T cells in aging mice: genetic, developmental, and biochemical analyses

A combination of approaches – gene mapping, biomarker analysis, and studies of signal transduction – has helped to clarify the mechanisms of age-related change in mouse immune status and the implications of immune aging for late-life disease. Mapping studies have documented multiple quantitative trait loci (QTL) that influence the levels of age-sensitive T-cell subsets. Some of these QTL have effects that are demonstrable in young-adult mice (8 months of age) and others demonstrable only in middle-aged mice (18 months). Biomarker studies show that T-cell subset levels measured at 8 or 18 months are significant predictors of lifespan for mice dying of lymphoma, fibrosarcoma, mammary adenocarcinoma, or all causes combined. Mice whose immune systems resemble that of young animals, i.e. with low levels of CD4 + and CD8 + memory T cells and relatively high levels of CD4 + T cells, tend to outlive their siblings with the opposite subset pattern. Biochemical analyses show that T cells from aged mice show defects in the activation process within a few minutes of encountering a stimulus and that the defects precede the recognition by the T-cell receptor of agonist peptides on the antigen-presenting cell. Defective assembly of cytoskeletal fibers and hyperglycosylation of T-cell surface glycoproteins contribute to the immunodeficiency state, and indeed treatment with a sialylglycoprotein endopeptidase can restore full function to CD4 + T cells from aged donors in vitro .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75195/1/j.0105-2896.2005.00254.x.pd

The colonization history of British water vole (Arvicola amphibius (Linnaeus, 1758)): origins and development of the Celtic fringe.

The terminal Pleistocene and Early Holocene, a period from 15 000 to 18 000 Before Present (BP), was critical in establishing the current Holarctic fauna, with temperate-climate species largely replacing cold-adapted ones at mid-latitudes. However, the timing and nature of this process remain unclear for many taxa, a point that impacts on current and future management strategies. Here, we use an ancient DNA dataset to test more directly postglacial histories of the water vole (Arvicola amphibius, formerly A terrestris), a species that is both a conservation priority and a pest in different parts of its range. We specifically examine colonization of Britain, where a complex genetic structure can be observed today. Although we focus on population history at the limits of the species' range, the inclusion of additional European samples allows insights into European postglacial colonization events and provides a molecular perspective on water vole taxonomy

Control of human toxoplasmosis.

Toxoplasmosis is caused by Toxoplasma gondii, an apicomplexan parasite that is able to infect any nucleated cell in any warm-blooded animal. Toxoplasma gondii infects around 2 billion people and, whilst only a small percentage of infected people will suffer serious disease, the prevalence of the parasite makes it one of the most damaging zoonotic diseases in the world. Toxoplasmosis is a disease with multiple manifestations: it can cause a fatal encephalitis in immunosuppressed people; if first contracted during pregnancy, it can cause miscarriage or congenital defects in the neonate; and it can cause serious ocular disease, even in immunocompetent people. The disease has a complex epidemiology, being transmitted by ingestion of oocysts that are shed in the faeces of definitive feline hosts and contaminate water, soil and crops, or by consumption of intracellular cysts in undercooked meat from intermediate hosts. In this review we examine current and future approaches to control toxoplasmosis, which encompass a variety of measures that target different components of the life cycle of T. gondii. These include: education programs about the parasite and avoidance of contact with infectious stages; biosecurity and sanitation to ensure food and water safety; chemo- and immunotherapeutics to control active infections and disease; prophylactic options to prevent acquisition of infection by livestock and cyst formation in meat; and vaccines to prevent shedding of oocysts by definitive feline hosts

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites

© 2017 The Author(s). Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites

When Models Interact with their Subjects: The Dynamics of Model Aware Systems

A scientific model need not be a passive and static descriptor of its subject. If the subject is affected by the model, the model must be updated to explain its affected subject. In this study, two models regarding the dynamics of model aware systems are presented. The first explores the behavior of "prediction seeking" (PSP) and "prediction avoiding" (PAP) populations under the influence of a model that describes them. The second explores the publishing behavior of a group of experimentalists coupled to a model by means of confirmation bias. It is found that model aware systems can exhibit convergent random or oscillatory behavior and display universal 1/f noise. A numerical simulation of the physical experimentalists is compared with actual publications of neutron life time and {\Lambda} mass measurements and is in good quantitative agreement.Comment: Accepted for publication in PLoS-ON

Systematic review of sensory processing in preterm children reveals abnormal sensory modulation, somatosensory processing and sensory-based motor processing

Aim Preterm birth poses concerns in daily functioning and behaviour in childhood, possibly connected to sensory processing disorder. This review aimed to systematically identify assessments, incidence and nature of sensory processing disorder in preterm-born infants and children. Methods We searched literature through CINAHL-EBSCOhost, Cochrane, Ovid/PsychINFO, PubMed/Medline, Scopus and Google Scholar, published until November 2018. We included electronically available, peer-reviewed studies of preterm-born children that applied standardised sensory processing assessments. We excluded studies of preterm-born children with major neurodevelopmental impairments. Results We identified 27 studies of premature children, aged from birth to 9 years 7 months. The assessments represented three versions of Sensory Profile questionnaires and three clinical tests, Test of Sensory Functions in Infants, the Miller Assessment for Preschoolers, and the Sensory Integration and Praxis Test. The studies revealed wide variation of atypical sensory processing: 28%-87% in sensory modulation, 9%-70% in somatosensory processing and 20%-70% in sensory-based motor processing. Conclusion Preterm-born children exhibited elevated risk for sensory processing disorder from infancy into school age. Routine screening of sensory processing, intervention intervals and parental consultations should be considered in ameliorating sensory processing and neurocognitive development. Moreover, a larger body of intervention studies is needed.Peer reviewe

Risk of congenital anomalies in pregnant users of statin drugs

What is already known about this subjectCholesterol is known to be essential for fetal development.Statins, which inhibit cholesterol production, have therefore been considered as potential teratogens and are contraindicated in pregnancy.Data available thus far on the risks of congenital anomalies associated with statin therapy have come from non-analytic postmarketing surveillance studies.Given the increasing use of statins in women of childbearing age, there is a need for a population-based study on the risks of congenital anomalies associated with gestational statin use.What this study addsIn this pharmacoepidemiological study, we determined the risk of congenital anomalies in women who filled prescriptions for statins during the first trimester of pregnancy, compared with women who had stopped statins before pregnancy or those who used fibrates during pregnancy.We found no evidence of an increased risk of fetal anomalies among first-trimester statin users, or any discernable pattern of congenital anomalies among live births.However, in the absence of outcome data on nonlive births, conclusions remain uncertain

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies