The topology of connections between rat prefrontal and temporal cortices

Understanding the structural organization of the prefrontal cortex (PFC) is an important step toward determining its functional organization. Here we investigated the organization of PFC using different neuronal tracers. We injected retrograde (Fluoro-Gold, 100 nl) and anterograde [Biotinylated dextran amine (BDA) or Fluoro-Ruby, 100 nl] tracers into sites within PFC subdivisions (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) along a coronal axis within PFC. At each injection site one injection was made of the anterograde tracer and one injection was made of the retrograde tracer. The projection locations of retrogradely labeled neurons and anterogradely labeled axon terminals were then analyzed in the temporal cortex: area Te, entorhinal and perirhinal cortex. We found evidence for an ordering of both the anterograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) and retrograde (anterior-posterior, dorsal-ventral, and medial-lateral axes: p < 0.001) connections of PFC. We observed that anterograde and retrograde labeling in ipsilateral temporal cortex (i.e., PFC inputs and outputs) often occurred reciprocally (i.e., the same brain region, such as area 35d in perirhinal cortex, contained anterograde and retrograde labeling). However, often the same specific columnar temporal cortex regions contained only either labeling of retrograde or anterograde tracer, indicating that PFC inputs and outputs are frequently non-matched

The connectivity of the mammalian prefrontal cortex

The fine scale connections of prefrontal cortex (PFC) were investigated in the rat brain, in order to determine organizational properties of PFC pathways which were previously undefined. Neuroanatomical tract tracers (Fluro-Gold, Fluoro-Ruby, Fluoro-Emerald, Biotinylated dextran amines; Fluorescein and Texas red) were injected (20 -100 nl) into subdivisions of PFC (prelimbic, infralimbic, medial-orbital, ventral-orbital, ventrolateral-orbital, lateral-orbital and dorsolateral-orbital) and their projections studied. Tracer studies identified clear evidence of significantly ordered projections from PFC to temporal and sensory-motor cortices in three axes of orientation (p<0.001), showing differential ordering of input and output connections (p<0.001). Ordered connections were consistent across PFC (from anterior to posterior) and showed evidence of changes in organisation in anterior compared to posterior PFC, in both the PFC-temporal and PFC-sensory-motor cortex pathways. Detailed analysis revealed evidence for an organizational gradient in the relationship between inputs and outputs from anterior to posterior PFC, in which retrograde and anterograde labelling become increasingly differentiated as PFC injection site is moved from posterior to anterior. Analysis of fine scale tracer injections (20-30 nl) revealed evidence to show underlying complex organizational properties of connections from PFC to temporal and sensory-motor cortices. Taken together, the findings show that PFC displays ordered arrangements of connections to temporal and sensory-motor cortex, input and output connections are consistently not found in the same locations and the relationship between inputs and outputs differs in relation to the anterior-posterior location in PFC

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies

Is word-level lexical stress sensitivity affected by downregulation to the left superior temporal gyrus using TMS?

This paper reports two experiments using Transcranial Magnetic Stimulation (TMS) to investigate whether word-level lexical stress involves the left superior temporal gyrus (STG) using a grammar classification task designed to elicit a typicality effect. Experiment 1 used text presented stimuli and, although was not able to elicit a typicality effect, found response times were significantly slower in the no TMS condition compared to when the, control, right PAR region was downregulated. In Experiment 2, speech was presented instead of text and accuracy and response times were similar across all three conditions. A lexical decision control task found evidence, from response time analysis, that the left STG and the right PAR were involved in word and nonword judgments. The discussion explores the findings relative to lexical stress and the role of cortical regions in word and response processing

Low frequency repetitive transcranial magnetic stimulation to right parietal cortex disrupts perception of briefly presented stimuli

Right parietal cortex has recently been linked to the temporal resolution of attention. We therefore sought to investigate whether disruption to right parietal cortex would affect attention to visual stimuli presented for brief durations. Participants performed a visual discrimination task before and after 10 minutes rTMS (1Hz) to right or central parietal cortex as well as 20 minutes after the second block. Participants reported the spatial frequency of a masked Gabor patch presented for a brief duration of 60, 120 or 240ms. We calculated error magnitudes by comparing accuracy to a guessing model. We then compared error magnitudes to blocks with no stimulation, producing a measure of baselined performance. Baselined performance was poorer at longer stimulus durations after right parietal than central parietal stimulation, suggesting that right parietal cortex is involved in attention to briefly presented stimuli, particularly in situations where rapid accumulation of visual evidence is needed

Nanoparticle-induced enhancement of cholinesterase activity in the presence of malathion: A potential nerve agent therapeutic

Organophosphate nerve agents are associated with assassination, terrorism and chemical warfare, but there has been slow progress in developing a broad-spectrum response to poisoning. For some nerve agents the oxime component of the therapy may not be effective, limiting the effectiveness of emergency treatment that is desperately needed. An alternative therapy may be possible based on accelerating enzyme (acetylcholinesterase) catalysis in unaffected adjacent enzymes. Herein we demonstrate a restoration of acetylcholinesterase activity in malathion-inhibited cell membrane preparations by the administration of functional nanoparticles. The molecularly imprinted polymer nanoparticles were designed to bind selectively to designated enzyme epitopes. Enzyme activity of membrane-bound acetylcholinesterase was measured in the presence of the organophosphate malathion and the selected nanoparticles. Enzymatic acceleration of the cholinesterase was observed at 162 ± 17 % the rate of erythrocyte ghosts without bound nanoparticles. This may restore sufficient acetylcholine hydrolysis to mitigate the effects of poisoning, offsetting the acetylcholine accumulation resulting from enzyme inhibition

New protocol for optimisation of polymer composition for imprinting of peptides and proteins

We present here a novel screening tool for optimisation of polymerisation mixtures used in imprinting of peptides and proteins. To facilitate rapid synthesis and screening of a combinatorial library of polymers the solid-phase synthesis method developed by Piletsky and co-workers was scaled down to 50 mg of template-immobilised solid phase, allowing a single well of a 96-well microplate to function as an individual reaction vessel. In this way, 32 different polymer compositions containing N-isopropylacrylamide, acrylic acid, N-(3-aminopropyl)methacrylamide hydrochloride, and N-tert-butylacrylamide, were tested in imprinting of three peptides and three proteins. Utilising filtration microplates has allowed the elution and washing steps to be performed in a similar manner to the large-scale synthesis, whilst incorporation of a fluorescent monomer (N-fluoresceinylacrylamide) made it possible to analyse the binding of synthesised polymer nanoparticles to the solid phase with immobilised templates under different washing conditions. The experiment has proven that the variations in monomer compositions had an effect on the yield and affinity of synthesised molecularly imprinted polymers for the peptides, but not for the proteins. Imprinting in this way presents an ideal method for performing small-scale syntheses for testing polymerisation mixtures, as information regarding the molecularly imprinted polymers affinity can be assessed as part of the elution process, without a need for time-consuming analysis such as quartz crystal microbalance or surface plasmon resonance