Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and function of muscarinic receptor subtypes on human cornea and conjunctiva.

PURPOSE To investigate the cellular distribution of the muscarinic receptor (MR) subtypes m1-m5 on the ocular surface and to determine their function in cell growth. METHODS Human limbal and conjunctival epithelial cells and conjunctival fibroblasts were isolated and cultured. RT-PCR, real-time PCR, immunostaining and Western blot analyses for m1-m5 were performed on cultured cells and tissues and a human conjunctival epithelial cell line (IOBA-NHC). Cell proliferation and p42/44 mitogen-activated protein (MAP) kinase (MAPK) activation in response to MR agonists and antagonists were analyzed by bromodeoxyuridine [BrdU] incorporation and Western blot analysis, respectively. RESULTS RT-PCR revealed the presence of m1-m5 transcripts in cultured limbal and conjunctival epithelial cells and conjunctival fibroblasts. Relative quantitative real-time PCR showed that the m1 transcript level in conjunctival cells was higher than that in limbal cells; m2, m3, and m4 expression levels were higher in conjunctival fibroblasts than in epithelial cells. Absolute quantitative real-time PCR showed that the m5 mRNA level in the three cell types was higher than those of m1-m4. Immunohistochemistry and Western blot analysis confirmed the presence of m1-m5 proteins in the cultured cells and in tissues. Carbachol increased the incorporation of BrdU into conjunctival epithelial cells in a dose-dependent manner, which was totally inhibited by atropine, but only partially inhibited by pirenzepine, AF-DX116, and 4-DAMP. Carbachol also activated p42/44 MAPK in a time-dependent manner. Preincubation with U0126 abolished carbachol-induced p42/44 MAPK activation and cell proliferation. CONCLUSIONS All five MR subtypes were found on corneal and conjunctival cells. The MRs have a role in epithelial cell proliferation through the phosphorylation of p42/44 MAPK in a time-dependent fashion similar to EGF.
The ECG Vertigo in Diabetes and Cardiac Autonomic Neuropathy

The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers a quick, noninvasive clinical and research screen for the early detection of cardiovascular disease in diabetes. In this paper, the clinical and research value of the ECG is readdressed in diabetes and in the presence of cardiac autonomic neuropathy.
African Swine Fever Virus Inhibits Induction of the Stress-Induced Proapoptotic Transcription Factor CHOP/GADD153

ABSTRACT Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (ASFV) is assembled on the cytoplasmic face of the ER and ultimately enveloped by ER membrane cisternae. The virus also recruits mitochondria to sites of viral replication and induces the mitochondrial stress protein hsp60. Here we studied the effects of ASFV on the induction of CHOP/GADD153 in infected cells. Interestingly, unlike other ER-tropic viruses, ASFV did not activate CHOP and was able to inhibit the induction of CHOP/GADD153 by a number of exogenous stimuli.
Self-Alignments to Detect Mutually Exclusive Exon Usage

The surprisingly low number of about 25,000 genes in the human genome [1] confirmed a fairly accurate estimate given by King and Jukes in 1969 based on population genetical arguments [2]. On the other hand, the number of different transcripts vastly exceeds gene number. This fact intensified the search for alternatively spliced genes. Recent results [1,3,4-7] suggest that more than 60% of the human genes are alternatively spliced, some of them with a myriad of different splice forms. Alternative splicing is found in all higher eukaryotic species in varying frequency. In this paper we focus on a particular form of alternative splicing, the so-called mutually exclusive exon usage (MEEU). In most known examples mutually exclusive exons are arranged in cassettes of highly similar exons suggesting that they have been derived by exon duplication [8-10]. Since classical gene-finding programs may fail to correctly predict such genes [11-16], we present a method, which is based on local similarity of exons, to detect gene candidates with mutually exclusive exon usage. We have screened the entire genome of D. melanogaster and found five new genes with MEEU in addition to eight previously described cases. Additional 1703 candidate regions of putative mutually exclusive exons were identified.
Genetic Instability in Paediatric and Adult Brain Tumours

1.1 Brain tumours in children and adults Primary Central Nervous System (CNS) tumours are considered to be those that originate in the CNS and usually remain there. Primary CNS tumours, despite not leading the cancer frequency rates, rank first among cancer types for the average years of life lost (Burnet et al., 2005). By contrast with other malignancies, where research has lead to the establishment of more successful treatment options, the diagnosis of a CNS tumour, particularly the more malignant histological types, still has devastating effects on the patients and their relatives, not only due to the dismal prognosis of these tumours with extremely high rates of mortality, but also to the great morbidity that actual treatment options cause (Laughton et al., 2008; Mulhern et al., 2004; Silber et al., 1992). The estimated annual worldwide age-standardized incidence of malignant primary CNS tumours is 3.5 per 100,000 people, which represents more than 200,000 cases. The rate is slightly higher in males (3.9 per 100,000 people per year) than in females (3.1 per 100,000 people per year) (Ferlay et al., 2008). The frequency of brain tumours is also higher in more developed countries (5.2 per 100,000 people per year) compared to less developed countries (3.0 per 100,000 people per year), probably due to diagnostic advances, as well as access to adequate health care in the developed regions (Ferlay et al., 2008; Wrensch et al., 2005). Similarly, estimated annual global age-standardized mortality of malignant primary CNS tumours is higher in males (3.0 per 100,000 people) than in females (2.2 per 100,000 people), with higher rates also in more developed countries (3.2 per 100,000 people) than in less developed regions (2.3 per 100,000 people) (Ferlay et al., 2008). The median age of diagnosis for all primary CNS tumours is 57 years, however the histology-specific median age ranges from 9 to 70 years ( Central Brain Tumor Registry of the United States [CBTRUS], 2010).
Social influence and the invocation of rights: The effects of accountability, reputation and political skill on legal claiming

Issues relating to litigation and other forms of employee legal claiming are at the forefront of the practice of human resource management. However, organizational scholars have paid scant attention to this important aspect of organizational life. Underrepresented in this collective research have been investigations into how social influence variables impact the legal claiming process. We add to the understanding of legal claiming by evaluating how perceived levels of accountability, reputation and political skill affect individuals’ willingness to engage in contentious and non-contentious legal claiming. We also investigate the impact that social influence has on individuals’ advice to other potential claimants. This study employed a longitudinal design utilizing both scenarios and survey data collection. Results from our study partially support the conclusion that individuals are more risk-averse in their own legal claiming considerations than they are in the advice they offer to similarly-situated others. Furthermore, accountability, reputation and interpersonal influence (one aspect of political skill) were found to significantly influence the likelihood of legal claiming. The pattern of results indicates that social influence variables play a role in determining whether legal claiming will be pursued and what type of claiming will be chosen.
Approaching patients with irritable bowel syndrome

Treatment of functional gastrointestinal disorders remains difficult with many very different approaches showing similar response rates, regardless of whether they target luminal contents (e.g., presumed bacterial overgrowth), signaling within the gut wall (e.g., serotonin agonists or antagonists) or processing in the brain (e.g., cognitive behavioral therapy). Discrepancies between recent clinical trials and a meta-analysis have forced us to re-examine the use of antidepressants. Other studies have looked beyond the traditional drug therapies and have suggested other options such as dietary interventions and communication strategies that address relevant disease mechanisms and enable us to understand patient concerns, with the ultimate goal being to individualize and thus improve treatment outcomes.
Faint High-Latitude Carbon Stars Discovered by the Sloan Digital Sky Survey: An Initial Catalog

A search of more than 3000 deg2 of high-latitude sky by the Sloan Digital Sky Survey has yielded 251 faint high-latitude carbon stars (FHLCs), the large majority previously uncataloged. We present homogeneous spectroscopy, photometry, and astrometry for the sample. The objects lie in the 15.6 < r < 20.8 range and exhibit a wide variety of apparent photospheric temperatures, ranging from spectral types near M to as early as F. Proper-motion measurements for 222 of the objects show that at least 50%, and quite probably more than 60%, of these objects are actually low-luminosity dwarf carbon (dC) stars, in agreement with a variety of recent, more limited investigations that show that such objects are the numerically dominant type of star with C2 in the spectrum. This SDSS homogeneous sample of ∼110 dC stars now constitutes 90% of all known carbon dwarfs and will grow by another factor of 2–3 by the completion of the survey. As the spectra of the dC and the faint halo giant C stars are very similar (at least at spectral resolution of 103), despite a difference of 10 mag in luminosity, it is imperative that simple luminosity discriminants other than proper motion be developed. We use our enlarged sample of FHLCs to examine a variety of possible luminosity criteria, including many previously suggested, and find that, with certain important caveats, JHK photometry may segregate dwarfs and giants.
A virtual-decision-maker library considering personalities and dynamically changing preference structures for interactive multiobjective optimization

Interactive multiobjective optimization (IMO) methods aim at supporting human decision makers (DMs) to find their most preferred solutions in solving multiobjective optimization problems. Due to the subjectivity of human DMs, human fatigue, or other limiting factors, it is hard to design experiments involving human DMs to evaluate and compare IMO methods. In this paper, we propose a framework of a virtual-DM library consisting of a variety of virtual DMs which reflect characteristics of different types of human DMs. The virtual-DM library is used to replace human DMs to interact with IMO methods. The virtual DMs in the library can express different types of preference information and their most preferred solutions are known. When interacting with an IMO method, the library can select an appropriate virtual DM to provide preference information that the method asks for based on solutions offered by the method. Four types of hybrid virtual DMs are constructed to emulate human DMs with different personalities and dynamically changing preference structures. They can be used to test the ability of IMO methods to adapt to different human DMs and capture DMs' preferences. The usage of these four types of virtual DMs are demonstrated by comparing two IMO algorithms.
Learning to see otherwise

This article reports on data from two research projects with people whose own illness narratives and etiologies challenge the western biomedical ontology of the body. This paper argues that Reed’s ‘landscapes of meaning’ allow researchers to make sense of the invisible, causal mechanisms operating in these particular epistemic communities. If ontology is an issue of perspective, then part of the ethnographer’s task is to ‘learn to see otherwise’ by situating themselves in people’s systems of signification and thereby grasping and analyzing the causal forces at work. And yet exploring data from these cases also allows for intervention into Reed’s account of causality which lends causal primacy to symbolic systems over structural and agential ones.
No genomic mosaicism in a putative hybrid butterfly species

Recent descriptions of hybrid animal species have spurred interest in this phenomenon, but little genomic data exist to support it. Here, we use frequency variation for 657 amplified fragment length polymorphism (AFLP) markers and DNA sequence variation from 16 genes to determine whether the genome of Heliconius pachinus, a suspected hybrid butterfly species, is a mixture of the putative parental species, Heliconius cydno and Heliconius melpomene. Despite substantial shared genetic variation among all three species, we show that the genome of H. pachinus is not a mosaic; both AFLP and DNA sequence data overwhelmingly associate H. pachinus with just one of the potential parents, H. cydno. This pattern also applies to the gene wingless, which is tightly linked to the locus that determines forewing colour—one specific H. pachinus trait that has been hypothesized to have originated from H. melpomene. As a whole, the data support a traditional, bifurcating model of speciation in which H. pachinus split from a common ancestor with H. cydno without a genetic contribution from H. melpomene. However, comparison of our data to DNA sequence data for another putative hybrid Heliconius species, Heliconius heurippa, suggests that the H. heurippa genome may be a mosaic.
Towards a Cognitive Probabilistic Representation of Space for Mobile Robots

Robots are rapidly evolving from factory workhorses to robot-companions. The future of robots, as our companions, is highly dependent on their abilities to understand, interpret and represent the environment in an efficient and consistent fashion, in a way that is comprehensible to humans. This paper is oriented in this direction. It suggests a hierarchical probabilistic representation of space that is based on objects. A global topological representation of places with object graphs serving as local maps is suggested. Experiments on place classification and place recognition are also reported in order to demonstrate the applicability of such a representation in the context of understanding space and thereby performing spatial cognition. Thus the theme of the work is - representation for spatial cognition.
Cyclosporin A Promotes in vivo Myogenic Response in Collagen VI-Deficient Myopathic Mice

Mutations of genes encoding for collagen VI cause various muscle diseases in humans, including Bethlem myopathy and Ullrich congenital muscular dystrophy. Collagen VI null (Col6a1−/−) mice are affected by a myopathic phenotype with mitochondrial dysfunction, spontaneous apoptosis of muscle fibers, and defective autophagy. Moreover, Col6a1−/− mice display impaired muscle regeneration and defective self-renewal of satellite cells after injury. Treatment with cyclosporin A (CsA) is effective in normalizing the mitochondrial, apoptotic, and autophagic defects of myofibers in Col6a1−/− mice. A pilot clinical trial with CsA in Ullrich patients suggested that CsA may increase the number of regenerating myofibers. Here, we report the effects of CsA administration at 5 mg/kg body weight every 12 h in Col6a1−/− mice on muscle regeneration under physiological conditions and after cardiotoxin (CdTx)-induced muscle injury. Our findings indicate that CsA influences satellite cell activity and triggers the formation of regenerating fibers in Col6a1−/− mice. Data obtained on injured muscles show that under appropriate administration, regimens CsA is able to stimulate myogenesis in Col6a1−/− mice by significantly increasing the number of myogenin (MyoG)-positive cells and of regenerating myofibers at the early stages of muscle regeneration. CsA is also able to ameliorate muscle regeneration of Col6a1−/− mice subjected to multiple CdTx injuries, with a concurrent maintenance of the satellite cell pool. Our data show that CsA is beneficial for muscle regeneration in Col6a1−/− mice.
Altered functional magnetic resonance imaging resting‐state connectivity in periaqueductal gray networks in migraine

The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine.
Retinal Vessel Analysis as a Tool to Quantify Risk of Diabetic Retinopathy

Abstract Diabetic retinopathy remains a leading cause of visual impairment and blindness worldwide. Identifying high-risk asymptomatic individuals who will likely develop the sight-threatening forms of diabetic retinopathy is an important clinical goal as it allows early, targeted implementation of preventive strategies to reduce their risk of vision loss. However, diabetic retinopathy is not a linear disease. Predicting the risk of diabetic retinopathy is challenging, and the current approach simply based on an assessment of traditional risk factors lacks precision. Retinal vessel analysis may offer a novel and noninvasive tool to improve risk prediction for diabetic retinopathy. With the use of this technology, studies have shown that a spectrum of structural alterations in the retinal vasculature can now be reliably quantified. In particular, variations in retinal vessel caliber have been consistently associated with the risks of retinopathy development and progression and shown to have prognostic predictive value above and beyond the conventional risk factors. Despite the promising results, there remain several unresolved issues that need to be addressed before the research findings on retinal vessel analysis are translated into clinical application. Coupling with standard clinical assessment, the additional information obtained from this technology could potentially guide clinical decision making, patient prognostication, and possibly monitor therapeutic response.
Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C

The response to interferon (IFN) therapy in patients with chronic hepatitis C is characterized by normalization of the serum alanine aminotransferase (ALT) activity during treatment, but relapse within 6 months of cessation of therapy is common. Viral characteristics, such as the genotype and viral load, may influence the patient response to IFN. The aim of this study was to examine host factors, namely the genetically determined human leucocyte antigen (HLA) class II alleles, in patients with chronic hepatitis C, and their relationship to the response to IFN therapy. Seventy white patients with chronic hepatitis C, treated with IFN‐α for 6 months, were enrolled in the study. Serum ALT was measured at the end of treatment to assess short‐term response and again 6 months post‐treatment to assess sustained response. Sequence‐specific primers were used in the polymerase chain reaction (PCR) to amplify genomic DNA isolated from peripheral mononuclear cells. HLA class II alleles were determined by analysis of the amplicon by gel electrophoresis and hybridization of sequence‐specific oligonucleotide probes. At the end of treatment, 25 of the 70 patients (36%) had a normal ALT. By 6 months post‐treatment, only six patients (9%) had a sustained normalization of ALT. The frequency of the allele DRB1*0404 was significantly higher in patients with a sustained response as compared to those lacking such a response (25.0%vs 2.3%, with a Bonferonni‐corrected P‐value of 0.019). There was no difference in the frequency of other class II alleles at the DRB1 and DQB1 loci in responders as compared with non‐responders. Therefore, we conclude that the maintenance of a response to IFN in chronic hepatitis C may be, in part, determined by genetic factors in the host.
Gene flow and population structure of a solitary top carnivore in a human-dominated landscape

While African leopard populations are considered to be continuous as demonstrated by their high genetic variation, the southernmost leopard population exists in the Eastern and Western Cape, South Africa, where anthropogenic activities may be affecting this population's structure. Little is known about the elusive, last free-roaming top predator in the region and this study is the first to report on leopard population structuring using nuclear DNA. By analyzing 14 microsatellite markers from 40 leopard tissue samples, we aimed to understand the populations' structure, genetic distance, and gene flow (Nm). Our results, based on spatially explicit analysis with Bayesian methods, indicate that leopards in the region exist in a fragmented population structure with lower than expected genetic diversity. Three population groups were identified, between which low to moderate levels of gene flow were observed (Nm 0.5 to 3.6). One subpopulation exhibited low genetic differentiation, suggesting a continuous population structure, while the remaining two appear to be less connected, with low emigration and immigration between these populations. Therefore, genetic barriers are present between the subpopulations, and while leopards in the study region may function as a metapopulation, anthropogenic activities threaten to decrease habitat and movement further. Our results indicate that the leopard population may become isolated within a few generations and suggest that management actions should aim to increase habitat connectivity and reduce human–carnivore conflict. Understanding genetic diversity and connectivity of populations has important conservation implications that can highlight management of priority populations to reverse the effects of human-caused extinctions.