Sawyerasmussen3549

Diversity of cell-types that collectively shape the cortical microcircuit ensures the necessary computational richness to orchestrate a wide variety of behaviors. The information content embedded in spiking activity of identified cell-types remain unclear to a large extent. Here, we recorded spike responses upon whisker touch of anatomically identified excitatory cell-types in primary somatosensory cortex in naive, untrained rats. We find major differences across layers and cell-types. The temporal structure of spontaneous spiking contains high-frequency bursts (≥100 Hz) in all morphological cell-types but a significant increase upon whisker touch is restricted to layer L5 thick-tufted pyramids (L5tts) and thus provides a distinct neurophysiological signature. We find that whisker touch can also be decoded from L5tt bursting, but not from other cell-types. We observed high-frequency bursts in L5tts projecting to different subcortical regions, including thalamus, midbrain and brainstem. We conclude that bursts in L5tts allow accurate coding and decoding of exploratory whisker touch.BRAFV600E melanoma patients, despite initially responding to the clinically prescribed anti-BRAFV600E therapy, often relapse, and their tumors develop drug resistance. While it is widely accepted that these tumors are originally driven by the BRAFV600E mutation, they often eventually diverge and become supported by various signaling networks. Therefore, patient-specific altered signaling signatures should be deciphered and treated individually. In this study, we design individualized melanoma combination treatments based on personalized network alterations. Using an information-theoretic approach, we compute high-resolution patient-specific altered signaling signatures. These altered signaling signatures each consist of several co-expressed subnetworks, which should all be targeted to optimally inhibit the entire altered signaling flux. Based on these data, we design smart, personalized drug combinations, often consisting of FDA-approved drugs. We validate our approach in vitro and in vivo showing that individualized drug combinations that are rationally based on patient-specific altered signaling signatures are more efficient than the clinically used anti-BRAFV600E or BRAFV600E/MEK targeted therapy. Furthermore, these drug combinations are highly selective, as a drug combination efficient for one BRAFV600E tumor is significantly less efficient for another, and vice versa. The approach presented herein can be broadly applicable to aid clinicians to rationally design patient-specific anti-melanoma drug combinations.Classical biological control is a pest control tool involving the release of imported natural enemies. The Sterile Insect Technique (SIT) comprises releasing sexually sterile insects of a pest into the wild population for suppression or eradication. Both these approaches are environmentally friendly and their combination can result in a synergistic impact on pest populations and improve eradication. However, stringent regulation surrounding the introduction of biological control agents limits their use in eradication owing to the perceived risk of effects on non-target organisms. We investigated the irradiation biology of the egg parasitoid Trissolcus basalis to ascertain whether sterile parasitoids could mitigate the risk of potential sustained non-target impacts. Mated female T. basalis were gamma-irradiated at doses between 120 and 150 Gy and exposed to egg masses of their host Nezara viridula throughout their lifespans. This resulted in host mortality, despite a substantial reduction in developing parasitoid offspring, which followed a negative dose-response. There was no emergence of parasitoid offspring at 140 Gy and above. Irradiation did not affect oviposition behaviour but caused an increase in longevity. Consequently, sterile parasitoids could possibly alleviate concerns regarding the irreversibility of biological control release, which promotes further investigation of their potential role in eradication.Traditionally Caenorhabditis elegans lifespan assays are performed by manually inspecting nematodes with a dissection microscope, which involves daily counting of live/dead worms cultured in Petri plates for 21-25 days. This manual inspection requires the screening of hundreds of worms to ensure statistical robustness, and is therefore a time-consuming approach. In recent years, various automated artificial vision systems have been reported to increase the throughput, however they usually provide less accurate results than manual assays. The main problems identified when using these vision systems are the false positives and false negatives, which occur due to culture media changes, occluded zones, dirtiness or condensation of the Petri plates. In this work, we developed and described a new C. elegans monitoring machine, SiViS, which consists of a flexible and compact platform design to analyse C. elegans cultures using the standard Petri plates seeded with E. coli. Our system uses an active vision illumination technique and different image-processing pipelines for motion detection, both previously reported, providing a fully automated image processing pipeline. In addition, this study validated both these methods and the feasibility of the SiViS machine for lifespan experiments by comparing them with manual lifespan assays. Results demonstrated that the automated system yields consistent replicates (p-value log rank test 0.699), and there are no significant differences between automated system assays and traditionally manual assays (p-value 0.637). Finally, although we have focused on the use of SiViS in longevity assays, the system configuration is flexible and can, thus, be adapted to other C. elegans studies such as toxicity, mobility and behaviour.Age and sex are major risk factors in Alzheimer's disease (AD) with a higher incidence of the disease in females. Neuroinflammation, which is a hallmark of AD, contributes to disease pathogenesis and is inexorably linked with inappropriate microglial activation and neurodegeneration. selleckchem We investigated sex-related differences in microglia in APP/PS1 mice and in post-mortem tissue from AD patients. Changes in genes that are indicative of microglial activation were preferentially increased in cells from female APP/PS1 mice and cells from males and females were morphological, metabolically and functionally distinct. Microglia from female APP/PS1 mice were glycolytic and less phagocytic and associated with increased amyloidosis whereas microglia from males were amoeboid and this was also the case in post-mortem tissue from male AD patients, where plaque load was reduced. We propose that the sex-related differences in microglia are likely to explain, at least in part, the sexual dimorphism in AD.