Emerging role of the KCNT1 Slack channel in intellectual disability

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed IKNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the Fragile X Mental Retardation protein (FMRP) and IKNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal IKNa currents

INVESTIGATIONS OF THE BIOGEOCHEMICAL AND HYDRODYNAMIC IMPACTS OF OPTICAL ATTENUATION BY COLORED DETRITAL MATTER IN AN EARTH SYSTEM MODEL

Light in the surface ocean is necessary for photosynthesis by marine algae. It is also a major source of heating. Visible light diminishes approximately exponentially with increasing depth in the upper ocean. In most of the current generation of Earth System Models used for climate projection, the vertical profile of in-water shortwave radiation is calculated as an exponentially decaying function where the attenuation coefficient is parameterized in terms of phytoplankton photosynthetic pigment (chlorophyll-a) concentration. In doing so, the attenuation of light by all other aquatic constituents is assumed to co-vary with chlorophyll-a concentration. The work in this dissertation presents a revised parameterization for the light attenuation coefficient that varies as a function of chlorophyll-a concentration and the light absorption coefficient for colored detrital matter (CDM). By separating the contribution by CDM, it is free to vary independently. Two ESM model runs were conducted: the experimental run, where the light attenuation coefficient was calculated as a function of both chlorophyll-a concentration and light absorption by CDM and the control run, where the light attenuation coefficient was calculated as a function of chlorophyll-a concentration only. The geographical distribution of light absorption by CDM was prescribed using an ocean color satellite data product using data retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) on the Aqua Earth-observing satellite. The difference between the results of these two model runs showed increased light attenuation by CDM decreased total ocean biological productivity, increased wintertime ice formation and resulted in more extreme sea surface temperatures compared to the control run. These studies are the first global-scale investigations of the biological and hydrodynamic impacts of optical attenuation by CDM in an Earth System Model. They demonstrate the importance of accurately representing light attenuation by independently varying aquatic constituents

Impacts of Water Clarity Variability on Temperature and Biogeochemistry in the Chesapeake Bay

Estuarine water clarity depends on the concentrations of aquatic constituents, such as colored dissolved organic matter, phytoplankton, inorganic suspended solids, and detritus, which are influenced by variations in riverine inputs. These constituents directly affect temperature because when water is opaque, sunlight heats a shallower layer of the water compared to when it is clear. Despite the importance of accurately predicting temperature variability, many numerical modeling studies do not adequately account for this key process. In this study, we quantify the effect of water clarity on heating by comparing two simulations of a hydrodynamic-biogeochemical model of the Chesapeake Bay for the years 2001-2005, in which (1) water clarity is constant in space and time for the computation of solar heating, compared to (2) a simulation where water clarity varies with modeled concentrations of light-attenuating materials. In the variable water clarity simulation, the water is more opaque, particularly in the northern region of the Bay. This decrease in water clarity reduces the total heat, phytoplankton, and nitrate throughout the Bay. During the spring and summer months, surface temperatures in the northern Bay are warmer by 0.1 degrees C and bottom temperatures are colder by 0.2 degrees C in the variable light attenuation simulation. Warmer surface temperatures encourage phytoplankton growth and nutrient uptake near the head of the Bay, and fewer nutrients are transported downstream. These impacts are greater during higher river flow years, when differences in temperature, nutrients, phytoplankton, and zooplankton extend further seaward compared to other years. This study demonstrates the consequences of utilizing different light calculations for estuarine heating and biogeochemistry

Rebels with a Cause: VCU Student Emergency Fund

The project’s mission is to establish a VCU Student Emergency Fund to support the well-being of students who face financial emergencies and to increase student retention and academic success. The fund will provide financial relief to students facing sudden and unexpected financial hardships that can impact their financial stability, academic success, and ability to remain enrolled at VCU. The project will support the work of student support services personnel administering the fund by providing a campus outreach plan to those who can recognize students in financial crises and refer them to the fund\u27s administrators. The project will also support the work of development personnel who will raise money for the fund by providing a donor outreach plan

The Distal Cytoplasmic Tail Of The Influenza A M2 Protein Dynamically Extends From The Membrane

The influenza A M2 protein is a multifunctional membrane-associated homotetramer that orchestrates several essential events in the viral infection cycle. The monomeric subunits of the M2 homotetramer consist of an N-terminal ectodomain, a transmembrane domain, and a C-terminal cytoplasmic domain. The transmembrane domain forms a four-helix proton channel that promotes uncoating of virions upon host cell entry. The membrane-proximal region of the C-terminal domain forms a surface-associated amphipathic helix necessary for viral budding. The structure of the remaining ~34 residues of the distal cytoplasmic tail has yet to be fully characterized despite the functional significance of this region for influenza infectivity. Here, we extend structural and dynamic studies of the poorly characterized M2 cytoplasmic tail. We used SDSL-EPR to collect site-specific information on the mobility, solvent accessibility, and conformational properties of residues 61–70 of the full-length, cell-expressed M2 protein reconstituted into liposomes. Our analysis is consistent with the predominant population of the C-terminal tail dynamically extending away from the membranes surface into the aqueous medium. These findings provide insight into the hypothesis that the C-terminal domain serves as a sensor that regulates how M2 protein participates in critical events in the viral infection cycle

A Method for generating marker-less gene deletions in multidrug-resistant Acinetobacter baumannii

10.1186/1471-2180-13-158BMC Microbiology131581-1

Treatment With Mycophenolate and Cyclophosphamide Leads to Clinically Meaningful Improvements in Patient‐Reported Outcomes in Scleroderma Lung Disease: Results of Scleroderma Lung Study II

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156000/1/acr211125.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156000/2/acr211125_am.pd

Treatment of neonatal infections: a multi-country analysis of health system bottlenecks and potential solutions.

BACKGROUND: Around one-third of the world's 2.8 million neonatal deaths are caused by infections. Most of these deaths are preventable, but occur due to delays in care-seeking, and access to effective antibiotic treatment with supportive care. Understanding variation in health system bottlenecks to scale-up of case management of neonatal infections and identifying solutions is essential to reduce mortality, and also morbidity. METHODS: A standardised bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the development of the Every Newborn Action Plan. Country workshops involved technical experts to complete a survey tool, to grade health system "bottlenecks" hindering scale up of maternal-newborn intervention packages. Quantitative and qualitative methods were used to analyse the data, combined with literature review, to present priority bottlenecks and synthesise actions to improve case management of newborn infections. RESULTS: For neonatal infections, the health system building blocks most frequently graded as major or significant bottlenecks, irrespective of mortality context and geographical region, were health workforce (11 out of 12 countries), and community ownership and partnership (11 out of 12 countries). Lack of data to inform decision making, and limited funding to increase access to quality neonatal care were also major challenges. CONCLUSIONS: Rapid recognition of possible serious bacterial infection and access to care is essential. Inpatient hospital care remains the first line of treatment for neonatal infections. In situations where referral is not possible, the use of simplified antibiotic regimens for outpatient management for non-critically ill young infants has recently been reported in large clinical trials; WHO is developing a guideline to treat this group of young infants. Improving quality of care through more investment in the health workforce at all levels of care is critical, in addition to ensuring development and dissemination of national guidelines. Improved information systems are needed to track coverage and adequately manage drug supply logistics for improved health outcomes. It is important to increase community ownership and partnership, for example through involvement of community groups