Miracle-dz/UniFAR-FTUs huggingface dataset:
RNF168 forms a functional complex with RAD6 during the DNA damage response

Summary Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade.
Influence of slope aspect on Mediterranean woody formations: Comparison of a semiarid and an arid site in Israel

This study investigates the effects of slope aspect on plant community characteristics such as plant cover, species composition and above-ground biomass production in Mediterranean trees and shrubs in two climatological regions. Two experimental sites were selected in a climatic gradient that runs from the foothills of the Judean Hills to the northern Negev desert in Israel. In each site, 16 quadrats of 10 m × 10 m (eight south-facing and eight north-facing slopes) were established and the vegetation was recorded. Dominant tree and shrub species were measured using allometric parameters of area and volume, and representative branches were cut and weighed. Species studied were Quercus calliprinos, Phillyrea latifolia, Pistacia lentiscus, Cistus creticus, Coridothymus capitatus, and Sarcopoterium spinosum. The results showed that slope aspect had significant effects on the composition, structure and density of the plant communities developing in both sites. Vegetation structure within a site changed significantly in the short distance separating the north and south-facing slopes, and that pattern remained generally constant when comparing the two sites along the rainfall gradient. The data collected here provides new insight into the slope aspect effects on biomass allocation of different woody life forms of eastern Mediterranean plant communities.
Relationship between shift work and clustering of the metabolic syndrome diagnostic components.

AIM To examine the relationship between the type of work and the number of metabolic syndrome diagnostic components(MetS-DC), as well as the risk of MetS, with adjustment for lifestyle habits in Japanese workers. METHODS We examined the baseline data from 4,427 participants(81.4% male) aged 19 to 69 years old. The physical activity of each participant was classified according to the International Physical Activity Questionnaire(IPAQ). We defined the four MetS-DC in this study as follows: 1) high blood pressure(BP): systolic BP ≥130 mmHg, or diastolic BP ≥85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration ＜40 mg/dl or triglyceride concentration ≥150 mg/dl, or on medication for dyslipidemia; 3) dysglycemia: fasting blood sugar level ≥110 mg/dl, or if less than eight hours after meals ≥140mg/dl, or on medication for diabetes mellitus; 4) overweight: a body mass index ≥25kg/m(2). We defined MetS as overweight plus two or more of the MetS-DC. RESULTS There were 3,094 subjects in the daytime work group, 73 in the fixed nighttime work group, 1,017 in the shift work group and 243 in the day-to-night work group. The Poisson regression analysis revealed that fixed nighttime (regression coefficient [b]=-0.233, P=0.028) and shift work (b=0.098, P=0.034) independently contributed to the number of MetS-DC, compared to daytime work. The multivariate logistic analysis not including sleep hours in the model showed that shift work was positively related to MetS (odd ratio=1.47, P＜0.01). CONCLUSION Shift work were significantly associated with the number of MetS-DC, and was related to risk of MetS compared to daytime work.
Adiponectin to leptin index as a marker of endometrial cancer in postmenopausal women with abnormal vaginal bleeding: an observational study.

OBJECTIVES To evaluate the correlation between endometrial cancer and adiponectin plasma concentration, leptin plasma concentration as well as adiponectin to leptin index in the population of postmenopausal women with abnormal vaginal bleeding. DESIGN An observational study SETTINg: Department of Gynecology and Obstetrics, Specialist Teaching Hospital in Tychy, Poland. Population. 99 women between 47 and 88 years old, in postmenopausal state. METHODS The cases (54 women) were females hospitalized due to postmenopausal vaginal bleeding in whom dilation and curettage (D&C) was performed and endometrial intraepithelial neoplasia (EIN) was diagnosed in anathomopathology. Hysterectomy was then performed in all cases and the endometrial cancer diagnosis was confirmed. The controls (45 women) consists of females with no postmenopausal uterine bleeding in whom endometrial thickness in transvaginal ultrasound was greater than 5 mm. D&C was than performed and no endometrial neoplasia was detected in any of the subjects. Adiponectin and leptin plasma concentration was measured in both groups. Mein outcome measures. The area under the curve, sensitivity, specificity and cutoffs for adiponectin, leptin and adiponectin to leptin index. RESULTS Adiponectin, leptin and adiponectin to leptin index were statistically correlated with the risk of endometrial cancer. At the suggested cutoffs, corresponding to the highest accuracy (minimal false-negative and false-positive results), adiponectin to leptin index resulted in the highest sensitivity and specificity compared to adiponectin and leptin alone. CONCLUSIONS Adiponectin to leptin index due to the highest sensitivity and specificity may be used as a marker of endometrial cancer in postmenopausal women with abnormal vaginal bleeding.
Silent, Slow Lifeworld: The Communication Experience of Nonvocal Ventilated Patients

The author explored communication experience of nonvocal ventilated individuals in rehabilitation settings with an aim to understand the reality of being voiceless using interpersonal relations theory as the theoretical study framework. Nineteen participants of varied ages and with varied ventilator courses shared their experiences while they were still nonvocal. The author used an interpretive phenomenological approach and analyzed the data using thematic analysis. Participants described the meaning of their nonvocal experience as “Being trapped in a silent world makes me feel frustrated and incomplete,” “Days pass in slow motion while the rest of the world speeds by,” “Making and preserving connections is of paramount importance,” and “The powerlessness of being nonvocal was ameliorated by developing coping strategies and by consistent and reliable nursing care. ” In the discussion, the author provides an expanded understanding of the complexities of living in a silent, slow world.
Abnormal Organogenesis in Salivary Gland Development May Initiate Adult Onset of Autoimmune Exocrinopathy

Objectives: Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues. Methods: Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice. Results: Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. Discussion: NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.
Design and Evaluation of a Functional Electrical Stimulation System for Hand Sensorimotor Augmentation

The aim of this study was to perform a preliminary evaluation of a new method for therapeutic exercise of grasping in patients with upper limb disability. The new method combines active voluntary exercise augmented with electrical stimulation and controlled by using force feedback. The feedback has two functions: automatic control of the intensity of electrical stimulation by minimizing the tracking error, and biofeedback to the patient on the computer screen. The force feedback is realized by the use of a newly designed adjustable hand force measuring device, which comprises two force sensors. The therapy requires from patients to volitionally try to open and close the hand while tracking the target on the screen. The system was evaluated in a pilot study in five healthy and two chronic incomplete tetraplegic subjects. Results in healthy subjects were used for reference and for stimulation controller evaluation. The therapy in incomplete tetraplegic subjects of 45‐min daily session delivered during four weeks. The results of pilot study show that augmentation of voluntary grip force control with presented system is possible.
Monitoring blood volume and saturation using superficial fibre optic reflectance spectroscopy during PDT of actinic keratosis

Optically monitoring the vascular physiology during photodynamic therapy (PDT) may help understand patient‐specific treatment outcome. However, diffuse optical techniques have failed to observe changes herein, probably by optically sampling too deep. Therefore, we investigated using differential path‐length spectroscopy (DPS) to obtain superficial measurements of vascular physiology in actinic keratosis (AK) skin. The AK‐specific DPS interrogation depth was chosen up to 400 microns in depth, based on the thickness of AK histology samples. During light fractionated aminolevulinic acid‐PDT, reflectance spectra were analyzed to yield quantitative estimates of blood volume and saturation. Blood volume showed significant lesion‐specific changes during PDT without a general trend for all lesions and saturation remained high during PDT. This study shows that DPS allows optically monitoring the superficial blood volume and saturation during skin PDT. The patient‐specific variability supports the need for dosimetric measurements. In DPS, the lesion‐specific optimal interrogation depth can be varied based on lesion thickness. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Identification and characterization of a cAMP-responsive element in the region upstream from promoter 1.3 of the human aromatase gene.

Aromatase converts androgens to estrogens. The expression of this enzyme is driven by multiple tissue-specific promoters which are differentially regulated. Aromatase expression in breast cancer and the surrounding adipose cells is directed mainly by promoters I.3 and II, while its expression in the normal breast adipose tissue is driven by promoter I.4. Like promoter II, promoters I.3 is thought to be a cAMP-driven promoter, demonstrated previously by cell culture experiments. In the present study, we have identified and characterized a cAMP-responsive element (CREaro) upstream from promoter 1.3. This positive element, TGAAGTCA, between -66 and -59 bp relative to the transcriptional start site of promoter 1.3 was identified by DNA deletion and mutation analyses. The sequence of CREaro is one base different from the consensus CRE sequence (CREpal; TGACGTCA), and the mutational analysis revealed that CREaro had a higher enhancer activity to promoter I.3 than CREpal. Nuclear proteins from both WS3TF breast tumor fibroblasts and SK-BR-3 breast cancer cells bound to this CREaro, as demonstrated by DNA mobility shift assay. The molecular weight of the major binding protein in fibroblasts was determined to be approximately 60 kDa, as shown by UV crosslinking, which is different from those of known CRE-binding proteins. It is thought that CREB1 is not expressed in tumor fibroblasts because the Western blot analysis using anti-CREB1 antibody was not able to detect CREB1 in the nuclear protein extract from these cells. DNA mobility shift analysis using a nuclear protein extract from SK-BR-3 cells revealed that at least two proteins bound to the CREaro and that one of these proteins was identified to be CREB1. These studies provide direct evidence that promoter I.3 is a cAMP-responsive promoter.
Polymorphisms of the ADAM33 gene and chronic obstructive pulmonary disease risk: a meta‐analysis

The T1 (rs2280091), S1 (rs3918396) and S2 (rs528557) polymorphisms in a disintegrin and metalloprotease (ADAM33) gene has been implicated in susceptibility of chronic obstructive pulmonary disease (COPD). But, a number of studies have reported inconclusive results. The aim of this study is to investigate the relationship between T1 (rs2280091), S1 (rs3918396) and S2 (rs528557) polymorphisms in ADAM33 gene and COPD risk by meta‐analysis.
Dual‐polarity GRAPPA for simultaneous reconstruction and ghost correction of echo planar imaging data

The purpose of this study was to seek improved image quality from accelerated echo planar imaging (EPI) data, particularly at ultrahigh fields. Certain artifacts in EPI reconstructions can be attributed to nonlinear phase differences between data acquired using frequency‐encoding gradients of alternating polarity. These errors appear near regions of local susceptibility gradients and typically cannot be corrected with conventional Nyquist ghost correction (NGC) methods.
Observing touch activates human primary somatosensory cortex

We used magnetoencephalography to show that the human primary somatosensory (SI) cortex is activated by mere observation of touch. Somatosensory evoked fields were measured from adult human subjects in two conditions. First, the experimenter touched the subject’s right hand with her index finger (Experienced touch). In the second condition, the experimenter touched her own hand in a similar manner (Observed touch). Minimum current estimates were computed across three consecutive 300‐ms time windows (0–300, 300–600 and 600–900 ms) with respect to touch onset. During ‘Experienced touch’, as expected, the contralateral (left) SI cortex was strongly activated in the 0–300 ms time window. In the same time window, statistically significant activity also occurred in the ipsilateral SI, although it was only 2.5% of the strength of the contralateral activation; the ipsilateral activation continued in the 300–600 ms time window. During ‘Observed touch’, the left SI cortex was activated during the 300–600 ms interval; the activation strength was 7.5% of that during the significantly activated period (0–300 ms) of ‘Experienced touch’. The results suggest that when people observe somebody else being touched, activation of their own somatosensory circuitry may contribute to understanding of the other person’s somatosensory experience.
Antibody Protects Macaques against Vaginal Challenge with a Pathogenic R5 Simian/Human Immunodeficiency Virus at Serum Levels Giving Complete Neutralization In Vitro

ABSTRACT A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as a coreceptor, appear to have a selective advantage in transmission of HIV-1 in humans. Hence R5 viruses predominate during primary infection and persist throughout the course of disease in most infected people. Vaginal challenge of macaques with chimeric simian/human immunodeficiency viruses (SHIV) is perhaps one of the best available animal models for human HIV-1 infection. Passive transfer studies are widely used to establish the conditions for antibody protection against viral challenge. Here we show that passive intravenous transfer of the human neutralizing monoclonal antibody b12 provides dose-dependent protection to macaques vaginally challenged with the R5 virus SHIV162P4. Four of four monkeys given 25 mg of b12 per kg of body weight 6 h prior to challenge showed no evidence of viral infection (sterile protection). Two of four monkeys given 5 mg of b12/kg were similarly protected, whereas the other two showed significantly reduced and delayed plasma viremia compared to control animals. In contrast, all four monkeys treated with a dose of 1 mg/kg became infected with viremia levels close to those for control animals. Antibody b12 serum concentrations at the time of virus challenge corresponded to approximately 400 (25 mg/kg), 80 (5 mg/kg), and 16 (1 mg/kg) times the in vitro (90%) neutralization titers. Therefore, complete protection against mucosal challenge with an R5 SHIV required essentially complete neutralization of the infecting virus. This suggests that a vaccine based on antibody alone would need to sustain serum neutralizing antibody titers (90%) of the order of 1:400 to achieve sterile protection but that lower titers, around 1:100, could provide a significant benefit. The significance of such substerilizing neutralizing antibody titers in the context of a potent cellular immune response is an important area for further study.
Contextual risk, maternal parenting and adolescent externalizing behaviour problems: the role of emotion regulation.

BACKGROUND The objective of this study was to test if emotion regulation mediates the association between mothers' parenting and adolescents' externalizing behaviour problems (conduct problems and hyperactivity). The parenting dimensions were warmth, psychological control and behavioural control (measured with knowledge, monitoring and discipline). Adjustment was made for contextual risk (measured with the number of proximal adverse life events experienced), gender, age and English as an additional language. METHOD Data were from a UK community sample of adolescents aged 11-18 from a comprehensive school in a disadvantaged area. RESULTS At the multivariate level, none of the parenting variables predicted hyperactivity, which was associated only with difficulties in emotion regulation, contextual risk and English as a first language. The parenting variables predicting conduct problems at the multivariate level were warmth and knowledge. Knowledge did not predict emotion regulation. However, warmth predicted emotion regulation, which was negatively associated with conduct problems. Contextual risk was a significant predictor of both difficulties in emotion regulation and externalizing behaviour problems. Its effect on conduct problems was independent of parenting and was not via its association with difficulties in emotion regulation. CONCLUSIONS The findings add to the evidence for the importance of maternal warmth and contextual risk for both regulated emotion and regulated behaviour. The small maternal control effects on both emotion regulation and externalizing behaviour could suggest the importance of paternal control for adolescent outcomes.
Single muscle fiber contractile properties of young competitive distance runners.

The purpose of this investigation was to characterize the contractile properties of individual slow- and fast-twitch myofibers from highly trained distance runners. Muscle biopsies were obtained from the gastrocnemius of eight competitive runners (Run) and eight recreationally active individuals (Rec). Slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) myofibers were isolated and analyzed for diameter (microm), peak force (Po; mN), unloaded contraction velocity (Vo; fiber lengths/s), and power. Maximum oxygen uptake was higher (P<0.05) in Run (71+/-1 vs. 47+/-2 ml.kg(-1). min(-1)). Diameter of MHC I and MHC IIa fibers from Run subjects was approximately 20% greater (P<0.05) than Rec. Peak force of the MHC IIa fibers was 31% higher (P<0.05) in Run, whereas Po of MHC I fibers was not different between groups. No differences for specific tension (Po/cross-sectional area) were present between groups for either fiber type. Vo was higher (P<0.05) in MHC I (+70%) and MHC IIa (+18%) fibers from Run subjects. In vitro peak absolute power (microN.s(-1)) of both fiber types was greater (P<0.05) in Run (131 and 85% for MHC I and MHC IIa, respectively). Additionally, normalized power (W/l) of the MHC I fibers was 64% higher in Run, whereas no differences were noted for normalized power of MHC IIa fibers. These data indicate that highly trained endurance runners have elevated contraction velocity in both slow- and fast-twitch myofibers. These characteristics of the fast-twitch muscle fibers have not been previously reported in competitive endurance athletes and may contribute to the high level of running performance in these athletes.
Analytic and Clinical Validation of an Ultrasensitive, Quantitative Polymerase Chain Reaction Assay for EGFR Mutation Analysis With Circulating Tumor DNA.

CONTEXT - The mutation analysis of epidermal growth factor receptor (EGFR) has become a common test to guide therapeutic decision making for lung cancer. Molecular testing with circulating tumor DNA in plasma allows diagnosis of mutations when tumor tissue is not available as well as monitoring treatment response with repeat biopsies. OBJECTIVES - To develop a timely and cost-effective assay that can accurately detect EGFR mutations in circulating tumor DNA and to evaluate the analytic and clinical performance of the assay. DESIGN - Analytic assessment was conducted with a set of reference materials carrying classic EGFR mutations. A recently developed Poisson distribution-based approach was employed to understand the assay sensitivity. Clinical evaluation was performed with 224 pairs of plasma and matched tissues from patients with stage I to IV disease. EGFR mutation rates of 390 consecutive plasma samples processed in the central service laboratory were compared with previously reported prevalence in an Asian population. RESULTS - Our results suggested that limit of detection for the EGFR quantitative polymerase chain reaction assay was 10 mutation copies, and the lowest detectable copy numbers could be extended to a single-digit level. The clinical sensitivity was 53.3% for all stages combined and 81.4% for late stages, with a high specificity of 100%. Clinical observations showed an overall positive finding rate of 32.5% and 41.4% for stage IV disease, which is consistent with previously reported EGFR mutation prevalence in an Asian population. CONCLUSIONS - Our results supported the clinical utility of the ultrasensitive, quantitative polymerase chain reaction assay for EGFR mutation analysis with circulating tumor DNA.