The substantia Nigra pars compacta and temporal processing

The basal ganglia and cerebellum are considered to play a role in timing, although their differential roles in timing remain unclear. It has been proposed that the timing of short milliseconds-range intervals involves the cerebellum, whereas longer seconds-range intervals engage the basal ganglia (Ivry, 1996). We tested this hypothesis using positron emission tomography to measure regional cerebral blood flow in eight right-handed males during estimation and reproduction of long and short intervals. Subjects performed three tasks: (1) reproduction of a short 500 ms interval, (2) reproduction of a long 2 s interval, and (3) a control simple reaction time (RT) task. We compared the two time reproduction tasks with the control RT task to investigate activity associated with temporal processing once additional cognitive, motor, or sensory processing was controlled. We found foci in the left substantia nigra and the left lateral premotor cortex to be significantly more activated in the time reproduction tasks than the control RT task. The left caudate nucleus and right cerebellum were more active in the short relative to the long interval, whereas greater activation of the right putamen and right cerebellum occurred in the long rather than the short interval. These results suggest that the basal ganglia and the cerebellum are engaged by reproduction of both long and short intervals but play different roles. The fundamental role of the substantia nigra in temporal processing is discussed in relation to previous animal lesion studies and evidence for the modulating influence of dopamine on temporal processing

The genetic basis of larval resistance to a host plant toxin in Drosophila sechellia

The larvae of Drosophila sechellia are highly resistant to octanoic acid, a toxin found in D. sechellia's host plant, Morinda citrifolia. In contrast, close relatives of D. sechellia, D. simulans and D. melanogaster, are not resistant. In a series of interspecific backcrosses, 11 genetic markers were used to map factors affecting egg-to-adult ('larval') resistance in D. sechellia. The third chromosome harbours at least one partially dominant resistance factor. The second chromosome carries at least two mostly dominant resistance factors but no recessive factors. However, neither the X chromosome - which contains 20% of D. sechellia's genome - nor the fourth chromosome appear to affect resistance. These data suggest that larval resistance to Morinda toxin may involve only a handful of genes. These results, when compared with a previous analysis of adult resistance to Morinda toxin in D. sechellia, suggest that larval resistance may involve a subset of the genes underlying adult resistance

Challenges and solutions for analysing dual RNA-seq data for non-model host–pathogen systems

Dual RNA-seq simultaneously profiles the transcriptomes of a host and of a pathogen during infection and may reveal the mechanisms underlying host–pathogen interactions. Dual RNA-seq is inherently a mixture of transcripts from at least two species (host and pathogen), so this mixture must be computationally sorted into host and pathogen components. Sorting relies on aligning reads to respective reference genomes, which may be unavailable for both species in non-model host–pathogen pairs. This lack of genomic resources may present challenges to applying dual RNA-seq to non-model systems. We assessed the accuracy of alignments of dual RNA-seq when using the genomic resources of a closely related species to the species of interest by simulating datasets of mixed transcripts from a host and pathogen. Specifically, we compared how different aligners performed across different proportions of pathogen-to-host transcripts and across variation in the genetic distance between the pathogen genome and reference genome. We performed extensive analyses for a host plant with a fungal pathogen, and then, we extended the plant–fungus results by repeating key analyses in vertebrate (human)–fungus and vertebrate–bacterium systems. Aligners that were able to map pathogen transcripts to the reference genome of a species closely related to the pathogen (a ‘related reference genome’) also mismapped transcripts originating from the host to the pathogen's related reference genome. This resulted in regions where this occurred being quantified as overexpressed. If a host reference genome was available, we show that, to minimize host transcript mismapping and retain the ability to map pathogen transcripts, one could concatenate the host genome with the pathogen's related reference genome, then map transcripts to the concatenated genomes. If a host genome was unavailable, assembling reads de novo prior to aligning substantially decreased host read mismapping, while retaining the ability to map pathogen transcripts to a related reference genome. The application of dual RNA-seq to organisms without reference genomes is currently limited. We propose an analytical workflow that leverages the genomic resources of species closely related to species of interest to facilitate the application of dual RNA-seq to reveal the mechanisms of host–pathogen interactions across a wider array of systems

A note on optimal sampling strategy for structural variant detection using optical mapping

Structural variants compose the majority of human genetic variation, but are difficult to accurately assess using current genomic sequencing technologies. Optical mapping technologies, which measure the size of chromosomal fragments between labeled markers, offer an alternative approach. As these technologies mature toward becoming clinical tools, there is a need to develop an approach for determining the optimal strategy for sampling biological material in order to detect a structural variant at some threshold. Here we develop an optimization approach using a simple, yet realistic, model of the genomic mapping process using a hypergeometric distribution and probabilistic concentration inequalities. Our approach is both computationally and analytically tractable and includes a novel approach to getting tail bounds of hypergeometric distribution. We show that if a genomic mapping technology can sample most of the chromosomal fragments within a sample, comparatively little biological material is needed to detect a variant at high confidence

Plastic potential: how the phenotypes and adaptations of pathogens are influenced by microbial interactions within plants

Predicting the effects of plant-associated microbes on emergence, spread, and evolution of plant pathogens demands an understanding of how pathogens respond to these microbes at two levels of biological organization: that of an individual pathogen and that of a pathogen population across multiple individual plants. We first examine the plastic responses of individual plant pathogens to microbes within a shared host, as seen through changes in pathogen growth and multiplication. We then explore the limited understanding of how within-plant microbial interactions affect pathogen populations and discuss the need to incorporate population-level observations with population genomic techniques. Finally, we suggest that integrating across levels will further our understanding of the ecological and evolutionary impacts of within-plant microbial interactions on pathogens

Acute Visual Loss Induced by Dexamethasone During Neoadjuvant Docetaxol

We present a case of a female patient who developed acute onset of visual loss due to central serous retinopathy as a consequence of steroid premedication for docetaxol given as second line neoadjuvant chemotherapy for breast cancer. Central serous retinopathy is a recognised association with steroids but has not been previously reported in association with the management of solid tumours. Reduction in steroid dose and duration permitted recovery of her visual acuity while allowing completion of the prescribed chemotherapy regimen. An overview of the presentation, pathogenesis, aetiologies and management of central serous retinopathy is given

Carbon sequestration and biogeochemical cycling in a saltmarsh subject to coastal managed realignment

Globally, wetlands provide the largest terrestrial carbon (C) store, and restoration of degraded wetlands provides a potentially important mechanism for climate change mitigation. We examined the potential for restored saltmarshes to sequester carbon, and found that they can provide a modest, but sustained, sink for atmospheric CO2. Rates of C and nutrient cycling were measured and compared between a natural saltmarsh (high- and low-shore locations), claimed arable land on former high-shore saltmarsh and a managed realignment restoration site (high- and low-shore) in transition from agricultural land to saltmarsh 15 years after realignment, at Tollesbury, Essex, UK. We measured pools and turnover of C and nitrogen (N) in soil and vegetation at each site using a range of methods, including gas flux measurement and isotopic labelling. The natural high-shore site had the highest soil organic matter concentrations, topsoil C stock and below-ground biomass, whereas the agricultural site had the highest total extractable N concentration and lowest soil C/N ratio. Ecosystem respiration rates were similar across all three high-shore sites, but much higher in both low-shore sites, which receive regular inputs of organic matter and nutrients from the estuary. Total evolution of 14C-isotopically labelled substrate as CO2 was highest at the agricultural site, suggesting that low observed respiration rates here were due to low substrate supply (following a recent harvest) rather than to inherently low microbial activity. The results suggest that, after 15 years, the managed realignment site is not fully equivalent to the natural saltmarsh in terms of biological and chemical function. While above ground biomass, extractable N and substrate mineralisation rates in the high-shore site were all quite similar to the natural site, less dynamic ecosystem properties including soil C stock, C/N ratio and below-ground biomass all remained more similar to the agricultural site. These results suggest that reversion to natural biogeochemical functioning will occur following restoration, but is likely to be slow; we estimate that it will take approximately 100 years for the restored site to accumulate the amount of C currently stored in the natural site, at a rate of 0.92 t C ha−1 yr−1

Cognitive phenotype and differential gene expression in a hippocampal homologue in two species of frog

The complexity of an animal's interaction with its physical and/or social environment is thought to be associated with behavioral flexibility and cognitive phenotype, though we know little about this relationship in amphibians. We examined differences in cognitive phenotype in two species of frog with divergent natural histories. The greenand- black poison frog (Dendrobates auratus) is diurnal, displays enduring social interactions, and uses spatially distributed resources during parental care. Tungara frogs (Physalaemus=Engystomops pustulosus) are nocturnal, express only fleeting social interactions, and use ephemeral puddles to breed in a lek-type mating system. Comparing performance in identical discrimination tasks, we find that D. auratus made fewer errors when learning and displayed greater behavioral flexibility in reversal learning tasks than tungara frogs. Further, tungara frogs preferred to learn beacons that can be used in direct guidance whereas D. auratus preferred position cues that could be used to spatially orient relative to the goal. Behavioral flexibility and spatial cognition are associated with hippocampal function in mammals. Accordingly, we examined differential gene expression in the medial pallium, the amphibian homolog of the hippocampus. Our preliminary data indicate that genes related to learning and memory, synaptic plasticity, and neurogenesis were upregulated in D. auratus, while genes related to apoptosis were upregulated in tungara frogs, suggesting that these cellular processes could contribute to the differences in behavioral flexibility and spatial learning we observed between poison frogs and tungara frogs