What have we learned from two-pore potassium channels? Their molecular configuration and function in the human heart

Two-pore domain potassium channels (K2P) control excitability, stabilize the resting membrane potential below firing threshold, and accelerate repolarisation in different cells. Until now, fifteen different genes for the six K2P channel subfamily were cloned. The pore-forming part is translated from two genes and they are built up from a dimer of two two-unit transmembrane domains functioning with a wide spectrum of physiological profiles. K2P ion channels were discovered in the last two decades and gave novel opportunity to recognize the complex molecular mechanism of the potassium ion flux, and may lead to the design of individual drug targeting in the future. In this review, we summarise the structure, function, channelopathies and pharmacological silhouette of the two-pore potassium channels in the human tissues. In addition, we present the computer model of the partially reconstructed wild type K2P1/TWIK1 lacking the intracellular C and N terminal loop

Smoking in Systemic Sclerosis: a Longitudinal European Scleroderma Trials and Research Group Study

Data on the role of tobacco exposure in systemic sclerosis (SSc) severity and progression are scarce. We aimed to assess the effects of smoking on the evolution of pulmonary and skin manifestations in the EUSTAR database

Dentate total molecular layer interneurons mediate cannabinoid-sensitive inhibition.

Activity of the dentate gyrus, which gates information flow to the hippocampus, is under tight inhibitory regulation by interneurons with distinctive axonal projections, intrinsic and synaptic characteristics and neurochemical identities. Total molecular layer cells (TML-Cs), a class of morphologically distinct GABAergic neurons with axonal projections across the molecular layer, are among the most frequent interneuronal type in the dentate subgranular region. However, little is known about their synaptic and neurochemical properties. We demonstrate that synapses from morphologically identified TML-Cs to dentate interneurons are characterized by low release probability, facilitating short-term dynamics and asynchronous release. TML-Cs consistently show somatic and axonal labeling for the cannabinoid receptor type 1 (CB1 R) yet fail to express cholecystokinin (CCK) indicating their distinctive neurochemical identity. In paired recordings, the release probability at synapses between TML-Cs was increased by the CB1 R antagonist AM251, demonstrating baseline endocannabinoid regulation of TML-C synapses. Apart from defining the synaptic and neurochemical features of TML-Cs, our findings reveal the morphological identity of a class of dentate CB1 R-positive neurons that do not express CCK. Our findings indicate that TML-Cs can mediate cannabinoid sensitive feed-forward and feedback inhibition of dentate perforant path inputs

Detection of equid herpesviruses among different Arabian horse populations in Egypt

Equid herpesviruses (EHVs) threaten equine health and can cause significant economic losses to the equine industry worldwide. Different equid herpesviruses, EHV‐1, EHV‐2, EHV‐4 and EHV5 are regularly detected among horse populations. In Egypt, monitoring is sporadic but EHV‐1 or EHV‐4 have been reported to circulate in the horse population. However, there is a lack of reports related to infection and health status of horses, likely due to the absence of regular diagnostic procedures. In the current study, the circulation of four infectious equid herpesviruses (EHV‐1, EHV‐2, EHV‐4 and EHV‐5) among different Arabian horse populations and donkeys residing the same farm was monitored. Different samples were collected and DNA was extracted and subjected to quantitative (q)‐PCR to detect the four equid herpesviruses using specific primers and probes. Antibody titres against EHV‐1 and EHV‐4 were tested using virus neutralization test and type‐specific ELISA. The results showed that EHV‐1, EHV‐2, EHV‐4 and EHV‐5 are endemic and can be a continuous threat for horses in the absence of vaccination programs and frequent virus reactivation. There is an urgent need for introduction of active regular surveillance measures to investigate the presence of different equid herpesviruses, and other equine viral pathogens, in various horse populations around Egypt and to establish a standardized cataloguing of equine health status

MicroRNAs in Human Pituitary Adenomas

MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers

The hippocampal CA3 region can generate two distinct types of sharp wave-ripple complexes, in vitro.

Hippocampal sharp wave-ripples (SPW-Rs) occur during slow wave sleep and behavioral immobility and are thought to play an important role in memory formation. We investigated the cellular and network properties of SPW-Rs with simultaneous laminar multielectrode and intracellular recordings in a rat hippocampal slice model, using physiological bathing medium. Spontaneous SPW-Rs were generated in the dentate gyrus (DG), CA3 and CA1 regions. These events were characterized by a local field potential gradient (LFPg) transient, increased fast oscillatory activity and increased multiple unit activity (MUA). Two types of SPW-Rs were distinguished in the CA3 region based on their different LFPg and current source density (CSD) pattern. Type 1 (T1) displayed negative LFPg transient in the pyramidal cell layer, and the associated CSD sink was confined to the proximal dendrites. Type 2 (T2) SPW-Rs were characterized by positive LFPg transient in the cell layer, and showed CSD sinks involving both the apical and basal dendrites. In both types, consistent with the somatic CSD source, only a small subset of CA3 pyramidal cells fired, most pyramidal cells were hyperpolarized, while most interneurons increased firing rate before the LFPg peak. Different neuronal populations, with different proportions of pyramidal cells and distinct subsets of interneurons were activated during T1 and T2 SPW-Rs. Activation of specific inhibitory cell subsets - with the possible leading role of perisomatic interneurons - seems to be crucial to synchronize distinct ensembles of CA3 pyramidal cells finally resulting in the expression of different SPW-R activities. This suggests that the hippocampus can generate dynamic changes in its activity stemming from the same excitatory and inhibitory circuits, and so, might provide the cellular and network basis for an input-specific and activity-dependent information transmission. (c) 2014 Wiley Periodicals, Inc