Baf60c is a component of the neural progenitor-specific BAF complex in developing retina

Remodeling of the chromatin network plays an important role regulating embryonic development as well as differentiation. The SWI/SNF complex is an ATP-dependent chromatin-remodeling complex. It consists of several proteins, including an ATPase subunit, either Brg1 or Brm. Two subunits of this complex, Baf53a and Baf45, have been previously identified as being neural progenitor-specific. In this study, we show that Baf60c, another important part of this large complex, acts in a similar neural progenitor-specific manner. We show that during development Baf60c is expressed in neural progenitors in human retinas as well as mouse retina, cortex and spinal cord. Baf60c expression is lost during neural differentiation and its overexpression keeps the progenitors in a proliferative state through its interaction with the Notch pathway. Finally, we show that Baf60c is re-expressed in the Müller glial cells that re-enter the cell cycle after neurotoxic damage.     

Clamp loading,unloading and intrinsic stability of the PCNA, β and gp45 sliding clamps of human,E. coli and T4 replicases

Background: The high speed and processivity of replicative DNA polymerases reside in a processivity factor which has been shown to be a ring-shaped protein. This protein (‘sliding clamp’) encircles DNA and tethers the catalytic unit to the template. Although in eukaryotic, prokaryotic and bacteriophage-T4 systems, the processivity factors are ring-shaped, they assume different oligomeric states. The Escherichia coli clamp (the β subunit) is active as a dimer while the eukaryotic and T4 phage clamps (PCNA and gp45, respectively) are active as trimers. The clamp can not assemble itself on DNA. Instead, a protein complex known as a clamp loader utilizes ATP to assemble the ring around the primer-template. This study compares properties of the human PCNA clamp with those of E. coli and T4 phage. Results: The PCNA ring is a stable trimer down to a concentration below 100 nm (K_d ≈ 21 nm ). On DNA, the PCNA clamp slides freely and dissociates from DNA slowly (t_1/2 ≈ 24 min). β is more stable in solution (K_d < 60 pm ) and on DNA (t_1/2 ≈ 1 h) than PCNA which may be explained by its simpler oligomeric state. The T4 gp45 clamp is a much less stable trimer than PCNA (K_d ≈ 250 nm ) and requires association with the polymerase to stabilize it on DNA as observed previously. The consequence of this cooperation between clamp and polymerase is that upon finishing a template and dissociation of the polymerase from DNA, the gp45 clamp spontaneously dissociates from DNA without assistance. However, the greater stability of the PCNA and β clamps on DNA necessitates an active process for their removal. The clamp loaders (RF-C and γ complex) were also capable of unloading their respective clamps from DNA in the presence of ATP. Conclusions: The stability of the different clamps in solution correlates with their stability on DNA. Thus, the low stability of the T4 clamp explains the inability to isolate gp45 on DNA. The stability of the PCNA and β clamps predicts they will require an unloading factor to recycle them on and off DNA during replication. The clamp loaders of PCNA and β double as clamp unloaders presumably for the purpose of clamp recycling.     

Autocrine growth of human blymphocytes: Maintained response to autostimulatory factors is the special feature of immortalization by Epstein-Barr virus—A hypothesis

The autocrine growth profile of human B lymphocytes transformed with Epstein-Barr virus (EBV) was found to comprise three distinct components: a B-cell growth factor (BCGF); an interleukin-1 (IL-1)-like activity; an activity requiring cell-to-cell contact for its action. Observations on the inhibition of the EBV-carrying Daudi lymphoma line by α-interferon indicated that loss of response to these autostimulatory factors was underlying growth cessation. Furthermore, a putative for BCGF was found to be down-regulated on B cells stimulated with non-transforming mitogens but constitutively expressed following EBV-transformation. Taken together with recent evidence that normal B cells produce autostimulatory factors, these findings suggest that the special feature of autocrine growth by EBV-immortalized cells is a maintenance of what should normally be a transient phenotype, possibly through deregulation of receptor expression. This hypothesis is discussed.     

Social–Emotional Profiles of PTSD,Complex PTSD,and Borderline Personality Disorder Among Racially and Ethnically Diverse Young Adults: A Latent Class Analysis

The debate around the construct validity of complex posttraumatic stress disorder (CPTSD) has begun to examine whether CPTSD diverges from posttraumatic stress disorder (PTSD) when it co‐occurs with the diagnosis of borderline personality disorder (BPD). The present study (a) examined the construct validity of CPTSD through a latent class analysis of a non–treatment‐seeking sample of young trauma‐exposed adults and (b) characterized each class in terms of trauma characteristics, social emotions (e.g., shame, guilt, blame), and interpersonal functioning. A total of 23 dichotomized survey items were chosen to represent the symptoms of PTSD, CPTSD, and BPD and administered to 197 trauma‐exposed participants. Fit statistics compared models with 2–4 latent classes. The four‐class model showed the best fit statistics and clinical interpretability. Classes included a “high PTSD+CPTSD+BPD” class, characterized by high‐level endorsement of all symptoms for the three diagnoses; a “moderate PTSD+CPTSD+BPD” class, characterized by endorsement of some symptoms across all three diagnoses; a “PTSD” class, characterized by endorsement of the ICD‐11 PTSD criteria; and a “healthy” class, characterized by low symptom endorsement overall. Pairwise comparisons showed individuals in the high PTSD+CPTSD+BPD class to have the highest levels of psychological distress, traumatic event history, adverse childhood experiences, and PTSD symptoms. Shame was the only social emotion to significantly differ between the classes, p = .002, η² = .16. The findings diverge from the literature, indicating an overlap of PTSD, CPTSD, and BPD symptoms in a non–treatment‐seeking community sample. Further, shame may be a central emotion that differentiates between presentation severities following trauma exposure.     

Creating patient-centered radiology reports to empower patients undergoing prostate magnetic resonance imaging

IntroductionAs we progress to an era when patient autonomy and shared decision-making are highly valued, there is a need to also have effective patient-centered communication tools. Radiology reports are designed for clinicians and can be very technical and difficult for patients to understand. It is important for patients to understand their magnetic resonance imaging (MRI) report in order to make an informed treatment decision with their physician. Therefore, we aimed to create a patient-centered prostate MRI report to give our patients a better understanding of their clinical condition.MethodsA prototype patient-centered radiology report (PACERR) was created by identifying items to include based on opinions sought from a group of patients undergoing prostate MRI and medical experts. Data was collected in semi-structured interviews using a salient belief question. A prototype PACERR was created in collaboration with human factors engineering and design, medical imaging, biomedical informatics, and cancer patient education groups.ResultsFifteen patients and eight experts from urology, radiation oncology, radiology, and nursing participated in this study. Patients were particularly interested to have a report with laymen terms, concise language, contextualization of values, definitions of medical terms, and next course of action. Everyone believed the report should include the risk of MRI findings actually being cancer in the subsequent biopsy.ConclusionsA prostate MRI PACERR has been developed to communicate the most important findings relevant to decision-making in prostate cancer using patient-oriented design principles. The ability of this tool to improve patient knowledge and communication will be explored.     

Collaborative working in health and social care: Lessons learned from post-hoc preliminary findings of a young families’ pregnancy to age 2 project in South Wales,United Kingdom

Children of young and socially disadvantaged parents are more likely to experience adverse outcomes. In response to this, a unique young families’ project in Swansea, UK, was created, which drew together a team of multi-agency professionals, to support people aged 16–24 from 17 weeks of pregnancy throughout 1,001 days of the child's life. The aim of the JIGSO (the Welsh word for Jigsaw) project is for young people to reach their potential as parents and to break the cycle of health and social inequality. This evaluation analysed routinely collected data held by the project from January 2017 to December 2018 exploring health and social outcomes, including smoking and alcohol use in pregnancy, breastfeeding, maternal diet and social services outcomes. Outcomes were compared to local and national averages, where available. Data relating to parenting knowledge and skills were available via records of 10-point Likert scales, one collected at the start of the JIGSO involvement and one around 4–6 months later. Findings showed higher than average levels of breastfeeding initiation and lower smoking and alcohol use in pregnancy. Parents also reported enhanced knowledge and confidence in their child care skills, as well as improved family relationships. Parents with high levels of engagement with JIGSO also appeared to have positive outcomes with Social Services (their child's name was removed from child protection register or their case was closed to social services). This was a post-hoc evaluation, not an intervention study or trial, and thus findings must be interpreted with caution. Despite this, the findings are promising and more prospective research exploring similar services is required.     

Fragile X-related protein and VIG associate with the RNA interference machinery

RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded RNA by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) that contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, the Drosophila homolog of the fragile X mental retardation protein (FMRP), dFXR, and VIG (Vasa intronic gene), through their association with RISC. FMRP, the product of the human fragile X locus, regulates the expression of numerous mRNAs via an unknown mechanism. The possibility that dFXR, and potentially FMRP, use, at least in part, an RNAi-related mechanism for target recognition suggests a potentially important link between RNAi and human disease.