Differences in the postexercise threshold for cutaneous active vasodilation between men and women

The purpose of this study was to evaluate the possible differences in the postexercise cutaneous vasodilatory response between men and women. Fourteen subjects (7 men and 7 women) of similar age, body composition, and fitness status remained seated resting for 15 min or cycled for 15 min at 70% of peak oxygen consumption followed by 15 min of seated recovery. Subjects then donned a liquid-conditioned suit. Mean skin temperature was clamped at approximately 34 degrees C for 15 min. Mean skin temperature was then increased at a rate of 4.3 +/- 0.8 degrees C/h while local skin temperature was clamped at 34 degrees C. Skin blood flow was measured continuously at two forearm skin sites, one with (UT) and without (BT) (treated with bretylium tosylate) intact alpha-adrenergic vasoconstrictor activity. The exercise threshold for cutaneous vasodilation in women (37.51 +/- 0.08 degrees C and 37.58 +/- 0.04 degrees C for UT and BT, respectively) was greater than that measured in men (37.33 +/- 0.06 degrees C and 37.35 +/- 0.06 degrees C for UT and BT, respectively) (P < 0.05). Core temperatures were similar to baseline before the start of whole body warming for all conditions. Postexercise heart rate (HR) for the men (77 +/- 4 beats/min) and women (87 +/- 6 beats/min) were elevated above baseline (61 +/- 3 and 68 +/- 4 beats/min for men and women, respectively), whereas mean arterial pressure (MAP) for the men (84 +/- 3 mmHg) and women (79 +/- 3 mmHg) was reduced from baseline (93 +/- 3 and 93 +/- 4 mmHg for men and women, respectively) (P < 0.05). A greater increase in HR and a greater decrease in the MAP postexercise were noted in women (P < 0.05). No differences in core temperature, HR, and MAP were measured in the no-exercise trial. The postexercise threshold for cutaneous vasodilation measured at the UT and BT sites for men (37.15 +/- 0.03 degrees C and 37.16 +/- 0.04 degrees C, respectively) and women (37.36 +/- 0.05 degrees C and 37.42 +/- 0.03 degrees C, respectively) were elevated above no exercise (36.94 +/- 0.07 degrees C and 36.97 +/- 0.05 degrees C for men and 36.99 +/- 0.09 degrees C and 37.03 +/- 0.11 degrees C for women for the UT and BT sites, respectively) (P < 0.05). A difference in the magnitude of the thresholds was measured between women and men (P < 0.05). We conclude that women have a greater postexercise onset threshold for cutaneous vasodilation than do men and that the primary mechanism influencing the difference between men and women in postexercise skin blood flow is likely the result of an altered active vasodilatory response and not an increase in adrenergic vasoconstrictor tone.     

Adaptation for water balance in the partial gastrointestinal tract of summer flounder

Marine teleosts continually drink and absorb water across the intestine to prevent dehydration. Surprisingly, summer flounder that are missing most of their intestine, due to necrotizing enteritis, maintain osmotic homeostasis. Here, we tested the hypothesis that this remnant gastrointestinal tract undergoes compensatory adaptation for fluid uptake. Flounder (Paralicthys dentatus) with a partial gastrointestinal tract had an emaciated liver. Moisture content of muscle however was similar to healthy cohorts with an intact gastrointestinal tract, indicative of an undisturbed osmoregulatory status. Mass-specific rates of fluid uptake across all segments of the partial gastrointestinal tract were less than or similar to rates in corresponding segments from intact flounder. In contrast, weights (percent of body mass) were doubled in stomach and partial intestine of the remnant gastrointestinal tract. Consequently, total capacity for fluid uptake (microL h(-1) g body mass(-1)) was similar for both groups. The functional capacity of the remnant gastrointestinal tract was therefore of a magnitude sufficient to maintain osmoregulatory ability, further evidencing a critical role of the intestine in salt and water balance of marine teleosts.     

Regulation of plasma cholesterol esterification by sphingomyelin: effect of physiological variations of plasma sphingomyelin on lecithin-cholesterol acyltransferase activity

Although sphingomyelin (SM) is the most abundant phospholipid in the plasma, next to phosphatidylcholine (PC), its physiological function in plasma is unclear. Here we employed plasma from various genetic models of mice which naturally differ in their plasma SM/PC ratios, to study the role of SM as a modulator of LCAT, the enzyme responsible for HDL maturation and the synthesis of cholesteryl esters (CE) in normal plasma. Serine palmitoyltransferase deficient mice, and SM synthase deficient mice, both of which have below normal SM/PC ratios, showed significantly elevated LCAT activities when assayed with the endogenous substrates. On the other hand, LDL receptor knockout mice, and apo E knockout mice, both of which have high SM/PC ratios, had markedly reduced (-80%) LCAT activities. The LCAT levels in plasma, as assayed with an exogenous substrate, were similar in all groups, except for a 45% decrease in apo E knockout mice. Plasma samples with high SM/PC ratios had lower percentage of 20:4, 22:5, and 22:6 CE all of which are formed by LCAT, and a higher percentage of the atherogenic 18:1 CE which is mainly derived from the action of liver ACAT, showing that in vivo, the contribution of LCAT to plasma CE is reduced while that of liver ACAT is increased. These results show that SM is a physiological modulator of LCAT activity as well as plasma CE composition, and this may contribute to the previously reported pro-atherogenic effect of high plasma SM levels.     

In Vitro Analysis of the Role of Replication Protein A (RPA) and RPA Phosphorylation in ATR-mediated Checkpoint Signaling

Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair.     

Mutations in HPSE2 Cause Urofacial Syndrome

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.     

Molecular evidence of the survival of subterranean amphipods (Arthropoda) during Ice Age underneath glaciers in Iceland

Two endemic groundwater arthropod crustacean species, Crangonyx islandicus and Crymostygius thingvallensis, were recently discovered on the mid‐Atlantic volcanic island of Iceland. The extent of morphological differences from closest relatives, endemism, along with the geographic isolation of Iceland and its complete coverage by glaciers 21 000 years ago, suggests that these two species have survived glaciation periods in sub‐glacial refugia. Here we provide strong support for this hypothesis by an analysis of mitochondrial genetic variation within Crangonyx islandicus. Our results show that the species is divided into several distinct monophyletic groups that are found along the volcanic zone in Iceland, which have been separated by 0.5 to around 5 million years. The genetic divergence between groups reflects geographic distances between sampling sites, indicating that divergence occurred after the colonization of Iceland. The genetic patterns, as well as the dependency of genetic variation on distances from the tectonic plate boundary and altitude, points to recent expansion from several refugia within Iceland. This presents the first genetic evidence of multicellular organisms as complex as crustacean amphipods which have survived glaciations beneath an ice sheet. This survival may be explained by geothermal heat linked to volcanic activities, which may have maintained favourable habitats in fissures along the tectonic plate boundary in Iceland during glaciations.     

Chromate and selenate hydrocalumite solid solutions and their applications in waste treatment

Hydrocalumite, a calcium aluminate hydrate phase, consists of positively-charged structure units, and is therefore an ideal candidate for accommodating anionic contaminants. In this study, a series of batch experiments was carried out to examine the uptake of chromate and selenate by hydrocalumite. To determine the uptake capacity and long-term stability, hydrocalumite solid solutions between chromate/selenate and hydroxyl were synthesized over a reaction time of more than one year. At a ratio of water to initial solids added (CaAl2O4+CaO) of 75: 1, the maximum uptake capacities were over 77 and 114 g/kg for Cr and Se, respectively.These values are very close to the theoretical uptake capacities of chromate and selenate hydrocalumite end-members (81 and 118 g/kg, respectively). The oxyanion removal efficiency from solution was above 95%. Due to the high uptake capacity and anion removal efficiency of hydrocalumites, their application in wastewater treatment is promising. Hydrocalumites are also important hydration products of cementitious materials and the long-term stability of these phases is of significance for application in solidification/stabilization technology.     

Nonthermoregulatory control of cutaneous vascular conductance and sweating during recovery from dynamic exercise in women.

The purpose of the study was to examine the effect of 1) active (loadless pedaling), 2) passive (assisted pedaling), and 3) inactive (motionless) recovery modes on mean arterial pressure (MAP), cutaneous vascular conductance (CVC), and sweat rate during recovery after 15 min of dynamic exercise in women. It was hypothesized that an active recovery mode would be most effective in attenuating the fall in MAP, CVC, and sweating during exercise recovery. Ten female subjects performed 15 min of cycle ergometer exercise at 70% of their predetermined peak oxygen consumption followed by 20 min of 1) active, 2) passive, or 3) inactive recovery. Mean skin temperature (Tsk), esophageal temperature (Tes), skin blood flow, sweating, cardiac output (CO), stroke volume (SV), heart rate (HR), total peripheral resistance (TPR), and MAP were recorded at baseline, end exercise, and 2, 5, 8, 12, 15, and 20 min postexercise. Cutaneous vascular conductance (CVC) was calculated as the ratio of laser-Doppler blood flow to MAP. In the active recovery mode, CVC, sweat rate, MAP, CO, and SV remained elevated over inactive values (P < 0.05). The passive mode was equally as effective as the active mode in maintaining MAP. Sweat rate was different among all modes after 12 min of recovery (P < 0.05). TPR during active recovery remained significantly lower than during recovery in the inactive mode (P < 0.05). No differences in either Tes or Tsk were observed among conditions. The results indicate that CVC can be modulated by central command and possibly cardiopulmonary baroreceptors in women. However, differences in sweat rate may be influenced by factors such as central command, mechanoreceptor stimulation, or cardiopulmonary baroreceptors.     

Increased levels of invariant natural killer T lymphocytes worsen metabolic abnormalities and atherosclerosis in obese mice

Obesity is a chronic inflammatory state characterized by infiltration of adipose tissue by immune cell populations, including T lymphocytes. Natural killer T (NKT) cells, a specialized lymphocyte subset recognizing lipid antigens, can be pro- or anti-inflammatory. Their role in adipose inflammation continues to be inconclusive and contradictory. In obesity, the infiltration of tissues by invariant NKT (iNKT) cells is decreased. We therefore hypothesized that an excess iNKT cell complement might improve metabolic abnormalities in obesity. Vα14 transgenic (Vα14tg) mice, with increased iNKT cell numbers, on a LDL receptor-deficient (Ldlr^−/−) background and control Ldlr^−/− mice were placed on an obesogenic diet for 16 weeks. Vα14tg.Ldlr^−/− mice gained 25% more weight and had increased adiposity than littermate controls. Transgenic mice also developed greater dyslipidemia, hyperinsulinemia, insulin resistance, and hepatic triglyceride accumulation. Increased macrophage Mac2 immunostaining and proinflammatory macrophage gene expression suggested worsened adipose inflammation. Concurrently, these mice had increased atherosclerotic lesion area and aortic inflammation. Thus, increasing the complement of iNKT cells surprisingly exacerbated the metabolic, inflammatory, and atherosclerotic features of obesity. These findings suggest that the reduction of iNKT cells normally observed in obesity may represent a physiological attempt to compensate for this inflammatory condition.