Characteristics of long-duration inhibitory postsynaptic potentials in rat neocortical neurons in vitro

1. The characteristics of long-duration inhibitory postsynaptic potentials (l-IPSPs) which are evoked in rat frontal neocortical neurons by local electrical stimulation were investigated with intracellular recordings from anin vitro slice preparation. 2. Stimulation with suprathreshold intensities evoked l-IPSPs with typical durations of 600–900 msec at resting membrane potential. Conductance increases of 15–60% were measured at the peak amplitude of l-IPSPs (150–250 msec poststimulus). 3. The duration of the conductance increases during l-IPSPs displayed a significant voltage dependence, decreasing as the membrance potential was depolarized and increasing with hyperpolarization. 4. The reversal potential of l-IPSPs is significantly altered by reductions in the extracellular potassium concentration. Therefore it is concluded that l-IPSPs in rat neocortical neurons are generated by the activation of a potassium conductance. 5. l-IPSPs exhibit stimulation fatigue. Stimulation with a frequency of 1 Hz produces a complete fatigue of the conductance increases during l-IPSPs after approximately 20 consecutive stimuli. Recovery from this fatigue requires minutes. 6. l-IPSPs are not blocked by bicuculline but are blocked by baclofen

Ivermectin 1% efficacy by different routes and doses against resistant nematodes in cattle

La resitencia antielmintica (RA) a ivermectina (IVM) y otras lactonas macrocíclicas(LM) es un fenómeno mundialmente conocido . En ovinos, la administración de LMpor vía oral o intra-ruminal y en alta dosis ha logrado mejorar la eficacia frente aparásitos gastrointestinales (PGI), sin embargo no abundan aún experienciassimilares bovinos. El objetivo del presente ensayo fue evaluar la eficacia de IVM aalta dosis y por diferentes vías en terneros portadores de PGI resistentes a IVM enun engorde a corral comercial. De un total de 125 se seleccionaron 44 ternerosmachos, clínicamente sanos, los cuales fueron asignados a 4 grupos (n=11animales/grupo) que recibieron IVM a dosis estándar (0,2 mg/kg) y alta (1 mg/kg) ypor vía subcutánea e intra-ruminal. Previo al día del tratamiento (día ? 6) setomaron muestras de materia fecal para recuento de huevos de PGI por gramo ycoprocultivo; además se registró el peso individual de cada animal. El día deltratamiento fue considerado el día 0. En los días +14 y +27 se tomaron muestrasde materia fecal mientras que en el día +27 se registró nuevamente el peso. Lareducción en el recuento de huevos en materia fecal en el día +14 y +27 no mostró diferencias entre los grupos, dejando en evidencia la falta de eficacia de la droga aún en dosis quíntuple. No se observó diferencias en la ganancia diaria de peso entre los grupos. En el presente ensayo el uso de IVM en los diferentes grupos aalta dosis y por diferentes vías no obtuvo mejoras en los porcentajes de reducciónde huevos en materia fecal en bovinos portadores de PGI resistentes.Anthelmintic resistance to ivermectin and macrocyclic lactones (ML) is a worldwide spread problem. A high dose schedule of ML was effective against resistant nematodes in sheep, given oral and intra-ruminal. However, no enough data are available from cattle on this issue. Thus, the goal of this work was the efficacy assessment of IVM given at different doses and routes. To achieve this goal, 44 male feedlot calves, infected with IVM resistant nematodes, were assigned to four groups (n=11 calves per group). They received standard (0.2 mg/kg), or high doses (1 mg/kg) of IVM by subcutaneous or intra-ruminal routes. Before treatment (day -6), feces were sampled for eggs per gram counts (EPG) and copocultures; weight was also measured on this date. The treatments were administered on day 0. Later, on days +14 and +27, feces were re-sampled, and calves were weighed again just in the last date. Fecal egg count reductions showed no statistical differences between groups. This evidenced the lack of efficacy for IVM, even at a fivefold dose. Weight was neither different between groups. In conclusion, higher doses of IVM given by subcutaneous or intra-ruminal routes were insufficient to kill IVM-resistant nematodes in calves.Fil: Galvan, Walter Ruben. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Fazzio, Luis Emilio. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Streitenberger, Nicolás. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Galarza, E.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Lizarraga, R.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Sánchez, Ricardo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Sanabria, Rodrigo Eduardo Fabrizio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

Efficacy and productive performance of moxidectin in feedlot calves infected with nematodes resistant to ivermectin

Anthelmintic resistance (AR) of gastrointestinal nematodes to macrocyclic lactones is an increasingly common worldwide phenomenon limiting cattle production. This has motivated the search for alternatives, such as new active compounds, added drug synergisms, different doses, and alternate administration routes. The aim of this study was the assessment of moxidectin (MXD) performance in feedlot calves with a history of AR to ivermectin (IVM). Crossbred female calves aged 6-7 months and weighing 163 kg (SD = 34 kg) were divided into 3 groups of 35 animals each. They were assigned to the following antiparasitic treatment groups: IVM group (0.2 mg/kg IVM); MXD group (0.2 mg/kg MXD), and ricobendazole + levamisole (RBZ + LEV) group (7.5 mg/kg RBZ + 8 mg/kg LEV). On days 0, 26, and 47, fecal samples were taken and the weight of each animal was registered. Anthelmintic efficacy (by fecal egg count reduction), total weight gain (TWG) and average daily weight gain (AWG) were compared between the groups. A mixed SAS procedure was used for statistical analysis. Fecal egg count reduction 26 days post-treatment (PT) was calculated at 28% for the IVM group, 85% for the MXD group, and 99% for the RBZ + LEV group. AWGs (Standard Error) of 1.095 g (56), 1.264 g (49), and 1.340 g (52) were registered for the IVM, MXD, and RBZ + LEV groups, respectively (p < 0.05). Coprocultures revealed that MXD more effectively reduced Haemonchus spp. and Cooperia spp. egg counts than IVM. This resulted in higher AWGs and TWGs for this group; similar results were seen for the RBZ + LEV group as well. In this study, animals treated with MXD gained about 160 more g/day than animals treated with IVM. This represents a gain of 16 USD per animal over the 47 day trial.Fil: Fazzio, Luis Emilio. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Streitenberger, Nicolás. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Galvan, Walter Ruben. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Sánchez, R. O.. Laboratorio Mesopotámico de Diagnóstico Veterinario; ArgentinaFil: Gimeno, Eduardo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Sanabria, Rodrigo Eduardo Fabrizio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Pilot Study of COBAS PCR and Ligase Chain Reaction for Detection of Rectal Infections Due to Chlamydia trachomatis

We tested rectal specimens from men who have sex with men for Chlamydia trachomatis by using COBAS PCR (Roche Diagnostics) and ligase chain reaction LCR (Abbott laboratories) and compared three PCR specimen-processing procedures. Chlamydiae were detected by one or more procedures in 22 of 186 specimens. All three PCR tests were positive for 17 specimens, all of which also tested positive by LCR

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

A vesicle-trafficking protein commandeers Kv channel voltage sensors for voltage-dependent secretion

Growth in plants depends on ion transport for osmotic solute uptake and secretory membrane trafficking to deliver material for wall remodelling and cell expansion. The coordination of these processes lies at the heart of the question, unresolved for more than a century, of how plants regulate cell volume and turgor. Here we report that the SNARE protein SYP121 (SYR1/PEN1), which mediates vesicle fusion at the Arabidopsis plasma membrane, binds the voltage sensor domains (VSDs) of K+ channels to confer a voltage dependence on secretory traffic in parallel with K+ uptake. VSD binding enhances secretion in vivo subject to voltage, and mutations affecting VSD conformation alter binding and secretion in parallel with channel gating, net K+ concentration, osmotic content and growth. These results demonstrate a new and unexpected mechanism for secretory control, in which a subset of plant SNAREs commandeer K+ channel VSDs to coordinate membrane trafficking with K+ uptake for growth