Development of a rat model for respiratory infection with Bordetella pertussis.

Considerable effort directed toward designing a safe and effective vaccine for Bordetella pertussis in which the cellular and/or acellular antigens necessary to confer immunity are known has been hampered by lack of information on the pathogenesis of the natural infection. The study presented here describes an animal model of lung infection by B. pertussis encased in agar beads in adult (200- to 220-g) male Sprague-Dawley rats. At 3 and 7 days after inoculation with phase I B. pertussis, organisms could be recovered from the lungs of rats; however, organisms were not recoverable at days 10 and 14 but reappeared in lung homogenates at day 21. Histopathological examination revealed findings similar to those seen in human disease. At day 3, a mild lymphocytic infiltrate was present in the bronchi, with progressive lymphoid hyperplasia peribronchially. By day 7, a necrotizing inflammation of the tracheobronchial mucous membranes, characterized by both mononuclear and polymorphonuclear cells, was noted. Phase III B. pertussis organisms were not recoverable from the lungs of inoculated rats at day 3 after inoculation, nor were histological changes noted in these animals. Clinical findings in phase I B. pertussis-infected rats included hypoglycemia, circulating lymphocytosis, and paroxysms in which air was forcibly expelled from the mouth or nose.     

The Turner syndrome research registry: Creating equipoise between investigators and participants

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.     

Searching for archaic contribution in Africa

Abstract

Context: Africa’s role in the narrative of human evolution is indisputably emphasised in the emergence of Homo sapiens. However, once humans dispersed beyond Africa, the history of those who stayed remains vastly under-studied, lacking the proper attention the birthplace of both modern and archaic humans deserves. The sequencing of Neanderthal and Denisovan genomes has elucidated evidence of admixture between archaic and modern humans outside of Africa, but has not aided efforts in answering whether archaic admixture happened within Africa.

Objectives: This article reviews the state of research for archaic introgression in African populations and discusses recent insights into this topic.

Methods: Gathering published sources and recently released preprints, this review reports on the different methods developed for detecting archaic introgression. Particularly it discusses how relevant these are when implemented on African populations and what findings these studies have shown so far.

Results: Methods for detecting archaic introgression have been predominantly developed and implemented on non-African populations. Recent preprints present new methods considering African populations. While a number of studies using these methods suggest archaic introgression in Africa, without an African archaic genome to validate these results, such findings remain as putative archaic introgression.

Conclusion: In light of the caveats with implementing current archaic introgression detection methods in Africa, we recommend future studies to concentrate on unravelling the complicated demographic history of Africa through means of ancient DNA where possible and through more focused efforts to sequence modern DNA from more representative populations across the African continent.     

The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2

Neurofibromatosis 2 (NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1–5 had more severe disease than those with splice site mutations in exons 11–15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours.     

Comparison of Track XI fluorometric immunoassay with Bio-EnzaBead enzyme-linked immunosorbent assay for detection of serum antibody to mouse hepatitis virus.

The Track XI system (Microbiological Associates, Bethesda, Md.) was compared with the Bio-EnzaBead assay (Organon Teknika, Durham, N.C.) for the detection of antibody to mouse hepatitis virus (MHV). Strain A/J mice were inoculated intranasally with MHV type 3. Sera were collected at 1, 2, 4, and 9 weeks postinoculation and tested. Individual serum samples were retested twice by each method. The results suggested that the Track XI system was more sensitive and reliable than the Bio-EnzaBead assay in detecting antibody to MHV type 3 in individual serum samples from A/J mice.     

A multi-modal treatment program for childhood trauma recovery:Women Recovering from Abuse Program (WRAP).

This article describes the Women Recovering from Abuse Program (WRAP), an outpatient day-hospital program for women suffering from the sequelae of childhood abuse. WRAP was conceived in 1998 by clinicians who advocated for its development based on a growing need to provide women who had experienced childhood trauma an alternative to an inpatient program. WRAP draws from a Stage 1 treatment approach to address chronic interpersonal trauma and dissociation by incorporating psychopharmacology, individual and group psychotherapy. The program is structured into two phases: a preparatory Building Resources Group (BRG) and an intensive multimodal segment comprised of seven types of group therapy. Each group is described in terms of the treatment rationale and its structure and process. Two research studies to date support the effectiveness of WRAP.     

The relationship between women's subjective and physiological sexual arousal

Previous literature presents discordant results on the relationship between physiological and subjective sexual arousal in women. In this study, the use of hierarchical linear modeling (HLM) revealed a significant concordance between continuous measures of physiological and subjective sexual arousal as assessed during exposure to erotic stimuli in a laboratory setting. We propose that past studies that have found little or no association between the two measures may have been in part limited by the methodology and statistical analyses employed.     

The transplacental toxicity of methyl mercury to fetal rat liver mitochondria. Morphometric and biochemical studies.

Ultrastructural morphometric and biochemical changes in liver mitochondria of fetal rats whose mothers were exposed to methyl mercury hydroxide in their drinking water at concentrations of 0, 3, 5, or 10 p.p.m. for 4 weeks prior to mating and through day 19 of pregnancy are described. A dose-related decrease in the volume density of mitochondria was observed in fetal hepatocytes of dams given the 5- and 10-p.p.m. dose levels. This finding was associated with decreased mitochondrial protein synthesis, which appeared to result primarily from decreased synthesis of mitochondrial structural proteins. Loss of respiratory control was observed in mitochondria from animals in the 3-p.p.m. dose group whereas state 3 respiration was abolished in animals exposed to the 5- and 10-p.p.m. dose levels. The specific activities of monoamine oxidase and cytochrome oxidase, outer and inner mitochondrial membrane marker enzymes respectively, showed dose-related decreases of up to 62 and 78 per cent of control, respectively. delta-Aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane, also showed dose-related decreases of up to 68 per cent of control. Malate dehydrogenase, a mitochondrial matrix marker enzyme, showed no change in activity at any dose level tested. These observations were correlated with dose-related tissue concentrations of methyl and inormpaired mitochondrial biogenesis and functional development is one basis for explaining the sensitivity of fetal animals to methyl mercury toxicity.     

Induction of proliferative responses of T cells from Babesia bovis-immune cattle with a recombinant 77-kilodalton merozoite protein (Bb-1).

A major portion of a Babesia bovis-specific gene encoding a 77-kDa merozoite protein (Bb-1) produced during natural infection in cattle and in microaerophilous culture was subcloned into the pGEX1N expression vector. Recombinant Bb-1 protein fused to glutathione S-transferase (Bb-1-GST) was used to examine cellular immune responses in B. bovis-immune cattle. Sera from rabbits immunized with Bb-1-GST reacted with fusion protein and with the native antigen present in crude B. bovis but not with B. bigemina merozoites. Bb-1-GST but not GST induced strong proliferation of T lymphocytes from these immune cattle, and Bb-1-reactive T-cell lines which consisted of a mixed population of either CD4+ and CD8+ cells or CD4+, CD8+, and "null" (gamma delta T) cells were established by in vitro stimulation of peripheral blood mononuclear cells with the recombinant fusion protein. Three CD4+ CD8- and three CD4- CD8+ Bb-1-specific T-cell clones were identified after limiting-dilution cloning of the cell lines. The studies described here demonstrate that the 77-kDa protein of B. bovis contains T-cell epitopes capable of eliciting proliferation of two types of T cells in immune cattle, an important consideration for the design of a recombinant subunit vaccine.