CaM-dependent modulation of human Ca1.3 whole-cell and single-channel currents by C-terminal CaMKII phosphorylation site S1475.

Phosphorylation enables rapid modulation of voltage-gated calcium channels (VGCC) in physiological and pathophysiological conditions. How phosphorylation modulates human Ca1.3 VGCC, however, is largely unexplored.

Intestinal Dysbiosis in Carriers of Carbapenem-Resistant .

Infection with carbapenem-resistant (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization.

Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit αδ-1 with thrombospondin-4.

The αδ-1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of αδ-1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain.

Standard pre-travel consultation versus shorter consultation combined with smartphone support: a randomized controlled trial.

Immediate and long-term recalls of a pre-travel consultation are suboptimal. We aimed to assess the role of online consultation for travellers. We randomized travellers into two study groups.

Activated microglia/macrophage whey acidic protein (AMWAP) inhibits NFκB signaling and induces a neuroprotective phenotype in microglia.

Background: Microglia reactivity is a hallmark of neurodegenerative diseases. We have previously identified activated microglia/macrophage whey acidic protein (AMWAP) as a counter-regulator of pro-inflammatory response. Here, we studied its mechanisms of action with a focus on toll-like receptor (TLR) and nuclear factor κB (NFκB) signaling.

The June surprises: balls, strikes, and the fog of war.

At first, few constitutional experts took seriously the argument that the Patient Protection and Affordable Care Act exceeded Congress's power under the commerce clause. The highly political opinions of two federal district judges - carefully chosen by challenging plaintiffs - of no particular distinction did not shake that confidence that the act was constitutional. This disdain for the challengers' arguments was only confirmed when the act was upheld by two highly respected conservative court of appeals judges in two separate circuits.

Structure and dynamics of an Arp2/3 complex-independent component of the lamellipodial actin network.

Sea urchin coelomocytes contain an unusually broad lamellipodial region and have served as a useful model experimental system for studying the process of actin-based retrograde/centripetal flow. In the current study the small molecule drug 2,3-butanedione monoxime (BDM) was employed as a means of delocalizing the Arp2/3 complex from the cell edge in an effort to investigate the Arp2/3 complex-independent aspects of retrograde flow. Digitally-enhanced phase contrast, fluorescence and polarization light microscopy, along with rotary shadow transmission electron microscopy methods demonstrated that BDM treatment resulted in the centripetal displacement of the Arp2/3 complex and the associated dendritic lamellipodial (LP) actin network from the cell edge.

Bipolar, anastral spindle development in artificially activated sea urchin eggs.

The mitotic apparatus of the early sea urchin embryo is the archetype example of a centrosome-dominated, large aster spindle organized by means of the centriole of the fertilizing sperm. In this study, we tested the hypothesis that artificially activated sea urchin eggs possess the capacity to assemble the anastral, bipolar spindles present in many acentrosomal systems. Control fertilized Lytechinus pictus embryos and ammonia-activated eggs were immunolabeled for tubulin, centrosomal material, the spindle pole structuring protein NuMA and the mitotic kinesins MKLP1/Kinesin-6, Eg5/Kinesin-5, and KinI/Kinesin-13.

Evolutionary patterns of non-coding RNAs.

A plethora of new functions of non-coding RNAs (ncRNAs) have been discovered in past few years. In fact, RNA is emerging as the central player in cellular regulation, taking on active roles in multiple regulatory layers from transcription, RNA maturation, and RNA modification to translational regulation. Nevertheless, very little is known about the evolution of this "Modern RNA World" and its components.

A standard, noninvasive monitoring of hematocrit algorithm improves blood pressure control in pediatric hemodialysis patients.

Accurate dry weight assessment is difficult in pediatric hemodialysis patients but is essential to prevent chronic fluid overload, hypertension, and cardiovascular morbidity. A noninvasive monitoring (NIVM) of hematocrit-guided ultrafiltration algorithm was studied prospectively in 20 pediatric hemodialysis patients. The algorithm targeted the first 50% of total goal ultrafiltration to be removed during the first hour of dialysis with a maximum blood volume change of 8 to 12% per hour.

RNAs everywhere: genome-wide annotation of structured RNAs.

Starting with the discovery of microRNAs and the advent of genome-wide transcriptomics, non-protein-coding transcripts have moved from a fringe topic to a central field research in molecular biology. In this contribution we review the state of the art of "computational RNomics", i.e.

The expansion of the metazoan microRNA repertoire.

Background: MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.

Multiple sequence alignments of partially coding nucleic acid sequences.

Background: High quality sequence alignments of RNA and DNA sequences are an important prerequisite for the comparative analysis of genomic sequence data. Nucleic acid sequences, however, exhibit a much larger sequence heterogeneity compared to their encoded protein sequences due to the redundancy of the genetic code. It is desirable, therefore, to make use of the amino acid sequence when aligning coding nucleic acid sequences.

Molecular evolution of duplicated ray finned fish HoxA clusters: increased synonymous substitution rate and asymmetrical co-divergence of coding and non-coding sequences.

In this study the molecular evolution of duplicated HoxA genes in zebrafish and fugu has been investigated. All 18 duplicated HoxA genes studied have a higher non-synonymous substitution rate than the corresponding genes in either bichir or paddlefish, where these genes are not duplicated. The higher rate of evolution is not due solely to a higher non-synonymous-to-synonymous rate ratio but to an increase in both the non-synonymous as well as the synonymous substitution rate.

Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii.

Hox genes code for transcription factors that play a major role in the development of all animal phyla. In invertebrates these genes usually occur as tightly linked cluster, with a few exceptions where the clusters have been dissolved. Only in vertebrates multiple clusters have been demonstrated which arose by duplication from a single ancestral cluster.

Divergence of conserved non-coding sequences: rate estimates and relative rate tests.

In many eukaryotic genomes only a small fraction of the DNA codes for proteins, but the non-protein coding DNA harbors important genetic elements directing the development and the physiology of the organisms, like promoters, enhancers, insulators, and micro-RNA genes. The molecular evolution of these genetic elements is difficult to study because their functional significance is hard to deduce from sequence information alone. Here we propose an approach to the study of the rate of evolution of functional non-coding sequences at a macro-evolutionary scale.

Surveying phylogenetic footprints in large gene clusters: applications to Hox cluster duplications.

Evolutionarily conserved non-coding genomic sequences represent a potentially rich source for the discovery of gene regulatory regions. Since these elements are subject to stabilizing selection they evolve much more slowly than adjacent non-functional DNA. These so-called phylogenetic footprints can be detected by comparison of the sequences surrounding orthologous genes in different species.

Exclusion of repetitive DNA elements from gnathostome Hox clusters.

Despite their homology and analogous function, the Hox gene clusters of vertebrates and invertebrates are subject to different constraints on their structural organization. This is demonstrated by a drastically different distribution of repetitive DNA elements in the Hox cluster regions. While gnathostomes have a strong tendency to exclude repetitive DNA elements from the inside of their Hox clusters, no such trend can be detected in the Hox gene clusters of protostomes.

The shark HoxN cluster is homologous to the human HoxD cluster.

The statistical analysis of phylogenetic footprints in the two known horn shark Hox clusters and the four mammalian clusters shows that the shark HoxN cluster is HoxD-like. This finding implies that the most recent common ancestor of jawed vertebrates had at least four Hox clusters, including those which are orthologous to the four mammalian Hox clusters.

The footprint sorting problem.

Phylogenetic footprints are short pieces of noncoding DNA sequence in the vicinity of a gene that are conserved between evolutionary distant species. A seemingly simple problem is to sort footprints in their order along the genomes. It is complicated by the fact that not all footprints are collinear: they may cross each other.

Bichir HoxA cluster sequence reveals surprising trends in ray-finned fish genomic evolution.

The study of Hox clusters and genes provides insights into the evolution of genomic regulation of development. Derived ray-finned fishes (Actinopterygii, Teleostei) such as zebrafish and pufferfish possess duplicated Hox clusters that have undergone considerable sequence evolution. Whether these changes are associated with the duplication(s) that produced extra Hox clusters is unresolved because comparison with basal lineages is unavailable.

Actin-based centripetal flow: phosphatase inhibition by calyculin-A alters flow pattern, actin organization, and actomyosin distribution.

Previous studies have suggested that the actin-based centripetal flow process in sea urchin coelomocytes is the result of a two-part mechanism, actin polymerization at the cell edge coupled with actomyosin contraction at the cell center. In the present study, we have extended the testing of this two-part model by attempting to stimulate actomyosin contraction via treatment of coelomocytes with the phosphatase inhibitor Calyculin A (CalyA). The effects of this drug were studied using digitally-enhanced video microscopy of living cells combined with immunofluorescent localization and scanning electron microscopy.