Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival Strategies of Yeast and Filamentous Fungi against the Antifungal Protein AFP*

The activities of signaling pathways are critical for fungi to survive antifungal attack and to maintain cell integrity. However, little is known about how fungi respond to antifungals, particularly if these interact with multiple cellular targets. The antifungal protein AFP is a very potent inhibitor of chitin synthesis and membrane integrity in filamentous fungi and has so far not been reported to interfere with the viability of yeast strains. With the hypothesis that the susceptibility of fungi toward AFP is not merely dependent on the presence of an AFP-specific target at the cell surface but relies also on the cell's capacity to counteract AFP, we used a genetic approach to decipher defense strategies of the naturally AFP-resistant strain Saccharomyces cerevisiae. The screening of selected strains from the yeast genomic deletion collection for AFP-sensitive phenotypes revealed that a concerted action of calcium signaling, TOR signaling, cAMP-protein kinase A signaling, and cell wall integrity signaling is likely to safeguard S. cerevisiae against AFP. Our studies uncovered that the yeast cell wall gets fortified with chitin to defend against AFP and that this response is largely dependent on calcium/Crz1p signaling. Most importantly, we observed that stimulation of chitin synthesis is characteristic for AFP-resistant fungi but not for AFP-sensitive fungi, suggesting that this response is a successful strategy to protect against AFP. We finally propose the adoption of the damage-response framework of microbial pathogenesis for the interactions of antimicrobial proteins and microorganisms in order to comprehensively understand the outcome of an antifungal attack.
A systematic literature review of the effectiveness of occupational health and safety regulatory enforcement.

BACKGROUND We aimed to determine the strength of evidence on the effectiveness of legislative and regulatory policy levers in creating incentives for organizations to improve occupational health and safety processes and outcomes. METHODS A systematic review was undertaken to assess the strength of evidence on the effectiveness of specific policy levers using a "best-evidence" synthesis approach. RESULTS A structured literature search identified 11,947 citations from 13 peer-reviewed literature databases. Forty-three studies were retained for synthesis. Strong evidence was identified for three out of nine clusters. CONCLUSIONS There is strong evidence that several OHS policy levers are effective in terms of reducing injuries and/or increasing compliance with legislation. This study adds to the evidence on OHS regulatory effectiveness from an earlier review. In addition to new evidence supporting previous study findings, it included new categories of evidence-compliance as an outcome, nature of enforcement, awareness campaigns, and smoke-free workplace legislation. Am. J. Ind. Med. 59:919-933, 2016. © 2016 Wiley Periodicals, Inc.
Functional impact of silencing the Helicoverpa armigera sex‐peptide receptor on female reproductive behaviour

Female Helicoverpa armigera sex pheromone production is under the control of pheromone biosynthesis‐activating neuropeptide (PBAN). After mating, females undergo suppression of sex pheromone production and enhanced oviposition as a result of the transfer of male‐derived seminal peptides. In a previous study we identified a putative H. armigera sex‐peptide receptor (HeaSP‐R) and demonstrated a significant up‐regulation in gene expression levels of this receptor in brains and pheromone glands of mated females, thereby implicating a regulatory role for sex peptide in the reproductive behaviour of H. armigera. In the present study, we show that virgin females injected with Drosophila melanogaster SP (DrmSP), in addition to inhibition of pheromone production, also exhibited a suppression of calling behaviour and a significant reduction in the gene expression levels of the PBAN‐receptor. In addition, RNA interference (RNAi) silencing of the HeaSP‐R expression by 50–60% prevented DrmSP‐suppression of pheromone production and calling behaviour. Moreover, mated, silenced females failed to increase their oviposition rates as is normally observed in mated females, and their behaviour did not differ from that of virgin females. However, sex pheromone production by mated, silenced females remained low, comparable to mated, normal females, thereby indicating the probable involvement of additional factors in the suppression of sex pheromone production after mating.
Access to properly fitting personal protective equipment for female construction workers.

BACKGROUND Previous literature suggests that most personal protective equipment (PPE) for construction is designed for males and does not accommodate female anthropometry. We conducted a pilot study to identify whether female construction workers currently have adequate access to properly fitting PPE. METHODS Semi-structured focus group interviews were conducted with union female carpenters, laborers, and ironworkers. Researchers coded focus group transcriptions and extracted major themes using thematic framework analysis. RESULTS Participants (n = 23) had a mean of 15.1 years of construction experience (range 3-34.5 years). A majority reported fit problems for many types of PPE (gloves, harnesses, safety vests, work boots, outerwear), generally noting that the equipment provided by contractors was too large. Other emergent themes included female workers purchasing their own PPE, exposure to various safety hazards from poorly fitted PPE, and perceived indifferent safety culture. CONCLUSIONS Female construction workers continue to have difficulty accessing properly fitting PPE. Am. J. Ind. Med. 59:1032-1040, 2016. © 2016 Wiley Periodicals, Inc.
Ultrasound is a useful adjunct in diagnosis of eosinophilic fasciitis.

This 28-year-old male presented with progressive skin tightening and limited joint mobility for 11 months, involving legs up to mid-shin and forearms up to elbows, preceded by painless swelling involving affected regions, sparing fingers and toes. Systemic features were absent. There was peripheral eosinophilia (leucocytes: 11 600/ml, eosinophils 52%, absolute eosinophil count: 6032/ml), raised acute-phase reactants and hypergammaglobulinaemia. Nail-fold capillaroscopy was noncontributory. RP, digital ulcers, dysphagia, reflux and pulmonary arterial hypertension were absent. ANA was positive, and Scl70 and anticentromere antibodies were negative. High-resolution US of legs (Fig. 1A and C) using an 18-MHz linear array transducer showed thickening and altered echointensities afflicting the fascia, alongside deranged echotexture of subcutaneous fat (Fig. 1B is from a healthy person for comparison). MRI of legs (Fig. 1D) showed thickening of fascia, along with increased contrast enhancement of the myofascial plane, corroborating US findings. He was diagnosed as having eosinophilic fasciitis (EF) and put on prednisolone. Apart from histology, MRI is also useful for the diagnosis of EF [1]. The role of US elastography has been studied in scleroderma, and has demonstrated reduction of strain in the dermis of the forearm due to loss of elasticity [2]. Here we present a case of EF characterized ultrasonographically with MRI corroboration.
The frequency and outcome of lupus nephritis: results from an international inception cohort study.

OBJECTIVE To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. RESULTS There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. CONCLUSION LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN.
Characterization of a cryptic 3.3 Mb deletion in a patient with a “balanced t(15;22) translocation” using high density oligo array CGH and gene expression arrays

Patients with an apparently balanced translocation and an abnormal phenotype may carry a cryptic deletion/duplication at their translocation breakpoints that may explain their abnormalities. Using microarray CGH (aCGH) and gene expression arrays we studied a child with t(15;22)(q26.1;q11.2), developmental delay and mild dysmorphic features. A high density aCGH study with 244,000 oligo probes demonstrated a 3.3 Mb deletion immediately adjacent to the 15q breakpoint. Gene expression studies with 44,000 oligos displayed an approximately 50% reduction of the expression of IGF1R gene that was translocated to the der(22). There are 18 known or hypothetical protein coding genes within the deleted region according to UniProt, RefSeq, and GenBank mRNA (UCSC HG17, May 2004). Although two of these genes, RGMA and ST8SIA2, play an important role in neural development, the mild phenotype of our patient indicates that loss of one copy of these genes may not be critical developmentally. The 50% reduction of IGF1R expression could be responsible for the growth deficiency in the patient. Reviewing the few 15q26 microdeletion cases that have been characterized by aCGH, we discovered that deletion of the segment including distal 15q26.2 to the proximal part of 15q26.3 is associated with severe phenotypes. Our experience demonstrates that high‐density oligonucleotide‐based aCGH is a quick and precise way to identify cryptic copy number changes in “balanced translocations. ” Expression studies can also add valuable information regarding gene expression changes due to a chromosomal rearrangement. Both approaches can assist in the elucidation of the etiology of unexplained phenotypic differences in cases such as this one. © 2008 Wiley‐Liss, Inc.
Radiopacifiers do not induce genetic damage in murine fibroblasts: an in vitro study.

AIM To evaluate whether several radiopacifiers are able to induce genetic damage in a laboratory cell culture study. METHODOLOGY Murine fibroblasts were exposed to barium sulphate, bismuth oxide or zirconium oxide, at final concentrations ranging from 10 to 1000 microg mL(-1) for 1 h at 37 degrees C. The negative control group was treated with a vehicle control [phosphate buffered solution (PBS)] for 1 h at 37 degrees C and the positive control group was treated with hydrogen peroxide (at 10 microM) for 5 min on ice. Genotoxicity data were assessed by the single-cell gel (comet) assay. RESULTS All the tested compounds did not induce DNA breakage as depicted by the mean tail moment in all the concentrations analysed. CONCLUSION Exposure to the tested radiopacifiers may not be a factor that increases the level of DNA lesions in mammalian cells as detected by a single-cell gel (comet) assay.
The generation and differentiation of memory CD8 T cell responses in health and disease

Memory CD8 T cells provide protection to immune hosts by eliminating pathogeninfected cells during re-infection. While parameters influencing the generation of primary (1) CD8 T cells are well established, the factors controlling the development of secondary (2) CD8 T cell responses remain largely unknown. Here, we address the mechanisms involved in the generation and development of 2 memory (M) CD8 T cells. We observed that the time at which 1 M CD8 T cells enter into immune response impacts their fate and differentiation into 2 M CD8 T cells. Late-entry of 1 M CD8 T cells into an immune response (relative to the onset of infection) not only facilitated the expression of transcription factors associated with memory formation in 2 effector CD8 T cells, but also influenced the ability of 2 M CD8 T cells to localize within the lymph nodes, produce IL-2, and undergo Ag-driven proliferation. The timing of stimulation of 1 M CD8 T cells also impacted the duration of expression of the high-affinity IL-2 receptor (CD25) on 2 effector CD8 T cells and their sensitivity to IL-2 signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2 CD8 T cells, we provide direct evidence for the role of IL-2 in controlling the differentiation of 2 CD8 T cell responses. Thus, our data suggest that the process of 1 M to 2 M CD8 T cell differentiation is not fixed and can be manipulated, a notion with relevance for the design of future prime-boost vaccination approaches.
Evaluation of the dimensional changes of mineral trioxide aggregate sealer.

AIM To evaluate the setting time, early age restrained dimensional stability, fluid uptake, microstructure and porosity of a root canal sealer based on mineral trioxide aggregate (MTAS). METHODOLOGY The MTAS, mineral trioxide aggregate (MTA) and a commercially available sealer pulp canal sealer (PCS) were investigated. The setting time of the materials was determined according to ISO 6876; 2002. The dimensional change in the vertical direction was measured over a period of 7 days from setting time using a linear variable differential transducer. The test samples were restrained in lateral directions by the metal mould. The fluid uptake of the cements was evaluated in Hank's balanced salt solution (HBSS), and their porosity was investigated using light optical microscopy. RESULTS The addition of a water-soluble polymer to MTA reduced its setting time but PCS displayed the shortest setting time (P < 0.05). The dimensional stability of the materials was not affected by the test environmental conditions (P > 0.05). PCS exhibited a much higher degree of shrinkage than MTA (P = 0.997, 0.640, 0.449, 0.191) and MTAS (P = 0.952, 0.523, 0.380, 0.149) at 3 h and 1, 3, 7 days, respectively, when allowed to set at 100% humidity. An increase in weight and expansion was recorded for MTA when immersed in HBSS. Microscope investigation of test specimens revealed the highest degree of porosity in MTA followed by MTAS and PCS. CONCLUSIONS The novel sealer based on MTA demonstrated adequate setting time and was dimensionally stable. It has the potential to be used as root canal sealer cement in clinical practice.
An in vitro evaluation of two resin-based sealers on proliferation and differentiation of human periodontal ligament cells.

AIM To evaluate the effects of a polymethyl methacrylate resin-based sealer [Superbond sealer (SB)] on the proliferation and osteogenic differentiation of human periodontal ligament cells (HPDLCs) in vitro, compared with a methacrylate resin-based sealer [Epiphany SE sealer (EP)]. METHODOLOGY Human periodontal ligament cells were obtained from of healthy third molar teeth of two participants with informed consent. To determine the effects of the eluent from set resin sealers on HPDLCs, the 7-day-washed (washed) or non-washed freshly prepared (fresh) set SB or EP discs were prepared. Cells cultured on these discs were evaluated by the WST-1 proliferation assay and scanning electron microscopy (SEM). The osteogenic differentiation of HPDLCs on washed SB discs was then evaluated by gene expression analysis of osteopontin (OPN) and osteocalcin (OCN) by using quantitative RT-PCR. RESULTS Human periodontal ligament cells exhibited growth on washed SB discs, whereas fresh SB and EP discs and washed EP discs inhibited proliferation of HPDLCs. SEM observation revealed that HPDLCs tightly attached and spread on the surface of washed SB discs, whilst no HPDLCs were observed on the surface of fresh and washed EP discs. Furthermore, HPDLCs significantly upregulated gene expressions of OPN and OCN when cultured on washed SB discs in osteogenic differentiation medium for 2 weeks. CONCLUSIONS Although Superbond sealer initially exerted cytotoxic effects on HPDLCs, these effects were reduced during washing for 7 days compared to EP, which continued to be cytotoxic even though the specimens were washed for the same period of time. Washed Superbond allowed HPDLCs to differentiate into osteogenic cells.
Shwachman–Diamond syndrome is associated with structural brain alterations on MRI

Shwachman–Diamond syndrome (SDS) is an autosomal recessive condition that results from mutations in the SBDS gene, at chromosome 7q11. Main features include exocrine pancreatic failure, neutropenia and skeletal dysplasia. This study investigated brain structures by magnetic resonance imaging (MRI) in patients with SDS. MRI of the brain was performed in nine patients (7 males, age range 7–37 years) with SDS and mutations in the SBDS gene and in 18 age‐ and gender‐matched controls. MRI images were assessed visually, and volumetric analyses of the brain matter and structural midsagittal measurements were performed. Eight out of nine SBDS mutation‐verified patients reported learning difficulties. Patients with SDS had smaller occipitofrontal head circumferences than the controls (Z‐score −1.3 vs. +0.3, P = 0.021), and decreased global brain volume (1.74 L vs. 1.94 L, P = 0.019); both gray matter (P = 0.042) and white matter (P = 0.007) volumes were reduced. Patients with SDS had no macroscopic brain malformations, but they had significantly smaller age‐ and head size‐adjusted areas of posterior fossa (P = 0.006), vermis (P = 0.002), corpus callosum (P = 0.020), and pons (P = 0.002), and significantly larger cerebrum‐vermis ratio (P < 0.0001) than the healthy controls. SDS patients had structurally smaller posterior fossa and cerebellar vermis, corpus callosum, and brainstem than the healthy controls. The MRI findings may be related to the neuropsychological features described in SDS. © 2008 Wiley‐Liss, Inc.
Molybdenum Nitrogenase Catalyzes the Reduction and Coupling of CO to Form Hydrocarbons*♦

The molybdenum-dependent nitrogenase catalyzes the multi-electron reduction of protons and N2 to yield H2 and 2NH3. It also catalyzes the reduction of a number of non-physiological doubly and triply bonded small molecules (e.g. C2H2, N2O). Carbon monoxide (CO) is not reduced by the wild-type molybdenum nitrogenase but instead inhibits the reduction of all substrates catalyzed by nitrogenase except protons. Here, we report that when the nitrogenase MoFe protein α-Val70 residue is substituted by alanine or glycine, the resulting variant proteins will catalyze the reduction and coupling of CO to form methane (CH4), ethane (C2H6), ethylene (C2H4), propene (C3H6), and propane (C3H8). The rates and ratios of hydrocarbon production from CO can be adjusted by changing the flux of electrons through nitrogenase, by substitution of other amino acids located near the FeMo-cofactor, or by changing the partial pressure of CO. Increasing the partial pressure of CO shifted the product ratio in favor of the longer chain alkanes and alkenes. The implications of these findings in understanding the nitrogenase mechanism and the relationship to Fischer-Tropsch production of hydrocarbons from CO are discussed.
miR-200a Regulates SIRT1 Expression and Epithelial to Mesenchymal Transition (EMT)-like Transformation in Mammary Epithelial Cells*

Evidence supports a critical role for microRNAs (miRNAs) in regulation of tissue-specific differentiation and development. Signifying a disruption of these programs, expression profiling has revealed extensive miRNA dysregulation in tumors compared with healthy tissue. The miR-200 family has been established as a key regulator of epithelial phenotype and, as such, is deeply involved in epithelial to mesenchymal transition (EMT) processes in breast cancer. However, the effects of the miR-200 family on transformation of normal mammary epithelial cells have yet to be fully characterized. By examining a TGF-β driven model of transformation of normal mammary epithelium, we demonstrate that the class III histone deacetylase silent information regulator 1 (SIRT1), a proposed oncogene in breast cancer, is overexpressed upon EMT-like transformation and that epigenetic silencing of miR-200a contributes at least in part to the overexpression of SIRT1. We have established the SIRT1 transcript as subject to regulation by miR-200a, through miR-200a targeting of SIRT1 3′-UTR. We also observed SIRT1 and miR-200a participation in a negative feedback regulatory loop. Restoration of miR-200a or the knockdown of SIRT1 prevented transformation of normal mammary epithelial cells evidenced by decreased anchorage-independent growth and decreased cell migration. Finally, we observed SIRT1 overexpression in association with decreased miR-200a in breast cancer patient samples. These observations provide further evidence for a critical tumor suppressive role of the miR-200 family in breast epithelium in addition to identifying a novel regulatory mechanism, which may contribute to SIRT1 up-regulation in breast cancer.
Interaction of β2-Glycoprotein I with Lipopolysaccharide Leads to Toll-like Receptor 4 (TLR4)-dependent Activation of Macrophages*

Background: β2-Glycoprotein I (β2GPI) binds to negatively charged lipids, but its physiological role remains unknown. Results: β2GPI containing LPS, but not β2GPI depleted of LPS activity, stimulated macrophages in a TLR4-dependent manner. Conclusion: β2GPI interacts specifically with LPS. Significance: Apparent TLR4-mediated activation of macrophages by β2GPI is due to the presence of LPS. β2-Glycoprotein I (β2GPI) is an abundant plasma protein that binds to the surface of cells and particles expressing negatively charged lipids, but its physiological role remains unknown. Antibodies to β2GPI are found in patients with anti-phospholipid syndrome, a systemic autoimmune disease associated with vascular thrombosis and pregnancy morbidity. Although it has been suggested that anti-β2GPI antibodies activate endothelial cells and monocytes by signaling through TLR4, it is unclear how anti-β2GPI antibodies and/or β2GPI interact with TLR4. A number of mammalian proteins (termed “endogenous Toll-like receptor (TLR) ligands”) have been reported to bind to TLR4, but, in most cases, subsequent studies have shown that LPS interaction with these proteins is responsible for TLR activation. We hypothesized that, like other endogenous TLR ligands, β2GPI interacts specifically with LPS and that this interaction is responsible for apparent TLR4 activation by β2GPI. Here, we show that both LPS and TLR4 are required for β2GPI to bind to and activate macrophages. Untreated β2GPI stimulated TNF-α production in TLR4-sufficient (but not TLR4-deficient) macrophages. In contrast, neither polymyxin B-treated nor delipidated β2GPI stimulated TNF-α production. Furthermore, β2GPI bound to LPS in a specific and dose-dependent manner. Finally, untreated β2GPI bound to the surface of TLR4-sufficient (but not TLR4-deficient) macrophages. Polymyxin B treatment of β2GPI abolished macrophage binding. Our findings suggest a potential new biological activity for β2GPI as a protein that interacts specifically with LPS and point to the need to evaluate newly discovered endogenous TLR ligands for potential interactions with LPS.