Miracle-dz/UniFAR-FTUs huggingface dataset:
Rho Regulates Membrane Transport in the Endocytic Pathway to Control Plasma Membrane Specialization in Oligodendroglial Cells

Differentiation of oligodendrocytes is associated with dramatic changes in plasma membrane structure, culminating in the formation of myelin membrane sheaths. Previous results have provided evidence that regulation of endocytosis may represent a mechanism to control myelin membrane growth. Immature oligodendrocytes have a high rate of clathrin-independent endocytosis for the transport of membrane to late endosomes/lysosomes (LE/Ls). After maturation and receiving signals from neurons, endocytosis is reduced and transport of membrane from LE/Ls to the plasma membrane is triggered. Here, we show that changes in Rho GTPase activity are responsible for switching between these two modes of membrane transport. Strikingly, Rho inactivation did not only reduce the transport of cargo to LE/L but also increased the dynamics of LE/L vesicles. Furthermore, we provide evidence that Rho inactivation results in the condensation of the plasma membrane in a polarized manner. In summary, our data reveal a novel role of Rho: to regulate the flow of membrane and to promote changes in cell surface structure and polarity in oligodendroglial cells. We suggest that Rho inactivation is required to trigger plasma membrane specialization in oligodendrocytes.
Low-dose methotrexate may cause air trapping in patients with rheumatoid arthritis.

Both rheumatoid arthritis (RA) and methotrexate (MTX) are reported to be associated with the development of pulmonary disease. To determine whether MTX enhanced the risk of developing abnormalities in pulmonary function in patients with RA, we prospectively studied 31 subjects (12 male, 19 female) with the diagnosis of classic RA for an average period of 4.4 yr (range, 1 to 5 yr). Each subject was placed on low-dose weekly MTX (mean 17 mg, range 2.5 to 40) for control of RA symptoms. Other medications included non-steroidal anti-inflammatory agents and prednisone if required for control of arthritis symptoms. No other immunosuppressive therapy was used. Each subject was evaluated by pulmonary function tests (PFT) and chest X-ray initially, and at 1, 2, 3.5, and 5 yr. Chest X-rays obtained initially and at the end of the study period were found to be normal. The percent predicted values for initial PFTs in the study group were within the normal range. From the beginning to the end of the observation period, the following mean changes in lung function were observed: 1.9% increase in TLC, 5.1% increase in residual volume (RV), 1.8% increase in FVC, 0.71% decrease in FEV1, 14.7% improvement in alveolar-arterial oxygen (A-aO2) difference, and a 12.7% increase in single-breath diffusing capacity (DLCO). To determine whether MTX (average dose, weekly dose, or cumulative dose) was significantly related to changes in pulmonary function, we used multivariate techniques to control for the initial measure of lung function while assessing the relationship between MTX and the subsequent measures of lung function. (ABSTRACT TRUNCATED AT 250 WORDS)
Meta‐analysis of a continuous outcome combining individual patient data and aggregate data: a method based on simulated individual patient data

When some trials provide individual patient data (IPD) and the others provide only aggregate data (AD), meta‐analysis methods for combining IPD and AD are required. We propose a method that reconstructs the missing IPD for AD trials by a Bayesian sampling procedure and then applies an IPD meta‐analysis model to the mixture of simulated IPD and collected IPD. The method is applicable when a treatment effect can be assumed fixed across trials. We focus on situations of a single continuous outcome and covariate and aim to estimate treatment–covariate interactions separated into within‐trial and across‐trial effect. An illustration with hypertension data which has similar mean covariates across trials indicates that the method substantially reduces mean square error of the pooled within‐trial interaction estimate in comparison with existing approaches. A simulation study supposing there exists one IPD trial and nine AD trials suggests that the method has suitable type I error rate and approximately zero bias as long as the available IPD contains at least 10% of total patients, where the average gain in mean square error is up to about 40%. However, the method is currently restricted by the fixed effect assumption, and extension to random effects to allow heterogeneity is required. Copyright © 2014 John Wiley & Sons, Ltd.
Complementarity and contextualization of firm-level strategic orientations

Tatiana Beliaeva Complementarity and contextualization of firm-level strategic orientations Lappeenranta 2019 106 pages Acta Universitatis Lappeenrantaensis 841 Diss. Lappeenranta-Lahti University of Technology LUT ISBN 978-952-335-336-7, ISBN 978-952-335-337-4 (PDF), ISSN-L 1456-4491, ISSN 1456-4491 Strategic orientations, which reflect strategic behaviors implemented by a firm, have been widely associated with a firm’s competitiveness and performance. An extensive theoretical and empirical consideration has been received by entrepreneurial orientation, market orientation, and learning orientation, which reflect a firm’s behavior toward new product creation, market, and organizational learning, respectively. Extant literature has examined the relationship between strategic orientations and firm performance, yet research has often focused on one orientation in isolation without considering the orientations’ relative performance contributions and potential complementarities. Furthermore, previous results are ambiguous with regard to performance implications of strategic orientations, suggesting a closer examination of contextual effects. This dissertation aims to narrow these gaps by investigating how strategic orientations are individually and jointly related to firm performance in different environmental contexts. The study utilizes a quantitative methodology based on three datasets obtained from small and medium-sized enterprises from different countries. Complementarity of strategic orientations and their embeddedness in various countryand industry-level contexts are examined. The results suggest different individual effects of entrepreneurial, market, and learning orientations on firm performance, and highlight the significant role of their shared effect. By questioning complementarity of entrepreneurial and market orientations during an economic crisis and revealing distinctive effects of entrepreneurial orientation in developed and emerging markets, as well as across institutional and industry settings, the study emphasizes contextuality of strategic orientations–performance relationship. These results contribute to strategic orientations literature by applying an integrative approach to the phenomenon and specifying performance effects of strategic orientations in a wide variety of contexts. Moreover, the results have implications for research on complementarities in organizations as well as contextual research in management. The dissertation comprises an introductory part with an overview of the literature and discussion of the framing, methodology, results, and contributions of the whole study, as well as five independent publications.
Strong seedling recruitment does not limit mangrove vulnerability to harvest

Ecological studies on the impacts of timber harvesting contributed to inform sustainable management strategies of tropical forests. However, these studies rely strongly on two major assumptions: (i) strong seedlings recruitment predispose for positive population dynamics, and (ii) more adult trees is a guarantee for a strong reproductive capability of the population. These assumptions are applied without accounting for the life history of the harvested species. Here, we revisit these assumptions in light of the life history theory, which predicts different responses of short- and long-lived species to perturbation. We predict that harvesting adults, rather than reducing seedling recruitment of long-lived species, would have greater impact on population dynamics. We tested our prediction on three mangrove species in South Africa. First, we reconstructed the projection matrices for three mangrove species in the Mngazana Estuary of Eastern Cape province of South Africa. Next, we simulated a range of harvest intensities for different life stages and explored how harvesting influences population dynamics. Finally, we examined the age-specific mortality trajectories for all three species. We found that populations of all three species were closer to their stable stage distribution. Contrary to popular belief, we found that changes in seedling recruitment will have minimal effects on mangrove long-term population dynamics, a finding consistent with the life history theory. However, contrary to expectation, simulating harvest of adults had minimal effect on population dynamics. This is due to low reproductive values for these late stages. Our analysis of age-specific mortality trajectories further provided evidence for positive senescence particularly for Avicennia which was the least resilient to harvest. Our findings cast doubt on the traditional forest management strategies that rely strongly on seedling density as a metric of sustainability and forbid unquestionably harvesting large individuals. We call for caution while generalizing forest management strategies irrespective of the life history of the species at hand.
Social synchronization of circadian locomotor activity rhythm in the fruit fly Drosophila melanogaster

SUMMARY Circadian clocks regulate the physiology and behaviour of organisms across a wide range of taxa. To keep track of local time, these clocks use a variety of time cues such as light–dark, temperature, food availability and social interaction cycles. This study assessed the role of social cues in modulating circadian clocks of the fruit fly Drosophila melanogaster. Using pair-wise interactions, we first estimated the percentage contribution of each interacting partner on the cumulative rhythmic behaviour of the pairs. Subsequently, we studied the effects of multi-individual (group-wise) interactions on the rhythmic behaviour of the group by estimating phase synchrony between individuals of different strains (having different circadian periods) maintained in both homogeneous and heterogeneous groups. Although it is known that social interactions improve synchrony between interacting individuals, we asked whether such interactions are able to synchronize the circadian rhythms of highly phase-desynchronized flies. We found that, although interactions between fly strains possessing different circadian periods failed to produce synchrony, social interactions among phase-desynchronized flies did enhance the phase synchrony of the interacting individuals. Differently phased individuals living in social groups displayed significantly greater phase synchrony than those living solitarily. Social synchronization is olfaction mediated as group-wise interactions among phase-desynchronized flies possessing compromised olfactory ability (Or83b0) did not improve phase synchrony. These results suggest that social cues synchronize the circadian clocks of Drosophila provided that the interacting individuals have similar clock periods.
A motivation based shopper typology for short term retail events

The study focuses on the analysis of a short term retail event. Its success is similar to Black Friday, but differs in underlying consumer motivations. Using a mixed methodology, phenomenological interviews provided in-depth understanding of the participants’ lived experiences followed by an online survey with a sample size of 761 respondents. Exploratory factor analyses has been used to differentiate three distinctive groups with hierarchical cluster analysis. By adopting the ANOVA method, clusters and hypothesis were further analysed. This study is the first to employ quantitative study for a shopper taxonomy of such an event. Our results contribute valuable insights into retail shopping orientation and shopper taxonomic scheme literatures. The finding that a short term retail event’s shoppers form distinct groups of consumers indicates a new way of customers embracing retail events. Our research has identified three distinct shopper clusters based on the different weight of task and social orientations: Loyalists, Enthusiasts, Newbies. Each group applies different strategies to satisfy personal goals. The present shopper taxonomy offers new strategic ways to increase retail performance by targeting the most valuable customers.
MinK-Related Peptide 1 Associates With Kv4.2 and Modulates Its Gating Function: Potential Role as &bgr; Subunit of Cardiac Transient Outward Channel?

Abstract— Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (&agr;) subunits of transient outward (Ito) channels in the heart. We used the Xenopus oocyte expression system to examine the effects of MiRP1 on Kv4.x channel gating kinetics and current amplitude and correlated these effects with MiRP1 expression level. MiRP1 slowed the rates of Kv4.2 activation and inactivation and shifted the voltage dependence of channel gating in the positive direction. These effects had a similar “dose” dependence: they plateaued at a cRNA ratio (MiRP1:Kv4.2) of 13:1, with half-maximum effects at estimated cRNA ratios of 2 to 4. On the other hand, MiRP1 had no significant effects on Kv4.2 current amplitude in the same range of expression level. When expressed at a comparable low level, MiRP1 had similar (although smaller) effects on Kv4.3 but could not modulate Kv1.4 (another &agr; subunit of Ito channels in the heart). Kv4.2 could be coimmunoprecipitated with epitope-tagged MiRP1, indicating that the 2 could form a stable complex. Our data suggest that MiRP1 may serve as a regulatory (&bgr;) subunit of Ito channels in the heart. This is supported by the observation that MiRP1 induced an “overshoot” of Kv4.2 current amplitude during channel recovery from inactivation, similar to the overshoot of Ito described for human epicardial myocytes.
Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer

Exchange of information between the nucleus and cytosol depends on the metabolic state of the cell, yet the energy-supply pathways to the nuclear compartment are unknown. Here, the energetics of nucleocytoplasmic communication was determined by imaging import of a constitutive nuclear protein histone H1. Translocation of H1 through nuclear pores in cardiac cells relied on ATP supplied by mitochondrial oxidative phosphorylation, but not by glycolysis. Although mitochondria clustered around the nucleus, reducing the distance for energy transfer, simple nucleotide diffusion was insufficient to meet the energetic demands of nuclear transport. Rather, the integrated phosphotransfer network was required for delivery of high-energy phosphoryls from mitochondria to the nucleus. In neonatal cardiomyocytes with low creatine kinase activity, inhibition of adenylate kinase-catalyzed phosphotransfer abolished nuclear import. With deficient adenylate kinase, nucleoside diphosphate kinase, which secures phosphoryl exchange between ATP and GTP, was unable to sustain nuclear import. Up-regulation of creatine kinase phosphotransfer, to mimic metabolic conditions of adult cardiac cells, rescued H1 import, suggesting a developmental plasticity of the cellular energetic system. Thus, mitochondrial oxidative phosphorylation coupled with phosphotransfer relays provides an efficient energetic unit in support of nuclear transport.
TNF‐alpha inhibition reduces renal injury in DOCA‐salt hypertensive rats

We have previously shown that TNF‐α inhibition slowed the progression of hypertension and renal damage in salt‐sensitive hypertension. Thus, we hypothesize that TNF‐α contributes to renal injury in DOCA‐salt rats. Four groups of rats (n=5–6) were studied for 3 weeks with the following treatments 1) placebo, 2) placebo + TNF‐α inhibitor, etanercept (1.25 mg/kg/day, sc), 3) DOCA‐salt, or 4) DOCA‐salt + etanercept. Mean arterial blood pressure (MAP) measured by telemetry increased in DOCA‐salt rats compared to baseline (177±4 vs. 107±3 mmHg) and TNF‐α inhibition had no effect in the elevation in MAP in these rats (177±8 mmHg). Urinary protein excretion significantly increased in DOCA‐salt rats compared to placebo (703±76 vs. 198±5 mg/day, respectively); etanercept attenuated proteinuria in DOCA‐salt rats (514±64 mg/day). Urinary albumin excretion followed a similar pattern in each group. Urinary MCP‐1 and ET‐1 excretion were also increased in DOCA‐salt rats compared to placebo (MCP‐1: 939±104 vs. 43±7 ng/day, and ET‐1: 3.30±0.29 vs. 1.07±0.03 fmol/day, respectively); TNF‐α inhibition decreased both MCP‐1 and ET‐1 excretion (409±138 ng/day and 2.42±0.22 fmol/day, respectively). Renal cortical expression of ICAM‐1, NFκB, TGFβ, and TNF‐α mRNA increased in DOCA‐salt rats and etanercept reduced these changes. These data support the hypothesis that TNF‐α contributes to the increase in renal injury in DOCA‐salt rats, possibly through increased renal ET‐1 production.
Diverse cytokine production by NKT cell subsets and identification of an IL-17–producing CD4−NK1.1− NKT cell population

NKT cell subsets can be divided based on CD4 and NK1.1 expression and tissue of origin, but the developmental and functional relationships between the different subsets still are poorly understood. A comprehensive study of 19 cytokines across different NKT cell subsets revealed that no two NKT subpopulations exhibited the same cytokine profile, and, remarkably, the amounts of each cytokine produced varied by up to 100-fold or more among subsets. This study also revealed the existence of a population of CD4−NK1.1− NKT cells that produce high levels of the proinflammatory cytokine IL-17 within 2–3 h of activation. On intrathymic transfer these cells develop into mature CD4−NK1.1+ but not into CD4+NK1.1+ NKT cells, indicating that CD4−NK1.1− NKT cells include an IL-17–producing subpopulation, and also mark the elusive branch point for CD4+ and CD4− NKT cell sublineages.
Retinal hemorrhage as a consequence of epidural steroid injection.

OBJECTIVE To report that retinal hemorrhage is an important but uncommon complication of epidural steroid injection, a procedure frequently employed to alleviate chronic back pain. DESIGN Patients who complained of visual field defects or blurred vision after receiving the injection received complete eye examinations, including fundus photography and fluorescein angiography. They were then followed up as their clinical situation dictated. SETTING Patients were examined in an outpatient setting in our offices. PATIENTS Between 1989 and 1992, five eyes of four female patients ranging in age from 35 to 81 years were evaluated and followed up. RESULTS Examination and photographic documentation showed that these eyes had retinal hemorrhages, often distributed in a petaloid pattern, which resulted in transient loss of vision from 6 weeks to 6 months. CONCLUSIONS Retinal hemorrhage is an uncommon but significant and previously unemphasized complication of epidural steroid injection for chronic back pain. This procedure should be carefully considered, particularly in one-eyed patients and those with bleeding problems, and patients should be fully informed that this can happen despite appropriate care and technique.
Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines

p21/WAF1/CIP1/SDI1 is an important cell‐cycle mediator with tumor suppressor gene capabilities, and its inactivation could potentially lead to tumor progression. Because tumor suppressor genes are commonly inactivated by somatic and germline mutations, we analyzed a variety of human tumor cell lines for p21 mutations. We used single‐strand conformational analysis and direct sequencing to identify possible mutations in the p21 coding region. Two base‐alterations were observed in 41 immortalized human tumor cell lines. A previously reported polymorphism that results in a serine‐to‐arginine amino‐acid substitution at codon 31 was found in 24% (10 of 41) of the tumor cell lines but was also found in 10% (six of 62) of normal parental DNAs tested and 7% (three of 43) of normal DNAs from patients with primary endometrial tumors. Another nucleotide substitution found at codon 80 resulted in the replacement of threonine with methionine. Codon 80 changes were found in 7% (three of 41) of the tumor cell lines (all endometrial) and in 2% (one of 62) of the normal parental DNAs.
Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula-Fed Preterm Infants: Systematic Review and Meta-Analysis

Probiotics have been linked to a reduction in the incidence of necrotizing enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have also proved to reduce time to achieve full enteral feeding (FEF). However, the relationship between FEF achievement and type of feeding in infants treated with probiotics has not been explored yet. The aim of this systematic review and meta-analysis was to evaluate the effect of probiotics in reducing time to achieve FEF in preterm infants, according to type of feeding (exclusive human milk (HM) vs. formula). Randomized-controlled trials involving preterm infants receiving probiotics, and reporting on time to reach FEF were included in the systematic review. Trials reporting on outcome according to type of feeding (exclusive HM vs. formula) were included in the meta-analysis. Fixed-effect or random-effects models were used as appropriate. Results were expressed as mean difference (MD) with 95% confidence interval (CI). Twenty-five studies were included in the systematic review. In the five studies recruiting exclusively HM-fed preterm infants, those treated with probiotics reached FEF approximately 3 days before controls (MD −3.15 days (95% CI −5.25/−1.05), p = 0.003). None of the two studies reporting on exclusively formula-fed infants showed any difference between infants receiving probiotics and controls in terms of FEF achievement. The limited number of included studies did not allow testing for other subgroup differences between HM and formula-fed infants. However, if confirmed in further studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed preterm infants might have significant implications for their clinical management.
Establishing an Australian Nurse Practitioner‐Led Colorectal Cancer Screening Clinic

In Australia, colorectal cancer is the most commonly occurring internal cancer affecting both men and women, and the second most common cause of cancer-related death. Flexible sigmoidoscopy has not been commonly used as a screening tool in Australia due primarily to lack of resources. Until now, people at average risk of developing bowel cancer frequently undergo colonoscopy after referral to a specialist. To fill an identified need, a nurse practitioner-led colorectal screening service providing fecal occult blood testing and flexible sigmoidoscopy, health education and promotion, patient counseling, information and a referral point for general practitioners, and a referral service for above average-risk patients was established in a South Australian metropolitan teaching hospital. Establishment of this clinic required advanced and extended theoretical and clinical preparation for the nurse practitioner, as well as development of interdisciplinary relationships, referral processes, clinical infrastructure, and a marketing strategy. An audit of the first 100 flexible sigmoidoscopy patients revealed service and procedural outcomes that compared favorably with other colorectal screening services as well as a high level of patient satisfaction.