytocin administration exerts a behavioral and neurobiological response, and thus, the oxytocin system has become a promising potential therapeutical target for autism. Animal models represent a valuable tool to aid in the research into the potential therapeutic use of oxytocin. In this review, I aim to discuss the main findings related to oxytocin research in autism with a focus on findings in animal models. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 202–213, 2017
The immune system and aging: a review

Abstract The concept of immunosenescence reflects age-related changes in immune responses, both cellular and serological, affecting the process of generating specific responses to foreign and self-antigens. The decline of the immune system with age is reflected in the increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, autoimmune and other chronic diseases. Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be more affected by the age-related changes in the immune system. Additionally, aged individuals tend to present a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis and diabetes). However, some individuals arrive to advanced ages without any major health problems, referred to as healthy aging. The immune system dysfunction seems to be somehow mitigated in this population, probably due to genetic and environmental factors yet to be described. In this review, an attempt is made to summarize the current knowledge on how the immune system is affected by the aging process.
Accuracy of adult recall of childhood attention deficit hyperactivity disorder.

OBJECTIVE Although reports of childhood status are necessary for making a diagnosis of adult attention deficit hyperactivity disorder (ADHD), systematic investigation of the accuracy of retrospective self-reports has been limited. This study examined accuracy of adult recall of childhood ADHD. METHOD Participants were from a controlled, prospective 16-year follow-up of children with ADHD. At a mean age of 25 years, 176 probands (85% of the 207 subjects in the initial cohort) and 168 non-ADHD comparison subjects were interviewed by clinicians who were unaware of the subjects' childhood status. Subjects were asked about specific childhood ADHD behaviors, and the diagnosis of childhood ADHD was retrospectively established. RESULTS Seventy-eight percent of the probands and 11% of the comparison subjects were identified as having childhood ADHD. Six symptoms demonstrated high discriminating power in differentiating the subject groups: distractibility, concentration difficulties, complaints of inattention, acting before thinking, being on the go, and fidgeting/squirming. When findings were adjusted for the prevalence of ADHD in the general population, the power of prediction was low. Positive predictive value was 0.27, i.e., of all adults retrospectively given a diagnosis of childhood ADHD, only 27% would be correctly identified. As expected, positive predictive value increased with increases in the estimated prevalence of ADHD. CONCLUSIONS Retrospective diagnoses of childhood ADHD made on the basis of self-reports will in most cases be invalid in settings such as epidemiological surveys and primary care facilities. Greater accuracy can be expected in settings in which childhood ADHD is frequent. The results stress the importance of obtaining contemporaneous information on childhood symptoms in establishing a childhood history of ADHD. Future directions and implications for DSM-V are discussed.
Prognostic and clinicopathological significance of glypican-3 overexpression in hepatocellular carcinoma: a meta-analysis.

AIM To investigate the prognostic and clinicopathological significance of glypican-3 (GPC3) overexpression in hepatocellular carcinoma (HCC). METHODS Publications were searched using PubMed, EMBASE, the Cochrane Library and the Chinese Biomedical Literature Database up to March 2013. Inclusion and exclusion criteria were established to screen eligible studies for meta-analysis. The hazard ratios (HRs) of the eligible studies were pooled using RevMan 5.2 software to evaluate the impact of GPC3 overexpression on overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between GPC3 expression and clinicopathological parameters of HCC was also analyzed. RESULTS A total of five studies with 493 patients were included in the meta-analysis. The combined HRs indicated that GPC3 overexpression can predict poor OS (n = 362 in 3 studies, HR = 2.18, 95%CI: 1.47-3.24, Z = 3.86, P = 0.0001) and DFS (n = 325 in 3 studies, HR = 2.05, 95%CI: 1.43-2.93, Z = 3.94, P < 0.0001) in HCC patients without heterogeneity. Egger's and Begg's tests were applied to detect publication bias, and the results showed that there was no evidence of publication bias detected in the OS studies (the P value for Egger's test was 0.216) or DFS studies (the P value for Egger's test was 0.488). The combined odds ratios (ORs) suggested that GPC3 expression tends to be associated with tumor vascular invasion (OR = 2.74, 95%CI: 1.15-6.52, P = 0.02), hepatic cirrhosis (OR = 2.10, 95%CI: 1.31-3.36, P = 0.002), poor tumor differentiation (OR = 0.22, 95%CI: 0.13-0.40, P < 0.00001) and advanced TNM stage (OR = 0.31, 95%CI: 0.18-0.51, P < 0.00001). CONCLUSION From this study, we conclude that GPC3 overexpression tends to be associated with a poor prognosis (poor OS or DFS) in HCC.
A Natural History of Negation (review)

Vancouver Island” (p. 422). Despite the existence of national and regional dictionaries and style guides, CE remains largely understudied (p. 424), which unfortunately renders some of their generalizations questionable. A number of phonological and grammatical features characteristic of CE are discussed, including Canadian raising, the [ V ]/[ W ] merger and discourse eh. As a result of increasing influence from French, the English spoken in Quebec is said to be somewhat distinct from standard CE (pp. 425, 439), though more recent empirical studies of this variety (e.g., Boberg 2002; Poplack and Walker 2002) suggest that this claim is exaggerated. Similarly, the view that increasing multilingualism in the major urban centres (Toronto, Montreal, Vancouver) is likely to promote the maintenance of “ESL varieties” which will change standard CE in the future (p. 426) remains empirically untested. Although containing a number of assertions which specialists in the field may find misleading or controversial (e.g., the discussion of Labov’s study of New York City [p. 76]), the volume is relatively comprehensive and should be accessible to the general educated public. The inclusion of a list of phonetic symbols (pp. xxx–xxxii) and a glossary of linguistic terms (pp. 497–515) will be particularly helpful to those without a training in linguistics. Despite the abovementioned focus on American English, this volume serves as a good introduction to the various diachronic and synchronic issues in the origins, development and status of varieties of English spoken in North America.
Corticosterone analgesia is mediated by the spinal production of neuroactive metabolites that enhance GABAergic inhibitory transmission on dorsal horn rat neurons

Corticosterone (CORT) is a glucocorticoid produced by adrenal glands under the control of the hypothalamic–pituitary–adrenal axis. Circulating CORT can enter the central nervous system and be reduced to neuroactive 3α5α‐reduced steroids, which modulate GABAA receptors. In the dorsal spinal cord, GABAergic transmission modulates integration of nociceptive information. It has been shown that enhancing spinal inhibitory transmission alleviates hyperalgesia and allodynia. Therefore, the spinal neuronal network is a pivotal target to counteract pain symptoms. Thus, any increase in spinal 3α5α‐reduced steroid production enhancing GABAergic inhibition should reduce nociceptive message integration and the pain response. Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However, to our knowledge, nothing has been reported regarding direct non‐genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with measurement of nociceptive mechanical sensitivity and plasma CORT level measurement, to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via a reduction in C‐fiber‐mediated spinal responses. In the spine, CORT is reduced to the neuroactive metabolite allotetrahydrodeoxycorticosterone, which specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction in lamina II network excitability, reflecting a selective decrease in the processing of nociceptive inputs. The depressed neuronal activity at the spinal level then, in turn, leads to weaker nociceptive message transmission to supraspinal structures and hence to alleviation of pain.
Electrophysiological study of the dominant motor innervation to the extensor digitorum communis muscle and long head of triceps brachii at posterior divisions of brachial plexus

Background: Restoration of elbow and finger extension function is still challenging in management of complete brachial plexus avulsion injury, mainly because of fewer available donor nerves for transfer to the radial nerve. Selective neurotization could be a potentially alternative for overcoming this dilemma. This study was designed to identify the innervation dominance of the extensor digitorum communis muscle (EDCM) and long head of the triceps brachii (LTB) at the level of division of brachial plexus. Methods: From February 2008 to October 2009, 17 patients with complete brachial plexus avulsion injury underwent the procedure of contralateral C7 nerve root transfer. The posterior divisions of brachial plexus on the healthy donor side were intraoperatively stimulated and the compound muscle action potentials (CMAPs) from the extensor digitorum communis muscle and long head of triceps brachii were recorded by an electrophysiological device. Results: In 13 out of 17 patients (76.5%), the maximal amplitude of CMAP from EDCM was induced by stimulation of the posterior division of lower trunk (PDLT). The mean amplitudes of CMAP from EDCM with stimulation of the posterior division of upper trunk (PDUT), middle trunk (PDMT), and PDLT were 0.64 ± 0.95, 1.64 ± 1.56, and 5.32 ± 4.67 mV (P < 0.05), respectively. The maximal amplitude of CMAP from LTB was induced mainly by stimulation of the PDMT) and PDLT (6 out of 11 and 5 out of 11 patients). The mean amplitudes of CMAP from LTB with stimulation of the PDUT, PDMT, and PDLT were 0.15 ± 0.24, 5.20 ± 4.27, and 7.48 ± 9.90 mV, respectively. The differences of CMAPs between stimulation of PDUT and other two divisions were significant (P < 0.05). Conclusions: From the electrophysiological point of view, this study showed that the PDLT was the major motor division innervating EDCM, and the PDMT and PDLT shared the similar proportion of LTB innervation. © 2011 Wiley‐Liss, Inc. Microsurgery, 2011.
Evaluating the Prevention through Alternative Learning Styles Program

This article reports on the evaluation of a two-year alcohol, tobacco and other drug (ATOD) intervention, the Prevention through Alternative Learning Styles (PALS) program, targeting both teachers and middle-school students. Teachers are taught to recognize students' unique learning styles in the context of the ATOD curriculum and adapt the ATOD messages to these learning styles. The student curriculum consists of 5 topic areas with two lessons per topic area. Student goals include enhancing students' knowledge of the effects of ATOD, promoting students' use of refusal skills and decreasing students' intentions to use ATOD. The program was implemented in school districts in the greater Dayton Ohio area. Support was found for the intervention's overall effectiveness in both years, with statistically significant improvements demonstrated by the students who participated in the PALS program. Students had an increase in their knowledge of ATOD topic areas and a decrease in their intentions to use ATOD.
De-novo ‘pure’ partial trisomy (6)(p22.3→pter): a case report and review of the literature

Partial trisomy of the short arm of chromosome 6 is a rare and clinically distinct syndrome. The breakpoints have been found to be variable ranging from bands 6p11 to 6p25. This study reports partial trisomy for 6p22.3→pter in a 2-year-old boy referred with a complaint of developmental delay and facial dysmorphism. Conventional cytogenetic analysis showed the presence of an abnormal chromosome 5 resulting from an unbalanced translocation in the proband. Array comparative genomic hybridization revealed trisomy of distal 6p which was confirmed by fluorescence in situ hybridization using subtelomeric probes for chromosomes 5 and 6. A comparison of the phenotypic features in similar cases of trisomy for different segments of 6p will facilitate an accurate karyotype–phenotype correlation and, subsequently, in the identification of the candidate genes through molecular characterization of the potential genes mapped to these loci.
Random Work-Function-Induced Threshold Voltage Fluctuation in Metal-Gate MOS Devices by Monte Carlo Simulation

In this paper, we estimate the effect of random work function (WK) on the threshold voltage fluctuation (σVth) of 16-nm-gate metal-oxide-semiconductor field-effect transistors (MOSFETs) with metal-gate materials. To examine the random WK induced σVth, nanosized metal grains with different gate materials are considered in a large-scale statistical simulation. An analytical expression of the WK induced σVth is proposed based on the Monte Carlo simulation results which can outlook different extents of fluctuation resulting from various metal gates and benefit the device fabrication. Devices with a two-layer metal-gate are further studied for fluctuation suppression; the finding of this paper indicates the first layer of the gate structure plays the most significant role in the suppression of the WK induced σVth, compared with the second layer. This paper provides an insight into random work-function-induced threshold voltage fluctuation, which can, in turn, be used to assess metal gate characteristics of MOSFETs.