Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells

Aging of an organism is associated with the functional decline of tissues and organs, as well as a sharp decline in the regenerative capacity of stem cells. A prevailing view holds that the aging rate of an individual depends on the ratio of tissue attrition to tissue regeneration. Therefore, manipulations that favor the balance towards regeneration may prevent or delay aging. Skeletal muscle is a specialized tissue composed of postmitotic myofibers that contract to generate force. Satellite cells are the adult stem cells responsible for skeletal muscle regeneration. Recent studies on the biology of skeletal muscle and satellite cells in aging have uncovered the critical impact of systemic and niche factors on stem cell functionality and demonstrated the capacity of aged satellite cells to rejuvenate and increase their regenerative potential when exposed to a youthful environment. Here we review the current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, and which encourage the search for new anti‐aging strategies.
Molecular Characterization of Pantoea stewartii subsp. stewartii HrpY, a Conserved Response Regulator of the Hrp Type III Secretion System, and its Interaction with the hrpS Promoter

ABSTRACT Pantoea stewartii subsp. stewartii is a bacterial pathogen of corn. Its pathogenicity depends on the translocation of effector proteins into host cells by the Hrp type III secretion system. We previously showed by genetic analysis that the HrpX sensor kinase and the HrpY response regulator are at the head of a complex cascade of regulators controlling hrp/hrc secretion and wts effector genes. This cascade also includes the HrpS response regulator and the HrpL alternative sigma factor. These regulators are shared among many important plant pathogens in the genera Pantoea, Erwinia, and Pseudomonas. In this study, we dissect the regulatory elements in the hrpS promoter region, using genetic and biochemical approaches, and show how it integrates various environmental signals, only some of which are dependent on phosphorylation of HrpY. Primer extension located the transcriptional start site of hrpS at a σ70 promoter 601 bp upstream of the open reading frame. Electrophoretic mobility shift assays and DNase I footprinting analysis demonstrated that HrpY binds to conserved regulatory elements immediately adjacent to this promoter, and its binding affinity was increased by phosphorylation at D57. A consensus sequence for the two direct repeats bound by HrpY is proposed. Deletion analysis of the promoter region revealed that both the HrpY binding site and additional sequences farther upstream, including a putative integration host factor binding site, are required for hrpS expression. This finding suggests that other unknown regulatory proteins may act cooperatively with HrpY.
The Host Cell MAP Kinase ERK-2 Regulates Viral Assembly and Release by Phosphorylating the p6gag Protein of HIV-1*

The host cell MAP kinase ERK-2 incorporated within human immunodeficiency virus type 1 particles plays a critical role in virus infectivity by phosphorylating viral proteins. Recently, a fraction of the virus incorporated late (L) domain-containing p6gag protein, which has an essential function in the release of viral particles from the cell surface, was reported to be phosphorylated by an unknown virus-associated cellular protein kinase (Muller, B., Patschinsky, T., and Krausslich, H. G. (2002) J. Virol. 76, 1015–1024). The present study demonstrates the contribution of the MAP kinase ERK-2 in p6gag phosphorylation. According to mutational analysis, a single ERK-2-phosphorylated threonine residue, belonging to a highly conserved phosphorylation MAP kinase consensus site, was identified at position 23 within p6gag. Substitution by an alanine of the Thr23 phosphorylable residue within the pNL4.3 molecular clone was found to decrease viral release from various cell types. As observed from electron microscopy experiments, most virions produced from this molecular clone remained incompletely separated from the host cell membrane with an immature morphology and displayed a reduced infectivity in single round infection experiments. Analysis of protein processing by Western blotting experiments revealed an incomplete Pr55gag maturation and a reduction in the virion-associated reverse transcriptase proteins was observed that was not related to differences in intracellular viral protein expression. Altogether, these data suggest that phosphorylation of p6gag protein by virus-associated ERK-2 is involved in the budding stage of HIV-1 life cycle.
A Model of Adolescents' Seeking of Sexual Content in Their Media Choices

This article reports on the extent to which adolescents report actively seeking sexual content in media, identifies from which media they report seeking, estimates the association between seeking sexual information and romantic and sexual behavior, and shows that active seeking of sexual content in media sources is explained by an intention to seek such content using the Integrative Model of Behavioral Prediction, a reasoned action approach. The data are a national sample of 810 adolescents aged 13 to 18 years. Results show that 50% of adolescents reported actively seeking sexual content in their media choices, which included movies, television, music, Internet pornography sites, and magazines. Males sought sex content more than females, and gender differences were greatest for seeking from Internet pornography sites, movies, and television. Path analysis demonstrate that seeking sexual content is well-predicted by intentions to seek, and intentions are primarily driven by perceived normative pressure to seek sexual content.
Use of a static magnetic field to promote recovery after peripheral nerve injury.

OBJECT While pulsed electromagnetic stimulation has been shown to enhance peripheral nerve regeneration, the effect of a static magnetic field on nerve repair is less clear. The aim of this study was to establish what effect an imposed exogenous static magnetic field has on peripheral nerve regeneration after transection and repair. METHODS Three groups of six adult sheep were used. The first group acted as normal controls. In the second group, the median nerve was divided and immediately repaired by entubulation within a "controlled-release" biodegradable glass tube. In the third group, small magnets were applied to the sides of the biodegradable glass tubes before the median nerve was repaired using these magnetic tubes. The sheep were allowed to recover and were reexamined 10 months later. The animals underwent comprehensive morphometric (cross-sectional morphometry and measurement of internodal lengths), electrophysiological (determinations of stimulated jitter, maximum conduction velocity, refractory period, and F waves), and isometric tension (isometric twitch and tetanic tension) assessments. CONCLUSIONS Exogenously applied static electromagnetic fields do not enhance peripheral nerve regeneration.
The Concept of Ischemic Penumbra in Acute Stroke and Therapeutic Opportunities

Ischemic penumbra was first defined by Astrup in 1981 as perfused brain tissue at a level within the thresholds of functional impairment and morphological integrity, which has the capacity to recover if perfusion is improved. It exists, even for a short period of time in the center of ischemia, from which irreversible necrosis propagates to the neighboring tissues over time. Penumbra has become the focus of intense imaging research to differentiate it from infarction. Accurate detection of this ‘tissue at risk’ could be used to identify patients who would benefit most from acute treatment. Currently, recombinant tissue plasminogen activator (rtPA) is the only approved drug that has shown significant benefits in acute stroke patients when administered intravenously less than 4.5 h after stroke. However, its use is limited. Discrimination between infarct core and the surrounding potentially salvageable tissue is useful to better identify patients suitable for treatment. This can be achieved by positron emission tomography, single-photon-emission computed tomography, computed tomography perfusion scan and perfusion-weighted and diffusion-weighted magnetic resonance imaging. Identification of the penumbra might enable selective rtPA use in patients with large penumbras and small infarct cores, even beyond the 4.5-hour time window, where the penumbra may persist for more than 12 h. The purpose of this review was to describe neuroimaging modalities capable of identifying penumbra tissue so as to provide surrogate markers for new trials in acute ischemic stroke patients.
Impaired implicit sequence learning in depression: a probe for frontostriatal dysfunction?

Background. Implicit learning through motor sequencing tasks is sensitive to basal ganglia dysfunction. Consequently, it is ideally suited for testing elements of the frontostriatal model of major depression and performance can be related to key clinical, neuropsychological, vascular and biochemical data. Method. Twenty-one subjects with moderate to severe unipolar depression and 21 age-, sex- and education-matched controls were recruited. Clinical, vascular and biochemical data were recorded. Subjects were administered a battery of neuropsychological tests that assessed speed of processing, working memory, learning, memory, language, perceptual organization and executive functioning. Additionally, subjects were administered a motor sequencing implicit learning task. Implicit learning is assumed when reaction times improve during the sequenced condition as compared to the pseudo-random baseline condition. Results. The rate of implicit learning in persons with depression was only half that of control subjects (3·6% v. 7·3%). Lower rates of implicit learning in patients were associated with poorer performance on neuropsychological tests of visuomotor speed and mental flexibility, longer duration of depressive episode and severity of acute stress. In a small number of subjects, poorer performance was also related to past suicide attempt. Conclusions. Impaired implicit learning in persons with depression is consistent with frontostriatal dysfunction. Performance is related to some clinical characteristics and to neuropsychological functioning on tests of visuomotor speed and mental flexibility.
Prospective prognostic assessment of blood pressure response during exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND Previous studies revealed that an abnormal blood pressure response (ABPR) during exercise was common in young hypertrophic cardiomyopathy (HCM) patients and was associated with a family history of premature sudden cardiac death (SCD). This study was performed prospectively to assess the prognostic significance of blood pressure response during exercise in young patients with HCM. METHODS AND RESULTS Maximum symptom-limited treadmill exercise testing with continuous blood pressure monitoring was performed in 161 consecutive patients 8 to 40 years old (27+/-9). A normal blood pressure response, defined as an increase in the systolic pressure of at least 20 mm Hg from rest to peak exercise in the absence of a fall of >20 mm Hg from peak pressure, was seen in 101 (63%). In 60 (37%), the blood pressure response was abnormal. There was no significant difference in patients with normal blood pressure response and ABPR in terms of age, sex, follow-up, or recognized risk factors for SCD. During the follow-up period (mean, 44+/-20 months), SCD occurred in 12 patients: 3 (3%) in the normal blood pressure response group versus 9 (15%) in the ABPR group (P<.009). ABPR had a sensitivity of 75%, a specificity of 66%, a negative predictive value of 97%, and a positive predictive value of 15% for the prediction of SCD. There was no significant difference in the incidence of other recognized risk factors between patients with SCD and the survivors. CONCLUSIONS A normal exercise blood pressure response identifies low-risk young patients with HCM. An ABPR identifies the high-risk cohort; the low positive predictive accuracy, however, indicates that further risk stratification is warranted.
Long‐term survival in advanced ovarian carcinoma following cytoreductive surgery with standard peritonectomy procedures

The impact of cytoreductive surgery with standard peritonectomy procedures has not been extensively assessed in the treatment of advanced ovarian cancer. The aims of the study are to report the long-term results of patients with advanced ovarian cancer undergoing cytoreductive surgery with standard peritonectomy procedures and to identify the prognostic indicators that may affect outcome. The records of 74 women with advanced ovarian cancer were retrospectively reviewed. Clinical indicators were correlated to survival. The hospital mortality and morbidity rates were 13.5% and 28.4%, respectively. Complete or near-complete cytoreduction was possible in 78.4% of the patients. Overall 10-year survival rate was 52.5%. Complete cytoreductive surgery, small-volume tumor, low-grade tumor, the absence of distant metastases, the use of systemic adjuvant chemotherapy, performance status >70%, and limited extent of peritoneal carcinomatosis were favorable indicators of survival. Complete cytoreduction (P= 0.000) and treatment with systemic chemotherapy (P= 0.001) independently influenced survival. Recurrence was recorded in 37.8% of the patients and was independently influenced by the tumor grade (P= 0.037). Cytoreductive surgery with standard peritonectomy procedures followed by adjuvant chemotherapy offers long-term survival in women with advanced ovarian cancer who have limited peritoneal carcinomatosis and no distant and irresectable metastases.
Lysosome‐related organelles

Lysosomes are membrane‐bound cytoplasmic organelles involved in intracellular protein degradation. They contain an assortment of soluble acid‐dependent hydrolases and a set of highly glycosylated integral membrane proteins. Most of the properties of lysosomes are shared with a group of cell type‐specific compartments referred to as ‘lysosome‐related organelles’, which include melanosomes, lytic granules, MHC class II compartments, platelet‐dense granules, basophil granules, azurophil granules, and Drosophila pigment granules. In addition to lysosomal proteins, these organelles contain cell type‐specific components that are responsible for their specialized functions. Abnormalities in both lysosomes and lysosome‐related organelles have been observed in human genetic diseases such as the Chediak‐Higashi and Hermansky‐Pudlak syndromes, further demonstrating the close relationship between these organelles. Identification of genes mutated in these human diseases, as well as in mouse and Drosophila pigmentation mutants, is beginning to shed light on the molecular machinery involved in the biogenesis of lysosomes and lysosome‐related organelles. —Dell'Angelica, E. C. , Mullins, C. , Caplan, S. , Bonifacino, J. S. Lysosome‐related organelles. FASEB J. 14, 1265–1278 (2000)
Sensor fusion based energy efficient and sustainable smart parking system

With the rapid increase in urban population and hence the automobiles, parking has emerged as a resource with fair amount of energy consumption, air pollution and traffic congestion in almost every major city around the globe. Therefore, its efficient management in terms of both energy and space is not only necessitated to save a lot of energy, but also plays a pivotal role to obtain environment friendly green cities. In this article, we proposed a smart energy efficient parking system, which integrates the image recognition techniques for license plate recognition, infrared sensor for group control and wireless sensor network (WSN) for intelligent light emitting diode (LED) lighting. The system offers better guidance to parking position, controls LED lights based on traffic distribution for maximum energy efficiency, and offers enhanced security as compared to its counterpart conventional system. The system is built on ZigBee based Wireless Mesh network (WMN) nodes equipped with image sensor and RF module. The vehicles in the parking lot are detected and recognized using the grid based algorithm and license plate image recognition. The concept of zoning or lighting group control algorithm is integrated with moving object tracking algorithm to control the array of lights to attain the maximum energy efficiency and reduced Greenhouse gases (GHG) emissions. In comparison to conventional parking and normal lighting, the proposed system presents the substantial amount of energy savings, less environmental pollution and enhanced surveillance. Moreover, the embedded advantage of improved reliability, reduced maintenance and low cost due to smart control suggests very satisfactory and optimistic results for future implementation of the system as an integrated part of smart cities.
Oncogenic Activity of Ect2 Is Regulated through Protein Kinase Cι-mediated Phosphorylation*

The Rho GTPase guanine nucleotide exchange factor Ect2 is genetically and biochemically linked to the PKCι oncogene in non-small cell lung cancer (NSCLC). Ect2 is overexpressed and mislocalized to the cytoplasm of NSCLC cells where it binds the oncogenic PKCι-Par6 complex, leading to activation of the Rac1 small GTPase. Here, we identify a previously uncharacterized phosphorylation site on Ect2, threonine 328, that serves to regulate the oncogenic activity of Ect2 in NSCLC cells. PKCι directly phosphorylates Ect2 at Thr-328 in vitro, and RNAi-mediated knockdown of either PKCι or Par6 leads to a decrease in phospho-Thr-328 Ect2, indicating that PKCι regulates Thr-328 Ect2 phosphorylation in NSCLC cells. Both wild-type Ect2 and a phosphomimetic T328D Ect2 mutant bind the PKCι-Par6 complex, activate Rac1, and restore transformed growth and invasion when expressed in NSCLC cells made deficient in endogenous Ect2 by RNAi-mediated knockdown. In contrast, a phosphorylation-deficient T328A Ect2 mutant fails to bind the PKCι-Par6 complex, activate Rac1, or restore transformation. Our data support a model in which PKCι-mediated phosphorylation regulates Ect2 binding to the oncogenic PKCι-Par6 complex thereby activating Rac1 activity and driving transformed growth and invasion.
Chronic postsurgical pain in Europe: An observational study

BACKGROUND Chronic postsurgical pain (CPSP) is an important clinical problem. Prospective studies of the incidence, characteristics and risk factors of CPSP are needed. OBJECTIVES The objective of this study is to evaluate the incidence and risk factors of CPSP. DESIGN A multicentre, prospective, observational trial. SETTING Twenty-one hospitals in 11 European countries. PATIENTS Three thousand one hundred and twenty patients undergoing surgery and enrolled in the European registry PAIN OUT. MAIN OUTCOME MEASURES Pain-related outcome was evaluated on the first postoperative day (D1) using a standardised pain outcome questionnaire. Review at 6 and 12 months via e-mail or telephonic interview used the Brief Pain Inventory (BPI) and the DN4 (Douleur Neuropathique four questions). Primary endpoint was the incidence of moderate to severe CPSP (numeric rating scale, NRS ≥3/10) at 12 months. RESULTS For 1044 and 889 patients, complete data were available at 6 and 12 months. At 12 months, the incidence of moderate to severe CPSP was 11.8% (95% CI 9.7 to 13.9) and of severe pain (NRS ≥6) 2.2% (95% CI 1.2 to 3.3). Signs of neuropathic pain were recorded in 35.4% (95% CI 23.9 to 48.3) and 57.1% (95% CI 30.7 to 83.4) of patients with moderate and severe CPSP, respectively. Functional impairment (BPI) at 6 and 12 months increased with the severity of CPSP (P < 0.01) and presence of neuropathic characteristics (P < 0.001). Multivariate analysis identified orthopaedic surgery, preoperative chronic pain and percentage of time in severe pain on D1 as risk factors. A 10% increase in percentage of time in severe pain was associated with a 30% increase of CPSP incidence at 12 months. CONCLUSION The collection of data on CPSP was feasible within the European registry PAIN OUT. The incidence of moderate to severe CPSP at 12 months was 11.8%. Functional impairment was associated with CPSP severity and neuropathic characteristics. Risk factors for CPSP in the present study were chronic preoperative pain, orthopaedic surgery and percentage of time in severe pain on D1. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01467102.
Mind the Gap: 20 Years of Progress and Retrenchment in School Funding and Achievement Gaps: 20 Years of Progress in School Funding

Although there has been significant progress in the long term, achievement gaps among the nation's students persist. Many factors have contributed to the disparities in outcomes, and societal changes can explain progress, or lack thereof, over the past few decades. This is well documented in the 2010 Educational Testing Service (ETS) report Black–White Achievement Gaps: When Progress Stopped, which explored achievement gap trends and identified the changing conditions that may have influenced those trends. In this report, we extend that work by focusing on the relationship between school funding, resource allocation, and achievement among students from low-income families. We tackle the assumption that greater resources, delivered through fair and equitable school funding systems, could help raise academic outcomes and reduce the achievement gap. The goal is to provide convincing evidence that state finance policies have consequences in terms of the level and distribution of resources, here limited to staffing characteristics, and that the resulting allocation of resources is also associated with changes in both the level of academic achievement and achievement gaps between low-income children and their peers. Using more than 20 years of revenue and expenditure data for schools, we empirically test the idea that increasing investments in schools generally is associated with greater access to resources as measured by staffing ratios, class sizes, and the competitiveness of teacher wages. When the findings presented here are considered with the strong body of academic literature on the positive relationship between substantive and sustained state school finance reforms and improved student outcomes, a strong case can be made that state and federal policy focused on improving state finance systems to ensure equitable funding and improving access to resources for children from low-income families is a key strategy to improve outcomes and close achievement gaps.