Predicting types of human-related maritime accidents with explanations using selective ensemble learning and SHAP method.

Maritime accidents frequently lead to severe property damage and casualties, and an accurate and reliable risk prediction model is necessary to help maritime stakeholders assess the current risk situation. Therefore, the present study proposes a hybrid methodology to develop an explainable prediction model for maritime accident types. Based on the advantages of selective ensemble learning method, this study pioneers to introduce a two-stage model selection method, aiming to enhance the predictive accuracy and stability of the model. Then, SHAP (Shapley Additive Explanations) method is integrated to identify effective mapping associations of seafarers' unsafe acts and their risk factors with the prediction results. The results demonstrate that the model developed achieves good prediction performance with an accuracy of 87.50 % and an F1-score of 84.98 %, which benefits stakeholders in assessing the type of maritime accident in advance, so as to make proactive intervention measures.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

[Effect of Ca2+ on the Nitrification Activity and the Flocculation and Sedimentation Performances of the Activated Sludge].

Ca2+ is an important microbial growth factor that can affect the activity, flocculation, and sedimentation of activated sludge. In order to study the roles of Ca2+ in the activated sludge system, the activity changes of ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) were analyzed using the specific oxygen uptake rates (SOURAOB and SOURNOB). The changes in composition and structure of extracellular polymeric substances (EPS) were analyzed using Fourier transform infrared spectroscopy (FTIR) and three-dimensional excitation emission fluorescence spectroscopy (3D-EEM). The effects of Ca2+on the nitrification activity and microbial metabolites were investigated. The results showed that when the Ca2+concentration increased from 0.45 mmol·L-1 to 3 mmol·L-1, SOURAOB and SOURNOB increased from 6.3 mg·(g·h)-1 to 10.4 mg·(g·h)-1 and from 2.3 mg·(g·h)-1 to 3.7 mg·(g·h)-1, respectively. The EPS concentrations increased from 68 mg·g-1 to 93 mg·g-1, and the flocculation ability (FA) of the sludge was improved. When the Ca2+ concentration was higher than 3 mmol·L-1, SOURAOB and SOURNOBboth decreased. The FA was maintained at about 30%, and the particle size of the sludge continued to increase. Based on FTIR analysis, the main components of EPS were always amino, amide Ⅰ, and carboxyl with an increase in Ca2+ concentration. Based on EEM analysis, the composition of loosely-bound (LB)-EPS did not change, and humic acid substances appeared in the tightly-bound (TB)-EPS at low nitrification rates. Low concentrations of Ca2+ promoted nitrification activity and flocculation of the sludge. However, high concentrations of Ca2+ led to a decline in the sludge nitrification activity.

A Discovery of a Genetic Mutation Causing Reduction of Atrogin-1 Expression in Broiler Chicken Muscle.

Chickens are bred all over the world and have significant economic value as one of the major agricultural animals. The growth rate of commercial broiler chickens is several times higher than its Red Jungle fowl (RJF) ancestor. To further improve the meat production of commercial chickens, it is quite important to decipher the genetic mechanism of chicken growth traits. In this study, we found that broiler chickens exhibited lower levels of E3 ubiquitin ligase muscle atrophy F-box (MAFbx or Atrogin-1) relative to its RJF ancestor. As a ubiquitin ligase, Atrogin-1 plays a crucial role in muscle development in which its up-regulation often indicates the activation of muscle atrophic pathways. Here, we showed that the Atrogin-1 expression variance partly affects chicken muscle growth rates among different breeds. Furthermore, we demonstrated that the reduced expression of Atrogin-1 in broiler chickens was ascribed to a single nucleotide polymorphism (SNP), which inhibited the binding of transcription regulators and attenuated the enhancer activity. The decreased Atrogin-1 in broiler chickens suppresses the catabolism of muscle protein and preserves muscle mass. Our study facilitates the understanding of the molecular mechanism of chicken muscle development and has a high translational impact in chicken breeding.

[Research progress on analysis methods in electroencephalography-electromyography synchronous coupling].

The motor nervous system transmits motion control information through nervous oscillations, which causes the synchronous oscillatory activity of the corresponding muscle to reflect the motion response information and give the cerebral cortex feedback, so that it can sense the state of the limbs. This synchronous oscillatory activity can reflect connectivity information of electroencephalography-electromyography (EEG-EMG) functional coupling. The strength of the coupling is determined by various factors including the strength of muscle contraction, attention, motion intention etc. It is very significant to study motor functional evaluation and control methods to analyze the changes of EEG-EMG synchronous coupling caused by different factors. This article mainly introduces and compares coherence and Granger causality of linear methods, the mutual information and transfer entropy of nonlinear methods in EEG-EMG synchronous coupling, and summarizes the application of each method, so that researchers in related fields can understand the current research progress on analysis methods of EEG-EMG synchronous systematically.

[Effect of NaCl Salinity on Extracellular Polymeric Substances and Bioflocculation of Anoxic Sludge in A2/O Process].

In order to improve the biological removal efficiency of nitrogen and phosphorus and bioflocculation performance of salt-containing wastewater, the effect of NaCl salinity on the efficiency of denitrification and phosphorus removal in the anoxic zone of an A2/O process was investigated. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) were used to analyze the composition and structure of extracellular polymeric substances (EPS) in activated sludge of the anoxic zone, to discern the effect of salinity on bioflocculation. Results showed that when NaCl salinity was 0-5 g·L-1, flocculation ability (FA) in A2/O anoxic zone was about 44% and the sludge particle size was 45.5 µm. EPS content increased from 52.3 mg·L-1 to 62 mg·L-1 and protein (PN)/polysaccharide (PS) remained at 2.1. When NaCl salinity increased from 10 g·L-1 to 40 g·L-1, bioflocculation of sludge significantly decreased. FA decreased from 40% to 22% and sludge particle size decreased from 43.7 µm to 32.1 µm. EPS content increased from 76.5 mg·L-1 to 101.0 mg·L-1 and PN/PS decreased from 1.5 to 1.3. Based on FTIR analysis, with increase in salinity, the main components of EPS were always amino, amideⅠ, and carboxyl. Based on XPS analysis, increasing salinity led to charge transfer of some groups (such as C, O, and N groups) during the interaction between EPS and Na+, but its form did not change.

Improvement of Adipose Macrophage Polarization in High Fat Diet-Induced Obese GHSR Knockout Mice.

PURPOSE: Adipose tissue inflammation is the key linking obesity to insulin resistance. Over 50% of the interstitial cells in adipose tissue are macrophages, which produce inflammatory cytokines and therefore play an important role in the progression of insulin resistance. Within this classification view, macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). The unique functional receptor of ghrelin, growth hormone secretagogue receptor (GHSR), is a classic seven-transmembrane G protein-coupled receptor that is linked to multiple intracellular signaling pathways. Knockout of GHSR improves the obesity and glucose metabolic disorders, suggesting a crucial role of ghrelin activity in insulin resistance. Here, we discussed whether macrophage polarization phenotypes in adipose tissue were changed in GHSR knockout (GHSR-/-) mice. METHODS: GHSR-/- mice were fed with normal chow diet (NCD) or high fat diet (HFD). Markers of different macrophage polarization phenotypes were detected by real-time RT-PCR. RESULTS: The size of adipocytes decreased and interstitial cells, especially infiltrated macrophages, reduced in epididymal adipose tissue of GHSR-/- mice fed with HFD. Compared with wild type mice, the mRNA levels of inflammatory adipokines such as resistin, IL-6, and PAI-1 were significantly lower in epididymal adipose tissue of GHSR-/- mice, whereas anti-inflammatory adipokine, adiponectin, was significantly higher. M1 markers, MCP-1, TNF-α, and iNOS, were significantly lower in epididymal adipose tissue of GHSR-/- mice, whereas M2 markers, Arg-1, Mgl-1, were Mrc1, were significantly higher. CONCLUSION: The GHSR-/- mice fed with HFD showed suppressed adipose inflammation, reduced macrophage infiltration, and enhanced M2 polarization of macrophages in adipose tissue, which improved insulin sensitivity.

Ghrelin Stimulates Endothelial Cells Angiogenesis through Extracellular Regulated Protein Kinases (ERK) Signaling Pathway.

Adipose tissue is hyper-vascularized. Vessels in adipose tissue not only supply nutrients and oxygen to nourish adipocytes, but also provide cytokines that regulate mass and function of adipose tissue. Understanding the fundamental mechanisms how vessels modulate adipocyte functions would provide new therapeutic options for treatment of metabolic disease and obesity. In recent years, researches about ghrelin are focused on glucose and lipid metabolism, but its effect on vascular function remains uncharacterized. In the present study, ghrelin receptor gene deletion mice (Ghsr-/- mice) were used to study ghrelin-regulated vascular metabolism in white adipose tissue. Ghsr-/- mice demonstrated lower food intake, lower body weight, and resistance to high-fat diet-induced obesity. The number of vessels in white adipose tissue was decreased in Ghsr-/- mice when compared with wild type mice fed with high-fat diet. To further define ghrelin effects in vitro, we used endothelial progenitor cells from wild type and Ghsr-/- mice as well as human umbilical vein endothelial cells in our experiments. We found that ghrelin stimulated endothelial cells angiogenesis and migration through the MEK-ERK signaling pathway. [d-Lys3]-GHRP-6 and PD98059 could reverse the effects of ghrelin on endothelial cells. Our study indicates that ghrelin activates its receptor on endothelial cells to promote angiogenesis and migration via a mechanism involving the extracellular regulated protein kinases (ERK) signaling pathway.

[Preparation of Mn-Co/Ceramic Honeycomb Catalyst and Its Performance on Catalytic Ozonation of Hydroquinone].

In order to improve the activity and working life of metal catalysts in the heterogeneous catalytic ozonation of organic wastewater, four kinds of Mn-Co/ceramic honeycomb (CH) catalysts with different mass ratios of Mn and Co were prepared by coating method using cobalt nitrate hexahydrate [Co(NO3)2·6H2O] and manganese nitrate [Mn(NO3)2] as precursors, respectively, and CH as the carrier. The structure of the catalysts was analyzed via X-ray diffraction (XRD), N2 adsorption/desorption, field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). The mechanical properties of the catalysts were studied. The reaction kinetics model of O3 alone and catalytic ozonation of the hydroquinone were established and catalytic ozonation performance of catalysts was investigated. The results showed that the crystal phase of Mn0Co1/CH belonged to CoAl2O4 and that the crystal phase of the Mn-Co/CH catalyst (Mn1Co1, Mn2Co1, and Mn3Co1) mainly belonged to Mn3O4 and CoO. In particular, the Mn1Co1/CH catalyst had a large specific surface area of 190 m2·g-1, high pore volume of 0.25 cm3·g-1, and pore size of 4.8 nm. The highest catalytic activity was obtained when Mn∶Co was 1∶1 (Mn1Co1/CH catalyst). The catalytic activity of the Mn1Co1/CH catalyst was the highest, and removal efficiencies of hydroquinone and COD were 78% and 54%, respectively, using Mn1Co1/CH catalytic ozonation. The Mn-Co/CH catalyst had a high compressive strength (15.89-16.94 MPa). The degradation efficiency of hydroquinone decreased significantly after the addition of tert-butanol, which indicated that·OH played an important role in the Mn1Co1/CH catalytic ozonation. The catalytic ozonation process fitted the first-order kinetic model. The apparent rate constant k for O3 alone was only 0.0306. Furthermore, the Mn1Co1/CH catalyst had the highest rate, with an apparent rate constant k of 0.0535 min-1. The Mn-Co/CH catalyst was easy to industrialize owing to its lower consumption, excellent catalytic characteristics, and long working life.

Impact on acute myeloid leukemia relapse in granulocyte colony-stimulating factor application: a meta-analysis.

OBJECTIVES: This meta-analysis evaluated the impact of granulocyte colony-stimulating factor (G-CSF) added to chemotherapy on treatment outcomes including survival and disease recurrence in patients with acute myeloid leukemia (AML). METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 19 September 2016 using search terms. Studies that investigated patients with AML who underwent stem-cell transplantation were included. RESULTS: The overall analysis revealed a significant improvement in overall survival (OS) (P = .019) and disease-free survival (DFS) (P = .002) for patients receiving G-CSF with chemotherapy. Among patients without prior AML treatment, there was a significant improvement in DFS (P = .014) and reduction in incidence of relapse (P = .015) for those who received G-CSF. However, subgroup analyses found no significant difference between G-CSF (+) and G-CSF (-) treatments in rates of OS (P = .104) and complete remission (CR) (P = .572) for patients without prior AML treatment. Among patients with relapsed/refractory AML, there was no significant difference found between G-CSF (+) and G-CSF (-) groups for OS (P = .225), DFS (P = .209), and CR (P = .208). DISCUSSION: Treatment with chemotherapy plus G-CSF appears to provide better survival and treatment responses compared with chemotherapy alone, particularly for patients with previously untreated AML. ABBREVIATIONS: AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission; DFS, disease-free survival; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; HR, hazard ratio; MDS, myelodysplastic syndrome; OR, odds ratio; OS, overall survival; RCTs, randomized control trials; RR, relative risk.

Derivation of Transgene-Free Rat Induced Pluripotent Stem Cells Approximating the Quality of Embryonic Stem Cells.

Although a variety of reprogramming strategies have been reported to create transgene-free induced pluripotent stem (iPS) cells from differentiated cell sources, a fundamental question still remains: Can we generate safe iPS cells that have the full spectrum of features of corresponding embryonic stem (ES) cells? Studies in transgene-free mouse iPS cells have indicated a positive answer to this question. However, the reality is that no other species have a derived transgene-free iPS cell line that can truly mimic ES cell quality. Specifically, critical data for chimera formation and germline transmission are generally lacking. To date, the rat is the only species, other than the mouse, that has commonly recognized authentic ES cells that can be used for direct comparison with measure features of iPS cells. To help find the underlying reasons of the current inability to derive germline-competent ES/iPS cells in nonrodent animals, we first used optimized culture conditions to isolate and establish rat ES cell lines and demonstrated they are fully competent for chimeric formation and germline transmission. We then used episomal vectors bearing eight reprogramming genes to improve rat iPS (riPS) cell generation from Sprague-Dawley rat embryonic fibroblasts. The obtained transgene-free riPS cells exhibit the typical characteristics of pluripotent stem cells; moreover, they are amenable to subsequent genetic modification by homologous recombination. Although they can contribute significantly to chimeric formation, no germline transmission has been achieved. Although this partial success in achieving competency is encouraging, it suggests that more efforts are still needed to derive ground-state riPS cells. Stem Cells Translational Medicine 2017;6:340-351.

Efficient generation of selection-gene-free rat knockout models by homologous recombination in ES cells.

Embryonic stem cell (ES cell)-based rat knockout technology, although successfully developed in 2010, has seen very limited usage to date due to low targeting efficiency and a lack of optimized procedures. In this study, we performed gene targeting in ES cells from the Sprague-Dawley (SD) and the Fischer 344 (F344) rat strains using an optimized procedure and the self-excising neomycin (neo)-positive selection cassette ACN to successfully generate Leptin and Trp53 knockout rats that did not carry the selection gene. These results demonstrate that our simplified targeting strategy using ACN provides an efficient approach to knock out many other rat genes.

The Association Between HIV Disclosure Status and Perceived Barriers to Care Faced by Women Living with HIV in Latin America, China, Central/Eastern Europe, and Western Europe/Canada.

Generally, women are less likely than men to disclose their HIV status. This analysis examined the relationship between HIV disclosure and (1) perceived barriers to care and (2) quality of life (QoL) for women with HIV. The ELLA (EpidemioLogical study to investigate the popuLation and disease characteristics, barriers to care, and quAlity of life for women living with HIV) study enrolled HIV-positive women aged ≥18 years. Women completed the 12-item Barriers to Care Scale (BACS) questionnaire. QoL was assessed using the Health Status Assessment. BACS and QoL were stratified by dichotomized HIV disclosure status (to anyone outside the healthcare system). Multilevel logistic regression analysis was used to identify factors associated with disclosure. Of 1945 patients enrolled from Latin America, China, Central/Eastern Europe, and Western Europe/Canada between July 2012 and September 2013, 1929 were included in the analysis (disclosed, n = 1724; nondisclosed, n = 205). Overall, 55% of patients lived with a husband/partner, 53% were employed, and 88% were receiving antiretroviral therapy. Patients who were with a serodiscordant partner were more likely to disclose (p = 0.0003). China had a disproportionately higher percentage of participants who did not disclose at all (nearly 30% vs. <15% for other regions). Mean BACS severity scores for medical/psychological service barriers and most personal resource barriers were significantly lower for the disclosed group compared with the nondisclosed group (p ≤ 0.02 for all). Compared with the disclosed group, the nondisclosed group reported statistically significantly higher (p ≤ 0.03) BACS item severity scores for 8 of the 12 potential barriers to care. The disclosed group reported better QoL. Overall, HIV nondisclosure was associated with more severe barriers to accessing healthcare by women with HIV.

[Distribution Characteristics of Antibiotic Resistance Genes in Vegetable Soils in Beijing].

In order to study the distribution characteristics and pollution status of antibiotic resistance genes (ARGs) in the vegetable soils, greenhouse and field soil samples in 11 organic vegetable bases with long-term manure amended in Beijing were collected. All samples were subjected to the determination of 13-type antibiotics and related ARGs. The experimental results showed that tetracycline residues were the highest among all antibiotics tested, followed by sulfanilamides. Antibiotic residues were higher in greenhouse soils than in field soils. For all soil samples, sulfanilamide resistance genes sul 1 and sul 2, as well as the tetracycline resistance gene tetL were observed with 100% detection frequencies. Detection frequency for class I integron (intI 1) in greenhouse soils was 1.5 times higher than that in field soils. The relative abundance for sul 2 and tetL in soil samples ranged 10-4-10-2 as found by quantitative PCR (qPCR) detection. The relative abundance of sul 2 was significantly positively correlated with the contents of sulfadimidine and doxycycline (P<0.05), and the relative abundance of tetL did not exhibit evident correlation with the contents of antibiotics tested. These results would contribute to understanding of the pollution status of ARGs in vegetable soils in Beijing, and to evaluation of currently agricultural practices based on ARGs.

[Pollution Characteristics of Antibiotic Resistant Bacteria from Atmospheric Environment of Animal Feeding Operations].

Animal feeding operations is considered as a source of airborne human pathogens and antibiotics genes. In this study, we investigated the concentration, size distribution and aerodynamic diameter of airborne bacteria, tetracycline resistant bacteria and erythromycin resistant bacteria from 22 animal feeding operations in three districts of Beijing. The results indicated that the highest and lowest concentrations of these three types of bioaerosol were detected in pig and cow house, respectively. The concentration of airborne bacteria was higher in layer house, whereas concentration of antibiotic resistant bacteria was higher in broiler house. Tetracycline and erythromycin resistant bacteria were detected from the atmospheric environment from out door of layer and broiler house with the percentages of 8.81%, 15.89% and 23.19%, 36.53%, respectively. The size distribution and aerodynamic diameter varied from inside and outside of pig, cow, and layer and broiler house. Most of tetracycline resistant bacteria and erythromycin resistant bacteria from current four types of animal feeding operations mainly deposited in pharynx, larynx and bronchus of respiratory system. This study would offer the base data for evaluating the detriment of bioaerosol from animal feeding operations to the worker and environment.

Ghrelin inhibits the differentiation of T helper 17 cells through mTOR/STAT3 signaling pathway.

Enhanced activity of interleukin 17 (IL-17) producing T helper 17 (Th17) cells plays an important role in autoimmune and inflammatory diseases. Significant loss of body weight and appetite is associated with chronic inflammation and immune activation, suggesting the cross talk between immune and neuroendocrine systems. Ghrelin has been shown to regulate the organism immune function. However, the effects of ghrelin on the differentiation of Th17 cells remain elusive. In the present study, we observed the enhanced differentiation of Th17 cells in spleens of growth hormone secretagogue receptor 1a (GHSR1a)-/- mice. Treatment of ghrelin repressed Th17 cell differentiation in a time- and concentration-dependent manner. Phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) was increased in the spleens of GHSR1a-/- mice. Activation of mTOR signaling by injection of Cre-expressiong adenovirus into tuberous sclerosis complex 1 (TSC1) loxp/loxp mice increased the differentiation of Th17 cells in spleen, which was associated with an increment in the phosphorylation of STAT3. Activation of mTOR signaling by leucine or overexpression of p70 ribosome protein subunit 6 kinase 1 (S6K1) activated mTOR signaling in isolated T cells, while reversed the ghrelin-induced inhibition of iTh17 cell differentiation. In conclusion, mTOR mediates the inhibitory effect of ghrelin on the differentiation of Th17 cells by interacting with STAT3.

Tuberous sclerosis complex 1-mechanistic target of rapamycin complex 1 signaling determines brown-to-white adipocyte phenotypic switch.

Interconversion of white and brown adipocytes occurs between anabolic and catabolic states. The molecular mechanism regulating this phenotypic switch remains largely unknown. This study explores the role of tuberous sclerosis complex 1 (TSC1)-mechanistic target of rapamycin (mTOR) signaling in the conversion of brown to white adipose tissue (WAT). A colony of Fabp4-Tsc1(-/-) mice, in which the Tsc1 gene was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre, was established. Western blotting and immunostaining demonstrated the absence of TSC1 and activation of ribosomal protein S6 kinase 1, the downstream target of mTOR complex 1 (mTORC1) signaling, in the brown adipose tissues (BATs) of Fabp4-Tsc1(-/-) mice. Accumulation of lipid droplets in BAT was significantly increased. Levels of brown adipocyte markers were markedly downregulated, while white adipocyte markers were upregulated. Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1(-/-) mice. Deletion of the Tsc1 gene in cultured brown preadipocytes significantly increased the conversion to white adipocytes. FoxC2 mRNA, the transcriptional factor for brown adipocyte determination, was significantly decreased, while mRNAs for retinoblastoma protein, p107 and RIP140, the transcriptional factors for white adipocyte determination, increased in the BAT of Fabp4-Tsc1(-/-) mice. Our study demonstrates that TSC1-mTORC1 signaling contributes to the brown-to-white adipocyte phenotypic switch.

An Approach to the Synthesis of Functionalized Polycyclic Aromatic Hydrocarbons.

The application of a new benzannulation reaction for the regiocontrolled synthesis of functionalized chrysenes is reported. The initial benzannulation and the subsequent halogen displacement reactions are both highly regiospecific, which thereby enables the regiocontrolled synthesis of a variety of 4,10-disubstituted chrysenes from commercially available 1,5-dihydroxynaphthalene.

Effects of fasting and refeeding on expression of MAFbx and MuRF1 in chick skeletal muscle.

The present study investigated the effects of fasting and refeeding on the expression of proteasome-related genes and their downstream targets in the skeletal muscles of chicks. Seven-day-old chicks were fasted for 24 or 48 h and then refed for 4 h. The expression levels of MAFbx and MuRF1, which function as E3 ligases in the ubiquitin-proteasome system, were investigated at the mRNA and protein levels. MAFbx and MuRF1 expression were increased by fasting and these increases were downregulated by refeeding. The expression of the target proteins of these E3 ligases, MyoD and M-CK, was also analyzed. The levels of these proteins were downregulated by fasting, and these decreases were rescued by refeeding. The results of this study indicate that fasting stimulates MAFbx and MuRF1 expression in chicks, possibly leading to increased degradation of their corresponding target proteins.

Functional and structural nerve fiber findings in heterozygote patients with Fabry disease.

Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation between pain VAS score, quantitative sensory testing and intraepidermal nerve fiber density. Our study demonstrates that careful evaluation of symptoms in female Fabry patients is important as small fiber disease manifestations are present, which in some cases is only detected by skin biopsy.