The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia

© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits. Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.Peer reviewe

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Immune adjuvant effect of V. cholerae O1 derived Proteoliposome coadministered by intranasal route with Vi polysaccharide from Salmonella Typhi

Proteoliposome derived from Vibrio cholerae O1 (PLc) is a nanoscaled structure obtained by detergent extraction process. Intranasal (i.n) administration of PLc was immunogenic at mucosal and systemic level vs. V. cholerae; however the adjuvant potential of this structure for non-cholera antigens has not been proven yet. The aim of this work was to evaluate the effect of coadministering PLc with the Vi polysaccharide antigen (Poli Vi) of S. Typhi by i.n route. The results showed that Poli Vi coadministered with PLc (PLc+Poli Vi) induce higher IgA response in saliva (p0.05) to that induced in a group of mice immunised by parenteral route with the Cuban anti-typhoid vaccine vax-TyVi®, although this vaccine did not induce mucosal response. In conclusion, this work demonstrates that PLc can be used as mucosal adjuvant to potentiate the immune response against a polysaccharide antigen like Poli Vi

Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

The microsporidian parasites Nosema ceranae and Nosema apis are widespread in honeybee (Apis mellifera) colonies across Scotland

Nosema ceranae is spreading into areas where Nosema apis already exists. N. ceranae has been reported to cause an asymptomatic infection that may lead, ultimately, to colony collapse. It is thought that there may be a temperature barrier to its infiltration into countries in colder climates. In this study, 71 colonies from Scottish Beekeeper’s Association members have been screened for the presence of N. apis and N. ceranae across Scotland. We find that only 11 of the 71 colonies tested positive for spores by microscopy. However, 70.4 % of colonies screened by PCR revealed the presence of both N. ceranae and N. apis, with only 4.2 or 7 % having either strain alone and 18.3 % being Nosema free. A range of geographically separated colonies testing positive for N. ceranae were sequenced to confirm their identity. All nine sequences confirmed the presence of N. ceranae and indicated the presence of a single new variant. Furthermore, two of the spore-containing colonies had only N. ceranae present, and these exhibited the presence of smaller spores that could be distinguished from N. apis by the analysis of average spore size. Differential quantification of the PCR product revealed N. ceranae to be the dominant species in all seven samples tested. In conclusion, N. ceranae is widespread in Scotland where it exists in combination with the endemic N. apis. A single variant, identical to that found in France (DQ374655) except for the addition of a single nucleotide polymorphism, is present in Scotland

Frequency-specific hippocampal-prefrontal interactions during associative learning

Much of our knowledge of the world depends on learning associations (for example, face-name), for which the hippocampus (HPC) and prefrontal cortex (PFC) are critical. HPC-PFC interactions have rarely been studied in monkeys, whose cognitive and mnemonic abilities are akin to those of humans. We found functional differences and frequency-specific interactions between HPC and PFC of monkeys learning object pair associations, an animal model of human explicit memory. PFC spiking activity reflected learning in parallel with behavioral performance, whereas HPC neurons reflected feedback about whether trial-and-error guesses were correct or incorrect. Theta-band HPC-PFC synchrony was stronger after errors, was driven primarily by PFC to HPC directional influences and decreased with learning. In contrast, alpha/beta-band synchrony was stronger after correct trials, was driven more by HPC and increased with learning. Rapid object associative learning may occur in PFC, whereas HPC may guide neocortical plasticity by signaling success or failure via oscillatory synchrony in different frequency bands.National Institute of Mental Health (U.S.) (Conte Center Grant P50-MH094263-03)National Institute of Mental Health (U.S.) (Fellowship F32-MH081507)Picower Foundatio

Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

A framework for the first‑person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila

Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure-function details of the presented mechanism of perception

Neonicotinoid Insecticides and Their Impacts on Bees: A Systematic Review of Research Approaches and Identification of Knowledge Gaps

It has been suggested that the widespread use of neonicotinoid insecticides threatens bees, but research on this topic has been surrounded by controversy. In order to synthesize which research approaches have been used to examine the effect of neonicotinoids on bees and to identify knowledge gaps, we systematically reviewed research on this subject that was available on the Web of Science and PubMed in June 2015. Most of the 216 primary research studies were conducted in Europe or North America (82%), involved the neonicotinoid imidacloprid (78%), and concerned the western honey bee Apis mellifera (75%). Thus, little seems to be known about neonicotinoids and bees in areas outside Europe and North America. Furthermore, because there is considerable variation in ecological traits among bee taxa, studies on honey bees are not likely to fully predict impacts of neonicotinoids on other species. Studies on crops were dominated by seed-treated maize, oilseed rape (canola) and sunflower, whereas less is known about potential side effects on bees from the use of other application methods on insect pollinated fruit and vegetable crops, or on lawns and ornamental plants. Laboratory approaches were most common, and we suggest that their capability to infer real-world consequences are improved when combined with information from field studies about realistic exposures to neonicotinoids. Studies using field approaches often examined only bee exposure to neonicotinoids and more field studies are needed that measure impacts of exposure. Most studies measured effects on individual bees. We suggest that effects on the individual bee should be linked to both mechanisms at the sub-individual level and also to the consequences for the colony and wider bee populations. As bees are increasingly facing multiple interacting pressures future research needs to clarify the role of neonicotinoids in relative to other drivers of bee declines