Youth in Northern Ireland: Linking Violence Exposure, Emotional Insecurity, and the Political Macrosystem.

Growing up in the aftermath of armed conflict puts youth at a higher risk for psychopathology-particularly in societies like Northern Ireland which continue to be characterized by intergroup tension and cyclical violence. This risk may be heightened during adolescence, when youth are beginning to explore their identities and are becoming more aware of intergroup dynamics in both their immediate communities and the broader society. It is also during this stage when youth increasingly witness or engage in antisocial behavior and sectarian activities.

Integrase-RNA interactions underscore the critical role of integrase in HIV-1 virion morphogenesis.

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional IN multimerization.

Genome-Wide Analysis of Heterogeneous Nuclear Ribonucleoprotein (hnRNP) Binding to HIV-1 RNA Reveals a Key Role for hnRNP H1 in Alternative Viral mRNA Splicing.

Alternative splicing of HIV-1 mRNAs increases viral coding potential and controls the levels and timing of gene expression. HIV-1 splicing is regulated in part by heterogeneous nuclear ribonucleoproteins (hnRNPs) and their viral target sequences, which typically repress splicing when studied outside their native viral context. Here, we determined the location and extent of hnRNP binding to HIV-1 mRNAs and their impact on splicing in a native viral context.

Reduced insulin sensitivity in young, normoglycaemic subjects alters microvascular tissue oxygenation during postocclusive reactive hyperaemia.

New Findings: What is the central question of the study? Are measures of reduced insulin sensitivity in young, normoglycaemic subjects correlated with near-infrared spectroscopy-derived microvascular responsiveness [tissue oxygen saturation reperfusion rate (STO upslope)] during postocclusive reactive hyperaemia? What is the main finding and its importance? A sevenfold range of hepatic insulin sensitivity is significantly correlated (r = 0.44, P = 0.02) with STO upslope after transient tissue ischaemia.

Effect of assuming constant tissue scattering on measured tissue oxygenation values during tissue ischemia and vascular reperfusion.

The purpose of this study was to determine the effects of assuming constant tissue scattering properties on tissue oxygenation measurements during a vascular occlusion test (VOT). Twenty-one subjects (21.8 ± 1.

Insulin resistance and metabolic syndrome criteria in lean, normoglycemic college-age subjects.

Aims: The goal of this study was to determine insulin sensitivity in a fasted state and during an oral glucose tolerance test (OGTT), in normoglycemic (NGT), lean (L) (n = 35) and, for comparison, overweight/obese (OW/O) (n = 9) college-aged subjects.

Materials And Methods: Insulin sensitivity for 44 NGT, normotensive subjects, age 18-26 yrs., was determined by homeostasis model assessment (HOMA-IR) and from Matsuda index (ISI Matsuda).

Nucleotide resolution mapping of influenza A virus nucleoprotein-RNA interactions reveals RNA features required for replication.

Influenza A virus nucleoprotein (NP) association with viral RNA (vRNA) is essential for packaging, but the pattern of NP binding to vRNA is unclear. Here we applied photoactivatable ribonucleoside enhanced cross-linking and immunoprecipitation (PAR-CLIP) to assess the native-state of NP-vRNA interactions in infected human cells. NP binds short fragments of RNA (~12 nucleotides) non-uniformly and without apparent sequence specificity.

Allosteric HIV-1 Integrase Inhibitors Lead to Premature Degradation of the Viral RNA Genome and Integrase in Target Cells.

Recent evidence indicates that inhibition of HIV-1 integrase (IN) binding to the viral RNA genome by allosteric integrase inhibitors (ALLINIs) or through mutations within IN yields aberrant particles in which the viral ribonucleoprotein complexes (vRNPs) are eccentrically localized outside the capsid lattice. These particles are noninfectious and are blocked at an early reverse transcription stage in target cells. However, the basis of this reverse transcription defect is unknown.

HIV-1 Integrase Binds the Viral RNA Genome and Is Essential during Virion Morphogenesis.

While an essential role of HIV-1 integrase (IN) for integration of viral cDNA into human chromosome is established, studies with IN mutants and allosteric IN inhibitors (ALLINIs) have suggested that IN can also influence viral particle maturation. However, it has remained enigmatic as to how IN contributes to virion morphogenesis. Here, we demonstrate that IN directly binds the viral RNA genome in virions.

Relationship between brachial artery blood flow and total [hemoglobin+myoglobin] during post-occlusive reactive hyperemia.

The associations between macrovascular and microvascular responses reported previously during post-occlusive reactive hyperemia have been inconsistent. The purpose of this study was therefore to determine the temporal relationship between the reactive hyperemic responses within a conduit artery and the downstream microvessels. Conduit artery blood flow was measured in the brachial artery with pulsed Doppler ultrasound.

Characterizing near-infrared spectroscopy responses to forearm post-occlusive reactive hyperemia in healthy subjects.

During post-occlusive reactive hyperemia (PORH) there is a temporary increase in the total hemoglobin + myoglobin (T[Hb+Mb]) signal as measured by near-infrared spectroscopy (NIRS). This transient increase predicts differences in the kinetic responses of deoxy[Hb+Mb] and oxy[Hb+Mb] during PORH. The purpose of this study was to determine whether sigmoidal (Gompertz or logistic) or exponential functions better describe these response curves during PORH.

Effects of a high-fat meal on pulmonary function in healthy subjects.

Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.

Matching of blood flow to metabolic rate during recovery from moderate exercise in humans.

It is unclear whether measurement of limb or conduit artery blood flow during recovery from exercise provides an accurate representation of flow to the muscle capillaries where gas exchange occurs. To investigate this, we: (a) examined the kinetic responses of femoral artery blood flow (QFA), estimated muscle capillary blood flow (Qcap) and estimated muscle oxygen uptake (VO2m) following cessation of exercise; and (b) compared these responses to verify the adequacy of O2 delivery during recovery. Pulmonary VO2 (VO2p) was measured breath by breath, QFA was measured using Doppler ultrasonography, and deoxy-haemoglobin/myoglobin (deoxy-[Hb/Mb]) was estimated by near-infrared spectroscopy over the rectus femoris in nine healthy subjects during a series of transitions from moderate knee-extension exercise to rest.

Muscle microvascular hemoglobin concentration and oxygenation within the contraction-relaxation cycle.

Inability to directly measure microvascular oxygen distribution and extraction in striated muscle during a contraction/relaxation cycle limits our understanding of oxygen transport to and utilization by contracting muscle. We examined muscle microvascular hemoglobin concentration (total [Hb/Mb]) and oxygenation within the contraction-relaxation cycle to determine if microvascular RBC volume would be preserved and if oxygen extraction continued during the actual contraction phase. Eight subjects performed dynamic knee extension exercise (40 contractions/min) at moderate ( approximately 30% of peak work rate) and heavy ( approximately 80% of peak) work rates.

Effects of inspiratory muscle training on exercise responses in normoxia and hypoxia.

The purpose of this study was to determine the effects of inspiratory muscle training (IMT) on exercise in hypoxia (H) and normoxia (N). A 4-week IMT program was implemented with 12 healthy subjects using an inspiratory muscle trainer set at either 15% (C; n=5) or 50% (IMT; n=7) maximal inspiratory mouth pressure (PImax). Two treadmill tests (85% VO2max) to exhaustion and measures of diaphragm thickness (Tdi) and function were completed before and after training in H and N.

Human femoral artery and estimated muscle capillary blood flow kinetics following the onset of exercise.

The purpose of this study was to compare the kinetics of estimated capillary blood flow (Qcap) to those of femoral artery blood flow (QFA) and estimated muscle oxygen uptake (VO2m). Nine healthy subjects performed a series of transitions from rest to moderate (below estimated lactate threshold, 6 min bouts) knee extension exercise. Pulmonary oxygen uptake (VO2) was measured breath by breath, (QFA) was measured continuously using Doppler ultrasound, and deoxyhaemoglobin ([HHb]) was estimated by near-infrared spectroscopy over the rectus femoris throughout the tests.

Effects of pedal frequency on estimated muscle microvascular O2 extraction.

An increase in muscle contraction frequency could limit muscle blood flow QM compromising the matching of QM and muscle oxygen uptake VO2M. This study examined the effects of pedal cadence on skeletal muscle oxygenation at low, moderate and peak exercise. Nine healthy subjects [24.

Kinetics of estimated human muscle capillary blood flow during recovery from exercise.

The kinetic characteristics of muscle capillary blood flow (Qcap) during recovery from exercise are controversial (e.g. one versus two phases).

Dynamics of skeletal muscle oxygenation during sequential bouts of moderate exercise.

In rat muscle, faster dynamics of microvascular P(O2) (approximately blood flow (Q(m) to O2 uptake (V(O2) ratio) after prior contractions that did not alter blood [lactate] have been considered to be a consequence of faster V(O2) kinetics. However, in humans, prior exercise below the lactate threshold does not affect the pulmonary V(O2) kinetics. To clarify this apparent discrepancy, we examined the effects of prior moderate exercise on the kinetics of muscle oxygenation (deoxyhaemoglobin, [HHb] alpha V(O2m)/Q(m)) and pulmonary V(O2) (V(O2p) in humans.

Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy.

The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q(cap)) and muscle O(2) uptake (Vo(2)(m)) in the microcirculation. The purposes of the present study were to estimate the time course of Q(cap) from the kinetics of the primary component of pulmonary O(2) uptake (Vo(2)(p)) and [HHb] throughout exercise, and compare the Q(cap) kinetics with the Vo(2)(p) kinetics. Nine subjects performed moderate- (M; below lactate threshold) and heavy-intensity (H, above lactate threshold) constant-work-rate tests.

Muscle contraction-blood flow interactions during upright knee extension exercise in humans.

To test for evidence of a muscle pump effect during steady-state upright submaximal knee extension exercise, seven male subjects performed seven discontinuous, incremental exercise stages (3 min/stage) at 40 contractions/min, at work rates ranging to 60-75% peak aerobic work rate. Cardiac cycle-averaged muscle blood flow (MBF) responses and contraction-averaged blood flow responses were calculated from continuous Doppler sonography of the femoral artery. Net contribution of the muscle pump was estimated by the difference between mean exercise blood flow (MBFM) and early recovery blood flow (MBFR).