Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15-30 Hz) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonian-like motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.DP2 NS082126 - NINDS NIH HHS; R01 NS081716 - NINDS NIH HHS; R21 NS078660 - NINDS NIH HHShttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896681/Published versio

The genome and proteome of coliphage T1

AbstractThe genome of enterobacterial phage T1 has been sequenced, revealing that its 50.7-kb terminally redundant, circularly permuted sequence contains 48,836 bp of nonredundant nucleotides. Seventy-seven open reading frames (ORFs) were identified, with a high percentage of small genes located at the termini of the genomes displaying no homology to existing phage or prophage proteins. Of the genes showing homologs (47%), we identified those involved in host DNA degradation (three endonucleases) and T1 replication (DNA helicase, primase, and single-stranded DNA-binding proteins) and recombination (RecE and Erf homologs). While the tail genes showed homology to those from temperate coliphage N15, the capsid biosynthetic genes were unique. Phage proteins were resolved by 2D gel electrophoresis, and mass spectrometry was used to identify several of the spots including the major head, portal, and tail proteins, thus verifying the annotation

Macroscelideans (Myohyracinae and Rhynchocyoninae) from the late Oligocene Nsungwe formation of the Rukwa Rift Basin, southwestern Tanzania

The fossil record of macroscelidean mammals is notoriously patchy, with a significant spatial and temporal gap separating faunas from the early Oligocene localities of northern Africa and the early Miocene localities of eastern and southern Africa. Here we describe fossil macroscelideans representing Myohyracinae and Rhynchocyoninae recovered from a rift-fill sequence of richly fossiliferous sandstones in the late Oligocene Nsungwe Formation in the Rukwa Rift Basin of southwestern Tanzania. Radiometrically dated to 25.2 Ma, a new Palaeogene myohyracine taxon (Rukwasengi butleri) is represented by a partial maxilla (RRBP 05409) preserving a lightly worn M2-M3. The M2 exhibits a less hypsodont and mesiodistally elongate morphology than the early Miocene Myohyrax oswaldi, and the three-rooted M3 exhibits a tiny mesially positioned fossette. A new rhynchocyonine (Oligorhynchocyon songwensis) is represented by specimens more brachyodont than the early Miocene Miorhynchocyon. Taken together these finds document a rare window into macroscelidean evolutionary history with diversification of the group near the Palaeogene-Neogene Transition (PNT). Continued exploration offers a refined perspective on mid-Cenozoic faunal and ecosystem dynamics on continental Africa, expanding opportunities for recognising trends in palaeobiological diversity across habitat types and through time

Correlation of Clinical Neuromusculoskeletal and Central Somatosensory Performance: Variability in Controls and Patients With Severe and Mild Focal Hand Dystonia

Focal hand dystonia (FHd) is a recalcitrant, disabling movement disorder, characterized by involuntary co-contractions of agonists and antagonists, that can develop in patients who overuse or misuse their hands. The aim of this study was to document clinical neuromusculoskeletal performance and somatosensory responses (magnetoencephalography) in healthy controls and in FHd subjects with mild versus severe hand dystonia. The performance of healthy subjects (n = 17) was significantly better than that of FHd subjects (n = 17) on all clinical parameters. Those with mild dystonia (n = 10) demonstrated better musculoskeletal skills, task-specific motor performance, and sensory discrimination, but the performance of sensory and fine motor tasks was slower than that of patients with severe dystonia. In terms of somatosensory evoked field responses (SEFs), FHd subjects demonstrated a significant difference in the location of the hand representation on the x and y axes, lower amplitude of SEFs integrated across latency, and a higher ratio of mean SEF amplitude to latency than the controls. Bilaterally,. those with FHd (mild and severe) lacked progressive sequencing of the digits from inferior to superior. On the affected digits, subjects with severe dystonia had a significantly higher ratio of SEF amplitude to latency and a significantly smaller mean volume of the cortical hand representation than those with mild dystonia. Severity of dystonia positively correlated with the ratio of SEF mean amplitude to latency (0.9029 affected, 0.8477 unaffected; p<0.01). The results of the present study strengthen the evidence that patients with FHd demonstrate signs of somatosensory degradation of the hand that correlates with clinical sensorimotor dysfunction, with characteristics of the dedifferentiation varying by the severity of hand dystonia. If these findings represent aberrant learning, then effective rehabilitation must incorporate the principles of neuroplasticity. Training must be individualized to each patient to rebalance the sensorimotor feedback loop and to restore normal fine motor control

Molecular Basis of Lysosomal Enzyme Recognition: Three-Dimensional Structure of the Cation-Dependent Mannose 6-Phosphate Receptor

AbstractTargeting of newly synthesized lysosomal hydrolases to the lysosome is mediated by the cation-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CI-MPR). The two receptors, which share sequence similarities, constitute the P-type family of animal lectins. We now report the three-dimensional structure of a glycosylation-deficient, yet fully functional form of the extracytoplasmic domain of the bovine CD-MPR (residues 3–154) complexed with mannose 6-phosphate at 1.8 Å resolution. The extracytoplasmic domain of the CD-MPR crystallizes as a dimer, and each monomer folds into a nine-stranded flattened β barrel, which bears a striking resemblance to avidin. The distance of 40 Å between the two ligand-binding sites of the dimer provides a structural basis for the observed differences in binding affinity exhibited by the CD-MPR toward various lysosomal enzymes

The Effects of Continuous Improvement Practices Using State Value-Added Data for Reading Educator Program Enhancement

Louisiana’s value-added evaluation of teacher preparation programs has provided a salient impetus for program improvement; however, due to the nature of the assessment, teacher preparation programs need to use additional sources of data to identify actionable responses to the value-added results. This paper describes one teacher preparation program’s approach to continuous program improvement in reading education and describes some of the limitations and benefits of value-added assessment results for that purpose

Soil Application Effects of Metarhizium anisopliae on Japanese Beetle (Coleoptera: Scarabaeidae) Behavior and Survival in Turfgrass Microcosms

The effect of mycelial and conidial formulations of the insect pathogenic fungi, M. anisopliae, on the survival and behavior Japanese beetle, Popillia japonica Newman, larvae and ovipositing adults in turfgrass-soil microcosms was explored. Changes in Japanese beetle grub feeding site selection on sod roots, movement patterns, and survival in Metarhizium anisopliae inoculated soil were examined in greenhouse studies and through the use of radiographic analysis in the laboratory. Our studies indicate that the application of mycelial particles in soil affected the behavior of both larval and adult Japanese beetles. Japanese beetle grubs avoided soil that contained high concentrations of pathogen for up to 20 d after application. Conversely, the incorporation of mycelial particles increased oviposition in both choice and no choice studies. Our findings on scarab response to inundative applications of M. anisopliae mycelium may help explain some of the inconsistency in results that often occur when fungal pathogens are used to control insects in the fiel

Postcolonial Transplants: Cinema, Diaspora and the Body Politic

This essay examines depictions of migrant workers in French and British postcolonial cinema as transplanted interlopers, 'exotic' or transgendered bodies that are perceived as a threat to the integrity of the body politic

Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes

Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented(1). The absence of crown catarrhine fossils older than similar to 20 million years (Myr) has stood in stark contrast to molecular divergence estimates of similar to 25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades(2-4). Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkey swell into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity(5) in the East African rift system

Evaluation of Coach-Based Technical Assistance: An Evolving Focus on Coachability and Goal Setting

In 2013, the National Institute of Food and Agriculture supported the creation of a professional development and technical assistance center to promote strong implementation and evaluation of University-led, community-based projects serving low-resource populations. Within this center, a coaching cadre was established to provide proactive and responsive technical assistance. Formative evaluation involving coaches and their primary contacts was used for refinement of coaching practices. Initially, coaches were encouraged to build strong interpersonal rapport. This set the stage for trusting, reciprocal interactions, but coaches recognized a need for targeted support and more tools for quality programming, evaluation, and sustainability. Greater emphasis was placed on goal-focused collaboration. Coaches received training and resources on topics such as goal setting, program quality, reduction of barriers (e.g., participant recruitment), and sustainability strategies. To assess coaching model enhancements, a survey of projects was expanded to gauge logic model usage, goal setting, strength of coaching relationships, and project implementation and sustainability progress. Overall, coaching was rated more favorably and effective when contact was consistent, inclusive of face-to-face interaction, met technical needs, and involved collaborative brainstorming and planning. Findings indicate coaching relationships strengthen over time and demand a collaborative, action-orientation to set goals, reduce barriers, and drive stronger outcomes