Miracle-dz/UniFAR-FTUs huggingface dataset:
C-Terminal Alternative Splicing of CaV1.3 Channels Distinctively Modulates Their Dihydropyridine Sensitivity

The transcripts of L-type voltage-gated calcium channels (CaV) 1.3 undergo extensive alternative splicing. Alternative splicing, particularly in the C terminus, drastically modifies gating properties of the channel. However, little is known about whether alternative splicing could modulate the pharmacologic properties of CaV1.3 in a manner similar to the paralogous CaV1.2. Here we undertook the screening of different channel splice isoforms harboring splice variations in either the IS6 segment or the C terminus. Unexpectedly, while inclusion of exon 8a or 8, which code for IS6, did not alter dihydropyridine (DHP) sensitivity, distinct pharmacologic properties were observed for the various C-terminal splice isoforms. In the presence of external Ca2+, fast inactivating splice variants including CaV1.342a and CaV1.343s with intact calmodulin-IQ domain interaction showed consistently low DHP sensitivity. Interestingly, attenuation of calcium-dependent inactivation with overexpression of calmodulin34 did not enhance the sensitivity of CaV1.342a, suggesting that the low DHP sensitivity may not be a result of fast channel inactivation. Alternatively, disruption of calmodulin-IQ domain binding in the CaV1.3Δ41 and full-length CaV1.342 channels was associated with heightened DHP sensitivity. In distinct contrast to the well-known modulation of DHP blockade of CaV1.2 channels, this study has therefore uncovered a novel mechanism for modulation of the pharmacologic properties of CaV1.3 channels through posttranscriptional modification of the C terminus.
Successful Aging in the United States and China

Successful aging is gaining increasing attention given the growth in the older adult population. Criteria and definitions within multiple disciplines vary greatly in Western literature, with no consensus on its meaning. Sociocultural, economic, and political differences between the Western view of successful aging and its view in China add to the confusion. Similarities and differences in the meaning of successful aging in the United States and China are examined, and potential for a common definition useful to nursing in both countries is explored. Using concept analysis, shared criteria for successful aging were the following: decreased incidence of disease and disability, life satisfaction, meaning and purpose in life, and ability to cope effectively to achieve goals based on personal values and priorities. A comprehensive, multidimensional definition of successful aging for nursing and a midrange nursing theory of successful aging were identified that may be useful to guide nursing research, practice, and policy.
International Perspectives on Sexual Harassment of College Students

Abstract: The incidence, psychological dimensions, reporting, and impact of sexual harassment of college students throughout the world are reviewed. Special attention is paid to methodological constraints in conducting cross‐cultural research in sexual harassment, including difficulty in securing research participants, different methodologies to collect incidence data, use of retrospective data, and varying, definitions of sexual harassment. Recommendations for implementing intervention programs are offered. The strategies suggested deal with the social causes that maintain the harassment, including renegotiating the balance of power between men and women.
Automatic discovery of regulatory patterns in promoter regions based on whole cell expression data and functional annotation

MOTIVATION The whole genomes submitted to GenBank contain valuable information about the function of genes as well as the upstream sequences and whole cell expression provides valuable information on gene regulation. To utilize these large amounts of data for a biological understanding of the regulation of gene expression, new automatic methods for pattern finding are needed. RESULTS Two word-analysis algorithms for automatic discovery of regulatory sequence elements have been developed. We show that sequence patterns correlated to whole cell expression data can be found using Kolmogorov-Smirnov tests on the raw data, thereby eliminating the need for clustering co-regulated genes. Regulatory elements have also been identified by systematic calculations of the significance of correlations between words found in the functional annotation of genes and DNA words occurring in their promoter regions. Application of these algorithms to the Saccharomyces cerevisiae genome and publicly available DNA array data sets revealed a highly conserved 9-mer occurring in the upstream regions of genes coding for proteasomal subunits. Several other putative and known regulatory elements were also found. AVAILABILITY Upon request.
An investigation into the existence of fads in the Initial Public Offering market in Kenya

The aim of the study was to test for the existence of fad explanation in the IPO market in Kenya. The study sought to examine the price behaviour of IPOs to test whether or not it was consistent with fad explanation. The research methodology was based on historical research design and relevant data was collected and evaluated of past IPOs. The data used in the study were offer prices, market prices and respective 20NSE indices which were historical and so secondary in nature and available at the NSE. The population included all companies that had been listed at the NSE since its inception in 1954 to ensure the selection of as large a sample. Judgment sampling was used where the sample had to conform to criteria and 25 IPOs were selected as the Sample. The data was analyzed by computing Price and Index Metrics to establish price behavior and determine market adjusted excess returns for both short and long term time. The study established that IPOs provided abnormal returns in the immediate aftermarket to investors who purchased at the initial offering. The mean rate of return earned over 1 day, 2 days, 20 days and 100 days respectively was 42.10 %, 41.71 %, 39.59 % and 23.87%. Under pricing of IPOs was observed with mean gain of 10.23% whereas median loss o f -13.26 was consistent with fad behaviour and alternative explanations. Also there were no excess returns in the long run to investors who purchase the new issue in the aftermarket, supporting presence of fads and inefficient IPO market. Investors who purchased at the first aftermarket price underperformed the market index by mean of 26.43% and median of 27.72%. From the finding it can be concluded that fad explanations or mass psychology affected excess returns and exist in the IPO market. EMH was supported in the early aftermarket where full price adjustment occurred on the first day of trading. Recommendations for further research include the possibility to increase the sample size to cover all IPOs at the NSE since its inception and if possible, to examine cross sectional differences by issue size, offering price and underwriter class.
Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice.

AIM To investigate the effect of T helper (Th) 17/T regulatory (Treg) cells on hepatic fibrosis in mice and its possible mechanism. METHODS Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. Hepatic pathological changes were observed by hematoxylin and eosin staining; the protein levels of interleukin (IL)-6, transforming growth factor (TGF)-β and α-smooth muscle actin (SMA) in liver tissue were determined by Western blotting; and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry. In addition, hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells. Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation. RESULTS In the model group, there were different degrees of fibroplasia, degeneration and necrosis. The protein levels of IL-6, TGF-β and α-SMA in liver tissue were significantly higher than those in the control group at 12 wk (P < 0.05). Compared with the control group, the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually. Furthermore, at 4, 8 and 12 wk, there were significant differences in the number of Th17 cells (0.52% ± 0.16%, 1.46% ± 0.24%, and 2.60% ± 0.41%, respectively, P < 0.05) and Treg cells (2.99% ± 0.40%, 2.16% ± 0.50%, and 1.49% ± 0.34%, respectively, P < 0.05). In vitro, Th17 cells promoted, whereas Treg cells inhibited the expression of α-SMA, both in a dose-dependent manner, compared with the control group. CONCLUSION Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.
An Overview of Chilli Thrips, Scirtothrips dorsalis (Thysanoptera: Thripidae) Biology, Distribution and Management

The industrial revolution, globalization and international trade liberalization are some of the important events that have afforded vast opportunities for invasive insect species to establish in new territories [1]. These invasive species, facing no challenge by their natural enemies, thrive well in the new environment [2]. In addition to the disturbance they cause to the biodiversity, pest invasion in any country results in increased pressure on biosecurity, national economy, and human health management systems [1, 3, 4]. Apart from economic loss in managing them, these pests pose a significant detrimental impact on tourism and recreational value of the region, which further adds in indirect economic damage to the nation [5]. Of this large group of invasive pests, thrips are one of the most important members. The invasive status gained by thrips across the globe is due to their high degree of polyphagy, wide host range and easy dispersal that can be anthropogenic or natural (wind-mediated).
Populations of the south-west Pacific malaria vector Anopheles farauti s.s. revealed by ribosomal DNA transcribed spacer polymorphisms

Malaria in the south-west Pacific is transmitted by members of the Anopheles punctulatus group which comprises 12 cryptic species with overlapping morphology. The most widely distributed species of the group is Anopheles farauti s.s. (An. farauti 1) found throughout northern Australia, Papua New Guinea, eastern Indonesia, the Solomon Islands and Vanuatu. A study of the population structure of this species using PCR-RFLP analysis on the ribosomal DNA internal transcribed spacer 1 reveals five genotypes which had distinct geographical distributions. Where these distributions overlap, genotype hybrids can be identified. Heteroduplex analysis of the ITS2 region reveals combinations of nonhomogenized ITS2 sequences and subsequently seven identifiable genotypes, reflecting the ITS1 distribution. Sequence analysis of these ITS2 polymorphisms reveals a minimum of 13 ITS2 sequence types present in heterogeneous combinations in individual mosquitoes. It appears that there are different levels of evolution occurring within the ITS1 and ITS2 regions. These data suggest that An. farauti s.s. may contain multiple loci for the rDNA gene family or that the homogenization of these regions is relatively slow and can be used in genetic studies of population distribution and structure.
Adapted bikes – what children and young people with cerebral palsy told us about their participation in adapted dynamic cycling

Purpose: Children and young people with Cerebral Palsy have limited opportunities for participation and there has been limited research to explore this concept. Adapted dynamic cycling (ADC) is one activity that can enable them to participate in the community. The aim of this paper is to report the views and experiences of children and young people with CP and their families regarding their participation in ADC. Methods: This was part of a mixed methods study of which the qualitative findings are reported here. Iterative creative methods were developed which involved semi-structured interviews and diaries about the ADC experience. Results: The themes that emerged were the staff and the environment at the cycling hire project, the facilitators and barriers to ADC, the technical set up of the bike and the impact on the child and family in terms of developments over time, future aspirations, learning cycling skills, social participation and health benefits. Conclusions: The data showed that children’s experiences of ADC were fun and enjoyable. This fun exercise should be incorporated into a physiotherapy programme as part of the child or young person with CP’s rehabilitation. Policy makers and parents may find the information useful to increase the child’s participation. Implications for Rehabilitation Children and young people with Cerebral Palsy (CP) may have difficulty participating in physical leisure activities. Dynamic cycling on specially adapted trikes (ADC) can give then this exciting opportunity, which has many psychological and physical health benefits. This paper describes a pilot study of 17 children and young people with CP who took part in six sessions of ADC. Therapists, educators and policy makers may consider providing this opportunity to children and young people with disabilities.
Netrin‐1‐independent adenosine A2b receptor activation regulates the response of axons to netrin‐1 by controlling cell surface levels of UNC5A receptors

Growth cone response to the bifunctional guidance cue netrin‐1 is regulated by the activity of intracellular signaling intermediates such as protein kinase C‐alpha (PKCα) and adenylyl cyclase. Among the diverse cellular events these enzymes regulate is receptor trafficking. Netrin‐1, itself, may govern the activity of these signaling intermediates, thereby regulating axonal responses to itself. Alternatively, other ligands, such as activators of G protein‐coupled receptors, may regulate responses to netrin‐1 by governing these signaling intermediates. Here, we investigate the mechanisms controlling activation of PKCα and the subsequent downstream regulation of cell surface UNC5A receptors. We report that activation of adenosine receptors by adenosine analogs, or activation of the putative netrin‐1 receptor, the G protein‐coupled receptor adenosine A2b receptor (A2bR) results in PKCα‐dependent removal of UNC5A from the cell surface. This decrease in cell surface UNC5A reduces the number of growth cones that collapse in response to netrin‐1 and converts repulsion to attraction. We show these A2bR‐mediated alterations in axonal response are not because of netrin‐1 because netrin‐1 neither binds A2bR, as assayed by protein overlay, nor stimulates PKCα‐dependent UNC5A surface loss. Our results demonstrate that netrin‐1‐independent A2bR signaling governs the responsiveness of a neuron to netrin‐1 by regulating the levels of cell surface UNC5A receptor.
Anterior Cruciate Ligament Injuries in Children with Open Physes

Injury to the anterior cruciate ligament is one of the most common sports-related injuries of the knee. Before the 1980s, the incidence of this injury in skeletally immature patients was thought to be rare. However, with the increasing participation of children in sports-related activities and an increased awareness and diagnostic capability of the medical community, midsubstance tears of the anterior cruciate ligament have become more common in patients with open physes. Significant controversy exists regarding management of anterior cruciate ligament injuries in children with open physes. Traditional management has been nonoperative, consisting of physical therapy, bracing, and activity modification. Surgical reconstruction has generally been postponed until the patient is nearing, or has reached, skeletal maturity. In contrast to this traditional treatment algorithm, the recent literature uniformly indicates that nonoperative management of anterior cruciate ligament tears in children results in less than optimal results. Compliance is certainly an issue, and even though patients may refrain from organized sports activities, they are still going to be “kids. ” Recurrent instability, pain, and an inability to return to the preinjury level of athletics often result. Even more worrisome are the risks of secondary meniscal tears and the possibility of early degenerative joint disease. Recently, there has been an increased interest in early, aggressive operative management to restore stability to the immature knee. Proponents of nonoperative treatment point to the risk of growth arrest associated with violation of the physis. Proponents of early operative stabilization advocate that restoration of stability provides for opportunity to return to full activity and provides good long-term outcomes, all with minimal risk to the physis. This article reviews both the basic science and clinical research on this controversial topic.
Psychological well-being after spinal cord injury: perception of loss and meaning making.

OBJECTIVE This study examined the influence of medical injury severity, perceived loss of physical functioning (conceptualized as physical resource loss), and global meaning making on psychological well-being among 79 veterans living with a spinal cord injury. MEASURES Structured interviews were completed to assess perceived loss of physical abilities using the Conservation of Resources-Evaluation and SF-36 Health Survey, global meaning making (Purpose in Life scale), and psychological well-being (Sense of Well-Being Inventory). Medical injury severity was calculated from medical records. RESULTS Medical injury severity was not related to psychological well-being, whereas perceived loss of physical functioning was inversely associated. Global meaning making was significantly related to and accounted for a large portion of the variance in psychological well-being. Results suggest that global meaning making partially mediates perceived loss of physical resources and psychological well-being. CONCLUSION The perceived loss of physical abilities and the generation of meaning and purpose in life are important variables that relate to positive adaptation following spinal cord injury. Treatment implications related to factors that increase quality of life following spinal cord injury are discussed.
Free Omental Flap for Partial Breast Reconstruction after Breast-Conserving Surgery

Summary: Recent advances in endoscopic surgery have allowed laparoscopic harvesting of the omental flap with reduced donor-site morbidity and deformity. Between August of 2004 and May of 2010, the authors performed immediate breast reconstruction with the free omental flap in 10 breast cancer patients, employing it either as a pedicle flap or as a free flap for volume replacement. Only one complication occurred during the follow-up. Cosmetic results were mostly satisfactory. The free omental flap is a safe procedure with minimal donor-site morbidity and deformity and can be an additional option for immediate partial breast reconstruction after breast-conserving surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
[Prevalence of nocturnal enuresis in the Valencian Community. Pediatric section of the National Incontinence Survey. The EPICC Study].

OBJECTIVE To ascertain the prevalence of enuresis among primary school children in Spain. MATERIALS AND METHODS A multicenter, observational, cross-sectional, epidemiologic, regional study. After sample size calculation, a total of 1687 questionnaires were sent to schools. Nocturnal enuresis was defined as <<loss of urine occurring during sleep, at least once a month>>. RESULTS The prevalence of enuresis found in primary school children aged 6-11 years was 7.8%, decrease with age, and was significantly greater in boys (70%). Children without enuresis were taller and had a greater weight than those with enuresis, but the differences were not statistically significant. No differences were found in the family or educational setting between children with and without enuresis. Seventy-three percent of children with enuresis had a family history of the condition. The disorder also occurred in some sibling of 21% of children with enuresis who had siblings. Fifty-five percent of the bedwetting population had primary enuresis. Thirty-one percent of children with enuresis reported losses every night, 38% at least once a week, and 31% at least once a month. Eighty-seven percent of this population was under treatment for this condition. As regards subjective symptoms, 96.9% said they felt fine, but there were more bedwetting children who reported feeling a little bit uncomfortable (76.7% vs 23.1%; P=.004). CONCLUSIONS Enuresis is a common disorder which is significantly more frequent in boys as compared to girls and whose prevalence decreases with age. It has a significant hereditary component. Most enuresis sufferers take measures against urine losses.
Simplified computer-aided detection scheme of microcalcification clusters in digital breast tomosynthesis images

A computer-aided detection (CADe) algorithm for clustered microcalcifications (MCs) in reconstructed digital breast tomosynthesis (DBT) images is suggested. The MC-like objects were enhanced by a Hessian-based 3D calcification response function, and a signal-to-noise ratio (SNR) enhanced image was also generated to screen the MC clustering seed objects. A connected component segmentation method was used to detect the cluster seed objects, which were considered as potential clustering centers of MCs. Bounding cubes for the accepted clustering seed candidate were generated and the overlapping cubes were combined and examined. After the MC clustering and false-positive (FP) reduction step, the average number of FPs was estimated to be 0.87 per DBT volume with a sensitivity of 90.5%.
Asymptomatic Atherosclerosis in Primary Sjögren Syndrome: Correlation Between Low Ankle Brachial Index and Autoantibodies Positivity

BackgroundPrimary Sjögren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjögren syndrome an interesting model for the study of atherosclerosis. ObjectivesThe aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjögren syndrome using noninvasive methods. MethodsWe assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjögren’s Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI). ResultsFifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjögren’s Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor). ConclusionsThe subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group.