[["Crystal-structure and biochemical characterization of recombinant human calcyphosine delineates a novel EF-hand-containing protein family.\nCalcyphosine is an EF-hand protein involved in both Ca(2+)-phosphatidylinositol and cyclic AMP signal cascades, as well as in other cellular functions. The crystal structure of Ca(2+)-loaded calcyphosine was determined up to 2.65 A resolution and reveals a protein containing two pairs of Ca(2+)-binding EF-hand motifs. Calcyphosine shares a highly similar overall topology with calmodulin. However, there are striking differences between EF-hand 4, both N-terminal and C-terminal regions, and interdomain linkers. The C-terminal domain of calcyphosine possesses a large hydrophobic pocket in the presence of calcium ions that might be implicated in ligand binding, while its N-terminal hydrophobic pocket is almost shielded by an additional terminal helix. Calcyphosine is largely monomeric, regardless of the presence of Ca(2+). Differences in structure, oligomeric state in the presence and in the absence of Ca(2+), a highly conserved sequence with low similarity to other proteins, and phylogeny define a new EF-hand-containing family of calcyphosine proteins that extends from arthropods to humans."],["Green kiwifruit modulates the colonic microbiota in growing pigs.\nTo investigate whether green kiwifruit modulates the composition of colonic microbiota in growing pigs. Thirty-two pigs were fed the control diet or one of the three test diets containing either cellulose, freeze-dried kiwifruit or kiwifruit fibre as the sole fibre source for 14-day study. A Ward's dendrogram of similarity cluster analysis on PCR-DGGE gels revealed that inclusion of freeze-dried kiwifruit and kiwifruit fibre into diets altered the bacterial community, indicating the presence of two distinct clusters. Quantification of different bacterial groups by qPCR demonstrated that pigs fed the freeze-dried kiwifruit or kiwifruit fibre diets had a significantly higher number (P < 0\u00b705) of total bacteria and Bacteroides group and a lower number of Enterobacteria and Escherichia coli group, as well as a greater ratio of Lactobacillus to Enterobacteria when compared to pigs fed the control or cellulose diets. Green kiwifruit, mainly because of fibre, modulated the colonic microbiota, leading to an improved intestinal environment in growing pigs. This is the first report regarding the effect of green kiwifruit on gut microbiota using the in vivo pig model. These results provide the first evidence of interaction between green kiwifruit and colonic microbiota."],["Increase of stability in external fracture fixation by hydroxyapatite-coated bone screws.\nA major problem in fracture treatment by external fixation is screw loosening, which often results in reduced stability and can lead to prolonged treatment. A load-carrying experiment was conducted to determine whether coating implants with bioactive hydroxyapatite (HA) increases screw stability. Twelve HA-coated ASIF screws with 3 different macroporosities were inserted in 12 sheep that had already been fitted with a 6-pin external fixator for the treatment of a tibial osteotomy. The same number of uncoated polished steel screws served as controls. Although initial stability was not different for HA-coated screws, average removal torque after a 9-week implantation period increased with increasing macroporosity of the HA coating (p < .002). Instability of some screws was accompanied by histologic findings of cartilagenous tissue and proliferation of periosteal callus. Near the threads in the tibial cortex and in the shaft area of the screw were seen large numbers of HA particles that had been sheared off during implantation as well as during screw removal because of high contact forces between the HA coating and bone. Particulate debris of HA particles as well as the release of small bone fragments during explanation is likely to be unavoidable since HA adherence to bone is greater than adherence to steel after several weeks of implantation."],["Interfering with free recall of words: Detrimental effects of phonological competition.\nWe examined the effect of different distracting tasks, performed concurrently during memory retrieval, on recall of a list of words. By manipulating the type of material and processing (semantic, orthographic, and phonological) required in the distracting task, and comparing the magnitude of memory interference produced, we aimed to infer the kind of representation upon which retrieval of words depends. In Experiment 1, identifying odd digits concurrently during free recall disrupted memory, relative to a full attention condition, when the numbers were presented orthographically (e.g. nineteen), but not numerically (e.g. 19). In Experiment 2, a distracting task that required phonological-based decisions to either word or picture material produced large, but equivalent effects on recall of words. In Experiment 3, phonological-based decisions to pictures in a distracting task disrupted recall more than when the same pictures required semantically-based size estimations. In Experiment 4, a distracting task that required syllable decisions to line drawings interfered significantly with recall, while an equally difficult semantically-based color-decision task about the same line drawings, did not. Together, these experiments demonstrate that the degree of memory interference experienced during recall of words depends primarily on whether the distracting task competes for phonological representations or processes, and less on competition for semantic or orthographic or material-specific representations or processes."],["Examining young children's social competence using functional ability profiles.\nTo explore the use of International Classification of Functioning, Disability, and Health for Children and Youth (ICF-CY) based profiles of children's functional abilities in relation to their social competence. Subgroups based on shared profiles of functional ability were investigated as an alternative or complement to subgroups defined by disability categories. Secondary analysis of a nationally representative data set of young children identified for special education services in the United States was used for the present study. Using five subgroups of children with shared profiles of functional ability, derived from latent class analysis in previous work, regression analyses were used to examine the relationships between social competence and functional abilities profile subgroup membership. Differences among the subgroups were examined using standardized effect sizes. R2 values were used to examine explained variance in social competence in relation to subgroup membership, disability category, and these variables in combination. Functional ability profile subgroup membership was moderately related to children's social competence outcomes: social skills and problem behaviors. Effect sizes showed significant differences between subgroups. Subgroup membership accounted for more variance in social competence outcomes than disability category. The results provide empirical support for the importance of functional ability profiles when examining social competence within a population of young children with disabilities. Implications for Rehabilitation The extent to which children with disabilities experience difficulty with social competence varies by their functional characteristics. Functional ability profiles can provide practitioners and researchers working young children with disabilities important tools to examine social competence and to inform interventions."],["Chimeric peptides as a vehicle for peptide pharmaceutical delivery through the blood-brain barrier.\nA new strategy for peptide delivery through the brain capillary wall, i.e., the blood-brain barrier (BBB), is the synthesis of chimeric peptides which are formed by the covalent coupling of a non-transportable peptide (e.g., beta-endorphin) to a transportable peptide that undergoes receptor- or absorptive-mediated transcytosis at the BBB. beta-endorphin was covalently coupled via disulfide linkage to cationized albumin (pI greater than or equal to 9) which, owing to it's highly basic charge, undergoes rapid absorptive-mediated transport into brain from blood. The [3H]labeled beta-endorphin-cationized albumin chimera was rapidly taken up by isolated brain capillaries in vitro and by rat brain in vivo; conversely, the BBB uptake of native [3H]beta-endorphin was negligible. The synthesis of chimeric peptides is a new strategy for solving the problem of peptide delivery through the BBB."],["The funny current: cellular basis for the control of heart rate.\nThe 'funny' (pacemaker, I(f)) current, first described almost 30 years ago in sinoatrial node (SAN) myocytes, is a mixed sodium/potassium inward current, activated on hyperpolarisation in the diastolic range of voltages. 'Funny' (f) channels are activated by intracellular cyclic adenosine monophosphate (cAMP) concentrations according to a mechanism mediating regulation of heart rate by the autonomic nervous system, as well as by voltage hyperpolarisation. Structural subunits of native f-channels are the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels; of the four HCN isoforms known, HCN4 is the most highly expressed in SAN tissue. The I(f) current is a natural target in the search for drugs aimed specifically at affecting heart rate, given its function in pacemaking. Increased heart rate has a negative influence on clinical outcome in patients with cardiovascular disease, and indeed is also an established risk factor for cardiovascular and all-cause mortality in the general population. Clearly, therefore, independent reduction of heart rate, through inhibition of the I(f) current, appears to be a suitable therapeutic option for patients with ischaemic heart disease.beta-Adrenoceptor antagonists (beta-blockers) reduce intracellular cAMP levels, and a substantial part of their negative chronotropic effect is therefore attributable to a reduction of the I(f) current. However, neither beta-blockers nor Ca(2+) channel antagonists, both of which have traditionally been used to reduce myocardial ischaemia, are 'pure' heart rate-lowering drugs. These agents may, in fact, have adverse cardiovascular and noncardiovascular effects.Conversely, the novel heart rate-reducing agent ivabradine is a specific blocker of f-channels, hence a selective inhibitor of the pacemaker I(f) current in the SAN. Ivabradine slows heart rate by reducing the I(f) current-regulated steepness of the diastolic depolarisation in SAN myocytes, thereby increasing diastolic duration, without altering action potential duration or causing negative inotropy. As such, ivabradine is particularly useful in patients with chronic stable angina pectoris. Further clinical studies are ongoing to evaluate the efficacy of ivabradine in patients with coronary heart disease, left ventricular dysfunction and heart failure. This short article reviews the current state of knowledge of the properties of the 'funny' current in relation to exploitation of the I(f) function in pacemaking generation and modulation for the pharmacological control of heart rate."],["Rheumatic fever, rheumatic heart disease, and the streptococcal connection: the role of streptococcal antigens cross-reactive with heart tissue.\nThe role of streptococcal infections in initiating the diverse clinical and pathological manifestations of rheumatic fever and rheumatic heart disease is considered in relation to the multiple cross-reactive relations of group A Streptococcus and tissue antigens. Autoantibodies to the following shared antigens have been demonstrated in sera of patients wit rheumatic fever: (1) cardiac, skeletal, and smooth muscle; (2) heart valve fibroblasts; (3) neurons in basal ganglia; and (4) a group A carbohydrate-related determinant in connective tissues. Circulating autoantibodies to these different antigens were present in higher titer or occurred more frequently in patients with rheumatic fever than in those with uncomplicated streptococcal infections. A direct correlation of the presence of these autoantibodies with carditis could not be established. The pathogenetic mechanisms that link streptococcal infection to rheumatic fever and rheumatic heart disease are not yet clear. Among the possibilities to be considered within the above frame of reference are combined cell-mediated and humoral autoimmune mechanisms directed to one or more cross-reactive antigens in the tissues, selective binding of streptococci to tissues, role of circulating immune complexes, and linkage with histocompatibility antigens."],["Spermatic cord abscess with concurrent prostatic abscess involving the seminal vesicle.\nProstatic abscess involving the seminal vesicle has become rare following the development of effective antibiotic treatments. To our knowledge, we report the first case in the English-language literature of a patient with a spermatic cord abscess and a concurrent prostatic abscess. We examined an 81-year-old man for swelling and pain in the left inguinal region and performed computed tomography (CT) that later confirmed the suspected diagnosis of left inguinal hernial strangulation. We performed urgent surgical drainage of a left spermatic cord abscess; and under the correct diagnosis by CT, he was successfully treated further with antibiotics and transperineal drainage of a prostatic abscess extending to the seminal vesicle. We highlight that familiarity with such a rare condition is overwhelmingly essential for patient management and that CT is the most valuable imaging procedure for diagnosing such cases."],["Neurohypophysial hormones and steroidogenesis in the interrenals of Xenopus laevis.\nThe influence of arginine vasotocin (AVT) on the interrenal secretion of the clawed toad (Xenopus laevis) was studied combining in vivo and in vitro experiments. In vivo: A single injection of 3 nmol AVT per 100 g body weight was given, and the concentrations of corticosterone and aldosterone in the serum were measured after 1, 3, 6, 12, and 24 hr. The serum levels of both steroids remained elevated over 6 hr and declined to normal levels within 12 hr. The increase of the aldosterone concentration was relatively stronger than that of corticosterone. In vitro: A perifusion system was used to study the influence of AVT concentrations ranging from 0.1 to 50 nM on the secretion rates of corticosterone and aldosterone. The response of the interrenals was dose dependent; corresponding to the in vivo results, the elevation rate was higher for aldosterone than for corticosterone. The effects of several nonapeptides were compared. AVT was most effective, followed by mesotocin and arginine vasopressin (AVP). Isotocin and oxytocin had less effect. The selective agonist of the mammalian V2 receptor (1-deamino-8-D-arginine)-vasopressin (DDAVP) did not stimulate the interrenals, while the V1 receptor-selective antagonist ((1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)-2-(O-methyl)-tyrosine)-AVP could not diminish the stimulation by AVT. Thus, the AVT receptor of the amphibian interrenal must be a special one and is different from the V1 and V2 types of mammals. In a comparison of the effects of AVT with other stimulators such as ACTH(1-28) or urotensin II, it was found that the sensitivity of the interrenals to AVT was similar to that of these peptides. The results indicate that AVT plays an important role in the osmomineral regulation of Xenopus laevis by acting on the corticosteroid secretion of the interrenals."]]
