Duration of sleep inertia after napping during simulated night work and in extended operations

Due to the mixed findings of previous studies, it is still difficult to provide guidance on how to best manage sleep inertia after waking from naps in operational settings. One of the few factors that can be manipulated is the duration of the nap opportunity. The aim of the present study was to investigate the magnitude and time course of sleep inertia after waking from short (20-, 40- or 60-min) naps during simulated night work and extended operations. In addition, the effect of sleep stage on awakening and duration of slow wave sleep (SWS) on sleep inertia was assessed. Two within-subject protocols were conducted in a controlled laboratory setting. Twenty-four healthy young men (Protocol 1: n = 12, mean age = 25.1 yrs; Protocol 2: n = 12, mean age = 23.2 yrs) were provided with nap opportunities of 20-, 40-, and 60-min (and a control condition of no nap) ending at 02:00 h after ～20 h of wakefulness (Protocol 1 [P1]: simulated night work) or ending at 12:00 h after ～30 h of wakefulness (Protocol 2 [P2]: simulated extended operations). A 6-min test battery, including the Karolinska Sleepiness Scale (KSS) and the 4-min 2-Back Working Memory Task (WMT), was repeated every 15 min the first hour after waking. Nap sleep was recorded polysomnographically, and in all nap opportunities sleep onset latency was short and sleep efficiency high. Mixed-model analyses of variance (ANOVA) for repeated measures were calculated and included the factors time (time post-nap), nap opportunity (duration of nap provided), order (order in which the four protocols were completed), and the interaction of these terms. Results showed no test x nap opportunity effect (i.e., no effect of sleep inertia) on KSS. However, WMT performance was impaired (slower reaction time, fewer correct responses, and increased omissions) on the first test post-nap, primarily after a 40- or 60-min nap. In P2 only, performance improvement was evident 45 min post-awakening for naps of 40 min or more. In ANOVAs where sleep stage on awakening was included, the test x nap opportunity interaction was significant, but differences were between wake and non-REM Stage 1/Stage 2 or wake and SWS. A further series of ANOVAs showed no effect of the duration of SWS on sleep inertia. The results of this study demonstrate that no more than 15 min is required for performance decrements due to sleep inertia to dissipate after nap opportunities of 60 min or less, but subjective sleepiness is not a reliable indicator of this effect. Under conditions where sleep is short, these findings also suggest that SWS, per se, does not contribute to more severe sleep inertia. When wakefulness is extended and napping occurs at midday (i.e., P2), nap opportunities of 40- and 60-min have the advantage over shorter duration sleep periods, as they result in performance benefits ～45 min after waking.     

Dynamics of Aerenchyma distribution in the cortex of sulfate-deprived adventitious roots of maize

BACKGROUND AND AIMS: Aerenchyma formation in maize adventitious roots is induced in nutrient solution by the deprivation of sulfate (S) under well-oxygenated conditions. The aim of this research was to examine the extent of aerenchyma formation in the cortex of sulfate-deprived adventitious roots along the root axis, in correlation with the presence of reactive oxygen species (ROS), calcium levels and pH of cortex cells and root lignification. METHODS: The morphometry of the second whorl of adventitious (W2) roots, subject to S-deprivation conditions throughout development, was recorded in terms of root length and lateral root length and distribution. W2 roots divided into sectors according to the mean length of lateral roots, and cross-sections of each were examined for aerenchyma. In-situ detection of alterations in ROS presence, calcium levels and pH were performed by means of fluorescence microscopy using H(2)DCF-DA, fluo-3AM and BCECF, respectively. Lignification was detected using the Wiesner test. KEY RESULTS: S-deprivation reduced shoot growth and enhanced root proliferation. Aerenchyma was found in the cortex of 77 % of the root length, particularly in the region of emerging or developing lateral roots. The basal and apical sectors had no aerenchyma and no aerenchyma connection was found with the shoot. S-deprivation resulted in alterations of ROS, calcium levels and pH in aerenchymatous sectors compared with the basal non-aerenchymatous region. Lignified epidermal layers were located at the basal and the proximal sectors. S-deprivation resulted in shorter lateral roots in the upper sectors and in a limited extension of the lignified layers towards the next lateral root carrying sector. CONCLUSIONS: Lateral root proliferation is accompanied by spatially localized induced cell death in the cortex of developing young maize adventitious roots during S-deprivation.     

Stabilization of a binary protein complex by intein-mediated cyclization

The study of protein-protein interactions can be hampered by the instability of one or more of the protein complex components. In this study, we showed that intein-mediated cyclization can be used to engineer an artificial intramolecular cyclic protein complex between two interacting proteins: the largely unstable LIM-only protein 4 (LMO4) and an unstructured domain of LIM domain binding protein 1 (ldb1). The X-ray structure of the cyclic complex is identical to noncyclized versions of the complex. Chemical and thermal denaturation assays using intrinsic tryptophan fluorescence and dynamic light scattering were used to compare the relative stabilities of the cyclized complex, the intermolecular (or free) complex, and two linear versions of the intramolecular complex (in which the interacting domains of LMO4 and ldb1 were fused, via a flexible linker, in either orientation). In terms of resistance to denaturation, the cyclic complex is the most stable variant and the intermolecular complex is the least stable; however, the two linear intramolecular variants show significant differences in stability. These differences appear to be related to the relative contact order (the average distance in sequence between residues that make contacts within a structure) of key binding residues at the interface of the two proteins. Thus, the restriction of the more stable component of a complex may enhance stability to a greater extent than restraining less stable components.     

Impact of egg harvesting on breeding success of black-headed gulls,Larus ridibundus

Gull colonies world-wide have been harvested for their eggs for centuries with minimal knowledge of the impacts on breeding. Although most Laridae can replace lost eggs, they have comparatively high energetic demands for egg production. In this paper we assess the impacts of a licensed egg harvest on the breeding success of black-headed gulls Larus ridibundus, which nest colonially in an EU Special Protection Area in Hampshire, southern England. We compared egg volume, hatching and chick survival from harvested and un-harvested nests in central and fringe positions within colonies of various sizes, including colonies with no harvesting activity. Eggs from various laying stages were collected from harvested and un-harvested colonies of similar pre-harvest intrinsic quality, for comparison of their volumes, yolk-to-albumen ratios and eggshell thickness. Egg volume and the yolk-to-albumen ratio depended on laying time and location, with the largest eggs laid during the peak period by birds breeding in central positions on large colonies. Eggs produced by these peak layers also had the largest yolk-to-albumen ratios. Harvested sites were characterised by reductions in egg volume, yolk-to-albumen ratio and eggshell thickness, which translated to poorer hatching success and chick survival. Harvested sites also had a higher proportion of abnormal eggs, particularly taking the forms of small yolkless eggs and unpigmented eggs. The reduced breeding success on harvested colonies is likely to be linked to depletion of the female's endogenous reserves which can also reduce future survival and breeding propensity.     

Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships

Background

To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy.

Methods

Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies) and gabapentin (4 studies) over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures) and "change from baseline in seizure-free days over the last 28 days (SFD)". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations.

Results

The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25) and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27). Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg) were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg) in terms of SFD over the last 28 days.

Conclusion

In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.

     

Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics

Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.     

Molecular control of vertebrate limb development, evolution and congenital malformations

The vertebrate limb is a powerful model system for studying the cellular and molecular interactions that determine morphological pattern during embryonic development. Recent advances in our understanding of these interactions have shed new light on the molecular mechanisms of vertebrate limb development, evolution and congenital malformations. The transfer of information has, until recently, been largely one way, with developmental studies informing our understanding of the fossil record and clinical limb anomalies; however, evolutionary and clinical studies are now beginning to shed light onto one another and onto basic developmental processes. In this review, we discuss recent advances in these fields and how they are interacting to improve our understanding of vertebrate limb biology.     

Deletion of one copy of the p16INK4A tumor suppressor gene is implicated as a predisposing factor in pediatric leukemia

The p16INK4A tumor suppressor gene is frequently disrupted by mutation or deletion in a wide range of cancer types, ranging from leukemia to cancers of the bladder, skin, lung, liver, and spleen. We have previously shown that deletion of at least one copy of the p16INK4A gene is associated with an increased risk of relapse in pediatric leukemia. Our data suggest that hemizygous p16INK4A deletion may be constitutional, conferring susceptibility to leukemia. Confirmation of this association is worthy of a larger study. Data from primary leukemia specimens are also presented here which examined the possibility that the remaining allele of the gene was inactivated by another mechanism such as mutation or was silenced by methylation. These possibilities were formally excluded in a case of hemizygous loss of the p16INK4A gene in leukemia, establishing that in this case the p16INK4A deletion was either semidominant or fully haploinsufficient for relapse susceptibility in this disease. Implementation of high throughput methods such as those used here for detecting hemizygous loss of tumor suppressor genes will become increasingly important for molecular diagnosis of cancer. This is particularly true for the emerging class of tumor suppressor genes where deletion of one allele is sufficient to confer cancer susceptibility or poor prognosis with standard treatment.     

Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles

Recently, it has been demonstrated that the human immunodeficiency virus type 1 (HIV-1) Nef from laboratory strains down-modulates cell surface expression of mature major histocompatibility complex class II (MHC-II) molecules, while up-regulating surface expression of the invariant chain (Ii) associated with immature MHC-II (P. Stumptner-Cuvelette, S. Morchoisne, M. Dugast, S. Le Gall, G. Raposo, O. Schwartz, and P. Benaroch, Proc. Natl. Acad. Sci. USA 98:12144-12149, 2001). These Nef functions could contribute to impaired CD4(+)-T-helper-cell responses found in HIV-1-infected patients with progressive disease. However, it is currently unknown whether nef alleles derived from HIV-1-infected individuals or from other primate lentiviruses also modulate MHC-II and Ii. In the present study, we demonstrate that both activities are conserved among primary HIV-1 nef alleles, as well as among HIV-2 and simian immunodeficiency virus (SIV) nef alleles. Down-modulation of mature MHC-II required high levels of Nef expression. In contrast, surface expression of Ii was already strongly increased at low to medium levels of Nef expression. Notably, nef genes derived from two of four HIV-1-infected long-term nonprogressors did not up-regulate Ii, whereas nef alleles derived from 10 individuals with progressive disease were active in this assay. Unlike other in vitro Nef functions, the average activity of Nef in modulating MHC-II and Ii surface expression did not change significantly during the course of infection. Mutational analysis confirmed that MHC-II down- and Ii up-regulation are functionally separable from each other and from other Nef functions and identified acidic residues, located at the base of the flexible C-proximal loop of Nef, that are critical for increased Ii expression. Overall, our results suggest that the ability of Nef to interfere with MHC-II antigen presentation might play a role in AIDS pathogenesis.