The role of the vestibular system in manual target localization

Astronauts experience perceptual and sensory-motor disturbances during spaceflight and immediately after return to the 1-g environment of Earth. During spaceflight, sensory information from the eyes, limbs and vestibular organs is reinterpreted by the central nervous system so that astronauts can produce appropriate body movements in microgravity. Alterations in sensory-motor function may affect eye-head-hand coordination and, thus, the crewmember's ability to manually locate objects in extrapersonal space. Previous reports have demonstrated that crewmembers have difficulty in estimating joint and limb position and in pointing to memorized target positions on orbit and immediately postflight. One set of internal cues that may assist in the manual localization of objects is information from the vestibular system. This system contributes to our sense of the body's position in space by providing information on head position and movement and the orientation of the body with respect to gravity. Research on the vestibular system has concentrated on its role in oculo-motor control. Little is known about the role that vestibular information plays in manual motor control, such as reaching and pointing movements. Since central interpretation of vestibular information is altered in microgravity, it is important to determine its role in this process. This summer, we determined the importance of vestibular information in a subject's ability to point accurately toward a target in extrapersonal space. Subjects were passively rotated across the earth-vertical axis and then asked to point back to a previously-seen target. In the first paradigm, the subjects used both visual and vestibular cues for the pointing response, while, in the second paradigm, subjects used only vestibular information. Subjects were able to point with 85 percent accuracy to a target using vestibular information alone. We infer from this result that vestibular input plays a role in the spatial programming of manual responses

A quick guide for student-driven community genome annotation

High quality gene models are necessary to expand the molecular and genetic tools available for a target organism, but these are available for only a handful of model organisms that have undergone extensive curation and experimental validation over the course of many years. The majority of gene models present in biological databases today have been identified in draft genome assemblies using automated annotation pipelines that are frequently based on orthologs from distantly related model organisms. Manual curation is time consuming and often requires substantial expertise, but is instrumental in improving gene model structure and identification. Manual annotation may seem to be a daunting and cost-prohibitive task for small research communities but involving undergraduates in community genome annotation consortiums can be mutually beneficial for both education and improved genomic resources. We outline a workflow for efficient manual annotation driven by a team of primarily undergraduate annotators. This model can be scaled to large teams and includes quality control processes through incremental evaluation. Moreover, it gives students an opportunity to increase their understanding of genome biology and to participate in scientific research in collaboration with peers and senior researchers at multiple institutions

Coronary Artery Remodeling in a Model of Left Ventricular Pressure Overload is Influenced by Platelets and Inflammatory Cells

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes\u27 accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1(-/-) mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation

ACTION:a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma

BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.</p

ACTION:a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma

BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.</p

Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience

Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized

Fecal Incontinence in US Adults: Epidemiology and Risk Factors

The study aims were to estimate the prevalence of different types and frequencies of fecal incontinence (FI), describe demographic factors, and identify risk factors

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial