The latent stem cell population is retained in the hippocampus of transgenic Huntington's disease mice but not wild-type mice

The demonstration of the brain's ability to initiate repair in response to disease or injury has sparked considerable interest in therapeutic strategies to stimulate adult neurogenesis. In this study we examined the effect of a progressive neurodegenerative condition on neural precursor activity in the subventricular zone (SVZ) and hippocampus of the R6/1 transgenic mouse model of Huntington's disease (HD). Our results revealed an age-related decline in SVZ precursor numbers in both wild-type (WT) and HD mice. Interestingly, hippocampal precursor numbers declined with age in WT mice, although we observed maintenance in hippocampal precursor number in the HD animals in response to advancement of the disease. This maintenance was consistent with activation of a recently identified latent hippocampal precursor population. We found that the small latent stem cell population was also maintained in the HD hippocampus at 33 weeks, whereas it was not present in the WT. Our findings demonstrate that, despite a loss of neurogenesis in the HD hippocampus in vivo, there is a unique maintenance of the precursor and stem cells, which may potentially be activated to ameliorate disease symptoms

New Symmetries in Crystals and Handed Structures

For over a century, the structure of materials has been described by a combination of rotations, rotation-inversions and translational symmetries. By recognizing the reversal of static structural rotations between clockwise and counterclockwise directions as a distinct symmetry operation, here we show that there are many more structural symmetries than are currently recognized in right- or left-handed handed helices, spirals, and in antidistorted structures composed equally of rotations of both handedness. For example, though a helix or spiral cannot possess conventional mirror or inversion symmetries, they can possess them in combination with the rotation reversal symmetry. Similarly, we show that many antidistorted perovskites possess twice the number of symmetry elements as conventionally identified. These new symmetries predict new forms for "roto" properties that relate to static rotations, such as rotoelectricity, piezorotation, and rotomagnetism. They also enable symmetry-based search for new phenomena, such as multiferroicity involving a coupling of spins, electric polarization and static rotations. This work is relevant to structure-property relationships in all material structures with static rotations such as minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Young people’s perceptions of smartphone-enabled self-testing and online care for sexually transmitted infections: qualitative interview study

Background Control of sexually transmitted infections (STI) is a global public health priority. Despite the UK’s free, confidential sexual health clinical services, those at greatest risk of STIs, including young people, report barriers to use. These include: embarrassment regarding face-to-face consultations; the time-commitment needed to attend clinic; privacy concerns (e.g. being seen attending clinic); and issues related to confidentiality. A smartphone-enabled STI self-testing device, linked with online clinical care pathways for treatment, partner notification, and disease surveillance, is being developed by the eSTI2 consortium. It is intended to benefit public health, and could do so by increasing testing among populations which underutilise existing services and/or by enabling rapid provision of effective treatment. We explored its acceptability among potential users. Methods In-depth interviews were conducted in 2012 with 25 sexually-experienced 16–24 year olds, recruited from Further Education colleges in an urban, high STI prevalence area. Thematic analysis was undertaken. Results Nine females and 16 males participated. 21 self-defined as Black; three, mixed ethnicity; and one, Muslim/Asian. 22 reported experience of STI testing, two reported previous STI diagnoses, and all had owned smartphones. Participants expressed enthusiasm about the proposed service, and suggested that they and their peers would use it and test more often if it were available. Utilizing sexual healthcare was perceived to be easier and faster with STI self-testing and online clinical care, which facilitated concealment of STI testing from peers/family, and avoided embarrassing face-to-face consultations. Despite these perceived advantages to privacy, new privacy concerns arose regarding communications technology: principally the risk inherent in having evidence of STI testing or diagnosis visible or retrievable on their phone. Some concerns arose regarding the proposed self-test’s accuracy, related to self-operation and the technology’s novelty. Several expressed anxiety around the possibility of being diagnosed and treated without any contact with healthcare professionals. Conclusions Remote STI self-testing and online care appealed to these young people. It addressed barriers they associated with conventional STI services, thus may benefit public health through earlier detection and treatment. Our findings underpin development of online care pathways, as part of ongoing research to create this complex e-health intervention

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

A Viral Dynamic Model for Treatment Regimens with Direct-acting Antivirals for Chronic Hepatitis C Infection

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents

Recent ecological change in ancient lakes

Ancient lakes are among the best archivists of past environmental change, having experienced more than one full glacial cycle, a wide range of climatic conditions, tectonic events, and long association with human settlements. These lakes not only record long histories of environmental variation and human activity in their sediments, but also harbor very high levels of biodiversity and endemism. Yet, ancient lakes are faced with a familiar suite of anthropogenic threats, which may degrade the unusual properties that make them especially valuable to science and society. In all ancient lakes for which data exist, significant warming of surface waters has occurred, with a broad range of consequences. Eutrophication threatens both native species assemblages and regional economies reliant on clean surface water, fisheries, and tourism. Where sewage contributes nutrients and heavy metals, one can anticipate the occurrence of less understood emerging contaminants, such as pharmaceuticals, personal care products, and microplastics that negatively affect lake biota and water quality. Human populations continue to increase in most of the ancient lakes' watersheds, which will exacerbate these concerns. Further, human alterations of hydrology, including those produced through climate change, have altered lake levels. Co-occurring with these impacts have been intentional and unintentional species introductions, altering biodiversity. Given that the distinctive character of each ancient lake is strongly linked to age, there may be few options to remediate losses of species or other ecosystem damage associated with modern ecological change, heightening the imperative for understanding these systems