Morphological characterization of bushy cells and their inputs in the laboratory mouse (Mus musculus) anteroventral cochlear nucleus.

PMC3753269Spherical and globular bushy cells of the AVCN receive huge auditory nerve endings specialized for high fidelity neural transmission in response to acoustic events. Recent studies in mice and other rodent species suggest that the distinction between bushy cell subtypes is not always straightforward. We conducted a systematic investigation of mouse bushy cells along the rostral-caudal axis in an effort to understand the morphological variation that gives rise to reported response properties in mice. We combined quantitative light and electron microscopy to investigate variations in cell morphology, immunostaining, and the distribution of primary and non-primary synaptic inputs along the rostral-caudal axis. Overall, large regional differences in bushy cell characteristics were not found; however, rostral bushy cells received a different complement of axosomatic input compared to caudal bushy cells. The percentage of primary auditory nerve terminals was larger in caudal AVCN, whereas non-primary excitatory and inhibitory inputs were more common in rostral AVCN. Other ultrastructural characteristics of primary auditory nerve inputs were similar across the rostral and caudal AVCN. Cross sectional area, postsynaptic density length and curvature, and mitochondrial volume fraction were similar for axosomatic auditory nerve terminals, although rostral auditory nerve terminals contained a greater concentration of synaptic vesicles near the postsynaptic densities. These data demonstrate regional differences in synaptic organization of inputs to mouse bushy cells rather than the morphological characteristic of the cells themselves.JH Libraries Open Access Fun

The Genealogical Population Dynamics of HIV-1 in a Large Transmission Chain:Bridging within and among Host Evolutionary Rates

Transmission lies at the interface of human immunodeficiency virus type 1 (HIV-1) evolution within and among hosts and separates distinct selective pressures that impose differences in both the mode of diversification and the tempo of evolution. In the absence of comprehensive direct comparative analyses of the evolutionary processes at different biological scales, our understanding of how fast within-host HIV-1 evolutionary rates translate to lower rates at the between host level remains incomplete. Here, we address this by analyzing pol and env data from a large HIV-1 subtype C transmission chain for which both the timing and the direction is known for most transmission events. To this purpose, we develop a new transmission model in a Bayesian genealogical inference framework and demonstrate how to constrain the viral evolutionary history to be compatible with the transmission history while simultaneously inferring the within-host evolutionary and population dynamics. We show that accommodating a transmission bottleneck affords the best fit our data, but the sparse within-host HIV-1 sampling prevents accurate quantification of the concomitant loss in genetic diversity. We draw inference under the transmission model to estimate HIV-1 evolutionary rates among epidemiologically-related patients and demonstrate that they lie in between fast intra-host rates and lower rates among epidemiologically unrelated individuals infected with HIV subtype C. Using a new molecular clock approach, we quantify and find support for a lower evolutionary rate along branches that accommodate a transmission event or branches that represent the entire backbone of transmitted lineages in our transmission history. Finally, we recover the rate differences at the different biological scales for both synonymous and non-synonymous substitution rates, which is only compatible with the 'store and retrieve' hypothesis positing that viruses stored early in latently infected cells preferentially transmit or establish new infections upon reactivation.status: publishe

The HIV-1 transmission bottleneck

It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient

Hospital costs of high-burden diseases: malaria and pulmonary tuberculosis in a high HIV prevalence context in Zimbabwe.

This paper explores the measurement of hospital costs and efficiency in a context where data is scarce, incomplete or of poor quality. It argues that there is scope for using tracers to examine and compare hospital cost structures and relative efficiency in such contexts. Two high-burden diseases, malaria and pulmonary tuberculosis, are used as tracers to calculate the average costs of inpatient care at selected tertiary hospitals. This study shows that it is feasible to prospectively collect cost data for specific diseases and explore in detail both patient cost distribution and susceptible areas for efficiency improvement. The present study found that the critical source of efficiency variation in public hospitals in Zimbabwe lies in the way hospital beds are used

The complex spectrum of forensic issues arising from obesity

The increasing numbers of obese and morbidly obese individuals in the community are having a direct effect on forensic facilities. In addition to having to install more robust equipment for handling large bodies, the quality of autopsy examinations may be reduced by the physical difficulties that arise in trying to position bodies correctly so that normal examinations can proceed. Accelerated putrefaction is often an added complication. Metabolic disturbances resulting from obesity increase susceptibility to a range of conditions that are associated with sudden and unexpected death, and surgery may have increased complications. The rates of a number of different malignancies, including lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium, are increased. In addition, obese individuals have higher rates of diabetes mellitus, and sepsis. The unexpected collapse of an obese individual should raise the possibility of a wide range of conditions, many of which may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index. Although sudden cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis in an unexpected collapse, the range of possible underlying conditions is extensive and often only determinable after full postmortem examination.Roger W. Byar