Malaria Liver Stage Susceptibility Locus Identified on Mouse Chromosome 17 by Congenic Mapping

Host genetic variants are known to confer resistance to Plasmodium blood stage infection and to control malaria severity both in humans and mice. This work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. First, we show that decreased susceptibility to the liver stage of Plasmodium berghei in the BALB/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection. We used QTL mapping techniques to identify a locus controlling this susceptibility phenotype (LOD score 4.2) on mouse chromosome 17 (belr1 locus). Furthermore, analysis of congenic mouse strains delimited the belr1 locus boundaries distally to the H2 region. Quantification of parasites in the liver of infected congenic mice strongly suggested that the belr1 locus represents a genetic factor controlling the expansion of P. berghei in the hepatic tissue. The mapping of belr1 locus raises the hypothesis that host gene variation is able to control the progression of Plasmodium liver stage infection and opens the possibility that the human genomic region orthologue to belr1 may contain genes that confer resistance to the human malaria liver stage

Bipartite life cycle of coral reef fishes promotes increasing shape disparity of the head skeleton during ontogeny: an example from damselfishes (Pomacentridae)

Background: Quantitative studies of the variation of disparity during ontogeny exhibited by the radiation of coral reef fishes are lacking. Such studies dealing with the variation of disparity, i.e. the diversity of organic form, over ontogeny could be a first step in detecting evolutionary mechanisms in these fishes. The damselfishes (Pomacentridae) have a bipartite life-cycle, as do the majority of demersal coral reef fishes. During their pelagic dispersion phase, all larvae feed on planktonic prey. On the other hand, juveniles and adults associated with the coral reef environment show a higher diversity of diets. Using geometric morphometrics, we study the ontogenetic dynamic of shape disparity of different head skeletal units (neurocranium, suspensorium and opercle, mandible and premaxilla) in this fish family. We expected that larvae of different species might be relatively similar in shapes. Alternatively, specialization may become notable even in the juvenile and adult phase. Results: The disparity levels increase significantly throughout ontogeny for each skeletal unit. At settlement, all larval shapes are already species-specific. Damselfishes show high levels of ontogenetic allometry during their postsettlement growth. The divergence of allometric patterns largely explains the changes in patterns and levels of shape disparity over ontogeny. The rate of shape change and the length of ontogenetic trajectories seem to be less variable among species. We also show that the high levels of shape disparity at the adult stage are correlated to a higher level of ecological and functional diversity in this stage. Conclusion: Diversification throughout ontogeny of damselfishes results from the interaction among several developmental novelties enhancing disparity. The bipartite life-cycle of damselfishes exemplifies a case where the variation of environmental factors, i.e. the transition from the more homogeneous oceanic environment to the coral reef offering a wide range of feeding habits, promotes increasing shape disparity of the head skeleton over the ontogeny of fishes

Target Identification for Stereotactic Thalamotomy Using Diffusion Tractography

BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery

The karyotype of three Brazilian Terrarana frogs (Amphibia, Anura) with evidence of a new Barycholos species

A recent substantial rearrangement of the 882 described eleutherodactyline frog species has considerably improved the understanding of their systematics. Nevertheless, many taxonomic aspects of the South American eleutherodactyline species remain unknown and require further investigation using morphological, cytogenetic and molecular approaches. In this work, the karyotypes of the Brazilian species Ischnocnema juipoca (Atibaia and Campos do Jordão, SP), Barycholos cf. ternetzi (Uberlândia, MG, and Porto Nacional, TO), and Pristimantis crepitans (Chapada dos Guimarães and São Vicente, MT) were analyzed using Giemsa staining, Ag-NOR labeling, and C-banding techniques. All individuals had a diploid number of 22 chromosomes, but the Fundamental Numbers were different among species. The herein described low chromosome number of Pristimantis crepitans is unique within this genus, suggesting that cytogenetically this species is not closely related either to its congeneric species or to Ischnocnema. In addition, karyotype differences, mainly in the NOR position, clearly distinguished the two Barycholos populations, besides indicating the existence of a so far undescribed species in this genus. A taxonomic review could clarify the systematic position of P. crepitans and verify the hypothetic new Barycholos species

Y-Like Retinal Ganglion Cells Innervate the Dorsal Raphe Nucleus in the Mongolian Gerbil (Meriones unguiculatus)

Background: The dorsal raphe nucleus (DRN) of the mesencephalon is a complex multi-functional and multi-transmitter nucleus involved in a wide range of behavioral and physiological processes. The DRN receives a direct input from the retina. However little is known regarding the type of retinal ganglion cell (RGC) that innervates the DRN. We examined morphological characteristics and physiological properties of these DRN projecting ganglion cells. Methodology/Principal Findings: The Mongolian gerbils are highly visual rodents with a diurnal/crepuscular activity rhythm. It has been widely used as experimental animals of various studies including seasonal affective disorders and depression. Young adult gerbils were used in the present study. DRN-projecting RGCs were identified following retrograde tracer injection into the DRN, characterized physiologically by extracellular recording and morphologically after intracellular filling. The result shows that DRN-projecting RGCs exhibit morphological characteristics typical of alpha RGCs and physiological response properties of Y-cells. Melanopsin was not detected in these RGCs and they show no evidence of intrinsic photosensitivity. Conclusions/Significance: These findings suggest that RGCs with alpha-like morphology and Y-like physiology appear to perform a non-imaging forming function and thus may participate in the modulation of DRN activity which includes regulation of sleep and mood

Regulation of Mycobacterium-Specific Mononuclear Cell Responses by 25-Hydroxyvitamin D3

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25(OH)D3) by the enzyme 1α-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1α-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D3 to 1,25(OH)2D3 in PBMC cultures regulated antigen-specific immune responses. Initially, we found that stimulation of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with purified protein derivative of M. bovis (M. bovis PPD) induced 1α-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D3 down-regulated IFN-γ and IL-17F gene expression. Next, we stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M. bovis PPD and sorted them by FACS according to surface markers for monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs revealed that 1α-hydroxylase expression was induced in the monocytes and B cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D3 down-regulated antigen-specific IFN-γ and IL-17F responses in the T cells, even though 1α-hydroxylase expression was not induced in the T cells. Based on evidence of no T cell 1α-hydroxylase we hypothesize that activated monocytes and B cells synthesize 1,25(OH)2D3 and that 1,25(OH)2D3 down-regulates antigen-specific expression of IFN-γ and IL-17F in T cells in a paracrine fashion

Relax "Vitality in Practice" (VIP) project and design of an RCT to reduce the need for recovery in office employees

<p>Abstract</p> <p>Background</p> <p>There is strong evidence to suggest that multiple work-related health problems are preceded by a higher need for recovery. Physical activity and relaxation are helpful in decreasing the need for recovery. This article aims to describe (1) the development and (2) the design of the evaluation of a daily physical activity and relaxation intervention to reduce the need for recovery in office employees.</p> <p>Methods/Design</p> <p>The study population will consist of employees of a Dutch financial service provider. The intervention was systematically developed, based on parts of the Intervention Mapping (IM) protocol. Assessment of employees needs was done by combining results of face-to-face interviews, a questionnaire and focus group interviews. A set of theoretical methods and practical strategies were selected which resulted in an intervention program consisting of Group Motivational Interviewing (GMI) supported by a social media platform, and environmental modifications. The Be Active & Relax program will be evaluated in a modified 2 X 2 factorial design. The environmental modifications will be pre-stratified and GMI will be randomised on department level. The program will be evaluated, using 4 arms: (1) GMI and environmental modifications; (2) environmental modifications; (3) GMI; (4) no intervention (control group). Questionnaire data on the primary outcome (need for recovery) and secondary outcomes (daily physical activity, sedentary behaviour, relaxation/detachment, work- and health-related factors) will be gathered at baseline (T0), at 6 months (T1), and at 12 months (T2) follow-up. In addition, an economic and a process evaluation will be performed.</p> <p>Discussion</p> <p>Reducing the need for recovery is hypothesized to be beneficial for employees, employers and society. It is assumed that there will be a reduction in need for recovery after 6 months and 12 months in the intervention group, compared to the control group. Results are expected in 2013.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): NTR2553</p

Enhanced Functional Recovery in MRL/MpJ Mice after Spinal Cord Dorsal Hemisection

Adult MRL/MpJ mice have been shown to possess unique regeneration capabilities. They are able to heal an ear-punched hole or an injured heart with normal tissue architecture and without scar formation. Here we present functional and histological evidence for enhanced recovery following spinal cord injury (SCI) in MRL/MpJ mice. A control group (C57BL/6 mice) and MRL/MpJ mice underwent a dorsal hemisection at T9 (thoracic vertebra 9). Our data show that MRL/MpJ mice recovered motor function significantly faster and more completely. We observed enhanced regeneration of the corticospinal tract (CST). Furthermore, we observed a reduced astrocytic response and fewer micro-cavities at the injury site, which appear to create a more growth-permissive environment for the injured axons. Our data suggest that the reduced astrocytic response is in part due to a lower lesion-induced increase of cell proliferation post-SCI, and a reduced astrocytic differentiation of the proliferating cells. Interestingly, we also found an increased number of proliferating microglia, which could be involved in the MRL/MpJ spinal cord repair mechanisms. Finally, to evaluate the molecular basis of faster spinal cord repair, we examined the difference in gene expression changes in MRL/MpJ and C57BL/6 mice after SCI. Our microarray data support our histological findings and reveal a transcriptional profile associated with a more efficient spinal cord repair in MRL/MpJ mice