Novel gating mechanism of polyamine block in the strong inward rectifier K channel Kir2.1.

Inward rectifying K channels are essential for maintaining resting membrane potential and regulating excitability in many cell types. Previous studies have attributed the rectification properties of strong inward rectifiers such as Kir2.1 to voltage-dependent binding of intracellular polyamines or Mg to the pore (direct open channel block), thereby preventing outward passage of K ions. We have studied interactions between polyamines and the polyamine toxins philanthotoxin and argiotoxin on inward rectification in Kir2.1. We present evidence that high affinity polyamine block is not consistent with direct open channel block, but instead involves polyamines binding to another region of the channel (intrinsic gate) to form a blocking complex that occludes the pore. This interaction defines a novel mechanism of ion channel closure

Dynamo driven accretion discs and dwarf nova eruptions

We explore the consequences of a magnetic dynamo origin for the viscosity in accretion discs, for the structure and evolution of discs in dwarf nova systems. We propose that the rapid cooling that sets in at the end of a dwarf nova eruption acts to inhibit the Balbus-Hawley instability, and thereby to quench dynamo action and so reduce disc viscosity. We demonstrate that a modified disc instability model can reproduce the basic properties of dwarf nova eruptions, as well as some properties of quiescent discs. We also discuss some observational consequences of our model.Comment: uu-encoded gz-compressed Postscript file, 18 pages including 6 figures. ApJ in pres

Patient safety and estimation of renal function in patients prescribed new oral anticoagulants for stroke prevention in atrial fibrillation

OBJECTIVE: In clinical trials of dabigatran and rivaroxaban for stroke prevention in atrial fibrillation (AF), drug eligibility and dosing were determined using the Cockcroft-Gault equation to estimate creatine clearance as a measure of renal function. This cross-sectional study aimed to compare whether using estimated glomerular filtration rate (eGFR) by the widely available and widely used Modified Diet in Renal Disease (MDRD) equation would alter prescribing or dosing of the renally excreted new oral anticoagulants. PARTICIPANTS: Of 4712 patients with known AF within a general practitioner-registered population of 930 079 in east London, data were available enabling renal function to be calculated by both Cockcroft-Gault and MDRD methods in 4120 (87.4%). RESULTS: Of 4120 patients, 2706 were <80 years and 1414 were ≥80 years of age. Among those ≥80 years, 14.9% were ineligible for dabigatran according to Cockcroft-Gault equation but would have been judged eligible applying MDRD method. For those <80 years, 0.8% would have been incorrectly judged eligible for dabigatran and 5.3% would have received too high a dose. For rivaroxaban, 0.3% would have been incorrectly judged eligible for treatment and 13.5% would have received too high a dose. CONCLUSIONS: Were the MDRD-derived eGFR to be used instead of Cockcroft-Gault in prescribing these new agents, many elderly patients with AF would either incorrectly become eligible for them or would receive too high a dose. Safety has not been established using the MDRD equation, a concern since the risk of major bleeding would be increased in patients with unsuspected renal impairment. Given the potentially widespread use of these agents, particularly in primary care, regulatory authorities and drug companies should alert UK doctors of the need to use the Cockcroft-Gault formula to calculate eligibility for and dosing of the new oral anticoagulants in elderly patients with AF and not rely on the MDRD-derived eGFR

Knowledge and practice of hypertensive patients as seen in a tertiary hospital in the middle belt of Nigeria

No Abstract

Assessment of Fertility Status of Soils Supporting Coconut (Cocus nucifera) Cultivation in Western and Central Regions of Ghana

Coconut cultivation is mostly practiced in the Western and Central regions of Ghana. Information on the fertility status of the soils on which coconuts are grown and possible fertilizer recommendation is not common. Sincecoconut yield is generally related to the fertility status of the soil, a study was conducted to evaluate the fertility status of soils supporting coconut in the Western and Central regions. The soils were sampled at three depths, 0–20 cm, 20–40 cm and 40–60 cm at 21 different sites. The soil physical properties do not constitute any major limitation to good coconut growth and yield. Evaluation of the top soil showed that the mean top soil pH was very strongly acidic (4.1 + 0.12) and far below the acceptable limits for good coconut yield. Mean exchangeable acidity [0.57 0.06 cmol(+)kg-1] was relatively high while exchangeable basic cations (Ca, Mg and K) were generally very low. Mean effective cation exchange capacity (ECEC) of 3.1 0.48 cmol (+) kg-1was very low. Mean organic matter status 22.1 1.9 gkg-1 was moderate. Mean available phosphorus of 2.8 0.56 mgkg-1 was very low and one of the major nutrients that will affect coconut yield. Except for soil pH, nutrient levels generally showed a decreasing trend in the order top soil &gt; subsoil &gt; sub-subsoil. The evaluation showed that the soils&nbsp; suffer from multi-nutrient deficiency. Nutrient levels of the soils are low to very low, and will not support good coconut growth and yield. Liming to improve the exchangeable basic cations and pH of the soils is&nbsp; recommended. Use of rock phosphate is also recommended for raising the levels of both phosphorus and some basic cations. Amendments and fertilizers with high K content must also be considered

Retroperitoneal and Genital Lymphangioma Therapeutic Challenges in a Developing Country

Background: Lymphangiomas occur most commonly in the head and neck region, while other sites are rarely affected. A combination of retroperitoneal and genital lymphangioma is very rare indeed. Though congenital, it may persist into adulthood due to missed diagnosis and inadequate or total lack of treatment. Materials and methods: A report of a 22-year-old male student who presented with recurrent multiloculated genital, thigh, groin and retroperitneal lymphangioma. He underwent surgical excision and adjuvant sclerotherapy using ethylene-diamine tetra acetic acid. Results and Conclusions: There was an initial recurrence after surgery which responded satisfactorily to sclerotherapy. Complete surgical excision of lymphangioma may be precluded by vital structures but sclerotherapy produces satisfactory resolution. The difficulties in management with limited facilities for diagnosis and treatment are highlighted

Computational workflow for investigating highly variable genes in single-cell RNA-seq across multiple time points and cell types.

Here, we present a computational approach for investigating highly variable genes (HVGs) associated with biological pathways of interest, across multiple time points and cell types in single-cell RNA-sequencing (scRNA-seq) data. Using public dengue virus and COVID-19 datasets, we describe steps for using the framework to characterize the dynamic expression levels of HVGs related to common and cell-type-specific biological pathways over multiple immune cell types. For complete details on the use and execution of this protocol, please refer to Arora et al.1