Immune correlates of herpes zoster in HIV-infected children and youth

To identify immunologic factors that modulate the risk of herpes zoster (HZ), we compared varicella-zoster virus (VZV)-specific and nonspecific T-cell subpopulations of 47 HIV-infected children before they developed HZ with those of 141 VZV-positive HZ-negative matched controls. Compared with controls, HZ cases had lower VZV-specific CD8(+) CD107a(+) cell percentages independently of CD4(+) percentages or HIV loads, suggesting that VZV-specific cytotoxic T cells are protective against HZ. In contrast, high nonspecific regulatory and activated T cells were associated with an increased risk of HZ.     

Diminished pheromone-induced sexual behavior in neurokinin-1 receptor deficient (TACR1(-/-)) mice

Studies in mice with targeted deletions of tachykinin genes suggest that tachykinins and their receptors influence emotional behaviors such as aggression, depression and anxiety. Here, we investigated whether TAC1- and TAC4-encoded peptides (substance P and hemokinin-1, respectively) and the neurokinin-1 receptor (NK-1R) are involved in the modulation of sexual behaviors. Male mice deficient for the NK-1R (TACR1 (-/-)) exhibited decreased exploration of female urine in contrast to C57BL/6 control mice and mice deficient for NK-1R ligands such as TAC1 (-/-), TAC4 (-/-) and the newly generated TAC1 (-/-) /TAC4 (-/-) mice. In comparison to C57BL/6 mice, mounting frequency and duration were decreased in male TACR1 (-/-) mice, while mounting latency was increased. Decreased preference for sexual pheromones was also seen in female TACR1 (-/-) mice. Furthermore, administration of the NK-1R-antagonist L-703,606 decreased investigation of female urine by male C57BL/6 mice, suggesting an involvement of NK-1R in urine sniffing behavior. Our results provide evidence for the NK-1R in facilitating sexual approach behavior, as male TACR1 (-/-) mice exhibited blunted approach behavior toward females following the initial interaction compared with C57BL/6 mice. NK-1R signaling may therefore play an important role in pheromone-induced sexual behavior.     

Early breastfeeding experiences of adolescent mothers: a qualitative prospective study

Background

Teen mothers face many challenges to successful breastfeeding and are less likely to breastfeed than any other population group in the U.S. Few studies have investigated this population; all prior studies are cross-sectional and collect breastfeeding data retrospectively. The purpose of our qualitative prospective study was to understand the factors that contribute to the breastfeeding decisions and practices of teen mothers.

Methods

This prospective study took place from January through December 2009 in Greensboro, North Carolina in the U.S. We followed the cohort from pregnancy until two weeks after they ceased all breastfeeding and milk expression. We conducted semi-structured interviews at baseline and follow-up, and tracked infant feeding weekly by phone. We analyzed the data to create individual life and breastfeeding journeys and then identified themes that cut across the individual journeys.

Results

Four of the five teenagers breastfed at the breast for nine days: in contrast, one teen breastfed exclusively for five months. Milk expression by pumping was associated with significantly longer provision of human milk. Breastfeeding practices and cessation were closely connected with their experiences as new mothers in the context of ongoing multiple roles, complex living situations, youth and dependency, and poor knowledge of the fundamentals of breastfeeding and infant development. Breastfeeding cessation was influenced by inadequate breastfeeding skill, physically unpleasant and painful early experiences they were unprepared to manage, and inadequate health care response to real problems.

Conclusions

Continued breastfeeding depends on a complex interplay of multiple factors, including having made an informed choice and having the skills, support and experiences needed to sustain the belief that breastfeeding is the best choice for them and their baby given their life situation. Teenagers in the US context need to have a positive early breastfeeding experience, be able to identify and claim a reliable support system supportive of breastfeeding, and gain through their experience, a belief in their own agency and competency as mothers.

     

Detection of Bacterial 16S rRNA and Identification of Four Clinically Important Bacteria by Real-Time PCR

Within the paradigm of clinical infectious disease research, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa represent the four most clinically relevant, and hence most extensively studied bacteria. Current culture-based methods for identifying these organisms are slow and cumbersome, and there is increasing need for more rapid and accurate molecular detection methods. Using bioinformatic tools, 962,279 bacterial 16S rRNA gene sequences were aligned, and regions of homology were selected to generate a set of real-time PCR primers that target 93.6% of all bacterial 16S rRNA sequences published to date. A set of four species-specific real-time PCR primer pairs were also designed, capable of detecting less than 100 genome copies of A. baumannii, E. coli, K. pneumoniae, and P. aeruginosa. All primers were tested for specificity in vitro against 50 species of Gram-positive and –negative bacteria. Additionally, the species-specific primers were tested against a panel of 200 clinical isolates of each species, randomly selected from a large repository of clinical isolates from diverse areas and sources. A comparison of culture and real-time PCR demonstrated 100% concordance. The primers were incorporated into a rapid assay capable of positive identification from plate or broth cultures in less than 90 minutes. Furthermore, our data demonstrate that current targets, such as the uidA gene in E.coli, are not suitable as species-specific genes due to sequence variation. The assay described herein is rapid, cost-effective and accurate, and can be easily incorporated into any research laboratory capable of real-time PCR.     

Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways

Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST) and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1) from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein.     

Venezuelan Equine Encephalitis Virus Activity in the Gulf Coast Region of Mexico, 2003–2010

Venezuelan equine encephalitis virus (VEEV) has been the causative agent for sporadic epidemics and equine epizootics throughout the Americas since the 1930s. In 1969, an outbreak of Venezuelan equine encephalitis (VEE) spread rapidly from Guatemala and through the Gulf Coast region of Mexico, reaching Texas in 1971. Since this outbreak, there have been very few studies to determine the northward extent of endemic VEEV in this region. This study reports the findings of serologic surveillance in the Gulf Coast region of Mexico from 2003–2010. Phylogenetic analysis was also performed on viral isolates from this region to determine whether there have been substantial genetic changes in VEEV since the 1960s. Based on the findings of this study, the Gulf Coast lineage of subtype IE VEEV continues to actively circulate in this region of Mexico and appears to be responsible for infection of humans and animals throughout this region, including the northern State of Tamaulipas, which borders Texas.     

Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts

Voltage-gated sodium channels are known to be expressed in neurons and other excitable cells. Recently, voltage-gated sodium channels have been found to be expressed in human prostate cancer cells. α-Hydroxy-α-phenylamides are a new class of small molecules that have demonstrated potent inhibition of voltage-gated sodium channels. The hydroxyamide motif, an isostere of a hydantoin ring, provides an active scaffold from which several potent racemic sodium channel blockers have been derived. With little known about chiral preferences, the development of chiral syntheses to obtain each pure enantiomer for evaluation as sodium channel blockers is important. Using Seebach and Frater's chiral template, cyclocondensation of (R)-3-chloromandelic acid with pivaldehyde furnished both the cis- and trans-2,5-disubsituted dioxolanones. Using this chiral template, we synthesized both enantiomers of 2-(3-chlorophenyl)-2-hydroxynonanamide, and evaluated their ability to functionally inhibit hNa(v) isoforms, human prostate cancer cells and xenograft. Enantiomers of lead demonstrated significant ability to reduce prostate cancer in vivo.     

The Effects of Landscape Characteristics on Northern Bobwhite Density

The northern bobwhite (Colinus virginianus) is an ecologically and economically valuable species in the United States. Managers rely on autumn density estimates to set harvest regulations, balancing the interests of hunters and long-term bobwhite population viability. Spatial capture-recapture (SCR) is a useful framework for estimating population size and modeling spatial variation in density. We used SCR to quantify the effect of landscape structure on spatial variation in density for a population of bobwhites on the Di-Lane Wildlife Management Area in Waynesboro, Georgia, USA. Without additional telemetry or nesting data, we were also able to estimate a spatially explicit metric of productivity. To sample the population, we deployed a fixed array of 395, 262, and 268 funnel traps in 2016, 2017, and 2018, respectively. We estimated age structure, with the highest density of juveniles (0.32 birds/ha, 95% CI = 0.28–0.37) and adults (0.10 birds/ha, 95% CI = 0.08–0.12) estimated in 2016. In our top model, density was negatively related to the proportion of closed canopy hardwoods. To increase bobwhite density on the landscape, managers should reduce the amount of closed canopy hardwood forest. Furthermore, the spatially explicit age ratio we estimated could be used to target management towards increasing the recruitment of chicks into the autumn population. An SCR approach may require additional logistical and financial resources relative to other data collection methods, but it makes modeling spatial variation in density straightforward and can be used to gather data to simultaneously understand population structure, vital rates, and movement. © 2021 The Wildlife Society.     

Rac2 is involved in bleomycin-induced lung inflammation leading to pulmonary fibrosis

Background

Pulmonary fibrotic diseases induce significant morbidity and mortality, for which there are limited therapeutic options available. Rac2, a ras-related guanosine triphosphatase expressed mainly in hematopoietic cells, is a crucial molecule regulating a diversity of mast cell, macrophage, and neutrophil functions. All these cell types have been implicated in the development of pulmonary fibrosis in a variety of animal models. For the studies described here we hypothesized that Rac2 deficiency protects mice from bleomycin-induced pulmonary fibrosis.

Methods

To determine the role of Rac2 in pulmonary fibrosis we used a bleomycin-induced mouse model. Anesthetized C57BL/6 wild type and rac2 ^-/- mice were instilled intratracheally with bleomycin sulphate (1.25 U/Kg) or saline as control. Bronchoalveolar lavage (BAL) samples were collected at days 3 and 7 of treatment and analyzed for matrix metalloproteinases (MMPs). On day 21 after bleomycin treatment, we measured airway resistance and elastance in tracheotomized animals. Lung sections were stained for histological analysis, while homogenates were analyzed for hydroxyproline and total collagen content.

Results

BLM-treated rac2 ^-/- mice had reduced MMP-9 levels in the BAL on day 3 and reduced neutrophilia and TNF and CCL3/MIP-1α levels in the BAL on day 7 compared to BLM-treated WT mice. We also showed that rac2 ^-/- mice had significantly lower mortality (30%) than WT mice (70%) at day 21 of bleomycin treatment. Lung function was diminished in bleomycin-treated WT mice, while it was unaffected in bleomycin-treated rac2 ^-/- mice. Histological analysis of inflammation and fibrosis as well as collagen and hydroxyproline content in the lungs did not show significant differences between BLM-treated rac2 ^-/- and WT and mice that survived to day 21.

Conclusion

Rac2 plays an important role in bleomycin-induced lung injury. It is an important signaling molecule leading to BLM-induced mortality and it also mediates the physiological changes seen in the airways after BLM-induced injury.