Miracle-dz/UniFAR-FTUs huggingface dataset:
Extent of constitutive histone H2AX phosphorylation on Ser‐139 varies in cells with different TP53 status

Abstract. In response to DNA damage by genotoxic agents, histone H2AX is phosphorylated on Ser‐139. However, during the cell cycle, predominantly in S and G2M phase, histone H2AX is also phosphorylated in untreated normal and tumour cells. This constitutive H2AX phosphorylation is markedly reduced by exposure of cells to the reactive oxygen species scavenger N‐acetyl‐L‐cysteine. Therefore, it appears likely that constitutive H2AX phosphorylation reflects the ongoing oxidative DNA damage induced by the reactive oxygen species during progression through the cell cycle. Because the tumour suppressor p53 (tumour protein p53) is known to induce transcription of genes associated with cell response to oxidative stress, we have compared the intensity of constitutive H2AX phosphorylation, and the effect of N‐acetyl‐L‐cysteine on it, in cells with different tumour protein p53 status. These were human lymphoblastoid cell lines derived from WIL2 cells: TK6, a p53 wt line, NH32, a tumour protein p53 knock‐out derived from TK6, and WTK1, a WIL2‐derived line that expresses a homozygous mutant of tumour protein p53. Also tested were the tumour protein p53‐null promyelocytic HL‐60 cells. The degree of constitutive H2AX phosphorylation was distinctly lower in NH32, WTK1 and HL‐60 compared to TK6 cells in all phases of the cell cycle. Also, the degree of attenuation of constitutive H2AX phosphorylation by N‐acetyl‐L‐cysteine was less pronounced in NH32, WTK1, and HL‐60, compared to TK6 cells. However, the level of reactive oxygen species detected by the cells’ ability to oxidize carboxyl‐dichlorodihydrofluorescein diacetate was not significantly different in the cell lines studied, which would suggest that regardless of tumour protein p53 status, the level of oxidative DNA damage was similar. The observed higher level of constitutive H2AX phosphorylation in cells harbouring wt tumour protein p53 may thus indicate that tumour protein p53 plays a role in facilitating histone H2AX phosphorylation, an important step in the mobilization of the DNA repair machinery at the site of DNA double‐strand breaks.
Family caregiver perspectives on caring for ventilator-assisted individuals at home.

BACKGROUND The trend of patients who are invasively ventilated to prefer home care is one that benefits both the patient and the health care system. However, this assumes a role for patients' family members to become informal caregivers. OBJECTIVE To explore the impact of caring for a ventilator-assisted individual on informal caregivers. METHODS A descriptive design with semistructured caregiver interviews and the Caregiver Burden Inventory were used. Participants were informal caregivers of a family member with a progressive neuromuscular disease on invasive ventilation for at least six months. Transcript coding was performed and regularly reviewed, and recruitment continued until data saturation. Qualitative analysis was based on 'thematic analysis'. RESULTS A total of 21 caregivers were interviewed. Five themes developed: a sense of duty; restriction of day-to-day life; physical and emotional burden; training and education; and the need for more paid support. Caregivers described a sense of duty to take care of loved ones, but suffered a significant restriction of their own time with a negative impact on their physical and mental health. The initial transfer home was highlighted as the most stressful part of the process. The Caregiver Burden Inventory scores supported a high level of burden: median 49 (interquartile range 39.5 to 53.0) of a maximum 96. CONCLUSION Homecare for ventilator-assisted individuals with progressive neuromuscular disease causes significant burden to informal caregivers. Approaches to lessen this burden, such as increased paid care, improved professional support and respite care, may enable home ventilation to be a more sustainable modality of care.
Strain-Specific Polymorphisms in Paneth Cell α-Defensins of C57BL/6 Mice and Evidence of Vestigial Myeloid α-Defensin Pseudogenes

ABSTRACT Paneth cells at the base of small intestinal crypts secrete microbicidal α-defensins, termed cryptdins (Crps) in mice, as mediators of innate immunity. Proteomic studies show that five abundant Paneth cell α-defensins in C57BL/6 mice are strain specific in that they have not been identified in other inbred strains of mice. Two C57BL/6-specific peptides are coded for by the Defcr20 and -21 genes evident in the NIH C57BL/6 genome but absent from the Celera mixed-strain assembly, which excludes C57BL/6 data and differs from the NIH build with respect to the organization of the α-defensin gene locus. Conversely, C57BL/6 mice lack the Crp1, -2, -4, and -6 peptides and their corresponding Defcr1, -2, -4, and -6 genes, which are common to several mouse strains, including those of the Celera assembly. In C57BL/6 mice, α-defensin gene diversification appears to have occurred by tandem duplication of a multigene cassette that was not found in the mixed-strain assembly. Both mouse genome assemblies contain conserved α-defensin pseudogenes that are closely related to functional myeloid α-defensin genes in the rat, suggesting that the neutrophil α-defensin defect in mice resulted from progressive gene loss. Given the role of α-defensins in shaping the composition of the enteric microflora, such polymorphisms may influence outcomes in mouse models of disease or infection.
DISC1 as a Possible Genetic Contribution to Opioid Dependence in a Polish Sample.

OBJECTIVE Disrupted-in-schizophrenia 1 (DISC1) has been linked to vulnerability to a variety of psychiatric disorders and neuropsychiatric phenotypes. However, DISC1 has not been frequently examined as a potential risk factor for substance dependence. An association between opioid dependence and DISC1 rs2738888 polymorphism has been recently reported. In addition, opioid dependence was associated with rs6419156 located close to the protein phosphatase 3 catalytic subunit alpha isoform (PPP3CA) gene. The aim of the present study was to examine the associations between opioid dependence with rs2738888 and rs6419156 in an independent sample. METHOD The selected polymorphisms were genotyped in a sample of 392 individuals (69.9% male) diagnosed as alcohol- and/or opioid-dependent. A control group (n = 257; 67.7% male) was derived from the Polish National Health Survey (N = 14,350). RESULTS The frequency of rs2738888 C allele was higher in controls than in opioid-dependent cases (OR = 0.65, p = .045). Phenotypic-oriented analyses performed within opioid-dependent individuals revealed the association between lifetime suicide attempt and rs2738888. The C allele of rs2738888 had a protective effect on lifetime suicide attempt in opioid-dependent patients (OR = 0.25, p = .003). Rs6419156 was not associated with substance dependence in the examined sample. CONCLUSIONS The DISC1 may play an important role in vulnerability to opioid dependence. In addition, DISC1 may also be a genetic risk factor for suicide attempt in opioid-dependent individuals.
Association of carboxylesterase B electrophoretic pattern with presence and expression of urovirulence factor determinants and antimicrobial resistance among strains of Escherichia coli that cause urosepsis

We determined the carboxylesterase B electrophoretic profiles of 74 blood isolates of Escherichia coli from patients with urosepsis. Most strains (64%) exhibited the B2 electrophoretic pattern. P fimbrial and hemolysin genetic determinants were present and expressed significantly more often among strains with the B2 than with the B1 electrophoretic pattern. In contrast, aerobactin determinants were significantly more prevalent and more commonly expressed among the B1 strains; this difference was attributable to the presence of plasmid-encoded aerobactin in one-third of the B1 strains (P = 0.02, B1 versus B2). The prevalence and extent of antimicrobial resistance was significantly greater among the B1 strains, and the B1 electrophoretic pattern was more often found in isolates from patients with urinary tract abnormalities. We conclude that the carboxylesterase B electrophoretic pattern differentiates two groups of E. coli isolates from patients with urosepsis: strains with the B1 electrophoretic pattern are associated with urologically impaired hosts, characteristically lack P fimbrial and hemolysin determinants, and often carry a plasmid-encoded aerobactin system (possibly on multiple antimicrobial resistance plasmids), whereas B2 strains more commonly invade noncompromised hosts, express P fimbriae and hemolysin, carry chromosomal aerobactin determinants, and lack antimicrobial resistance.
[Effects of Xuebijing injection on thrombomodulin and endothelial cell protein C receptor in septic rats].

OBJECTIVE To investigate effects of the integrated traditional Chinese medicine Xuebijing injection on thrombomodulin (TM) and endothelial cell protein C receptor (EPCR) in septic rats. METHODS Ninety-six healthy Wistar rats were randomly divided into four groups: control group, sham operation group, cecal ligation and puncture (CLP) model group, and Xuebijing-treated group. Sepsis was reproduced by CLP. The two latter groups were divided into five subgroups of 2, 8, 24, 48 and 72-hour with 8 rats in each subgroup. Tissue samples from liver and lung were collected to determine tissue TM and EPCR mRNA expression. RESULTS TM and EPCR mRNA expressions were observed in liver and lung in control group and sham operation group, while with no significant differences at 2 hours post-CLP (both P>0.05). TM and EPCR gene expression levels in tissues were significantly increased to certain extent at 8-48 hours (all P<0.01), and were dramatically decreased following Xuebijing injection at 72 hours post-CLP (both P>0.05). Also, treatment with Xuebijing injection markedly decreased TM and EPCR mRNA levels to certain extents at 8 and 24 hours, and markedly increased at 48 and 72 hours compared with those of model group. CONCLUSION These data suggest that Xuebijing injection could raise TM and EPCR mRNA expression, thereby it might be effective in prevention of development of severe sepsis.
[Effects of icariin on inflammation model stimulated by lipopolysaccharide in vitro and in vivo].

OBJECTIVE To evaluate the anti-inflammatory effects of icariin, from aspects of pro-inflammatory cytokines, inflammatory mediators and adhesion molecules. METHODS Mouse inflammation model in vitro was established by stimulating macrophage cell line RAW264. 7 with lipopolysaccharide (LPS); and the inflammation model in vivo was established by stimulating C57BL/6J mouse with LPS. Taking dexamethasone as the positive control, both models were treated with icariin, and the cell viability in model mice was detected with CCK-8 kit; tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) in cell culture medium and serum were detected by ELISA; nitric oxide (NO) in cell culture medium by Griess Reagent method; CD11b expression on the surface of neutrophil in mice by flow cytometry, and pulmonary inflammatory cell infiltration in mice by pathological section as well. RESULTS in vitro studies showed that icariin at the doses of 1 microg/mL, 10 microg/mL and 100 microg/mL, all displayed no cytotoxicity (P < 0.01); 10 microg/mL and 100 microg/mL icariin effectively lowered the levels of TNF-alpha and IL-6 (P < 0.01) in medium; and 100 microg/mL icariin significantly reduced level of NO (P < 0.01) in medium. in vivo studies showed that icariin at the dose of 20 mg/kg significantly lowered serum TNF-alpha and IL-6 levels (P < 0.01), reduced the average fluorescence intensity of adhesion molecules CD11b (P < 0.01), and alleviated pulmonary inflammatory cell infiltration. CONCLUSION Icariin is a safe and effective natural anti-inflammatory drug, its partial mechanism is possible the multiple links intervention on pro-inflammatory cytokines (TNF-alpha, IL-6), inflammatory mediators (NO) and adhesion molecules (CD11b).
High resolution MRI and MRS: A feasibility study for the investigation of focal cerebral ischemia in mice

Combined NMR imaging and spectroscopy have been applied to mouse brain during focal cerebral ischemia. The present study evaluated the feasibility of NMR measurements on mice in order to fine‐tune the sequences and experimental setup for systematic investigations on stroke including future studies on transgenic animals. The acquisition of high quality diffusion‐weighted, perfusion‐weighted, and T2‐weighted images (DWI, PWI, T2‐WI, respectively) is demonstrated and complemented by measurements of 1H volume‐selective spectroscopy and spectroscopic imaging (SI). Despite the small volume of the mouse brain, a satisfactory signal‐to‐noise ratio can be achieved with reasonably short measurement times. C57black/6J mice with an average body weight of 25 g were studied using state‐of‐the‐art NMR sequences at 4.7 T. After induction of focal cerebral ischemia, the lesion was found clearly distinguishable in all imaging techniques. The apparent diffusion coefficient (ADC) was reduced in the ischemic region, and an expansion of the affected volume was observed with ongoing ischemia time. In the 1H spectra of ischemic animals a distinct change in the concentrations of NAA and lactate was visible. This is the first report on both SI data and perfusion‐weighted imaging on mouse brain. It is demonstrated that the perfusion deficit during ischemia can be well demarcated. The spatial resolution of changes in metabolite concentrations allows the clear differentiation of elevated lactate levels in ischemic brain tissue. Copyright © 1998 John Wiley & Sons, Ltd.
Reaching target lipid levels in patients at high risk of cardiovascular event: the experience of a Canadian tertiary care lipid clinic.

OBJECTIVES To determine the proportion of high risk patients followed at a tertiary care lipid clinic who met recommended lipid targets and to identify predictors of reaching goal lipid levels. RESEARCH DESIGN AND METHODS A retrospective cohort study of 502 high risk patients followed between 1983 and 2003. Clinical and demographic data and fasting lipid profiles were extracted from each patient's first two clinic visits as well as the most recent visit. RESULTS All patients in this study were at high risk of cardiovascular events due to dyslipidemia. At "Visit 1", only 55 (11.0%) of patients were at target TC/HDL-C < 4.0, and 97 (19.3%) of patients met target LDL-C < 2.5 mmol/l. At "Visit 3", 229 (45.8%) patients reached TC/HDL-C target, and 216 (43.2%) patients were at LDL-C target. The mean change in lipid values between Visit 1 and Visit 3 was significant (p = 0.0002) for LDL-C and (p < 0.0001) for TC/HDL-C. The use of statins, niacin, or salmon oil were all significantly associated with reaching TC/HDL-C target and LDL-C target, as well male gender, diabetes mellitus and peripheral vascular disease were also associated with reaching LDL-C target. Increasing age and lower body mass index were associated with reaching goal TC/HDL-C. CONCLUSIONS The mean absolute changes in lipid values were significant and median lipid levels approached target levels in patients followed at specialized clinic, however the majority of high risk patients are not meeting goal lipid levels.
White matter lesions and poor outcome after intracerebral hemorrhage

Background: The ability to predict poor outcome is important for patient care and treatment decision-making in cases of intracerebral hemorrhage (ICH). Previous studies have included relatively brief follow-up periods and small numbers of patients, and are limited in terms of considerations regarding individual brain vulnerabilities. Methods: The authors prospectively enrolled 1,321 ICH patients nationwide from 33 hospitals. Clinical, laboratory, and imaging variables, including white matter lesions (WMLs), were collected at admission. Immediate outcome after ICH was measured using total Glasgow Coma Scale (GCS) score at admission, early outcome using 30-day mortality, and long-term outcome using relative risk for mortality. The vital status of included patients was ascertained on December 31, 2006, using Korean National Death Certificates (mean follow-up, 32.6 months). Results: Of the 1,321 ICH patients included, 352 (27.8%) presented with a moderate GCS score (8.5–12.4) and 249 (19.7%) with a severe GCS score (≤8.4). The mortality rate was 9.1% at day 30 post-ICH and 381 patients (29.8%) had died up to the end of December 2006. Extensive WMLs were associated with severe GCS scores at admission (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.73–3.46), 30-day mortality (OR 2.52, 95% CI 1.33–4.75), and the relative risk for mortality (RR 2.61, 95% CI 1.79–3.82) after adjusting for relevant covariates. Conclusions: These findings suggest that white matter lesions, which may reflect the vulnerability of individual brains to pathologic insults, should be considered when assessing immediate, early, and long-term outcomes after intracerebral hemorrhage.
Identification of a novel rickettsial infection in a patient diagnosed with murine typhus

Identification of ELB agent-infected fleas and rodents within several foci of murine typhus in the United States has prompted a retrospective investigation for this agent among human murine typhus patients. This agent is a recently described rickettsia which is indistinguishable from Rickettsia typhi with currently available serologic reagents. Molecular analysis of the 17-kDa antigen gene and the citrate synthase gene has discriminated this bacterium from other typhus group and spotted fever group rickettsiae. Current sequencing of its 16S ribosomal DNA gene indicates a homology of 98.5% with R. typhi and 99.5% with R. rickettsii. Through a combination of restriction fragment length polymorphism and Southern hybridization analysis of rickettsia-specific PCR products, one of five tested patient blood samples was shown to be infected with ELB while R. typhi infections were confirmed in the remaining samples. This is the first reported observation of a human infection by the ELB agent and underscores the utility of PCR-facilitated diagnosis and discrimination of these closely related rickettsial infections.
Identification of AbrB‐regulated genes involved in biofilm formation by Bacillus subtilis

Bacillus subtilis is a ubiquitous soil bacterium that forms biofilms in a process that is negatively controlled by the transcription factor AbrB. To identify the AbrB‐regulated genes required for biofilm formation by B. subtilis, genome‐wide expression profiling studies of biofilms formed by spo0A abrB and sigH abrB mutant strains were performed. These data, in concert with previously published DNA microarray analysis of spo0A and sigH mutant strains, led to the identification of 39 operons that appear to be repressed by AbrB. Eight of these operons had previously been shown to be repressed by AbrB, and we confirmed AbrB repression for a further six operons by reverse transcription‐PCR. The AbrB‐repressed genes identified in this study are involved in processes known to be regulated by AbrB, such as extracellular degradative enzyme production and amino acid metabolism, and processes not previously known to be regulated by AbrB, such as membrane bioenergetics and cell wall functions. To determine whether any of these AbrB‐regulated genes had a role in biofilm formation, we tested 23 mutants, each with a disruption in a different AbrB‐regulated operon, for the ability to form biofilms. Two mutants had a greater than twofold defect in biofilm formation. A yoaW mutant exhibited a biofilm structure with reduced depth, and a sipW mutant exhibited only surface‐attached cells and did not form a mature biofilm. YoaW is a putative secreted protein, and SipW is a signal peptidase. This is the first evidence that secreted proteins have a role in biofilm formation by Bacillus subtilis.
Selective facilitation of different hand muscles by single corticospinal neurones in the conscious monkey.

1. Post‐spike facilitation of e.m. g. activity by monkey motor cortex neurones has been investigated in different hand and forearm muscles. 2. Seventy‐eight neurones were recorded concurrently with between five and ten different muscles. Forty‐seven neurones were identified as cortico‐motor by the presence of post‐spike facilitation in the spike‐triggered average of at least one of the tested muscles. 3. All forty‐seven cortico‐motor neurones showed clear increases in activity during performance of a precision grip task by the monkey, and all of them were co‐activated with the sampled muscles. 4. To assess the divergence of facilitation from a single cortico‐motor neurone to different muscles, spike‐triggered averages were constructed with all of the concurrently recorded muscles. The number of muscles in the sample, and the number of muscles showing post‐spike facilitation, were corrected by excluding any post‐spike facilitation which could have arisen by cross‐talk between the different pairs of e.m. g. electrodes. 5. Most cortico‐motor neurones produced post‐spike facilitation in a restricted number of tested muscles. The mean number of post‐spike facilitation‐bearing muscles per cortico‐motor cell rose from 1.4 +/‐ 0.5 (S.D.) when five muscles were sampled to 2.0 +/‐ 1.5 when ten were sampled. On average, each cortico‐motor neurone produced post‐spike facilitation in 27% of the tested muscles. Only three of forty‐seven cortico‐motor neurones gave post‐spike facilitation in half or more of the tested muscles. 6. The distribution pattern of post‐spike facilitation among the muscles sampled with a given cortico‐motor neurone was not altered when the spike‐triggered averages were constructed from cortico‐motor cell and e.m. g. activity recorded during two different phases of the precision grip task, or during performance of a quite different, power grip, task. 7. Cortico‐motor cells which produced post‐spike facilitation in two or more different muscles often did so in muscles with synergistic functions. 8. It is suggested that cortico‐motor neurones may contribute to relatively independent finger movements by virtue of their selective facilitation of hand muscles leading to a fractionated pattern of muscle activity.
[Molecular epidemiological study on rubella virus].

OBJECTIVE To understand the hereditary and variant characteristics of rubella virus(RV), especially the strains isolated from China, investigating the epidemical trend and variation principle of RV. METHODS The envelope glycoprotein E1 gene was amplified from rubella virus by RT-PCR. After sequencing, the gene sequence was handled by the software DNASTAR and the phylogenetic tree was drawn to analyze the molecular epidemiological characteristics of RV. RESULTS The sequence of RV strain JR23 was sequenced, the phylogenetic tree was drawn taking 30 strains isolated at different times and locations in GenBank, including three strains from China as reference. The regions that encode the peptides which react with the HI antibody and the neutralization antibody were compared to show if there was any amino acid mutation in the sequence. (1) In general, the nucleotide and amino acid sequences of RV were highly conserved. The four strains isolated from China had relatively large variations. Strain 379 and strain BRD constituted genotype II, which is different from the other 29 strains. Further study is needed to understand their heritable resources and biological characteristics. (2) Strain JR23 showed little difference from the strains that were epidemic during 1960s in UK, USA and Japan, so maybe it is the derivative strain of that in epidemic 1960s. But the accurate epidemic time is not known. CONCLUSION There are differences among areas and time in epidemics of rubella. The mobility and the region difference seem to be the key factors that affect the epidemic characteristics of RV.