Attention or instruction: do sustained attentional abilities really differ between high and low hypnotisable persons?

Previous research has suggested that highly hypnotisable participants (‘highs’) are more sensitive to the bistability of ambiguous figures—as evidenced by reporting more perspective changes of a Necker cube—than low hypnotisable participants (‘lows’). This finding has been interpreted as supporting the hypothesis that highs have more efficient sustained attentional abilities than lows. However, the higher report of perspective changes in highs in comparison to lows may reflect the implementation of different expectation-based strategies as a result of differently constructed demand characteristics according to one’s level of hypnotisability. Highs, but not lows, might interpret an instruction to report perspective changes as an instruction to report many changes. Using a Necker cube as our bistable stimulus, we manipulated demand characteristics by giving specific information to participants of different hypnotisability levels. Participants were told that previous research has shown that people with similar hypnotisability as theirs were either very good at switching or maintaining perspective versus no information. Our results show that highs, but neither lows nor mediums, were strongly influenced by the given information. However, highs were not better at maintaining the same perspective than participants with lower hypnotisability. Taken together, these findings favour the view that the higher sensitivity of highs in comparison to lows to the bistability of ambiguous figures reflect the implementation of different strategies

Combinatorial Polymer Electrospun Matrices Promote Physiologically-Relevant Cardiomyogenic Stem Cell Differentiation

Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques

Intrinsic Thermal Sensing Controls Proteolysis of Yersinia Virulence Regulator RovA

Pathogens, which alternate between environmental reservoirs and a mammalian host, frequently use thermal sensing devices to adjust virulence gene expression. Here, we identify the Yersinia virulence regulator RovA as a protein thermometer. Thermal shifts encountered upon host entry lead to a reversible conformational change of the autoactivator, which reduces its DNA-binding functions and renders it more susceptible for proteolysis. Cooperative binding of RovA to its target promoters is significantly reduced at 37°C, indicating that temperature control of rovA transcription is primarily based on the autoregulatory loop. Thermally induced reduction of DNA-binding is accompanied by an enhanced degradation of RovA, primarily by the Lon protease. This process is also subject to growth phase control. Studies with modified/chimeric RovA proteins indicate that amino acid residues in the vicinity of the central DNA-binding domain are important for proteolytic susceptibility. Our results establish RovA as an intrinsic temperature-sensing protein in which thermally induced conformational changes interfere with DNA-binding capacity, and secondarily render RovA susceptible to proteolytic degradation

Saudi Arabian Y-Chromosome diversity and its relationship with nearby regions

<p>Abstract</p> <p>Background</p> <p>Human origins and migration models proposing the Horn of Africa as a prehistoric exit route to Asia have stimulated molecular genetic studies in the region using uniparental loci. However, from a Y-chromosome perspective, Saudi Arabia, the largest country of the region, has not yet been surveyed. To address this gap, a sample of 157 Saudi males was analyzed at high resolution using 67 Y-chromosome binary markers. In addition, haplotypic diversity for its most prominent J1-M267 lineage was estimated using a set of 17 Y-specific STR loci.</p> <p>Results</p> <p>Saudi Arabia differentiates from other Arabian Peninsula countries by a higher presence of J2-M172 lineages. It is significantly different from Yemen mainly due to a comparative reduction of sub-Saharan Africa E1-M123 and Levantine J1-M267 male lineages. Around 14% of the Saudi Arabia Y-chromosome pool is typical of African biogeographic ancestry, 17% arrived to the area from the East across Iran, while the remainder 69% could be considered of direct or indirect Levantine ascription. Interestingly, basal E-M96* (n = 2) and J-M304* (n = 3) lineages have been detected, for the first time, in the Arabian Peninsula. Coalescence time for the most prominent J1-M267 haplogroup in Saudi Arabia (11.6 ± 1.9 ky) is similar to that obtained previously for Yemen (11.3 ± 2) but significantly older that those estimated for Qatar (7.3 ± 1.8) and UAE (6.8 ± 1.5).</p> <p>Conclusion</p> <p>The Y-chromosome genetic structure of the Arabian Peninsula seems to be mainly modulated by geography. The data confirm that this area has mainly been a recipient of gene flow from its African and Asian surrounding areas, probably mainly since the last Glacial maximum onwards. Although rare deep rooting lineages for Y-chromosome haplogroups E and J have been detected, the presence of more basal clades supportive of the southern exit route of modern humans to Eurasian, were not found.</p

Maternal Fish Consumption and Infant Birth Size and Gestation: New York State Angler Cohort Study

BACKGROUND: The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size. METHODS: 2,716 infants born between 1986–1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1–2, 3–7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age. RESULTS: Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size. CONCLUSIONS: The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size

FLP Recombinase-Mediated Site-Specific Recombination in Silkworm, Bombyx mori

A comprehensive understanding of gene function and the production of site-specific genetically modified mutants are two major goals of genetic engineering in the post-genomic era. Although site-specific recombination systems have been powerful tools for genome manipulation of many organisms, they have not yet been established for use in the manipulation of the silkworm Bombyx mori genome. In this study, we achieved site-specific excision of a target gene at predefined chromosomal sites in the silkworm using a FLP/FRT site-specific recombination system. We first constructed two stable transgenic target silkworm strains that both contain a single copy of the transgene construct comprising a target gene expression cassette flanked by FRT sites. Using pre-blastoderm microinjection of a FLP recombinase helper expression vector, 32 G3 site-specific recombinant transgenic individuals were isolated from five of 143 broods. The average frequency of FLP recombinase-mediated site-specific excision in the two target strains genome was approximately 3.5%. This study shows that it is feasible to achieve site-specific recombination in silkworms using the FLP/FRT system. We conclude that the FLP/FRT system is a useful tool for genome manipulation in the silkworm. Furthermore, this is the first reported use of the FLP/FRT system for the genetic manipulation of a lepidopteran genome and thus provides a useful reference for the establishment of genome manipulation technologies in other lepidopteran species

Translational Systems Biology of Inflammation

Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation. “Systems biology” is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians

Structural Differences between the Streptococcus agalactiae Housekeeping and Pilus-Specific Sortases: SrtA and SrtC1

The assembly of pili on the cell wall of Gram-positive bacteria requires transpeptidase enzymes called sortases. In Streptococcus agalactiae, the PI-1 pilus island of strain 2603V/R encodes two pilus-specific sortases (SrtC1 and SrtC2) and three pilins (GBS80, GBS52 and GBS104). Although either pilus-specific sortase is sufficient for the polymerization of the major pilin, GBS80, incorporation of the minor pilins GBS52 and GBS104 into the pilus structure requires SrtC1 and SrtC2, respectively. The S. agalactiae housekeeping sortase, SrtA, whose gene is present at a different location and does not catalyze pilus polymerization, was shown to be involved in cell wall anchoring of pilus polymers. To understand the structural basis of sortases involved in such diverse functions, we determined the crystal structures of S. agalactiae SrtC1 and SrtA. Both enzymes are made of an eight-stranded beta-barrel core with variations in their active site architecture. SrtA exhibits a catalytic triad arrangement similar to that in Streptococcus pyogenes SrtA but different from that in Staphylococcus aureus SrtA. In contrast, the SrtC1 enzyme contains an N-terminal helical domain and a ‘lid’ in its putative active site, which is similar to that seen in Streptococcus pneumoniae pilus-specific sortases, although with subtle differences in positioning and composition. To understand the effect of such differences on substrate recognition, we have also determined the crystal structure of a SrtC1 mutant, in which the conserved DP(W/F/Y) motif was replaced with the sorting signal motif of GBS80, IPNTG. By comparing the structures of WT wild type SrtA and SrtC1 and the ‘lid’ mutant of SrtC1, we propose that structural elements within the active site and the lid may be important for defining the role of specific sortase in pili biogenesis

Moderate Traumatic Brain Injury Causes Acute Dendritic and Synaptic Degeneration in the Hippocampal Dentate Gyrus

Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI). Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI) induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared. Less research has been focused on these spared neurons, which may also be injured or compromised by TBI. Here we examined the dendrite morphologies, dendritic spines, and synaptic structures using a genetic approach in combination with immunohistochemistry and Golgi staining. We found that although most of the mature granular neurons were spared following TBI at a moderate level of impact, they exhibited dramatic dendritic beading and fragmentation, decreased number of dendritic branches, and a lower density of dendritic spines, particularly the mushroom-shaped mature spines. Further studies showed that the density of synapses in the molecular layer of the hippocampal dentate gyrus was significantly reduced. The electrophysiological activity of neurons was impaired as well. These results indicate that TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration in pathohistology. TBI also impairs the function of the spared mature granular neurons in the hippocampal dentate gyrus. These observations point to a potential anatomic substrate to explain, in part, the development of posttraumatic memory deficits. They also indicate that dendritic damage in the hippocampal dentate gyrus may serve as a therapeutic target following TBI