Miracle-dz/UniFAR-FTUs huggingface dataset:
H2AX facilitates classical non-homologous end joining at the expense of limited nucleotide loss at repair junctions

Abstract Phosphorylated histone H2AX, termed ‘γH2AX’, mediates the chromatin response to DNA double strand breaks (DSBs) in mammalian cells. H2AX deficiency increases the numbers of unrepaired DSBs and translocations, which are partly associated with defects in non-homologous end joining (NHEJ) and contributing to genomic instability in cancer. However, the role of γH2AX in NHEJ of general DSBs has yet to be clearly defined. Here, we showed that despite little effect on overall NHEJ efficiency, H2AX deficiency causes a surprising bias towards accurate NHEJ and shorter deletions in NHEJ products. By analyzing CRISPR/Cas9-induced NHEJ and by using a new reporter for mutagenic NHEJ, we found that γH2AX, along with its interacting protein MDC1, is required for efficient classical NHEJ (C-NHEJ) but with short deletions and insertions. Epistasis analysis revealed that ataxia telangiectasia mutated (ATM) and the chromatin remodeling complex Tip60/TRRAP/P400 are essential for this H2AX function. Taken together, these data suggest that a subset of DSBs may require γH2AX-mediated short-range nucleosome repositioning around the breaks to facilitate C-NHEJ with loss of a few extra nucleotides at NHEJ junctions. This may prevent outcomes such as non-repair and translocations, which are generally more destabilizing to genomes than short deletions and insertions from local NHEJ.
Selection of platelets for refractory patients by HLA matching and prospective crossmatching

A multi‐site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA‐based selection. Seventy‐three patients who were refractory to random‐donor platelets received two plateletpheresis components, one chosen by HLA‐based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA‐based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch‐based method of donor selection. 2) HLA‐based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA‐ cross‐reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA‐ compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch‐selected platelets are acceptable as an alternative component.
Primary Radiation Therapy for Early Glottic Cancer

OBJECTIVES/HYPOTHESIS: Early glottic squamous cell carcinoma can be effectively treated with either radiation or surgical intervention. We evaluated our experience treating early glottic cancer with primary radiation therapy and our vertical hemilaryngectomy (VHL) salvage experience. STUDY DESIGN/METHODS: Retrospectively, patient records between January 1986 and December 1994 were reviewed and 45 patients with early glottic squamous cell carcinoma who received fullcourse radiation therapy at the Cleveland Clinic Foundation were identified. RESULTS: Local control after radiation therapy was 80% overall, 87.5% for T1 lesions, and 75% for T2 lesions. Four patients underwent VHL for salvage after local recurrence; 1 was successfully salvaged with VHL. Five patients underwent total laryngectomy salvage after radiation therapy; all were successful. Only 1 of the 6 patients who were originally candidates for VHL before radiation therapy was successfully salvaged with the larynx preserved. CONCLUSIONS: Our local control rates using primary radiation therapy are consistent with prior published series, but voice sparing salvage is poor. (Otolaryngol Head Neck Surg 2001; 124:35-9.)
Induced Pluripotent Stem Cells without c-Myc Attenuate Acute Kidney Injury via Downregulating the Signaling of Oxidative Stress and Inflammation in Ischemia–Reperfusion Rats

Induced pluripotent stem (iPS) cells have potential for multilineage differentiation and provide a resource for stem cell-based treatment. However, the therapeutic effect of iPS cells on acute kidney injury (AKI) remains uncertain. Given that the oncogene c-Myc may contribute to tumorigenesis by causing genomic instability, herein we evaluated the therapeutic effect of iPS cells without exogenously introduced c-Myc on ischemia–reperfusion (I/R)-induced AKI. As compared with phosphate-buffered saline (PBS)-treated group, administration of iPS cells via intrarenal arterial route into kidneys improved the renal function and attenuated tubular injury score at 48 h after ischemia particularly at the dose of 5 × 105 iPS cells. However, a larger number of iPS cells (5 × 107 per rat) diminished the therapeutic effects for AKI and profoundly reduced renal perfusion detected by laser Doppler imaging in the reperfusion phase. In addition, the green fluorescence protein-positive iPS cells mobilized to the peritubular area at 48 h following ischemia, accompanied by a significant reduction in infiltration of macrophages and apoptosis of tubular cells, and a remarkable enhancement in endogenous tubular cell proliferation. Importantly, transplantation of iPS cells reduced the expression of oxidative substances, proinflammatory cytokines, and apoptotic factors in I/R kidney tissues and eventually improved survival in rats of ischemic AKI. Six months after transplantation in I/R rats, engrafted iPS cells did not result in tumor formation in kidney and other organs. In summary, considering the antioxidant, anti-inflammatory, and antiapoptotic properties of iPS cells without c-Myc, transplantation of such cells may be a treatment option for ischemic AKI.
Population genetics and dynamics at short spatial scale in Bulinus truncatus, the intermediate host of Schistosoma haematobium, in Morocco

The population biology of the schistosome–vector snail Bulinus truncatus was studied in an irrigation system near Marrakech, Morocco using both genetic and demographic approaches. The population genetic survey was conducted in 4 sites, 2 sites being sampled on 2 separate occasions. Individuals were genotyped at 6 microsatellite loci. No variability was found at 4 loci, and the 2 other loci had less than 4 alleles. The differentiation, both spatial and temporal, among populations was extremely weak. The demographic survey was conducted using 2 capture-mark-recapture analyses in 2 separate sites, the first in 1999 and the second in 2000. The second analysis permitted the estimation of parameters based on recent methodological developments (multisite models). Although these studies provided information on several traits, we report here on dispersal only. Both analyses showed that individual dispersal is of the order of a few hundreds of metres per reproductive life, that is the scale of the whole irrigation area. Both the genetic and demographic studies indicated that this area harbours a single – or no more than a few – populations of B. truncatus. This has implications for our understanding of the coevolutionary process between snails and flukes.
Human UDP-glucuronosyltransferase UGT2A2: cDNA construction, expression, and functional characterization in comparison with UGT2A1 and UGT2A3

ObjectivesCharacterize the expression and glucuronidation activities of the human uridine 5′-diphospho (UDP)-glucuronosyltransferase (UGT) 2A2. MethodUGT2A1 was cloned from nasal mucosa mRNA. Synthetic cDNA for UGT2A2 was constructed assuming exon sharing between UGT2A1 and UGT2A2 (Mackenzie et al., Pharmacogenetics and Genomics 2005, 15:677–685). Exon 1 of UGT2A2 was amplified from genomic DNA and combined with exons 2–6 of UGT2A1. UGT2A3 was cloned from liver mRNA. Quantitative reverse-transcribed-PCR (RT-PCR) was used to evaluate the expression of all the three UGTs of subfamily 2A in different tissues. Recombinant UGT2A1, UGT2A2 and UGT2A3 were expressed in baculovirus-infected insect cells and analyzed for glucuronidation activity towards different substrates. ResultsDNA sequencing of RT-PCR products from human nasal mucosa mRNA, confirmed exon sharing between UGT2A1 and UGT2A2. In addition, it indicated that the N-terminal signal peptide sequence of UGT2A2 is the longest among the human UGTs. Quantitative RT-PCR revealed that both UGT2A1 and UGT2A2 are mainly expressed in the nasal mucosa, and that their expression level in fetal samples was much higher than in adults. Activity assays with recombinant UGTs 2A1–2A3 showed broad substrate selectivity for UGT2A1 and UGT2A2. Although glucuronidation rates and substrate affinities were mostly higher in UGT2A1, the Km values for UDP-glucuronic acid were similar in both UGTs. In addition, there were regioselectivity differences between the two UGTs and, with a few substrates, particularly ethinylestradiol, the activity of UGT2A2 was higher. ConclusionUGT2A2 is mainly expressed in the nasal mucosa and it has glucuronidation activity towards several different endobiotic and xenobiotic substrates.
Time-Dependent Effects of Rifampicin on Staphylococcal Biofilms

Objective To test the time-dependent effects of rifampicin on established biofilms of Staphylococcus epidermidis isolated from patients with cardiac implant infections and catheter-related bacteremia. Methods Biofilms were grown in microtiter plates for 24 hours, dyed and stained with crystal violet. The mean optical density (OD) was used for quantification. The OD ratio (ODr = OD of the treated biofilm/OD of the untreated biofilm) was used to measure changes in the thickness of the biofilms over the time. Biofilms were incubated with rifampicin (0.6 mg/mL) for 1, 5, 15, 30 and 60 minutes. Unstained biofilms were sonicated and plated on Columbia agar for time-kill curves. Results The incubation of the biofilms with rifampicin led to a significant reduction of the OD of the biofilms within 1 minute (ODr baseline: 1; ODr 1 min: 0.333 ± 0.131) (p<0.001). With regard to bacterial killing, rifampicin reduced the mean log count, but viable bacteria were still grown from biofilms in 13 out of 28 isolates despite MIC values < 0.01 mg/L. Conclusions In conclusion, our results confirm that rifampicin at a concentration of 1.2 mg/mL immediately reduces established biofilms formed by S. epidermidis although it is not bactericidal despite very low MICs at planktonic conditions.
Models for spatial information encoding in neuronal populations

The work described here has the goal of providing mathematical models for important spatial information processing mechanisms in the brain. Two original models were developed targeting two core mechanisms: one dedicated to the phase precession effect and the other to the formation of hexagonal firing patterns of grid cells. Both mechanisms are embedded on the general problem of spatial information coding in the animal brain and, possibly in the human brain. The models were constructed in close relation with the known biophysical details of the brain areas being modeled. Phase precession is one of the most well-known examples within the temporal coding hypothesis. Here we present a biophysical spiking model for phase precession in hippocampal CA1 which focuses on the interaction between place cells and local inhibitory interneurons. The model's functional block is composed by a place cell (PC) connected with a local inhibitory cell (IC) which is modulated by the population theta rhythm. Both cells receive excitatory inputs from the entorhinal cortex (EC). These inputs are both theta modulated and space modulated. The dynamics of the two neuron types are described by integrate-and-fire models with conductance synapses. The EC inputs are described using non homogeneous Poisson processes. Phase precession in our model is caused by increased drive to specific PC/IC pairs when the animal is in their place field. The excitation increases the IC's firing rate, and this modulates the PC's firing rate such that both cells precess relative to theta. Our model implies that phase coding in place cells may not be independent from rate coding. The absence of restrictive connectivity constraints in this model predicts the generation of phase precession in any network with similar architecture and subject to a clocking rhythm, independently of the involvement in spatial tasks. The second model addresses grid field formation. Grid cells (GCs) in the medial entorhinal cortex (mEC) share the property of having their firing activity spatially tuned to a regular triangular lattice. Several theoretical models for grid fields formation have been proposed but most of them fail to account for important biological constraints such as the lack of high recurrence levels and absence of topographic organization in mEC. As such, models for grid fields’ formation are still under active improvement. In this thesis we present an original model for the formation of grid like firing patterns supported on
Entropy-based non-line of sight identification for wireless positioning systems

Indoor positioning has gained considerable attention over the last decade. For time-of arrival based systems, operating in urban and indoor environments the availability of line-of-sight signals is not always guaranteed due to physical obstructions such as buildings, walls, elevator shafts, etc. Specifically non-line-of-sight (NLOS) conditions introduce a bias to the distance estimation which results in significant localization errors. It is therefore vital to be able to identify NLOS channels accurately in real-time and mitigate their impact on location estimation. Channel-based metrics such as RMS delay spread and kurtosis have been proposed for Ultra Wideband systems to identify NLOS channels. Their performance under different system bandwidths (e.g. WLAN), however, has not been investigated in the literature. In this paper we introduce a novel NLOS identification metric based on the entropy of the Channel Impulse Response (CIR) which exhibits distinct statistical properties in different channel conditions. Using frequency domain wireless propagation measurements in a typical indoor environment we show that the entropy metric has a higher detection/identification rate compared to RMS delay spread and kurtosis. We provide empirical evaluation of the test metrics under different system bandwidths and illustrate that entropy shows significant performance gains especially at lower bandwidths. The performance of NLOS identification depends on the accuracy of the estimated metric. Thus in order to estimate the entropy metric accurately we have selected the autoregressive (AR) modeling method which has shown accurate and consistent performance. Finally, we present an investigation of the impact of AR modeling parameters on the performance of entropy-based NLOS identification.
Genetic Factors and the Risk of Periodontitis Development: Findings from a Systematic Review Composed of 13 Studies of Meta-Analysis with 71,531 Participants

Purpose. This work aimed to synthesize the results of recent meta-analysis focusing on polymorphism in inflammatory mediators and its relation with the risk of periodontitis development. Materials and Methods. A systematic search was conducted using databases for publications prior to October 2016. Three examiners extracted data from articles with a clear association between polymorphisms in the inflammatory mediator gene and the development of periodontitis through meta-analysis using the fixed or randomized statistical models to calculate the Odds Ratio with values of P < 0.05 considered significant. Results. A total of 13 meta-analysis articles with 25 polymorphisms in seven interleukins (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, and IL-18), three cellular receptors (Fcγ receptors: FCGR2A, FCGR3A, and FCGR3B), and five inflammatory mediators (COX-2, MMP-2, MMP-3, MMP-8, and MMP-9), with a total of 71,531 participants, approaching different classifications of the disease. Conclusion. The study demonstrated that polymorphisms in the IL-1A, IL-1B, IL-6, IL-10, MMP-3 (chronic form), and MMP-9 (chronic form) polymorphisms were significantly associated with the risk of developing periodontitis, whereas other polymorphisms in the IL-4, IL-8, IL-18, Fcγ, COX-2, MMP-2, MMP-3 (aggressive), MMP-8, and MMP-9 (aggressive) polymorphisms had no significant association with risk of developing periodontitis.
Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle

Abstract Protein synthesis is mediated via numerous molecules including the ribosome, mRNA, tRNAs, as well as translation initiation, elongation and release factors. Some of these factors play several roles throughout the entire process to ensure proper assembly of the preinitiation complex on the right mRNA, accurate selection of the initiation codon, errorless production of the encoded polypeptide and its proper termination. Perhaps, the most intriguing of these multitasking factors is the eukaryotic initiation factor eIF3. Recent evidence strongly suggests that this factor, which coordinates the progress of most of the initiation steps, does not come off the initiation complex upon subunit joining, but instead it remains bound to 80S ribosomes and gradually falls off during the first few elongation cycles to: (1) promote resumption of scanning on the same mRNA molecule for reinitiation downstream—in case of translation of upstream ORFs short enough to preserve eIF3 bound; or (2) come back during termination on long ORFs to fine tune its fidelity or, if signaled, promote programmed stop codon readthrough. Here, we unite recent structural views of the eIF3–40S complex and discus all known eIF3 roles to provide a broad picture of the eIF3’s impact on translational control in eukaryotic cells.
Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload

BACKGROUND The mechanism of iron absorption by the intestine and its transfer to the main iron storage site, the liver, is poorly understood. Recently an iron carrier was cloned and named DMT1 (divalent metal transporter 1). AIMS To determine the level of DMT1 gene expression and protein distribution in duodenum and liver. METHODS A DMT1 cRNA and antibody were produced and used in in situ hybridisation and immunohistochemistry, respectively, in rats in which the iron stores were altered by feeding diets with normal, low, and high iron content. RESULTS Duodenal DMT1 mRNA was low in crypts and increased at the crypt-villus junction in iron deficient and control rats; it fell in the iron loaded state. Staining for DMT1 protein was not detected in crypts. In villus enterocytes, protein staining was localised to the microvillus membrane in iron deficiency, in the cytoplasm and to a lesser extent in the membrane in controls, and entirely in the cytoplasm of iron loaded animals. Liver DMT1 mRNA was distributed evenly across hepatocytes. DMT1 protein staining was observed on hepatocyte plasma membranes, with highest values in the iron loaded state, lower values in control animals, and none after iron depletion. CONCLUSIONS Results are consistent with a role for DMT1 in the transmembrane transport of non-transferrin bound iron from the intestinal lumen and from the portal blood.
Personal Recovery as a Protective Factor Against Suicide Ideation in Individuals With Schizophrenia

Abstract Suicide rates are elevated in individuals with schizophrenia, yet evidence is mixed regarding the roles of positive and negative symptoms as risk factors for suicide in this population, suggesting that there may be other influential variables. One such variable may be personal recovery. Therefore, the purpose of this study was to test the hypothesis that personal recovery would moderate the relationship between symptoms of schizophrenia and suicide ideation. This hypothesis was tested in a sample of 169 individuals diagnosed with schizophrenia or schizoaffective disorder using a Poisson regression model. Results suggested that there was no significant interaction between recovery and symptoms of schizophrenia. However, recovery was a significant predictor of suicide ideation after controlling for psychiatric symptoms. These findings indicate that recovery is associated with lower suicide ideation and thus may protect against it. Thus, recovery should be assessed, and potentially intervened upon, to reduce suicide risk in individuals with schizophrenia.
Response of Solanum tuberosum to Myzus persicae infestation at different stages of foliage maturity

Young leaves of the potato Solanum tuberosum L. cultivar Kardal contain resistance factors to the green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) and normal probing behavior is impeded. However, M. persicae can survive and reproduce on mature and senescent leaves of the cv. Kardal plant without problems. We compared the settling of M. persicae on young and old leaves and analyzed the impact of aphids settling on the plant in terms of gene expression. Settling, as measured by aphid numbers staying on young or old leaves, showed that after 21 h significantly fewer aphids were found on the young leaves. At earlier time points there were no difference between young and old leaves, suggesting that the young leaf resistance factors are not located at the surface level but deeper in the tissue. Gene expression was measured in plants at 96 h postinfestation, which is at a late stage in the interaction and in compatible interactions this is long enough for host plant acceptance to occur. In old leaves of cv. Kardal (compatible interaction), M. persicae infestation elicited a higher number of differentially regulated genes than in young leaves. The plant response to aphid infestation included a larger number of genes induced than repressed, and the proportion of induced versus repressed genes was larger in young than in old leaves. Several genes changing expression seem to be involved in changing the metabolic state of the leaf from source to sink.