Miracle-dz/UniFAR-FTUs huggingface dataset:
FoxO1‐AMPK‐ULK1 Regulates Ethanol‐Induced Autophagy in Muscle by Enhanced ATG14 Association with the BECN1‐PIK3C3 Complex

BACKGROUND Excessive alcohol (EtOH) consumption causes an imbalance in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces protein degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK. METHODS C2C12 myoblasts were incubated with EtOH for various periods of time, and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation. Expression of targeted genes was suppressed using electroporation of specific siRNAs and chemical inhibitors. RESULTS Incubation of C2C12 myoblasts with 100 mM EtOH increased the autophagy markers LC3B-II and ATG7, whereas levels of SQSTM1/p62 decreased. The lysosomal inhibitor bafilomycin A1 caused a similar response, although there was no additive effect when combined with EtOH. EtOH altered ULK1 S555 and S757 phosphorylation in a time- and AMPK-dependent manner. The activation of AMPK and ULK1 was associated with increased BECN1 (S93, S14) and PIK3C3/VPS34 (S164) phosphorylation as well as increased total ATG14 and PIK3C3. These changes promoted formation of the ATG14-AMBRA1-BECN1-PIK3C3 proautophagy complex that is important in autophagosome formation. EtOH-induced changes were not associated with increased production of PtdIns3P, which may be due to enhanced PIK3C3 complex binding with 14-3-3θ. Reduction of AMPK using siRNA suppressed the stimulatory effect of EtOH on BECN1 S93, BECN1 S14, and PIK3C3 S164 phosphorylation in a time-dependent manner. Likewise, knockdown of AMPK or chemical inhibition of FoxO1 attenuated phosphorylation of ULK1 at both residues. Knockdown of ULK1 or BECN1 antagonized the effect of EtOH on LC3B-II, SQSTM1, and ATG7 protein expression. CONCLUSIONS EtOH-induced autophagy is mediated through changes in phosphorylation and interaction of various PIK3C3 complex components. This, in turn, is regulated either directly via FoxO1-AMPK or indirectly via the FoxO1-AMPK-ULK1 signaling cascade in a mTORC1-independent or mTORC1-dependent manner.
Infrared Laser Improves Collagen Organization in Muscle and Tendon Tissue During the Process of Compensatory Overload.

BACKGROUND The photobiomodulation using the low-level laser therapy (LLLT) exerts a positive modulating effect on the synthesis of collagen in skeletal muscles and tendons. However, few studies have addressed this effect during the compensatory overload. OBJECTIVE Evaluate the effect of infrared laser on the deposition and organization of collagen fibers in muscle and tendon tissue during compensatory overload of the plantar muscle in rats. MATERIALS AND METHODS Wistar rats were submitted to bilateral ablation of the synergist muscles of the hind paws and divided in groups: Control, Hypertrophy, and Hypertrophy (H)+LLLT (780 nm, 40 mW, 9.6 J/cm2 and 10 s/point, 8 points, total energy 3.2 J, daily), evaluated at 7 and 14 days. Muscle cuts were stained with Picrosirius-Red and hematoxylin-eosin and tendon cuts were submitted to birefringence for determination of collagen distribution and organization. RESULTS After 7 days an increase was observed in the area between beam muscles in H+LLLT (25.45% ± 2.56) in comparison to H (20.3% ± 3.31), in mature fibers and fibrilis in H+LLLT (29346.88 μm2 ± 2182.56; 47602.8 μm2 ± 2201.86 respectively) in comparison to H (26656.5 μm2 ± 1880.46; 45630.34 μm2 ± 2805.82 respectively) and in the collagen area in H+LLLT (2.25% ± 0.19) in comparison to H (2.0% ± 0.15). However, after 14 days a reduction was observed in the area between beam muscles in H+LLLT (13.88% ± 2.54) in comparison to H (19.1% ± 2.61), in fibrils and mature fibers in H+LLLT (17174.1 μm2 ± 2563.82; 32634.04 μm2 ± 1689.38 respectively) in comparison to H (55249.86 μm2 ± 1992.65; 44318.36 μm2 ± 1759.57) and in the collagen area in H+LLLT (1.76% ± 0.16) in comparison to H (2.09 ± 0.27). A greater organization of collagen fibers in the tendon was observed after 7 and 14 days in H+LLLT groups. CONCLUSIONS Infrared laser irradiation induces an improvement in collagen organization in tendons and a reduction in the total area of collagen in muscles during compensatory atrophy following the ablation of synergist muscles.
Impact of a Stress Management Intervention Program on Sexual Functioning and Stress Reduction in Women with Breast Cancer

Breast cancer as the most common cancer among women endangers various aspects of their sexual lives and is a major culprit regarding health impairment and low life quality. The aim of this study was to examine the effect of a stress management intervention program on sexual functioning and stress reduction in women with breast cancer. This study employed a quasi-experimental pre-test, post-test design which included follow-up checks and a control group. To this end, 104 women with breast cancer referring to Hamadan’s Mahdiyeh MRI Center at the time of data collection were conventionally selected in 2015. Using permuted blocks, they were randomly divided into experimental and control groups (n= 52), only the former receiving stress management counseling for 18 hours. Data were collected through a demographic questionnaire, the Female Sexual Function Index (FSFI) questionnaire, and Harry’s stress questionnaire, filled out by patients before and after the intervention. To analyze the data, descriptive statistics and two-way ANOVA were used. The results showed that cognitive - behavioral stress management group therapy improved total sexual functioning and its subscales. After the treatment, there was a significant difference in mean scores between the groups (p=0.01). Moreover, significant differences were observed in the mean scores for stress with improvement in the experimental group in post-test results. Cognitive - behavioral group therapy for stress management was thuis found to improve total sexual functioning and its subscales and reduce the level of stress in the experimental group after the intervention and follow-up period with an interval of two weeks. Therefore, this method can be used as a complementary therapy along with medical treatment in oncology centers.
Identification and Characterization of an Unusual Double Serine/Threonine Protein Phosphatase 2C in the Malaria ParasitePlasmodium falciparum *

We have cloned a gene from Plasmodium falciparum with homology to the Mg2+-dependent serine/threonine protein phosphatase 2C (PP2C) family. The predicted coding region is 920 amino acids long, twice the size of other members of this family. We show that this protein can be divided into two halves (Pf2C-1 and Pf2C-2), each a complete phosphatase unit with homology to other phosphatases of this class. To study the function of this PP2C, we have tested the ability of different constructs to complement conditional null mutants of yeast. Our results show that expression of the full-length protein, the first half alone, the second half alone, or a hybrid with the N terminus of the first half and the C terminus of the second half was able to complement the heat shock response defect of aSchizosaccharomyces pombe strain with a PP2C (PTC1) deletion. Recombinant P. falciparum PP2C expressed in Escherichia coli was active in dephosphorylating 32P-labeled casein in an Mg2+- or Mn2+-dependent reaction. Each half alone was also active in recombinant form. Using the two-hybrid system, we have shown that the two halves can interact. Gel filtration assay of P. falciparum protein extracts suggests that full-length PfPP2C is a dimer, and phosphatase activity competition experiments indicate that dimerization of PfPP2C is required for its optimal activity. This unusual phosphatase molecule appears to be composed of four catalytic units on two polypeptide chains.
Glucose-Induced Trophic Shift in an Endosymbiont Dinoflagellate with Physiological and Molecular Consequences1[OPEN]

Glucose induces dramatic physiological changes in the dinoflagellate Symbiodinium strain SSB01, although there is very little modulation of nuclear gene expression. Interactions between the dinoflagellate endosymbiont Symbiodinium and its cnidarian hosts (e.g. corals, sea anemones) are the foundation of coral-reef ecosystems. Carbon flow between the partners is a hallmark of this mutualism, but the mechanisms governing this flow and its impact on symbiosis remain poorly understood. We showed previously that although Symbiodinium strain SSB01 can grow photoautotrophically, it can grow mixotrophically or heterotrophically when supplied with Glc, a metabolite normally transferred from the alga to its host. Here we show that Glc supplementation of SSB01 cultures causes a loss of pigmentation and photosynthetic activity, disorganization of thylakoid membranes, accumulation of lipid bodies, and alterations of cell-surface morphology. We used global transcriptome analyses to determine if these physiological changes were correlated with changes in gene expression. Glc-supplemented cells exhibited a marked reduction in levels of plastid transcripts encoding photosynthetic proteins, although most nuclear-encoded transcripts (including those for proteins involved in lipid synthesis and formation of the extracellular matrix) exhibited little change in their abundances. However, the altered carbon metabolism in Glc-supplemented cells was correlated with modest alterations (approximately 2x) in the levels of some nuclear-encoded transcripts for sugar transporters. Finally, Glc-bleached SSB01 cells appeared unable to efficiently populate anemone larvae. Together, these results suggest links between energy metabolism and cellular physiology, morphology, and symbiotic interactions. However, the results also show that in contrast to many other organisms, Symbiodinium can undergo dramatic physiological changes that are not reflected by major changes in the abundances of nuclear-encoded transcripts and thus presumably reflect posttranscriptional regulatory processes.
[Clinico-epidemiologic study of infantile hydrocephalus in Japan].

A nation-wide survey on congenital hydrocephalus, including secondary hydrocephalus occurring within one year after birth, was carried out in 1988. The number of patients with congenital hydrocephalus treated during the previous one year was estimated to be 3,200-3,500 throughout Japan. The number of new cases of this disease which occurred during the year was calculated to be 800. This indicates a rate of 0.58 per 1,000 live births. Clinico-epidemiologic features were compared with regard to three subjects listed below. (1) The difference between the epidemiologic profile of term and preterm infants with hydrocephalus was investigated. As for etiology, the incidences of primary hydrocephalus and hydrocephalus complicated by Arnold-Chiari malformation type II and meningocele were significantly higher in term infants than in preterm infants. It was estimated that about 30% of the hydrocephalus in preterm infants and only 7.7% in term infants occurred as a consequence of intracranial hemorrhage. The degree of neurological impairment and the mortality rate were higher in preterm infants than term infants. (2) The changing panorama of infantile hydrocephalus in Japan was investigated comparing the epidemiologic data of four groups according to the birth year. As for pregnancy period, preterm infants with hydrocephalus were gradually increasing recently. Hydrocephalus secondary to intracranial hemorrhage was increasing and that secondary to intracranial infection was decreasing. The rate of shunt malfunction was decreasing significantly. (3) Clinico-epidemiologic features of intractable hydrocephalus based on the diagnostic criteria of the research committee was investigated comparing intractable with non-intractable groups. (ABSTRACT TRUNCATED AT 250 WORDS)
The Road to Language Learning Is Iconic

An arbitrary link between linguistic form and meaning is generally considered a universal feature of language. However, iconic (i.e., nonarbitrary) mappings between properties of meaning and features of linguistic form are also widely present across languages, especially signed languages. Although recent research has shown a role for sign iconicity in language processing, research on the role of iconicity in sign-language development has been mixed. In this article, we present clear evidence that iconicity plays a role in sign-language acquisition for both the comprehension and production of signs. Signed languages were taken as a starting point because they tend to encode a higher degree of iconic form-meaning mappings in their lexicons than spoken languages do, but our findings are more broadly applicable: Specifically, we hypothesize that iconicity is fundamental to all languages (signed and spoken) and that it serves to bridge the gap between linguistic form and human experience.
Determining the level of ability of football teams by dynamic ratings based on the relative discrepancies in scores between adversaries

Abstract A rating system provides relative measures of superiority between adversaries. We propose a novel and simple approach, which we call pi-rating, for dynamically rating Association Football teams solely on the basis of the relative discrepancies in scores through relevant match instances. The pi-rating system is applicable to any other sport where the score is considered as a good indicator for prediction purposes, as well as determining the relative performances between adversaries. In an attempt to examine how well the ratings capture a team’s performance, we have a) assessed them against two recently proposed football ELO rating variants and b) used them as the basis of a football betting strategy against published market odds. The results show that the pi-ratings outperform considerably the widely accepted ELO ratings and, perhaps more importantly, demonstrate profitability over a period of five English Premier League seasons (2007/2008–2011/2012), even allowing for the bookmakers’ built-in profit margin. This is the first academic study to demonstrate profitability against market odds using such a relatively simple technique, and the resulting pi-ratings can be incorporated as parameters into other more sophisticated models in an attempt to further enhance forecasting capability.
Integrating chytrid fungal parasites into plankton ecology: research gaps and needs

Chytridiomycota, often referred to as chytrids, can be virulent parasites with the potential to inflict mass mortalities on hosts, causing e.g. changes in phytoplankton size distributions and succession, and the delay or suppression of bloom events. Molecular environmental surveys have revealed an unexpectedly large diversity of chytrids across a wide range of aquatic ecosystems worldwide. As a result, scientific interest towards fungal parasites of phytoplankton has been gaining momentum in the past few years. Yet, we still know little about the ecology of chytrids, their life cycles, phylogeny, host specificity and range. Information on the contribution of chytrids to trophic interactions, as well as co-evolutionary feedbacks of fungal parasitism on host populations is also limited. This paper synthesizes ideas stressing the multifaceted biological relevance of phytoplankton chytridiomycosis, resulting from discussions among an international team of chytrid researchers. It presents our view on the most pressing research needs for promoting the integration of chytrid fungi into aquatic ecology.
Asymmetric Information and the Pecking (Dis)Order

In this paper we show that when growth options represent a significant component of overall firm value, equity financing can dominate (i.e., be less dilutive than) debt financing under asymmetric information. In particular, we find that equity is more likely to dominate debt for younger firms with larger investment needs and with riskier growth opportunities. Thus, our model can explain why high-growth firms may prefer equity over debt, and then switch to debt as they mature. We also fid that equity financing is relatively more attractive when a firm already has debt in its capital structure. In addition, equity can dominate debt in multidivisional firms. Finally, we provide new predictions on the cross-sectional variation of capital structures.
Performance Analysis of Millimeter-Wave Multi-hop Machine-to-Machine Networks Based on Hop Distance Statistics

As an intrinsic part of the Internet of Things (IoT) ecosystem, machine-to-machine (M2M) communications are expected to provide ubiquitous connectivity between machines. Millimeter-wave (mmWave) communication is another promising technology for the future communication systems to alleviate the pressure of scarce spectrum resources. For this reason, in this paper, we consider multi-hop M2M communications, where a machine-type communication (MTC) device with the limited transmit power relays to help other devices using mmWave. To be specific, we focus on hop distance statistics and their impacts on system performances in multi-hop wireless networks (MWNs) with directional antenna arrays in mmWave for M2M communications. Different from microwave systems, in mmWave communications, wireless channel suffers from blockage by obstacles that heavily attenuate line-of-sight signals, which may result in limited per-hop progress in MWNs. We consider two routing strategies aiming at different types of applications and derive the probability distributions of their hop distances. Moreover, we provide their baseline statistics assuming the blockage-free scenario to quantify the impact of blockages. Based on the hop distance analysis, we propose a method to estimate the end-to-end performances (e.g., outage probability, hop count, and transmit energy) of the mmWave MWNs, which provides important insights into mmWave MWN design without time-consuming and repetitive end-to-end simulation.
Efficacy of an asynchronous electronic curriculum in emergency medicine education in the United States

Purpose The aim of this study was to measure the effect of an iPad-based asynchronous curriculum on emergency medicine resident performance on the in-training exam (ITE). We hypothesized that the implementation of an asynchronous curriculum (replacing 1 hour of weekly didactic time) would result in non-inferior ITE scores compared to the historical scores of residents who had participated in the traditional 5-hour weekly didactic curriculum. Methods The study was a retrospective, non-inferiority study. conducted at the University of California, Irvine Emergency Medicine Residency Program. We compared ITE scores from 2012 and 2013, when there were 5 weekly hours of didactic content, with scores from 2014 and 2015, when 1 hour of conference was replaced with asynchro-nous content. Examination results were compared using a non-inferiority data analysis with a 10% margin of difference. Results Using a non-inferiority test with a 95% confidence interval, there was no difference between the 2 groups (before and after implementation of asynchronous learning), as the confidence interval for the change of the ITE was −3.5 to 2.3 points, whereas the 10% non-inferiority margin was 7.8 points. Conclusion Replacing 1 hour of didactic conference with asynchronous learning showed no negative impact on resident ITE scores.
Childhood Maltreatment, Self-esteem, and Suicidal Ideation in a Low-SES Emerging Adult Sample: The Moderating Role of Heart Rate Variability

Childhood maltreatment is associated with risk for suicidal ideation later in life, yet more research is needed on the indirect effects and bioregulatory protective factors in this association. The present study aimed to investigate the indirect influence of childhood maltreatment on suicidal ideation in emerging adulthood via level of self-esteem, and examine the moderating role of heart rate variability (HRV; a proxy for emotion regulation) in this indirect association. The study included a sample of 167 non-metropolitan emerging adults (Mage = 21.17, 55.8% female) of low-socioeconomic status (low-SES). HRV data were obained using an electrocardigram, whereas childhood maltreatment, suicidal ideation, and self-esteem data were obtained via self-report. Childhood maltreatment was indirectly associated with suicidal ideation via reduced self-esteem. HRV buffered this indirect association. Childhood maltreatment poses a risk for the development of suicidal ideation. Interventions that bolster self-esteem and emotion regulation may reduce suicide risk for emerging adults with a history of childhood maltreatment.
Innervation zone of the vastus medialis muscle: position and effect on surface EMG variables

The aim of this study was to investigate the position of the innervation zone (IZ) of the vastus medialis (VM) and its effect on the electromyographic (EMG) amplitude and mean frequency estimates. Eighteen healthy subjects performed maximal isometric knee extensions at three knee angles. Surface EMG signals were collected by using a 16 × 8 electrode grid placed on the VM muscle. The position of the IZ was estimated through visual analysis, and traditional bipolar signals were obtained from channels over and away from it; amplitude and mean frequency values were extracted and compared using an analysis of variance (ANOVA) with repeated measures. The IZ is shaped as a line running from the proximal–lateral to the distal–medial aspect of the VM muscle. The presence of an IZ under the electrodes lowered the EMG amplitude (P < 0.001, F = 58.11) and increased the EMG mean frequency (P < 0.001, F = 26.47); variations of these parameters due to the knee flexion angle were less frequently observed in EMG signals collected over than away from the IZ. Electrodes placed ‘over the belly of the VM muscle’ are likely to collect EMG signals influenced by the presence of the IZ, thus hindering the detection of changes in muscle activity.
Stem cell transplantation for primary immunodeficiency diseases: the North American experience

Purpose of reviewThis review describes recent studies on outcomes after allogeneic hematopoietic cell transplantation for primary immunodeficiency in North America, including severe combined immunodeficiency (SCID), Wiskott–Aldrich syndrome and chronic granulomatous disease. Recent findingsUsing uniform diagnostic criteria, the Primary Immune Deficiency Treatment Consortium described the baseline characteristics of newly diagnosed infants with SCID in North America. Analysis of outcomes of hematopoietic cell transplantation for SCID in North America from 2000 to 2009 showed that young infants, and older infants without active infection, had excellent survival irrespective of type of donor or transplant approach with regard to conditioning. Although pretransplant conditioning with chemotherapy had a clear and strong negative impact on survival in infants with active infection at the time of transplant, among survivors, conditioning was associated with improved immune reconstitution. However, the potential late effects of conditioning in these infants remain to be characterized. Advances in transplant outcomes for Wiskott–Aldrich syndrome and chronic granulomatous disease support the strategy of early transplantation before the onset of severe complications; additional multicenter studies are needed to fully define optimal approaches. SummaryThe formation of the Primary Immune Deficiency Treatment Consortium, a multiinstitutional North American consortium, has contributed to our understanding of outcomes after transplant for primary immunodeficiency.