Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of O-Antigen Gene Clusters of All O-Serogroups of Escherichia coli and Proposal for Adopting a New Nomenclature for O-Typing

Escherichia coli strains are classified based on O-antigens that are components of the lipopolysaccharide (LPS) in the cell envelope. O-antigens are important virulence factors, targets of both the innate and adaptive immune system, and play a role in host-pathogen interactions. Because they are highly immunogenic and display antigenic specificity unique for each strain, O-antigens are the biomarkers for designating O-types. Immunologically, 185 O-serogroups and 11 OX-groups exist for classification. Conventional serotyping for O-typing entails agglutination reactions between the O-antigen and antisera generated against each O-group. The procedure is labor intensive, not always accurate, and exhibits equivocal results. In this report, we present the sequences of 71 O-antigen gene clusters (O-AGC) and a comparison of all 196 O- and OX-groups. Many of the designated O-types, applied for classification over several decades, exhibited similar nucleotide sequences of the O-AGCs and cross-reacted serologically. Some O-AGCs carried insertion sequences and others had only a few nucleotide differences between them. Thus, based on these findings, it is proposed that several of the E. coli O-groups may be merged. Knowledge of the O-AGC sequences facilitates the development of molecular diagnostic platforms that are rapid, accurate, and reliable that can replace conventional serotyping. Additionally, with the scientific knowledge presented, new frontiers in the discovery of biomarkers, understanding the roles of O-antigens in the innate and adaptive immune system and pathogenesis, the development of glycoconjugate vaccines, and other investigations, can be explored.
Posttranscriptional regulation of Galectin-3 by miR-128 contributes to colorectal cancer progression

Here we demonstrated that Galectin-3 protein level was frequently up-regulated in colorectal cancer (CRC) cells and tissues. Galectin-3 up-regulation correlated with CRC progression and predicted a shorter overall survival of CRC patients. Galectin-3 overexpression attenuated the chemo-sensitivity of cancer cells, but enhanced the potential invasiveness. To explore the mechanism for Galectin-3 dysregulation, we found that miR-128 level was frequently down-regulated in CRC and negatively correlated with Galectin-3 level. Using bioinformatics analysis and experimental validation, we showed that miR-128 could directly target Galectin-3 to repress its protein level. MiR-128 decrease associated with CRC progression and predicted a worse overall survival of CRC patients. Ectopic miR-128 expression enhanced the chemo-sensitivity of CRC cells in vitro and in vivo, and inhibited the potential invasiveness. Galectin-3 expression impaired the cancer suppressive effects of miR-128. These data highlighted the role of miR-128/Galectin-3 axis in colorectal cancer.
Mid-term results of revision total hip arthroplasty with an uncemented modular femoral component

Introduction: During revision total hip arthroplasty (THA), the surgeon commonly faces deficient proximal femoral bone. In this situation, distal fixation of the prosthesis is required. The aim of the current retrospective study is to assess the clinical and radiographic mid-term outcome of revision total hip arthroplasty using a modular uncemented, tapered, grit-blasted, distal straight stem system. Methods: This retrospective study included 70 femoral revisions that were performed in 67 patients using the device of interest. All patients were operated on via an extended trochanteric osteotomy. 60 revisions were performed as 1-stage (12 infected) and 10 as 2-stage (all infected) revisions. At 3 months postoperatively and at final follow-up, patients were assessed radiographically for the presence of osteolysis and for distal integration. Results: The mean follow-up time was 4.3 (2.0-7.6) years. 4 patients had a removal of at least 1 prosthetic component. Stem survival for any reason was 92% after 5 years (95% confidence interval [CI], 83%-100%). With aseptic loosening of the stem as the endpoint of interest, survival after 5 years was 96% (95% CI, 88%-100%). A postoperative subsidence rate of 14.7% was found. No perioperative femoral fractures were found in the current patient series. Conclusions: This study showed excellent mid-term survival and good clinical and radiographic outcomes in patients who had undergone revision THA with a modular uncemented, tapered, straight design.
Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation

Recent advances have recognized metabolic reprogramming as an underlying mechanism for cancer drug resistance. However, the role of cholesterol metabolism in drug resistance remain elusive. Herein, we report an increased accumulation of cholesteryl ester in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells. A potent inhibitor of acyl-CoA cholesterol acyltransferase-1 (ACAT-1), avasimibe, effectively suppressed proliferation of gemcitabine-resistant PDAC cells. Combination of avasimibe and gemcitabine showed strong synergistic effect in suppressing PDAC cell viability in vitro and tumor growth in vivo. Immunoblotting analysis suggests downregulation of Akt by avasimibe is likely to contribute to the synergism. Collectively, our study demonstrates a new combinational therapeutic strategy to overcome gemcitabine resistance for PDAC treatment.
RNA interference of chitin synthase genes inhibits chitin biosynthesis and affects larval performance in Leptinotarsa decemlineata (Say)

Dietary introduction of bacterially expressed double-stranded RNA (dsRNA) has great potential for management of Leptinotarsa decemlineata. Identification of the most attractive candidate genes for RNA interference (RNAi) is the first step. In the present paper, three complete chitin synthase cDNA sequences (LdChSAa, LdChSAb and LdChSB) were cloned. LdChSAa and LdChSAb, two splicing variants of LdChSA gene, were highly expressed in ectodermally-derived epidermal cells forming epidermis, trachea, foregut and hindgut, whereas LdChSB was mainly transcribed in midgut cells. Feeding bacterially expressed dsChSA (derived from a common fragment of LdChSAa and LdChSAb), dsChSAa, dsChSAb and dsChSB in the second- and fourth-instar larvae specifically knocked down their target mRNAs. RNAi of LdChSAa+LdChSAb and LdChSAa lowered chitin contents in whole body and integument samples, and thinned tracheal taenidia. The resulting larvae failed to ecdyse, pupate, or emerge as adults. Comparably, knockdown of LdChSAb mainly affected pupal-adult molting. The LdChSAb RNAi pupae did not completely shed the old larval exuviae, which caused failure of adult emergence. In contrast, silencing of LdChSB significantly reduced foliage consumption, decreased chitin content in midgut sample, damaged midgut peritrophic matrix, and retarded larval growth. As a result, the development of the LdChSB RNAi hypomorphs was arrested. Our data reveal that these LdChSs are among the effective candidate genes for an RNAi-based control strategy against L. decemlineata.
Evaluation of the effects on rock fi sh and kelp artisanal fi sheries of the proposed Mejillones Peninsula marine protected area ( northern Chile , SE Paci fi c coast )

1 One shortcoming of marine protected areas (MPA) implementation is the potential for unintended consequences, such as fisheries effort displacement, that cause negative economic and social effects for fishermen and undermine social support for MPA implementation efforts. 2 The objective of this work is to analyse the effects of a proposed MPA system on fisheries in a biodiversity conservation priority site in northern Chile using a spatial dynamic modelling approach and incorporating ecological, social and economic criteria. 3 We developed an Ecospace model representing the ecological benthic subsystems dominated by kelp beds off the Mejillones Peninsula, Chile. We compared changes in fisheries indicators and the spatial distribution of effort among a no-MPA baseline scenario and four scenarios using proposed MPA core and buffer zones with high or low dispersal rates for the species in the model. 4 An overlay analysis was performed to identify which zones and users of the fishing grounds would be affected by the proposed MPA system and to what degree. 5 We found a high degree of overlap of the proposed MPA site with fishing grounds of high economic importance and with a fishing ground where women are allowed to work, this can cause significant displacement of women that have no alternative livelihood, with possible undesired social impacts on the fishing community. 6 Results from the kelp forest spatial food web model reveals that the biomass build-up of fished species is sensitive to dispersal rates, especially in scenarios with small reserves. A general pattern of fishing effort reallocation at the border of individual MPAs and open areas closer to the port was observed. Fisheries indicators show negative effects for both MPA scenarios, with undesirable changes in catch and profits for rockfish and kelp exploitation. 7 Our results suggest that implementation of the MPA proposal for the Mejillones Peninsula could generate negative consequences for the fishing community of Constitución cove. The inclusion of fisheries management objectives along with biodiversity conservation in the planning process of the Mejillones Peninsula MPA system may help to address putative negative effects on fisheries and may allow for the creation of support for future MPAs from the fishermen community. ã 2014 Elsevier B.V. All rights reserved. * Corresponding author. Present address: Proyecto GEF-PNUD-Ministerio de Medio Ambiente de Chile "Creación de un Sistema Nacional de Áreas Protegidas para Chile: Estructura Financiera y Operacional", Santiago, Chile. Tel. : +56 55 2637 866.
The novel vitamin D analog ZK191784 as an intestine‐ specific vitamin D antagonist

Vitamin D [1,25(OH)2D3] plays a crucial role in Ca2+ homeostasis by stimulating Ca2+ (re)absorption and bone turnover. The 1,25(OH)2D3 analog ZK191784 was recently developed to dissociate the therapeutic immunomodulatory activity from the hypercalcemic side effects of 1,25(OH)2D3 and contains a structurally modified side chain characterized by a 22,23‐double bond, 24R‐hydroxy group, 25‐cyclopropyl ring, and 5‐butyloxazole unit. We investigated the effect of ZK191784 on Ca2+ homeostasis and the regulation of Ca2+ transport proteins in wild‐type (WT) mice and mice lacking the renal epithelial Ca2+ channel TRPV5 (TRPV5‐/‐). The latter display hypercalciuria, hypervitaminosis D, increased intestinal expression of the epithelial Ca2+ channel TRPV6, the Ca2+‐binding protein calbindin‐D9K, and intestinal Ca2+ hyperabsorption. ZK191784 normalized the Ca2+ hyperabsorption and the expression of intestinal Ca2+ transport proteins in TRPV5‐/‐ mice. Furthermore, the compound decreased intestinal Ca2+ absorption in WT mice and reduced 1,25(OH)2D3‐dependent 45Ca2+ uptake by Caco‐2 cells, substantiating a 1,25(OH)2D3‐antagonistic action of ZK191784 in the intestine. ZK191784 increased renal TRPV5 and calbindin‐D28K expression and decreased urine Ca2+ excretion in WT mice. Both 1,25(OH)2D3 and ZK191784 enhanced transcellular Ca2+ transport in primary cultures of rabbit connecting tubules and cortical collecting ducts, indicating a 1,25(OH)2D3‐agonistic effect in kidney. ZK191784 enhanced bone TRPV6 mRNA levels and 1,25(OH)2D3 as well as ZK191784 stimulated secretion of the bone formation marker osteocalcin in rat osteosarcoma cells, albeit to a different extent. In conclusion, ZK191784 is a synthetic 1,25(OH)2D3 ligand displaying a unique tissue‐specific profile when administered in vivo. Because ZK191784 acts as an intestine‐specific 1,25(OH)2D3 antagonist, this compound will be associated with less hypercalcemic side effects compared with the 1,25(OH)2D3 analogs currently used in clinical practice. —Nijenhuis, T. , van der Eerden, B. C. J., Zügel, U. , Steinmeyer, A. , Weinans, H. , Hoenderop, J. G. J., van Leeuwen, J. P. T. M. , Bindels, R. J. M. The novel vitamin D analog ZK191784 as an intestine‐specific vitamin D antagonist. FASEB J. 20, E1589 –E1598 (2006)
Integration of Price-Responsive Appliances in the Energy Market Through Flexible Demand Saturation

This paper proposes a novel decentralized technique for efficient integration of flexible demand in the electricity market. The analysis focuses on price-responsive appliances that schedule their power consumption on the basis of a demand/price signal received by a central entity. Previous work has shown that, when the devices population is sufficiently large to be described as a continuum, it is possible to provide necessary and sufficient conditions for the existence of a Nash equilibrium (no device has unilateral interest in changing its scheduling when considering the resulting profile of aggregate demand). These results are now extended in order to achieve an equilibrium also when the mentioned conditions are violated. To this purpose, a time-varying proportional constraint (equal for all devices) is introduced on the power rate of the price-responsive appliances so as to limit the variation of flexible demand that they can introduce at critical time instants. The proposed design technique not only guarantees existence of a Nash equilibrium but it also minimizes the global operation time of the appliances population. Simulation results are provided and it is shown that, under the considered assumptions, each individual appliance completes its task in minimum time.
Overexpression of Aldehyde Dehydrogenase-2 (ALDH2) Transgene Prevents Acetaldehyde-induced Cell Injury in Human Umbilical Vein Endothelial Cells

Acetaldehyde, the major ethanol metabolite that is far more toxic and reactive than ethanol, has been postulated to be responsible for alcohol-induced tissue and cell injury. This study was to examine whether facilitated acetaldehyde metabolism affects acetaldehyde-induced oxidative stress and apoptosis. Transgene-encoding human aldehyde dehydrogenase-2 (ALDH2), which converts acetaldehyde into acetate, was constructed under chicken β-actin promoter and transfected into human umbilical vein endothelial cells (HUVECs). Efficacy of ALDH2 transfection was verified using green fluorescent protein and ALDH2 enzymatic assay. Generation of reactive oxygen species (ROS) was measured using chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by 4′,6′-diamidino-2′-phenylindoladihydrochloride fluorescence microscopy, quantitative DNA fragmentation, and caspase-3 assay. Acetaldehyde (0–200 μm) elicited ROS generation and apoptosis in HUVECs in a time- and concentration-dependent manner, associated with activation of the stress signal molecules ERK1/2 and p38 mitogen-activated protein (MAP) kinase. A close liner correlation was observed between the acetaldehyde-induced ROS generation and apoptosis. Interestingly, the acetaldehyde-induced ROS generation, apoptosis, activation of ERK1/2, and p38 MAP kinase were prevented by the ALDH2 transgene or antioxidant α-tocopherol. The involvement of ERK1/2 and p38 MAP kinase in acetaldehyde-induced apoptosis was confirmed by selective kinase inhibitors U0126, SB203580, and SB202190. Collectively, our data revealed that facilitation of acetaldehyde metabolism by ALDH2 transgene overexpression may prevent acetaldehyde-induced cell injury and activation of stress signals. These results indicated therapeutic potential of ALDH2 enzyme in the prevention and detoxification of acetaldehyde or alcohol-induced cell injury.
Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes

Objective The objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100). Methods Interferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9). Results Compared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1.00] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 (95% CI 0.86–1.00) and for MBP 82–100 0.95 (95% CI 0.88–1.00) compared to ON. Conclusion Cell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools.
A systematic evaluation of normalization methods in quantitative label-free proteomics

Abstract To date, mass spectrometry (MS) data remain inherently biased as a result of reasons ranging from sample handling to differences caused by the instrumentation. Normalization is the process that aims to account for the bias and make samples more comparable. The selection of a proper normalization method is a pivotal task for the reliability of the downstream analysis and results. Many normalization methods commonly used in proteomics have been adapted from the DNA microarray techniques. Previous studies comparing normalization methods in proteomics have focused mainly on intragroup variation. In this study, several popular and widely used normalization methods representing different strategies in normalization are evaluated using three spike-in and one experimental mouse label-free proteomic data sets. The normalization methods are evaluated in terms of their ability to reduce variation between technical replicates, their effect on differential expression analysis and their effect on the estimation of logarithmic fold changes. Additionally, we examined whether normalizing the whole data globally or in segments for the differential expression analysis has an effect on the performance of the normalization methods. We found that variance stabilization normalization (Vsn) reduced variation the most between technical replicates in all examined data sets. Vsn also performed consistently well in the differential expression analysis. Linear regression normalization and local regression normalization performed also systematically well. Finally, we discuss the choice of a normalization method and some qualities of a suitable normalization method in the light of the results of our evaluation.
Expression of Soluble Intercellular Adhesion Molecule 1 in Colorectal Cancer and Potential Use as Treatment Response Index

Background: It has been previously demonstrated that there is a positive correlation between serum concentrations of soluble intercellular adhesion molecule (sICAM-1) with stage of colorectal cancer (CRC) progression and metastases. The present study was performed primarily to examine whether sICAM-1 levels are indeed affected by chemotherapy treatment in patients with metastatic CRC and secondly to examine whether such values can be used compared to CEA as a more reliable alternative treatment indices for patient monitoring with metastatic CRC during systemic chemotherapy. Methods: The serum concentration of sICAM-1 and CEA in blood samples from 20 patients with advanced colorectal cancer were measured using enzyme-linked immunosorbent assay (ELISA) and electro-chemiluminescence immunoassay (ECLIA), respectively, and compared with those from 12 healthy adults volunteers. Results: Despite the tendency of serum sICAM-1 to fall during systemic chemotherapy, there was no significant reduction in serum sICAM-1 concentration between pre-chemotherapy levels and after five chemotherapy courses in patients with metastatic CRC (411.9 ± 196.6 ng/mL vs. 353.0 ± 124.1 ng/mL, p = 0.011). On the contrary, there was a statistically significant reduction in the expression of serum CEA levels during the same time period in the study group (330.5 ± 474.3 ng/mL vs. 167.1 ± 359.7 ng/mL, p = 0.005). No statistically significant correlation was observed between serum concentrations of both sICAM-1 and CEA and patient gender. Finally, the mean value of serum concentrations of sICAM-1 is elevated significantly in patients with advanced CRC compared to healthy volunteers with the pvalue lower than 0.001. Conclusions: Despite the declining tendency of serum sICAM-1 levels during systemic chemotherapy in patients with advanced CRC, there was not a statistically significant difference in serum levels of sICAM-1 before and after five courses of systemic chemotherapy. Further research is required to assess the correlation between soluble intercellular adhesion molecule sICAM-1’s kinetic and effectiveness of systemic chemotherapy in metastatic colorectal cancer patients.
A Systematic Review of the Effects of Physical Training on Load Carriage Performance

Knapik, JJ, Harman, EA, Steelman, RA, and Graham, BS. A systematic review of the effects of physical training on load carriage performance. J Strength Cond Res 26(2): 585–597, 2012—Soldiers are often required to carry heavy loads during military operations. This article reports on a systematic literature review examining the influence of physical training on load carriage performance. Several literature databases, reference lists, and other sources were explored to find studies that quantitatively examined the effects of physical training on the time taken for individuals to complete a set distance carrying an external load, with the majority of the load contained in a backpack. Effect sizes (Cohen's d statistic) were used in meta-analyses to examine the changes in load carriage performance after various modes of physical training. Effect sizes quantified training-related changes in terms of SD units. Ten original research studies met the review criteria. Meta-analysis indicated that large training effects (≥0.8SD units) were apparent when progressive resistance training was combined with aerobic training and when that training was conducted at least 3 times per week, over at least 4 weeks. When progressive load-carriage exercise was part of the training program, much larger training effects were evident (summary effect size [SES] = 1.7SD units). Field-based training that combined a wide variety of training modes and included progressive load-carriage exercise was also very effective in improving load carriage performance (SES = 1.1SD units). Aerobic training alone or resistance training alone had smaller and more variable effects, depending on the study. This review indicates that combinations of specific modes of physical training can substantially improve load carriage performance.