Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals,Independently of Calcium and Cyclic AMP Signalling

BackgroundCerebellar parallel fibres release glutamate at both the synaptic active zone and at extrasynaptic sites—a process known as ectopic release. These sites exhibit different short-term and long-term plasticity, the basis of which is incompletely understood but depends on the efficiency of vesicle release and recycling. To investigate whether release of calcium from internal stores contributes to these differences in plasticity, we tested the effects of the ryanodine receptor agonist caffeine on both synaptic and ectopic transmission.MethodsWhole cell patch clamp recordings from Purkinje neurons and Bergmann glia were carried out in transverse cerebellar slices from juvenile (P16-20) Wistar rats.ConclusionsWe conclude that caffeine increases release probability and inhibits vesicle recovery at parallel fibre synapses, independently of known pharmacological targets. This complex effect would lead to potentiation of transmission at fibres firing at low frequencies, but depression of transmission at high frequency connections.     

Overestimates of survival after HAART: implications for global scale-up efforts

Background

Monitoring the effectiveness of global antiretroviral therapy scale-up efforts in resource-limited settings is a global health priority, but is complicated by high rates of losses to follow-up after treatment initiation. Determining definitive outcomes of these lost patients, and the effects of losses to follow-up on estimates of survival and risk factors for death after HAART, are key to monitoring the effectiveness of global HAART scale-up efforts.

Methodology/Principal Findings

A cohort study comparing clinical outcomes and risk factors for death after HAART initiation as reported before and after tracing of patients lost to follow-up was conducted in Botswana''s National Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting for HAART were evaluated. The main outcome measures were death or loss to follow-up within the first year after HAART initiation. Of 68 patients initially categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient tracing resulted in reporting of significantly lower survival rates when death was used as the outcome and losses to follow-up were censored [1-year Kaplan Meier survival estimate 0.92 (95% confidence interval, 0.88–0.94 before tracing and 0.83 (95% confidence interval, 0.79–0.86) after tracing, log rank P<0.001]. In addition, a significantly increased risk of death after HAART among men [adjusted hazard ratio 1.74 (95% confidence interval, 1.05–2.87)] would have been missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence interval, 0.65–3.05)].

Conclusions/Significance

Due to high rates of death among patients lost to follow-up after HAART, survival rates may be inaccurate and important risk factors for death may be missed if patients are not actively traced. Patient tracing and uniform reporting of outcomes after HAART are needed to enable accurate monitoring of global HAART scale-up efforts.     

Telemetric monitoring of fetal blood pressure and heart rate in the freely moving pregnant sheep: a feasibility study

Remote telemetric monitoring of fetal haemodynamics in pregnant sheep would allow unrestricted animal movement, minimize suffering and distress, and improve animal welfare, while enhancing the quality of data collected. This may also be useful in clinical practice following fetal surgery. Using an open fetal surgical technique at approximately two-thirds of gestation, we implanted the catheter of a D70-PCTP haemodynamic telemetric device (Data Sciences International, Tilburg, The Netherlands) into the carotid artery of the fetal sheep (n = 4). The attached transmitter was secured to the posterior aspect of the maternal anterior abdominal wall. Two receivers, with a range of 1 m each, were sited in an 11 m2 sheep enclosure to maximize animal freedom while allowing continuous monitoring of the ewe. The receivers were connected by cable to a nearby computer. In the first two procedures, both fetuses died eight and 12 days after surgery, and the catheter tip was observed to be lying in the bicarotid trunk. In the next two procedures the catheter tip was threaded further upstream from the insertion point, in an attempt to reach the fetal aorta, and both fetuses survived until the scheduled postmortem examination at the end of pregnancy. After catheter implantation, fetal blood pressure (BP) and heart rate (HR) were successfully recorded continuously for seven days and then hourly per day for a further three weeks. The fetal BP and HR values were in the normal range for healthy sheep fetuses.     

Quantifying Host Potentials: Indexing Postharvest Fresh Fruits for Spotted Wing Drosophila,Drosophila suzukii

Novel methodology is presented for indexing the relative potential of hosts to function as resources. A Host Potential Index (HPI) was developed as a practical framework to express relative host potential based on combining results from one or more independent studies, such as those examining host selection, utilization, and physiological development of the organism resourcing the host. Several aspects of the HPI are addressed including: 1) model derivation; 2) influence of experimental design on establishing host rankings for a study type (no choice, two-choice, and multiple-choice); and, 3) variable selection and weighting associated with combining multiple studies. To demonstrate application of the HPI, results from the interactions of spotted wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), with seven “reported” hosts (blackberries, blueberries, sweet cherries, table grapes, peaches, raspberries, and strawberries) in a postharvest scenario were analyzed. Four aspects of SWD-host interaction were examined: attraction to host volatiles; population-level oviposition performance; individual-level oviposition performance; and key developmental factors. Application of HPI methodology indicated that raspberries (^meanHPI_varied = 301.9±8.39; rank 1 of 7) have the greatest potential to serve as a postharvest host for SWD relative to the other fruit hosts, with grapes (^meanHPI_varied = 232.4±3.21; rank 7 of 7) having the least potential.     

Tempo and mode of concerted evolution in the L1 repeat family of mice

A 300-bp DNA sequence has been determined for 30 (10 from each of three species of mice) random isolates of a subset of the long interspersed repeat family L1. From these data we conclude that members of the L1 family are evolving in concert at the DNA sequence level in Mus domesticus, Mus caroli, and Mus platythrix. The mechanism responsible for this phenomenon may be either duplicative transposition, gene conversion, or a combination of the two. The amount of intraspecies divergence averages 4.4%, although between species base substitutions accumulate at the rate of approximately 0.85%/Myr to a maximum divergence of 9.1% between M. platythrix and both M. domesticus and M. caroli. Parsimony analysis reveals that the M. platythrix L1 family has evolved into a distinct clade in the 10-12 Myr since M. platythrix last shared a common ancestor with M. domesticus and M. caroli. The parsimony tree also provides a means to derive the average half-life of L1 sequences in the genome. The rates of gain and loss of individual copies of L1 were estimated to be approximately equal, such that approximately one-half of them turn over every 3.3 Myr.      

Asthma induced by enkephalin.

A total of 291 diabetics were studied to see whether an asthmatic reaction was associated with facial flushing induced by chlorpropamide and alcohol. Of these patients, 191 reported facial flushing, of whom 12 reported breathlessness as well. Of these 12, five also described wheezing, and respiratory function tests showed them to have asthma. Three of these five patients underwent further tests, which showed that the asthmatic reaction could be prevented by giving disodium cromoglycate and the specific opiate antagonist naloxone. One patient developed wheezing when given an enkephalin analogue with opiate-like activity. Asthma induced by chlorpropamide and alcohol was concluded to be mediated by endogenous peptides with opiate-like activity such as enkephalin.     

The Acute Satellite Cell Response and Skeletal Muscle Hypertrophy following Resistance Training

The extent of skeletal muscle hypertrophy in response to resistance training is highly variable in humans. The main objective of this study was to explain the nature of this variability. More specifically, we focused on the myogenic stem cell population, the satellite cell (SC) as a potential mediator of hypertrophy. Twenty-three males (aged 18–35 yrs) participated in 16 wk of progressive, whole body resistance training, resulting in changes of 7.9±1.6% (range of −1.9–24.7%) and 21.0±4.0% (range of −7.0 to 51.7%) in quadriceps volume and myofibre cross-sectional area (CSA), respectively. The SC response to a single bout of resistance exercise (80% 1RM), analyzed via immunofluorescent staining resulted in an expansion of type II fibre associated SC 72 h following exercise (pre: 11.3±0.9; 72 h: 14.8±1.4 SC/type II fibre; p<0.05). Training resulted in an expansion of the SC pool associated with type I (pre: 10.7±1.1; post: 12.1±1.2 SC/type I fibre; p<0.05) and type II fibres (pre: 11.3±0.9; post: 13.0±1.2 SC/type II fibre; p<0.05). Analysis of individual SC responses revealed a correlation between the relative change in type I associated SC 24 to 72 hours following an acute bout of resistance exercise and the percentage increase in quadriceps lean tissue mass assessed by MRI (r² = 0.566, p = 0.012) and the relative change in type II associated SC following 16 weeks of resistance training and the percentage increase in quadriceps lean tissue mass assessed by MRI (r² = 0.493, p = 0.027). Our results suggest that the SC response to resistance exercise is related to the extent of muscular hypertrophy induced by training.     

Breeding season habitat associations and population declines of British Hawfinches Coccothraustes coccothraustes

Capsule At both landscape and local scales, breeding persistence in a declining Hawfinch population was greatest where broadleaved woodland cover was high, while at a fine scale, nest sites were associated with openings in the woodland canopy.

Aims To assess which components of habitat are associated with Hawfinch occupancy at landscape (10-km), local (tetrad) and fine (nest) spatial scales, during a period of population decline and range contraction.

Methods Bird Atlas 2008–11 data were used to determine areas of Hawfinch loss and persistence over 20 years. Current habitat was measured and compared to look for correlates that helped explain the differing status at both 10-km and tetrad scales. Fine scale habitat data collected at nest sites were compared with random locations to investigate within-wood nest site selection.

Results At both 10-km and tetrad scales, Hawfinch persistence is more likely where woodland cover is greater. Recent woodland management was less evident in tetrads where the species persisted. At the nest site scale, the only relationship detected was for nests to be close to canopy openings.

Conclusions Maintaining and increasing broadleaved woodland area is likely to benefit Hawfinch. Within woods, maintenance and creation of open areas may enhance nesting opportunities.