Influence of pimozide on a TRH induced TSH secretion in the rat during food deprivation.

Adult Wistar rats food deprived for 3 days had lower basal levels of TSH compared to normal fed animals. An increase of these lower levels to normal values was obtained following a prolonged (injections during 3 consecutive days) or acute treatment (single injection) with pimozide (1 mg/injection). Blood samples obtained after the last or an only injection of pimozide contained profound increased prolactin levels. Prolactin increase was more than 100-fold in fed and more than 30-fold in starved rats following prolonged pimozide treatment and more than 25-fold and 10-fold following a single injection of pimozide. An injection of 250 ng of TRH increased plasma concentrations of TSH in all groups, but this increase was more pronounced in fasted rats injected with pimozide during 3 consecutive days. It is concluded that fasting results in a dopaminergic inhibition of the sensitivity of the thyrotrophs to a TRH challenge.     

Novel Kaposi's sarcoma-associated herpesvirus homolog in baboons

Kaposi's sarcoma (KS) and lymphoproliferative diseases induced by KS-associated herpesvirus (KSHV/human herpesvirus 8) cause substantial morbidity and mortality in human immunodeficiency virus-infected individuals. To understand KSHV biology it is useful to investigate closely related rhadinoviruses naturally occurring in nonhuman primates. Here we report evidence for a novel KSHV homolog in captive baboon species (Papio anubis and other). Using degenerate PCR we identified a novel rhadinovirus, PapRV2, that has substantial sequence identity to two essential KSHV genes, the viral polymerase and thymidylate synthase. A subset of animals exhibited detectable PapRV2 viral load in peripheral blood mononuclear cells. Extensive serological analysis of nearly 200 animals in the colony demonstrated that the majority carried cross-reacting antibodies that recognize KSHV or macaque rhadinovirus antigens. Seroreactivity increased with age, similar to the age-specific prevalence of KSHV in the human population. This establishes baboons as a novel resource to investigate rhadinovirus biology, which can be developed into an animal model system for KSHV-associated human diseases, vaccine development, and therapy evaluation.     

Functional analysis of the gene cluster involved in production of the bacteriocin circularin A by Clostridium beijerinckii ATCC 25752

A region of 12 kb flanking the structural gene of the cyclic antibacterial peptide circularin A of Clostridium beijerinckii ATCC 25752 was sequenced, and the putative proteins involved in the production and secretion of circularin A were identified. The genes are tightly organized in overlapping open reading frames. Heterologous expression of circularin A in Enterococcus faecalis was achieved, and five genes were identified as minimally required for bacteriocin production and secretion. Two of the putative proteins, CirB and CirC, are predicted to contain membrane-spanning domains, while CirD contains a highly conserved ATP-binding domain. Together with CirB and CirC, this ATP-binding protein is involved in the production of circularin A. The fifth gene, cirE, confers immunity towards circularin A when expressed in either Lactococcus lactis or E. faecalis and is needed in order to allow the bacteria to produce bacteriocin. Additional resistance against circularin A is conferred by the activity of the putative transporter consisting of CirB and CirD.     

Direct Observation of Li‐Ion Transport in Electrodes under Nonequilibrium Conditions Using Neutron Depth Profiling

One of the key challenges of Li‐ion electrodes is enhancement of (dis)charge rates. This is severely hindered by the absence of a technique that allows direct and nondestructive observation of lithium ions in operating batteries. Direct observation of the Li‐ion concentration profiles using operando neutron depth profiling reveals that the rate‐limiting step is depended not only on the electrode morphology but also on the cycling rate itself. In the LiFePO₄ electrodes phase nucleation limits the charge transport at the lowest cycling rates, whereas electronic conductivity is rate limiting at intermediate rates, and only at the highest rates ionic transport through the electrode is rate limiting. These novel insights into electrode kinetics are imperative for the improvement of Li‐ion batteries and show the large value of in situ NDP in Li‐ion battery research and development.     

The right to informed choice. A study and opinion poll of women who were or were not given the option of a sterilisation with their caesarean section

Background

In the Netherlands, caesarean sections (CSs) are rarely combined with tubal occlusion (TO), partly because discussing CS/TO near delivery is considered unethical and earlier hypothetical counselling – i.e. suppose you happen to need a CS – is rare. This results in more unintended pregnancies and is inconsistent with informed choice. We explored whether TO should indeed not be made routinely available to eligible women.

Methods and Findings

A questionnaire was mailed to 515 Para ≥2 who underwent in the past ≥1 CS. 498 (96.7%) responded. They were on average 35.3 years old, had 2.5 children, had undergone 1.6 CSs, and 3.3 years had passed since their index delivery, either a CS (393) or vaginal birth (105) after a previous CS. 87% of the 498 believed that pregnant mothers with ≥1 children should be routinely counselled about CS/TO. Indeed, 58% and 85% respectively, thought women/couples expecting their second or third child should still be given the TO option days before delivery, if omitted earlier. Counselled women, 138/498 (27.8%), were far more often satisfied than those without CS/TO option. 33/393 had a CS/TO. None indicated regret in the questionnaire. Another 119 also would have elected a CS/TO if given that option. Therefore, 152 (38.7%) of 393 Para ≥2 had or would have liked a concurrent TO. 118/119 wrote they still regretted missing this opportunity. The exception''s husband had had a vasectomy. 100/119 were good TO candidates: they were ≥28 years when they delivered an apparently healthy baby of ≥37 weeks. The current contraceptive use of these 100 suggests that this group will have at least 8 unintended pregnancies before age 50.

Conclusion

The experiences and opinions of previous potential candidates for a CS/TO do not support the reluctance of Dutch obstetricians to counsel pregnant Para ≥1 about the TO option for a (potential) CS.     

Expression clustering reveals detailed co-expression patterns of functionally related proteins during B cell differentiation: a proteomic study using a combination of one-dimensional gel electrophoresis, LC-MS/MS, and stable isotope labeling by amino acids in cell culture (SILAC)

B cells play an essential role in the immune response. Upon activation they may differentiate into plasma cells that secrete specific antibodies against potentially pathogenic non-self antigens. To identify the cellular proteins that are important for efficient production of these antibodies we set out to study the B cell differentiation process at the proteome level. We performed an in-depth proteomic study to quantify dynamic relative protein expression patterns of several hundreds of proteins at five consecutive time points after lipopolysaccharide-induced activation of B lymphocytes. The proteome analysis was performed using a combination of stable isotope labeling using [13C6]leucine added to the murine B cell cultures, one-dimensional gel electrophoresis, and LC-MS/MS. In this study we identified 1,001 B cell proteins. We were able to quantify the expression levels of a quarter of all identified proteins (i.e. 234) at each of the five different time points. Nearly all proteins revealed changes in expression patterns. The quantitative dataset was further analyzed using an unbiased clustering method. Based on their expression profiles, we grouped the entire set of 234 quantified proteins into a limited number of 12 distinct clusters. Functionally related proteins showed a strong correlation in their temporal expression profiles. The quality of the quantitative data allowed us to even identify subclusters within functionally related classes of proteins such as in the endoplasmic reticulum proteins that are involved in antibody production.