The yeast VPS genes affect telomere length regulation

Eukaryotic cells invest a large proportion of their genome in maintaining telomere length homeostasis. Among the 173 non-essential yeast genes found to affect telomere length, a large proportion is involved in vacuolar traffic. When mutated, these vacuolar protein-sorting (VPS) genes lead to telomeres shorter than those observed in the wild type. Using genetic analysis, we characterized the pathway by which VPS15, VPS34, VPS22, VPS23 and VPS28 affect the telomeres. Our results indicate that these VPS genes affect telomere length through a single pathway and that this effect requires the activity of telomerase and the Ku heterodimer, but not the activity of Tel1p or Rif2p. We present models to explain the link between vacuolar traffic and telomere length homeostasis.     

Biofluid Aspects of Embryo Transfer

Embryo transfer (ET) is the last stage of extracorporal fertilization during which the embryo is placed in the uterine cavity with a medium-filled catheter 2–3 days after in vitro fertilization. While fertilization in the laboratory occurs at very high rates (>:90%), the overall success of the procedure (i.e., take home baby) is still very low (<25%) and assumed to be mainly due to implantation failure. A computational model was developed to simulate ET within the uterine cavity by a fluid-filled catheter inserted into a two-dimensional channel with oscillating walls. The results showed that the speed at which the embryos are injected from the catheter dominates the procedure and controls the velocity of their transport within the uterine cavity. ET at excessively high injection speeds may lead to ectopic pregnancies, while uterine peristalsis affects transverse dispersion only during injection at low injection speeds. The presence of the catheter within the uterus does not affect flow patterns downstream of its tip. The potential risks to implantation failure due to mechanical factors involved in the ET processes are discussed. © 2003 Biomedical Engineering Society. PAC2003: 8719-j, 8710+e     

Using technology to advance type 1 diabetes care among women during the reproductive years and in pregnancy

The prevalence of diabetes is increasing globally. Technology to improve care among individuals with diabetes is constantly being developed. Women living with Type 1 Diabetes Mellitus (T1DM) have unique challenges affecting their glucose control relating to menstrual cycles, pregnancy, and menopause. The purpose of this review is to examine the literature related to the use of technology to help women with T1DM manage their diabetes during the reproductive years, pregnancy, and beyond. Continuous subcutaneous insulin infusion (CSII) therapy can provider equivalent or better glucose control when compared with multiple daily injections (MDI), with less hypoglycemia, diabetic ketoacidosis, and weight gain. The CSII therapy has features that could help improve glucose control over the menstrual cycle, menopause, and pregnancy, although the most studied of these stages is pregnancy. Continuous glucose monitoring (CGM) can be combined with any insulin delivery system (MDI or CSII) to provide data on glucose values every few minutes and show glucose trends over time. CGM introduction can highlight glucose variability for women with T1DM, may be beneficial during pregnancy, and can reduce hypoglycemia. Sensor-augmented pump therapy and hybrid artificial pancreas (closed-loop) systems are promising tools that improve outcomes among individuals with diabetes. The use of modern technology to improve glucose and metabolic control among menopausal women with diabetes has not been well studied. Internet and phone-based technologies are emerging as important tools that may help with diabetes self-care for women living with diabetes.     

Tensions Between the Epidemiology and Psychology of HIV Risk: Implications for Pre-exposure Prophylaxis

This study focuses on psychological differences in risk-taking patterns and their association with risk compensation motivations in the context of pre-exposure prophylaxis (PrEP). Participants were 257 HIV-negative MSM and transgender women recruited in New York City. The majority of participants (89.5 %, n = 230), could be classified as either: Intimates (40 %), who report unprotected anal intercourse (UAI) only with a main partner believed to be HIV-negative; Trusters (34 %), who engaged in UAI only with casual partners believed to be HIV-negative; and Gamblers (26 %) who report UAI with partners of unknown serostatus. Partner-based classifications were better predictors of HIV risk perception and other traditional correlates of risk-taking (e.g. impulsivity, sexual compulsivity) than rates of UAI. The three groups differed significantly in PrEP-related risk compensation motivations: sexual pleasure (Gamblers), intimacy (Trusters) and partner pressure (Intimates). These data underscore the importance of focusing the psychological dynamics of risk perception and sexual decision-making.     

Human intestinal epithelial cells respond to β‐glucans via Dectin‐1 and Syk

Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and may be involved in intestinal immune responses. Fungi are important components of the intestinal microflora. The potential role of fungi, and in particular their cell wall component β‐glucan, in modulating human intestinal epithelial responses is still unclear. Here we examined whether human IECs are capable of recognizing and responding to β‐glucans, and the potential mechanisms of their activation. We show that human IECs freshly isolated from surgical specimens, and the human IEC lines HT‐29 and SW480, express the β‐glucan receptor Dectin‐1. The β‐glucan‐consisting glycans curdlan and zymosan stimulated IL‐8 and CCL2 secretion by IEC lines. This was significantly inhibited by a Dectin‐1 blockade using its soluble antagonist laminarin. Spleen tyrosine kinase (Syk), a signaling mediator of Dectin‐1 activation, is expressed in human IECs. β‐glucans and Candida albicans induced Syk phosphorylation, and Syk inhibition significantly decreased β‐glucan‐induced chemokine secretion from IECs. Thus, IECs may respond to β‐glucans by the secretion of pro‐inflammatory chemokines in a Dectin‐1‐ and Syk‐dependent pathway, via receptors and a signaling pathway described to date only for myeloid cells. These findings highlight the importance of fungi–IEC interactions in intestinal inflammation.