TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections.

In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natural antibodies throughout life. B-1 cells can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections of mice with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 cells in immune defense via BCR-complex reorganization

Role of chondrolectin in motor axon development in zebrafish

Spinal Muscular Atrophy (SMA) is a childhood form of motor neuron disease (MND). It is monogenic, caused by loss of Smn1. Although Smn is ubiquitously expressed in all cells, and acts in a housekeeping function to correctly assemble the spliceosome, motor neurons are specifically vulnerable to loss of Smn. This leads to degeneration of the motor neurons. Mounting evidence shows that this degeneration starts at the neuromuscular junction and then proceeds to the motor axon. Studies have identified chondrolectin as a downstream gene adversely affected by the Smn deficiency. Chondrolectin is mis-spliced pre-symptomatically in mouse models of SMA. The protein is required for motor axon outgrowth in zebrafish, and over-expression of chondrolectin partially rescues smn knockdown. In this project, I generated a CRISPR/Cas9 knockout of chondrolectin in the zebrafish. The mutant is homozygous viable and has no gross morphological defects, but the primary motor axons phenocopy previously published morpholino knockdown. The axons are stalled at a choice point called the horizontal myoseptum, which is known to be rich in ECM proteins such as collagens. Using both acute manipulation and a stable transgenic line, I demonstrate that only full-length chondrolectin is able to rescue the axon length, and loss of any of its protein domains leaves the protein non-functional. From this, we hypothesise a mechanism of action for this protein where it binds an ECM molecule on the axon surface and transduces a signal via phosphorylation of its intracellular domain. We suggest the binding partner for chondrolectin to be collagenXIXa1. SMA has been linked to synaptic defects, therefore, I analysed the synaptic compartments of the axons in the chondrolectin mutant at embryonic and larval stages. At embryonic stages, the pre-synaptic compartment is enlarged around the horizontal myoseptum in the mutant compared to wild-types, and fully rescued in a stable chondrolectin-FLAG line. When the secondary motor neurons have also extended axons to innervate the myotome, there are fewer synaptic puncta in the mutant compared to wild-type. This synapse phenotype is partially rescued in the stable transgenic chondrolectin-FLAG line. Due to the stereotypical phenotype of the chondrolectin mutant, and its relationship with SMA, we developed a drug screening protocol to discover molecules that improve axon growth. We identified two hits after screening a 40-compound library. Developing this protocol allows refinement of potentially useful compounds from larger libraries to use in other models of SMA. Overall, this project offers new insight into the mechanism and function of chondrolectin, a gene linked to SMA. Novel findings include the domain analysis demonstrating that all protein domains are required for its function in zebrafish. We also found that loss of chondrolectin leads to synaptic defects, with embryonic synapse puncta enlarged in the mutant, and a loss of synaptic puncta in the larval stage. Finally, we have demonstrated potential translational uses for this mutant by designing a protocol to identify axon growth-enhancing compounds

Longer Electromechanical Delay Impairs Hamstrings Explosive Force versus Quadriceps

Introduction Explosive neuromuscular performance refers to the ability to rapidly increase force in response to neuromuscular activation. The lower explosive force production of the hamstrings relative to the quadriceps could compromise knee joint stability and increase the risk of anterior cruciate ligament injury. However, the time course of the rise in explosive force of the hamstrings and quadriceps from their initial activation, and thus the explosive hamstrings-to-quadriceps (H/Q) force ratio, has not been documented.Methods The neuromuscular performance of 20 untrained males was assessed during a series of isometric knee flexion and extension contractions, with force and surface EMG of the hamstrings and quadriceps recorded during explosive and maximum voluntary contractions. Hamstrings force was expressed relative to quadriceps force to produce hamstring-to-quadriceps ratios of explosive H/Q force and H/Q maximum voluntary force. For the explosive contractions, agonist electromechanical delay (EMD), agonist and antagonist neural activation were assessed.Results The quadriceps was 79% stronger than the hamstrings, but quadriceps explosive force was up to 480% greater than the hamstrings from 25 to 50 ms after first activation. Consequently, the explosive H/Q force ratio was very low at 25 and 50 ms (0%–17%) and significantly different from H/Q maximum voluntary force ratio (56%). Hamstrings EMD was 95% greater than quadriceps EMD (44.0 vs 22.6 ms), resulting in a 21-ms later onset of force in the hamstrings that appeared to explain the low explosive H/Q force ratio in the early phase of activation.Conclusions Prolonged hamstrings EMD appears to impair early phase (0–50 ms) explosive force production relative to the quadriceps and may render the knee unstable and prone to anterior cruciate ligament injury during this period

Social Support and Perceptions of COVID-19-Related Emotional Impact on Mental Health Among Early Adolescents in Appalachia

Background: Young people who experience higher levels of social support from their schools and families have been shown to be less likely to develop symptoms of negative mental health outcomes such as depression and anxiety.1–4 This raises questions concerning how young people\u27s stress and psychological changes due to the COVID-19 pandemic as well as social support during this time have affected their overall mental health. The aim of this study was to assess the association between sources of parental- and school-level social support and youth perceptions of COVID-19-related emotional impact on mental health among early adolescent girls and boys in Appalachia. Methods: Using linear regression, we analyzed the first and third wave of survey data from the larger parent study (Young Mountaineer Health Study) cohort, collected in 20 middle schools throughout West Virginia in the fall of 2020 and fall of 2021 (N = 1349, mean age: 11.5, response rate: 80.7%). Results: Approximately half of participants reported knowing someone that had been sick with COVID-19. Those experiencing higher levels of perceived COVID-19-related emotional impact reported greater levels of depression, anxiety, and anger. Both parental and school-level social support were associated with better mental health outcomes. Conclusions: Early adolescent perceptions of COVID-19-related emotional impact were associated with depression, anxiety, and anger and moderated by social support at home and in school among 11-12-year-old youth in Appalachia

Improving Mental Health Outcomes for Young Children Through the Implementation of the Primary Project

Primary Project (formerly known as Primary Mental Health Project) is one of the longest standing and wellestablished school-based preventative mental health interventions for addressing the social, emotional, behavioral, and learning needs of preschool through primary grade children. Existing now for over 60 years and building on its historical antecedents, this article describes the history, current state, and future implications of Primary Project. We discuss children’s mental health needs and the role of the school in addressing these needs. We present Primary Project’s current research efforts with a specific focus on University-community studies in Arkansas and Massachusetts. Implications for future research and school based counseling and policy and evaluation are addressed

Ruptured heterotopic pregnancy presenting as hemorrhagic shock

Background: Heterotopic pregnancy is a rare event consisting of simultaneous intrauterine and extrauterine pregnancies. If undiagnosed, it is probable the patient will present to an Emergency Department and require emergent care. Case Report: A 25 year-old woman arrived at the Emergency Department at 14 weeks gestation reporting sharp abdominal cramping and pelvic pain with a history of current tobacco use. Trans-abdominal ultrasound revealed a viable intrauterine pregnancy consistent with 14 weeks, closed cervix with free fluid noted in pelvis, and no evidence of ovarian torsion. Over the next three hours, the patient’s condition deteriorated and hemoglobin levels dropped. The surgeon on call was consulted and suspected ruptured hepatic adenoma versus hepatic hemangioma versus visceral aneurysm. A laparotomy was emergently performed with supraceliac control of aorta to permit resuscitation, and the right and left upper quadrants of the abdominal cavity were investigated without discovery of bleeding source. Further investigation revealed ruptured left tubal ectopic pregnancy and a partial salpingectomy was performed. Conclusions: This case serves as a clinical reminder that while heterotopic pregnancy is thought to be rare, when a patient presents with known intrauterine pregnancy and abdominal pain, heterotopic pregnancy should be included in the differential diagnosis. More common use of assisted reproductive technology may increase the incidence of heterotopic pregnancies, making familiarity with the signs, symptoms, and risk factors for this condition important

Factors shaping the lived experience of resettlement for former refugees in regional Australia

Refugees experience traumatic life events with impacts amplified in regional and rural areasdue to barriers accessing services. This study examined the factors influencing the lived experienceof resettlement for former refugees in regional Launceston, Australia, including environmental,social, and health-related factors. Qualitative interviews and focus groups were conducted withadult and youth community members from Burma, Bhutan, Sierra Leone, Afghanistan, Iran,and Sudan, and essential service providers (n = 31). Thematic analysis revealed four factorsas primarily influencing resettlement: English language proficiency; employment, education andhousing environments and opportunities; health status and service access; and broader socialfactors and experiences. Participants suggested strategies to overcome barriers associated with thesefactors and improve overall quality of life throughout resettlement. These included flexible Englishlanguage program delivery and employment support, including industry-specific language courses;the provision of interpreters; community events fostering cultural sharing, inclusivity and promotingwell-being; and routine inclusion of nondiscriminatory, culturally sensitive, trauma-informed practicesthroughout a former refugee’s environment, including within education, employment, housing andservice settings

Performance Testing of a Novel Off-plane Reflection Grating and Silicon Pore Optic Spectrograph at PANTER

An X-ray spectrograph consisting of radially ruled off-plane reflection gratings and silicon pore optics was tested at the Max Planck Institute for extraterrestrial Physics PANTER X-ray test facility. The silicon pore optic (SPO) stack used is a test module for the Arcus small explorer mission, which will also feature aligned off-plane reflection gratings. This test is the first time two off-plane gratings were actively aligned to each other and with a SPO to produce an overlapped spectrum. The gratings were aligned using an active alignment module which allows for the independent manipulation of subsequent gratings to a reference grating in three degrees of freedom using picomotor actuators which are controllable external to the test chamber. We report the line spread functions of the spectrograph and the actively aligned gratings, and plans for future development.Comment: Draft Version March 19, 201

Origin of Silicic Volcanic Rocks in Central Costa Rica: A Study of a Chemically Variable Ash-Flow Sheet in the Tiribí Tuff

Chemical heterogeneities of pumice clasts in an ash-flow sheet can be used to determine processes that occur in the magma chamber because they represent samples of magma that were erupted at the same time. The dominant ash-flow sheet in the Tiribí Tuff contains pumice clasts that range in composition from 55.1 to 69.2 wt% SiO2. It covers about 820 km2 and has a volume of about 25 km3 dense-rock equivalent (DRE). Based on pumice clast compositions, the sheet can be divided into three distinct chemical groupings: a low-silica group (55.1–65.6 wt% SiO2), a silicic group (66.2–69.2 wt% SiO2), and a mingled group (58.6–67.7 wt% SiO2; all compositions calculated 100% anhydrous). Major and trace element modeling indicates that the low-silica magma represents a mantle melt that has undergone fractional crystallization, creating a continuous range of silica content from 55.1–65.6 wt% SiO2. Eu/Eu*, MREE, and HREE differences between the two groups are not consistent with crystal fractionation of the low-silica magma to produce the silicic magma. The low-silica group and the silicic group represent two distinct magmas, which did not evolve in the same magma chamber. We suggest that the silicic melts resulted from partial melting of relatively hot, evolved calc-alkaline rocks that were previously emplaced and ponded at the base of an over-thickened basaltic crust. The mingled group represents mingling of the two magmas shortly before eruption. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00445-001-0188-8