Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair.

Histone post-translational modifications promote a chromatin environment that controls transcription, DNA replication and repair, but surprisingly few phosphorylations have been documented. We report the discovery of histone H3 serine-57 phosphorylation (H3S57ph) and show that it is implicated in different DNA repair pathways from fungi to vertebrates. We identified CHK1 as a major human H3S57 kinase, and disrupting or constitutively mimicking H3S57ph had opposing effects on rate of recovery from replication stress, 53BP1 chromatin binding, and dependency on RAD52.

MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution.

The linear sequence of DNA provides invaluable information about genes and their regulatory elements along chromosomes. However, to fully understand gene function and regulation, we need to dissect how genes physically fold in the three-dimensional nuclear space. Here we describe immuno-OligoSTORM, an imaging strategy that reveals the distribution of nucleosomes within specific genes in super-resolution, through the simultaneous visualization of DNA and histones.

Impact of DNA methylation on 3D genome structure.

Determining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization.

Oncogenic mutations at the EGFR ectodomain structurally converge to remove a steric hindrance on a kinase-coupled cryptic epitope.

Epidermal growth factor receptor (EGFR) signaling is initiated by a large ligand-favored conformational change of the extracellular domain (ECD) from a closed, self-inhibited tethered monomer, to an open untethered state, which exposes a loop required for strong dimerization and activation. In glioblastomas (GBMs), structurally heterogeneous missense and deletion mutations concentrate at the ECD for unclear reasons. We explore the conformational impact of GBM missense mutations, combining elastic network models (ENMs) with multiple molecular dynamics (MD) trajectories.

HIV Rapid Testing Programs in Non-Clinical Settings have the Potential to Constitute a Major Diagnostic Option for MSM in Spain.

We analyze the impact of HIV rapid testing (RT) programs in non-clinical settings (NCS) by evaluating their contribution to new diagnoses reported to the Spanish HIV Surveillance System (SINIVIH) from 2007 to 2012. We estimate the proportion of new diagnoses reported to SINIVIH attributable to them and the maximum annual contribution (MAC). Of 95.

Stabilization of apoptotic cells: generation of zombie cells.

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell.

Apoptotic cells subjected to cold/warming exposure disorganize apoptotic microtubule network and undergo secondary necrosis.

Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath the plasma membrane which plays a critical role in preserving cell morphology and plasma membrane integrity. The aim of this study was to examine the effect of cold/warming exposure on apoptotic microtubules and plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptotic H460 cells that cold/warming exposure disorganized apoptotic microtubules and allowed the access of active caspases to the cellular cortex and the cleavage of essential proteins in the preservation of plasma membrane permeability.

Verbal autopsy completion rate and factors associated with undetermined cause of death in a rural resource-poor setting of Tanzania.

Background: Verbal autopsy (VA) is a widely used tool to assign probable cause of death in areas with inadequate vital registration systems. Its uses in priority setting and health planning are well documented in sub-Saharan Africa (SSA) and Asia. However, there is a lack of data related to VA processing and completion rates in assigning causes of death in a community.

Preservation of ovarian function in young woman with hodgkin disease by laparoscopic medial transposition before abdominal irradiation.

A case of retro-uterine bilateral ovarian medial transposition in a 24-year-old women with Hodgkin's IIIB disease with bilateral compromised para-iliac ganglia is presented. A laparoscopic ovarian transposition toward a retro-uterine location out of the reach of the main radiation beam was made. The proximal pole of both ovaries was fixed to the ipsilateral uterosacral ligament.

Successful third consecutive TVT in a patient with two previous TVT failures.

Background: During 10 years of use, the transvaginal tape (TVT) technique has proved highly effective for the treatment of stress urinary incontinence. There is limited published information about experience with repeated TVT placements.

Case: A 47-year-old multiparous woman presented with a history of two previous TVT sling procedures but persistent urinary incontinence.

Small bowel obstruction caused by a congenital jejuno-jejuno band in a child.

A case of small bowel obstruction in a 4-year-old boy with pica is described. The child habitually chewed on his plastic toy action figures. Abdominal radiography and endoscopy confirmed the presence of chewed pieces of plastic within the digestive tract.

Cost-effectiveness of managing abortions: manual vacuum aspiration (MVA) compared to evacuation by curettage in Tanzania.

Cost effectiveness of managing 107 incomplete abortions by manual vacuum aspiration (MVA) is compared with management of 92 incomplete abortions by evacuation by curettage (E by C) at Muhimbili Medical Centre (September-November 1992). Pre-evacuation waiting times, duration of procedures and duration of hospital stay were less for MVA as compared to E by C. The total pre-evacuation waiting time, the durations of the procedure and hospital stay were 15.

Phantom pregnancy at Muhimbili.

This is a case report on phantom pregnancy at Muhimbili. Relevant factors pertaining to personality of the patient, the experienced psycho-social stresses, the medical history and possible causes of symptom formation culminating in pseudocyesis are looked into and discussed.

Alternative confirmatory strategies in HIV-1 antibody testing.

Alternatives to confirmation of human immunodeficiency virus (HIV)-1 seropositivity by Western blot analysis were evaluated retrospectively using combinations of six anti-HIV-1 screening assays, including four enzyme-linked immunosorbent assays (ELISA) and two simple tests (a rapid dot immunoassay and an agglutination assay), according to an algorithm where sera are first screened by one assay and those repeatedly reactive on this assay are tested repeatedly by a second assay. Two panels of sera collected in Dar es Salaam, Tanzania, were used. Panel 1 was composed of 1,465 consecutive blood donor sera of which 99 (6.

Outcome of pregnancy in diabetic patients in Dar es Salaam, Tanzania.

Between 1 June 1986 and 31 August 1987 all 47 pregnant diabetic Tanzanian women attending Muhimbili Medical Centre, Dar es Salaam were seen and managed by a small team of interested physicians and obstetricians. Of the 50 pregnancies there were 44 (88%) live births, five (10%) perinatal deaths, and one (2%) spontaneous abortion. One child was born with a serious congenital abnormality.

[Results of clinical and hematologic examination of donors infected with the human immunodeficiency virus].

The data on the myelogram, peripheral blood and the proteinogram of 30 donors infected with human immunodeficiency virus are provided. The donors were observed for 6 months in the Department of Hematology and Blood Transfusion of the Mukhimbili hospital (Dar-es-Salaam, Tanzania). It is concluded that the above-enumerated parameters should be controlled over time, which is likely to be instrumental in the diagnosis of a qualitatively new condition of the patients--a stage of human immunodeficiency infection transformation to AIDS.