Do Parents Meet Adolescents’ Monitoring Standards? Examination of the Impact on Teen Risk Disclosure and Behaviors if They Don’t

In this study, we examined how adolescents compare monitoring efforts by their parents to those of a "good parent" standard and assessed the impact of these comparisons on adolescent self-disclosure and risk behavior and their perceptions of their parents'' monitoring knowledge. Survey responses from 519 adolescents (12–17 years) at baseline of a larger, longitudinal study examining parental monitoring and adolescent risk were examined. Adolescents’ “good parent comparisons” differed greatly by monitoring areas (e.g., telephone use, health, money); however, between 5.5% and 25.8% of adolescents believed their parents needed to monitor their activities more than they currently were monitoring. Alternatively, between 8.5% and 23.8% of adolescents believed their parents needed to monitor their activities less often. These perceptions significantly distinguished adolescents in terms of their level of disclosure, perceived monitoring knowledge, and risk involvement. Adolescents who viewed their parents as needing to monitor more were less likely to disclose information to their parents (p<.001), less likely to perceive their parents as having greater monitoring knowledge (p<.001), and more likely to be involved in a risk behaviors (p<.001) than adolescents who perceived their parents needed no change. Adolescent disclosure to a parent is a powerful predictor of adolescent risk and poor health outcomes. These findings demonstrate that adolescents'' comparisons of their parents'' monitoring efforts can predict differences in adolescent disclosure and future risk. Obtaining adolescent "good parent" comparisons may successfully identify intervention opportunities with the adolescent and parent by noting the areas of need and direction of monitoring improvement.     

Haplotyping cryptic Adélie penguin taxa using low-cost,high-resolution melt curves

Distinguishing morphologically cryptic taxa, by definition, requires genetic data such as DNA sequences. However, DNA sequences may not be obtained easily for taxa from remote sites. Here we provide the details of a high-resolution melt-curve-based method using taxon-specific primers that can distinguish two taxa of Adélie penguins, and that will be usable in Antarctica when combined with some of the newly developed field-deployable thermal cyclers. We suggest that the wider adoption of field-deployable polymerase-chain-reaction-based techniques will enable faster assignation of haplotype to individuals in situ, and so allow the targeting of observations and sample collection to specimens relevant to the research question. Targeting individuals will also reduce the need to repeatedly handle animals and reduce the time and travel required to complete field work.     

1,3‐propanediol binds deep inside the channel to inhibit water permeation through aquaporins

Aquaporins and aquaglyceroporins (AQPs) are membrane channel proteins responsible for transport of water and for transport of glycerol in addition to water across the cell membrane, respectively. They are expressed throughout the human body and also in other forms of life. Inhibitors of human AQPs have been sought for therapeutic treatment for various medical conditions including hypertension, refractory edema, neurotoxic brain edema, and so forth. Conducting all‐atom molecular dynamics simulations, we computed the binding affinity of acetazolamide to human AQP4 that agrees closely with in vitro experiments. Using this validated computational method, we found that 1,3‐propanediol (PDO) binds deep inside the AQP4 channel to inhibit that particular aquaporin efficaciously. Furthermore, we used the same method to compute the affinities of PDO binding to four other AQPs and one aquaglyceroporin whose atomic coordinates are available from the protein data bank (PDB). For bovine AQP1, human AQP2, AQP4, AQP5, and Plasmodium falciparum PfAQP whose structures were resolved with high resolution, we obtained definitive predictions on the PDO dissociation constant. For human AQP1 whose PDB coordinates are less accurate, we estimated the dissociation constant with a rather large error bar. Taking into account the fact that PDO is generally recognized as safe by the US FDA, we predict that PDO can be an effective diuretic which directly modulates water flow through the protein channels. It should be free from the serious side effects associated with other diuretics that change the hydro‐homeostasis indirectly by altering the osmotic gradients.     

MHC class I molecules and KIRs in human history, health and survival

MHC class I molecules are ligands for the killer-cell immunoglobulin-like receptors (KIRs), which are expressed by natural killer cells and T cells. The interactions between these molecules contribute to both innate and adaptive immunity. KIRs and MHC class I molecules are encoded by unlinked polymorphic gene families that distinguish all but the most related individuals. Combinations of MHC class I and KIR variants influence resistance to infections, susceptibility to autoimmune diseases and complications of pregnancy, as well as outcome after haematopoietic stem-cell transplantation. Such correlations raise the possibility that interplay between KIR and MHC class I polymorphisms has facilitated human survival in the presence of epidemic infections and has influenced both reproduction and population growth.     

Measurement of hemodynamics in human carotid artery using ultrasound and computational fluid dynamics.

The objective of the study was to investigate the feasibility of using computational fluid dynamic modeling (CFD) with noninvasive ultrasound measurements to determine time-variant three-dimensional (3D) carotid arterial hemodynamics in humans in vivo. The effects of hyperoxia and hypoxic hypercapnia on carotid artery local hemodynamics were examined by use of this approach. Six normotensive volunteers followed a double-blind randomized crossover design. Blood pressure, heart rate, and carotid blood flow were measured while subjects breathed normal air, a mixture of 5% CO(2) and 15% O(2) (hypoxic hypercapnia), and 100% O(2) (hyperoxia). Carotid artery geometry was reconstructed on the basis of B-mode ultrasound images by using purpose-built image processing software. Time-variant 3D carotid hemodynamics were estimated by using finite volume-based CFD. Systemic blood pressure was not significantly affected by hyperoxia or hypoxic hypercapnia, but heart rate decreased significantly with hyperoxia. There was an increase in diastolic flow velocity in the external carotid artery after hypoxic hypercapnia, but otherwise carotid blood flow velocities did not change significantly. Compared with normal air, hyperoxic conditions were associated with a decrease in the width of the region of flow separation in the external carotid artery. During hyperoxia, there was also an increase in the minimum and a decrease in maximum shear stress in the bifurcation and hence a reduction in cyclic variation in shear stress. Hypoxic hypercapnia was associated with a reduced duration of flow separation in the external carotid artery and an increase in the minimum shear stress without affecting the cyclic variation in shear stress. This study demonstrates the feasibility of using noninvasive ultrasound techniques in conjunction with CFD to describe time-variant 3D hemodynamics in the human carotid arterial bifurcation in vivo.     

Reconstructing the Population Genetic History of the Caribbean

The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.     

Brachyspira (Serpulina) hyodysenteriae gyrB mutants and interstrain transfer of coumermycin A(1) resistance

To further develop genetic techniques for the enteropathogen Brachyspira hyodysenteriae, the gyrB gene of this spirochete was isolated from a lambdaZAPII library of strain B204 genomic DNA and sequenced. The putative protein encoded by this gene exhibited up to 55% amino acid sequence identity with GyrB proteins of various bacterial species, including other spirochetes. B. hyodysenteriae coumermycin A(1)-resistant (Cn(r)) mutant strains, both spontaneous and UV induced, were isolated by plating B204 cells onto Trypticase soy blood agar plates containing 0.5 microg of coumermycin A(1)/ml. The coumermycin A(1) MICs were 25 to 100 microg/ml for the resistant strains and 0.1 to 0.25 microg/ml for strain B204. Four Cn(r) strains had single nucleotide changes in their gyrB genes, corresponding to GyrB amino acid changes of Gly(78) to Ser (two strains), Gly(78) to Cys, and Thr(166) to Ala. When Cn(r) strain 435A (Gly(78) to Ser) and Cm(r) Km(r) strain SH (DeltaflaA1::cat Deltanox::kan) were cultured together in brain heart infusion broth containing 10% (vol/vol) heat-treated (56 degrees C, 30 min) calf serum, cells resistant to chloramphenicol, coumermycin A(1), and kanamycin could be isolated from the cocultures after overnight incubation, but such cells could not be isolated from monocultures of either strain. Seven Cn(r) Km(r) Cm(r) strains were tested and were determined to have resistance genotypes of both strain 435A and strain SH. Cn(r) Km(r) Cm(r) cells could not be isolated when antiserum to the bacteriophage-like agent VSH-1 was added to cocultures, and the numbers of resistant cells increased fivefold when mitomycin C, an inducer of VSH-1 production, was added. These results indicate that coumermycin resistance associated with a gyrB mutation is a useful selection marker for monitoring gene exchange between B. hyodysenteriae cells. Gene transfer readily occurs between B. hyodysenteriae cells in broth culture, a finding with practical importance. VSH-1 is the likely mechanism for gene transfer.     

Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation

A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.