Miracle-dz/UniFAR-FTUs huggingface dataset:
PPR proteins shed a new light on RNase P biology

A fast growing number of studies identify pentatricopeptide repeat (PPR) proteins as major players in gene expression processes. Among them, a subset of PPR proteins called PRORP possesses RNase P activity in several eukaryotes, both in nuclei and organelles. RNase P is the endonucleolytic activity that removes 5′ leader sequences from tRNA precursors and is thus essential for translation. Before the characterization of PRORP, RNase P enzymes were thought to occur universally as ribonucleoproteins, although some evidence implied that some eukaryotes or cellular compartments did not use RNA for RNase P activity. The characterization of PRORP reveals a two-domain enzyme, with an N-terminal domain containing multiple PPR motifs and assumed to achieve target specificity and a C-terminal domain holding catalytic activity. The nature of PRORP interactions with tRNAs suggests that ribonucleoprotein and protein-only RNase P enzymes share a similar substrate binding process.
Advances in Brief The Prognostic Implication of the Basal-Like ( Cyclin Ehigh / p 27 low / p 53 / Glomeruloid-Microvascular-Proliferation ) Phenotype of BRCA 1-Related Breast Cancer

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27, or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27, p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27 levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.
The Impact of Market Orientation on the Competitiveness of a Bank

The objective of the paper is to measure and compare market orientation of Swiss and Czech banks, as well as examine statistically the degree of influence it has on competitiveness of the institutions. The analysis of market orientation is based on the collecting, analysis and correct interpretation of the data. Descriptive analysis of market orientation describe current situation. Research of relation of competitiveness and market orientation in the sector of big international banks is suggested with the expectation of existence of a strong relationship. Partially, the work served as reconfirmation of suitability of classic methodologies to measurement of banks' market orientation. Two types of data were gathered. Firstly, by measuring subjectively perceived market orientation of a company and secondly, by quantifying its competitiveness. All data were collected from a sample of small, mid-sized and large banks. We used numerical secondary character data from the international statistical financial Bureau Van Dijk's BANKSCOPE database. Statistical analysis led to the following results. Assuming classical market orientation measures to be scientifically justified, Czech banks are statistically less market-oriented than Swiss banks. Secondly, among small Swiss banks, which are not broadly internationally active, small relationship exist between market orientation measures and market share based competitiveness measures. Thirdly, among all Swiss banks, a strong relationship exists between market orientation measures and market share based competitiveness measures. Above results imply existence of a strong relation of this measure in sector of big international banks. A strong statistical relationship has been proven to exist between market orientation measures and equity/total assets ratio in Switzerland. The Authors are thankful to the Internal Grant Agency of FaME TBU No. IGA/FaME/2013/029 (Measurement of market orientation of a firm and development of a new model with a focus on contemporary trends in management and marketing) for financial support to carry out this research.
Managing the Dyad Between Independence and Dependence: Case Studies of the American Elderly and Their Lives With Pets

: In this article, I research the dyad between independence and dependence in pet companionship for the American elderly, and how elderly pet owners treat pets as a tool to enable them to balance the adherent norms between independence and dependence in order to navigate a successful later life. First, I explore individual life with pets: independent lifestyle with pets, emotional dependence on pets, management of pet loss, and limitation in pet responsibilities. Second, I discuss family and social life with pets: relationships with children, grandchildren and pets; husband–wife interactions and pets; and neighbors and pets. I examine these subjects through in-depth interviews with five middle-class Caucasian and Asian elderly pet owners who live in Los Angeles and San Diego, California, conducted in July 2005. Pets greatly help the elderly pet owners to maintain a balance between independence and dependence. Both an independent lifestyle and emotional dependence on their pets are formed through pet responsibilities. Some of the informants treated their pets as if they were their children. The others appeared emotionally dependent on memories of former pets, which provided the elderly pet owners with a sense of security and calm. The informants managed pet loss effectively by treating their pet as a tool upon which they conferred replaceable meanings or roles depending on their situation. The elderly pet owners also used their pets to facilitate family and social interactions. Having a pet is one important way that American elderly people can achieve subjective manipulation of later life.
Comparative conservation analysis of the human mitotic phosphoproteome

MOTIVATION A key challenge in phosphoproteomic studies is to distinguish functionally relevant phosphorylation sites from potentially 'silent' phosphorylation. Considering that relevant phosphorylation sites are expected to be better conserved during evolution than overall Serine, Threonine and Tyrosine (S/ T/ Y) residues, we asked whether this can be directly demonstrated through statistic analysis, using a large experimental dataset. RESULTS Analyzing phosphoproteomic data derived from the human mitotic spindle apparatus, we found that 95.2% of 1744 phosphorylation sites are conserved in at least one of six other vertebrate species. Using a new score, termed conservation Z-score (CZ-score), we demonstrate that phosphorylation sites are significantly better conserved than other S/T/Y sites, a conclusion validated from several kinase consensus motifs. Most importantly, phosphorylation sites with experimentally verified biological functions were significantly better conserved than other phosphorylation sites, indicating that analysis utilizing evolutionary conservation may constitute a powerful basis for the development of improved phosphorylation site predictors. CONTACT malik@biochem.mpg. de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Validation of Catquest-9SF Questionnaire in a Chinese Cataract Population

Purpose To develop and validate a Chinese version of the Catquest-9SF questionnaire in a cataract population. Methods The Catquest-9SF Questionnaire was translated and back translated into Chinese. Preoperative patients were recruited at a tertiary eye hospital and their demographic information and visual acuity were documented. Psychometric properties of the Catquest-9SF, including ordered thresholds, the ability to distinguish between different strata of person ability, absence of misfitting items, unidimentionality, differential item functioning (DIF) and construct validity were tested, using Rasch analysis. Results A total of 102 patients (100% response rate) were enrolled. The participants'mean age was 70.2 year (SD = 12.1) and 46.9% were female. Rasch analysis showed that this version of the questionnaire had ordered response thresholds and was free of DIF. The items fit a single overall construct and unidimensional by principal components analysis of the residuals. Patients with visual impairment had significantly poorer Rasch scores on the Catquest-9SF (mean change, -2.5, p = 0.035, compared with non-visually impaired patients). Conclusion The Chinese version of Catquest-9SF is a valid and reliable questionnaire for assessing the visual disability outcomes of Chinese patients with cataract, and it may be recommended for routine clinical use.
Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa.

PURPOSE Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. The prevalence of RP in China had been reported at 1 in 3800, resulting in an estimated total of 340,000 Chinese RP patients. However, genetic studies of Chinese RP patients have been very limited. To date, no comprehensive molecular diagnosis has been done for Chinese RP patients. With the emergence of next-generation sequencing (NGS), comprehensive molecular diagnosis of RP is now within reach. The purpose of this study was to perform the first NGS-based comprehensive molecular diagnosis for Chinese RP patients. METHODS Thirty-one well-characterized autosomal recessive RP (arRP) families were recruited. For each family, the DNA sample from one affected member was sequenced using our custom capture panel, which includes 163 retinal disease genes. Variants were called, filtered, and annotated by our in-house automatic pipeline. RESULTS Twelve arRP families were successfully molecular diagnosed, achieving a diagnostic rate of approximately 40%. Interestingly, approximately 63% of the pathogenic mutations we identified are novel, which is higher than that observed in a similar study on European descent (45%). Moreover, the clinical diagnoses of two families were refined based on the pathogenic mutations identified in the patients. CONCLUSIONS We conclude that comprehensive molecular diagnosis can be vital for an accurate clinical diagnosis of RP. Applying this tool on patients from different ethnic groups is essential for enhancing our knowledge of the global spectrum of RP disease-causing mutations.
Non-thermal Biological Effects of Microwaves

The aim of this paper is to overview the diverse biological effects of non-thermal microwaves (NT MWs) and complex dependence of these effects on various physical and biological parameters. Besides dependencies on frequency and modulation, the available data suggest dependencies of the NT MW effects on intermittence and coherence time of exposure, polarization, static magnetic filed, electromagnetic stray field, genotype, gender, physiological and individual factors, cell density during of exposure and indicate that duration of exposure may be not less important than power density (PD) for the NT MW effects. Further evaluation of these dependencies are needed for understanding the mechanisms by which NT MWs affect biological systems, planning in vivo and epidemiological studies, developing medical treatments, setting safety standards, and minimizing the adverse effects of MWs from mobile communication.
The effect of smoking on the symptoms and progression of multiple sclerosis: a review

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder of the central nervous system with characteristic demyelinating lesions and axonal loss. MS accounts for the most common cause of neurological disability in young adults in the Western world. The clinical manifestations and the course of MS are highly variable. The early stage of the disease is usually characterized by attacks of neurological dysfunction with complete or incomplete recovery, however, with time disability accumulates in many patients. MS is believed to result from an interplay between susceptibility genes and environmental factors, one of which is smoking. Smoking, a worldwide epidemic, can be regarded as an important risk factor for MS particularly because of its modifiable nature in the quest to prevent or temper the disease course in MS as well as providing possible insights into MS pathogenesis. There are also reports that smoking may influence the symptoms and disease progression in patients with MS. The purpose of this article is to review the effects of smoking on MS symptoms and progression. We conclude that (1) although there are some early reports on worsening of MS symptoms by smoking, the existing evidence is insufficient to thoroughly assess the effects of smoking on the myriad of MS symptoms and (2) smoking seems to adversely influence disease progression in MS patients. We also discuss the potential biological mechanisms linking smoking and MS.
Critical Role of l-Arginine in Endothelial Cell Survival During Oxidative Stress

Background—Oxidative damage of vascular endothelium represents an important initiation step in the development of atherosclerosis. Recently, we reported about protection of inducible nitric oxide synthase (iNOS)-derived high-output NO in endothelial cells. Because iNOS activity critically depends on the availability of its substrate l-arginine, the present study aims at elucidating iNOS-mediated effects on H2O2-induced apoptosis of cytokine-activated rat aortic endothelial cells (AECs) subject to medium l-arginine concentrations. Methods and Results—In cytokine-activated AECs, iNOS activity was found to be half-maximal at 60 &mgr;mol/L arginine, which represents the medium serum level in rats but also in humans. Maximal activity is seen at and above 200 &mgr;mol/L arginine. Activated cells grown in the absence of arginine with minimal iNOS activity are highly sensitive toward H2O2-induced apoptosis, and increases in medium arginine concentrations result in increased cell survival. Moreover, competition experiments show that iNOS activity is completely dependent on cationic amino acid transporter-mediated arginine uptake. We also find that the arginine-dependent protection includes inhibition of endothelial lipid peroxidation and increases in the expression of vasoprotective stress response genes. Conclusions—Our data demonstrate that arginine concentrations corresponding to physiological serum levels do not allow for optimal endothelial iNOS activity. Thus, decreases in systemic arginine concentrations, or locally within atherosclerotic plaques, will impair the endothelial iNOS-mediated stress response and will significantly increase the risk of endothelial dysfunction.
Surgical Repair of Chronic Tears of the Hip Abductor Mechanism

Lateral sided hip pain frequently presents to the orthopaedic clinic. The most common cause of this pain is trochanteric bursitis. This usually improves with conservative treatment. In a few cases it doesn't settle and warrants further investigation and treatment. We present a series of 28 patients who underwent MRI scanning for such pain, 16 were found to have a tear of their abductors. All 16 underwent surgical repair using multiple soft tissue anchors inserted into the greater trochanter of the hip to reattach the abductors. There were 15 females and 1 male. All patients completed a self-administered questionnaire pre-operatively and 1 year post-operatively. Data collected included: A visual analogue score for hip pain, Charnley modification of the Merle D'Aubigne and Postel hip score, Oxford hip score, Kuhfuss score of Trendelenburg and SF36 scores. Of the 16 patients who underwent surgery 5 had a failure of surgical treatment. There were 4 re ruptures, 3 of which were revised and 1 deep infection which required debridement. In the remaining 11 patients there were statistically significant improvements in hip symptoms. The mean change in visual analogue score was 5 out of 10 (p=0.0024) The mean change of oxford hip score was 20.5 (p=0.00085). The mean improvement in SF-36 PCS was 8.5 (P=0.0020) and MCS 13.7 (P=0.134). 6 patients who had a Trendelenburg gait pre-surgery had normal gait 1 year following surgery. We conclude that hip abductor mechanism tear is a frequent cause of recalcitrant trochanteric pain that should be further investigated with MRI scanning. Surgical repair is a successful operation for reduction of pain and improvement of function. However there is a relatively high failure rate.
Hypoxia and CYP 1 A 1 induction-dependent regulation of proteins involved in glucose utilization in Caco-2 cells

Carrière, Véronique,Annie Rodolosse, Michel Lacasa, Danièle Cambier, Alain Zweibaum, and Monique Rousset. Hypoxia and CYP1A1 induction-dependent regulation of proteins involved in glucose utilization in Caco-2 cells. Am. J. Physiol. 274 (Gastrointest. Liver Physiol. 37): G1101–G1108, 1998. —Although induction of cytochrome P-450 1A1 (CYP1A1) in the Caco-2 clone TC7 alters glucose utilization and modifies the expression of sucrase-isomaltase (SI) and hexose transporters, nothing is known of the events that control these effects. In this study, we analyzed the effects of b-naphthoflavone (b-NF) and hypoxia on these parameters and expression of key enzymes of glucose metabolism. Both b-NF and hypoxia induce similar changes: 1) induction of CYP1A1 mRNA; 2) increased glucose consumption and lactic acid production and lower glycogen content; 3) downregulation of SI and upregulation of GLUT1 mRNAs; 4) downregulation of fructose-1,6-bisphosphatase and pyruvate kinase mRNAs and upregulation of phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase, lactate dehydrogenase, and phosphofructokinase mRNAs; and 5) upregulation of c-fos and c-jun mRNAs. Although addition of inhibitors of CYP1A1 catalytic activity to b-NF-treated cells totally inhibits the enzyme activity, it does not modify CYP1A1 mRNA response and associated effects, thus excluding a direct role for the enzyme per se. These results point to a possible physiological implication of the signal-transduction pathway responsible for CYP1A1 induction.
Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.
Intravesical oxybutynin: a local anesthetic effect on bladder C afferents.

PURPOSE Intravesical oxybutynin is used to control bladder overactivity in patients who are refractory to or cannot tolerate oxybutynin given orally. Although it is clinically effective, the mode of action of intravesical oxybutynin remains unclear. We tested the influence of intravesical oxybutynin on single fiber pelvic nerve afferents from the rat bladder. MATERIALS AND METHODS A total of 15 single afferent bladder units were identified. Based on conduction velocity they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. Oxybutynin was than instilled and left in the bladder for 15 minutes. Unitary afferent activity was again analyzed 15, 60 and 90 minutes after the drug was removed. RESULTS Repeat bladder filling did not change nerve activity in Adelta or C fibers. At 15 minutes after oxybutynin was washed out of the bladder C fiber afferents responded significantly less to intravesical pressure and volume compared with control filling. At 60 minutes C fibers partly regained mechanosensivity. After 90 minutes sensitivity still increased without achieving the response level before oxybutynin. No significant changes were noted in Adelta fibers during repeat bladder filling or after oxybutynin instillation. CONCLUSIONS In this study we showed that intravesical oxybutynin has a direct anesthetic effect within the bladder wall. It temporarily desensitizes C fiber afferents, which could explain its clinical benefits in decreasing symptoms of bladder overactivity. No measurable effect was found on Adelta fibers.
VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs), serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.
Video face replacement

We present a method for replacing facial performances in video. Our approach accounts for differences in identity, visual appearance, speech, and timing between source and target videos. Unlike prior work, it does not require substantial manual operation or complex acquisition hardware, only single-camera video. We use a 3D multilinear model to track the facial performance in both videos. Using the corresponding 3D geometry, we warp the source to the target face and retime the source to match the target performance. We then compute an optimal seam through the video volume that maintains temporal consistency in the final composite. We showcase the use of our method on a variety of examples and present the result of a user study that suggests our results are difficult to distinguish from real video footage.