Bcl-X(L) translocation in renal tubular epithelial cells in vitro protects distal cells from oxidative stress

BACKGROUND: The molecular pathogenesis of different sensitivities of the renal proximal and distal tubular cell populations to ischemic injury, including ischemia-reperfusion (IR)-induced oxidative stress, is not well-defined. An in vitro model of oxidative stress was used to compare the survival of distal [Madin-Darby canine kidney (MDCK)] and proximal [human kidney-2 (HK-2)] renal tubular epithelial cells, and to analyze for links between induced cell death and expression and localization of selected members of the Bcl-2 gene family (anti-apoptotic Bcl-2 and Bcl-X(L), pro-apoptotic Bax and Bad). METHODS: Cells were treated with 1 mmol/L hydrogen peroxide (H2O2) or were grown in control medium for 24 hours. Cell death (apoptosis) was quantitated using defined morphological criteria. DNA gel electrophoresis was used for biochemical identification. Protein expression levels and cellular localization of the selected Bcl-2 family proteins were analyzed (Western immunoblots, densitometry, immunoelectron microscopy). RESULTS: Apoptosis was minimal in control cultures and was greatest in treated proximal cell cultures (16.93 +/- 4.18% apoptosis) compared with treated distal cell cultures (2.28 +/- 0.85% apoptosis, P < 0.001). Endogenous expression of Bcl-X(L) and Bax, but not Bcl-2 or Bad, was identified in control distal cells. Bcl-X(L) and Bax had nonsignificant increases (P> 0.05) in these cells. Bcl-2, Bax, and Bcl-X(L), but not Bad, were endogenously expressed in control proximal cells. Bcl-X(L) was significantly decreased in treated proximal cultures (P < 0.05), with Bax and Bcl-2 having nonsignificant increases (P> 0.05). Immunoelectron microscopy localization indicated that control and treated but surviving proximal cells had similar cytosolic and membrane localization of the Bcl-2 proteins. In comparison, surviving cells in the treated distal cultures showed translocation of Bcl-X(L) from cytosol to the mitochondria after treatment with H2O2, a result that was confirmed using cell fractionation and analysis of Bcl-X(L) expression levels of the membrane and cytosol proteins. Bax remained distributed evenly throughout the surviving distal cells, without particular attachment to any cellular organelle. CONCLUSION: The results indicate that in this in vitro model, the increased survival of distal compared with proximal tubular cells after oxidative stress is best explained by the decreased expression of anti-apoptotic Bcl-X(L) in proximal cells, as well as translocation of Bcl-X(L) protein to mitochondria within the surviving distal cells.

French version of the Family Attitude Scale : psychometric properties and relation of attitudes to the respondent's psychiatric status

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.

Self-efficacy partially mediates between social support and health-related quality of life in family caregivers for dementia patients in Shanghai

Background: There is a paucity of research assessing health-related quality of life (HRQoL) and self-efficacy in caregivers of relatives with dementia in mainland China. Aims: To compare the level of HRQoL between caregivers and the general population in mainland China and to assess the role of caregiver self-efficacy in the relationship between caregiver social support and HRQoL. Methods: A cross-sectional study was conducted in Shanghai, China. The caregivers were recruited from the outpatient department of a teaching hospital. A total of 195 participants were interviewed, using a survey package including the Chinese version of the 36-Item Short-Form Health Survey (SF-36), demographic data, the variables associated with the impairments of care recipients, perceived social support and caregiver self-efficacy. The caregivers' SF-36 scores were compared with those of the general population in China. Results: The results indicated that the HRQoL of the caregivers was poorer compared with that of the general population when matched for age and gender. Multiple regression analyses revealed that caregiver self-efficacy is a partial mediator between social support and HRQoL, and a partial mediator between behavioral and psychological symptoms of dementia (BPSD) and caregiver mental health. Conclusion: Assisting with managing BPSD and enhancing caregiver self-efficacy can be considered integral parts of interventions to improve caregiver HRQoL.

Context-specific stressors, work-related social support and work-family conflict : a mediation study

Understanding the antecedents of work-family conflict is important as it allows organisations to effectively engage in work design for professional employees. This study examines the impact of sources of social support as antecedents of work-family conflict. The hypotheses were tests using Partial Least Squares modelling on a sample of 366 professional employees. The path model showed that context-specific stressors impacted positively on job demand, which led to higher levels of work-family conflict. Contrary to our expectation, non-work related social support did not have any statistical relationship with job demand and work-family conflict. In addition, individuals experiencing high job demands were found to obtain more social support from both work and non-work-related sources. Individuals with more work-related social support were less likely to have less work-family conflict. Surprisingly, non-work social support sources had no statistically significant relationship with work-family conflict.

Molecular characterization of "Candidatus Parilichlamydia carangidicola," a novel Chlamydia-like epitheliocystis agent in yellowtail kingfish, Seriola lalandi (Valenciennes), and the proposal of a new family, "Candidatus Parilichlamydiaceae" fam. nov. (order Chlamydiales).

Three cohorts of farmed yellowtail kingfish (Seriola lalandi) from South Australia were examined for Chlamydia-like organisms associated with epitheliocystis. To characterize the bacteria, 38 gill samples were processed for histopathology, electron microscopy, and 16S rRNA amplification, sequencing, and phylogenetic analysis. Microscopically, the presence of membrane-enclosed cysts was observed within the gill lamellae. Also observed was hyperplasia of the epithelial cells with cytoplasmic vacuolization and fusion of the gill lamellae. Transmission electron microscopy revealed morphological features of the reticulate and intermediate bodies typical of members of the order Chlamydiales. A novel 1,393-bp 16S chlamydial rRNA sequence was amplified from gill DNA extracted from fish in all cohorts over a 3-year period that corresponded to the 16S rRNA sequence amplified directly from laser-dissected cysts. This sequence was only 87% similar to the reported "Candidatus Piscichlamydia salmonis" (AY462244) from Atlantic salmon and Arctic charr. Phylogenetic analysis of this sequence against 35 Chlamydia and Chlamydia-like bacteria revealed that this novel bacterium belongs to an undescribed family lineage in the order Chlamydiales. Based on these observations, we propose this bacterium of yellowtail kingfish be known as "Candidatus Parilichlamydia carangidicola" and that the new family be known as "Candidatus Parilichlamydiaceae."

Migrants' use of the Internet in re-settlement

The project is a qualitative and ethnographic study investigating how the internet is used by migrants from cultural and linguistically diverse (CALD) groups. It examines how internet use assists the re- settlement process in Brisbane, Australia. The project aims to support strategies and initiatives in the successful re-settlement of migrants from CALD groups into urban localities. It has 2 main foci: • To find out how and what type of online information and services are used by migrants and what are the barriers to accessing the information. Information and resources about transport, housing, health, social services, education and other information is essential for successful re-settlement. • In what ways is the internet is used as a social medium, to communicate with friends and family in homeland countries and connect with people in local regions, in ways that might help to combat social isolation.

End-of-life care in the intensive care unit : a systematic review of qualitative studies investigating the experiences and perceptions of the patient's family

Review question/objective The review objective is to synthesise the best available evidence on experiences and perceptions of family members of intensive care unit patients on the adequacy of end-of-life care, where life-support modalities have been withheld or withdrawn. Inclusion criteria Types of participants This review will consider studies that report on the experiences and perceptions of patients’ families on EOLC in the ICU, where life-support modalities have been withheld or withdrawn. The family is defined as “those who are closest to the patient... the family may include the biological family, family by acquisition, and the family of choice and friends”. Phenomena of interest The phenomena of interest for this review are the patients’ families experiences, perceptions or views on the adequacy of EOLC delivered in the ICU, where life-support modalities were withheld or withdrawn. These experiences may refer to the following views on domains of care considered important at the end-of-life in the ICU, which have been described already in the existing literature: timely, consistent, and compassionate communication, clinician availability, clinical decision making based on patients’ preferences, goals and values, physical care implemented to maintain patient comfort, holistic interdisciplinary care and bereavement care for families of patients who died.

The uber-assumption family

We offer an exposition of Boneh, Boyen, and Goh’s “uber-assumption” family for analyzing the validity and strength of pairing assumptions in the generic-group model, and augment the original BBG framework with a few simple but useful extensions.

Osteogenic differentiation of murine embryonic stem cells is mediated by fibroblast growth factor receptors

The mechanisms involved in the control of embryonic stem (ES) cell differentiation are yet to be fully elucidated. However, it has become clear that the family of fibroblast growth factors (FGFs) are centrally involved. In this study we examined the role of the FGF receptors (FGFRs 1-4) during osteogenesis in murine ES cells. Single cells were obtained after the formation of embryoid bodies, cultured on gelatin-coated plates, and coaxed to differentiate along the osteogenic lineage. Upregulation of genes was analyzed at both the transcript and protein levels using gene array, relative-quantitative PCR (RQ-PCR), and Western blotting. Deposition of a mineralized matrix was evaluated with Alizarin Red staining. An FGFR1-specific antibody was generated and used to block FGFR1 activity in mES cells during osteogenic differentiation. Upon induction of osteogenic differentiation in mES cells, all four FGFRs were clearly upregulated at both the transcript and protein levels with a number of genes known to be involved in osteogenic differentiation including bone morphogenetic proteins (BMPs), collagen I, and Runx2. Cells were also capable of depositing a mineralized matrix, confirming the commitment of these cells to the osteogenic lineage. When FGFR1 activity was blocked, a reduction in cell proliferation and a coincident upregulation of Runx2 with enhanced mineralization of cultures was observed. These results indicate that FGFRs play critical roles in cell recruitment and differentiation during the process of osteogenesis in mES cells. In particular, the data indicate that FGFR1 plays a pivotal role in osteoblast lineage determination.

The impact of funding deadlines on personal workloads, stress and family relationships : a qualitative study of Australian researchers

Objective To examine the impact of applying for funding on personal workloads, stress and family relationships. Design Qualitative study of researchers preparing grant proposals. Setting Web-based survey on applying for the annual National Health and Medical Research Council (NHMRC) Project Grant scheme. Participants Australian researchers (n=215). Results Almost all agreed that preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. Almost all researchers agreed that they became stressed by the workload (93%) and restricted their holidays during the grant writing season (88%). Most researchers agreed that they submitted proposals because chance is involved in being successful (75%), due to performance requirements at their institution (60%) and pressure from their colleagues to submit proposals (53%). Almost all researchers supported changes to the current processes to submit proposals (95%) and peer review (90%). Most researchers (59%) provided extensive comments on the impact of writing proposals on their work life and home life. Six major work life themes were: (1) top priority; (2) career development; (3) stress at work; (4) benefits at work; (5) time spent at work and (6) pressure from colleagues. Six major home life themes were: (1) restricting family holidays; (2) time spent on work at home; (3) impact on children; (4) stress at home; (5) impact on family and friends and (6) impact on partner. Additional impacts on the mental health and well-being of researchers were identified. Conclusions The process of preparing grant proposals for a single annual deadline is stressful, time consuming and conflicts with family responsibilities. The timing of the funding cycle could be shifted to minimise applicant burden, give Australian researchers more time to work on actual research and to be with their families.

Partial mediation role of self-efficacy between positive social interaction and mental health in family caregivers for dementia patients in Shanghai

We explored the mediation effect of caregiver self-efficacy on the influences of behavioral and psychological symptoms (BPSD) of dementia care recipients (CRs) or family caregivers’ (CGs) social supports (informational, tangible and affectionate support and positive social interaction) on CGs’ mental health. We interviewed 196 CGs, using a battery of measures including demographic data of the dyads, CRs’ dementia-related impairments, and CGs’ social support, self-efficacy and the Medical Outcome Study (MOS) Short-Form (SF-36) Health Survey. Multiple regression analyses showed that gathering information on self-efficacy and managing CG distress self-efficacy were the partial mediators of the relationship between positive social interaction and CG mental health. Managing caregiving distress self-efficacy also partial mediated the impact of BPSD on CG mental health. We discuss implications of the results for improving mental health of the target population in mainland China.

Cryptanalysis of the LAKE hash family

We analyse the security of the cryptographic hash function LAKE-256 proposed at FSE 2008 by Aumasson, Meier and Phan. By exploiting non-injectivity of some of the building primitives of LAKE, we show three different collision and near-collision attacks on the compression function. The first attack uses differences in the chaining values and the block counter and finds collisions with complexity 233. The second attack utilizes differences in the chaining values and salt and yields collisions with complexity 242. The final attack uses differences only in the chaining values to yield near-collisions with complexity 299. All our attacks are independent of the number of rounds in the compression function. We illustrate the first two attacks by showing examples of collisions and near-collisions.