Control of landslide retrogression by discontinuities: Evidence by the integration of airbone- and ground-based geophysical information

The objective of this work is to present a multitechnique approach to define the geometry, the kinematics, and the failure mechanism of a retrogressive large landslide (upper part of the La Valette landslide, South French Alps) by the combination of airborne and terrestrial laser scanning data and ground-based seismic tomography data. The advantage of combining different methods is to constrain the geometrical and failure mechanism models by integrating different sources of information. Because of an important point density at the ground surface (4. 1 points m?2), a small laser footprint (0.09 m) and an accurate three-dimensional positioning (0.07 m), airborne laser scanning data are adapted as a source of information to analyze morphological structures at the surface. Seismic tomography surveys (P-wave and S-wave velocities) may highlight the presence of low-seismic-velocity zones that characterize the presence of dense fracture networks at the subsurface. The surface displacements measured from the terrestrial laser scanning data over a period of 2 years (May 2008?May 2010) allow one to quantify the landslide activity at the direct vicinity of the identified discontinuities. An important subsidence of the crown area with an average subsidence rate of 3.07 m?year?1 is determined. The displacement directions indicate that the retrogression is controlled structurally by the preexisting discontinuities. A conceptual structural model is proposed to explain the failure mechanism and the retrogressive evolution of the main scarp. Uphill, the crown area is affected by planar sliding included in a deeper wedge failure system constrained by two preexisting fractures. Downhill, the landslide body acts as a buttress for the upper part. Consequently, the progression of the landslide body downhill allows the development of dip-slope failures, and coherent blocks start sliding along planar discontinuities. The volume of the failed mass in the crown area is estimated at 500,000 m3 with the sloping local base level method.

Diet diversity and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

Diet diversity (defined as the number of different foods consumed) has been considered an indicator of a healthy diet, and favorably related to the risk of several digestive tract cancers. We analyzed the relation between diet diversity and the risk of laryngeal cancer using data from a case-control study carried out between 1992 and 2000 in Italy and Switzerland. The subjects of the study were 527 patients with histologically confirmed incident cancers of the larynx and 1297 patients admitted for acute, non-neoplastic diseases, unrelated to tobacco or alcohol consumption. Total diversity was computed as the number of different foods (overall and within four food groups, i.e., vegetables, fruit, meat, and cereals) consumed at least once per week. A significant inverse association was observed for vegetable diversity (OR=0.41, 95% CI: 0.28-0.59, for the highest versus the lowest quartile) and fruit diversity (OR=0.40, 95% CI: 0.27-0.59). Conversely, a direct association was found for meat diversity (OR=1.67, 95% CI: 1.11-2.50), while no meaningful association was found for total diet and cereal diversity. The results were consistent across strata of age, alcohol drinking and tobacco smoking. This study suggests that a diet not only rich but also varied in fruit and vegetables is related to a decreased risk of laryngeal cancer risk.

Do glial cells control pain?

Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer's and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not only cause neurodegeneration in these disease conditions, but also cause abnormal pain by acting on spinal cord dorsal horn neurons in injury conditions. Pain can also be potentiated by growth factors such as BDNF and bFGF that are produced by glia to protect neurons. Thus, glia cells can powerfully control pain when they are activated to produce various pain mediators. We will review accumulating evidence supporting an important role of microglia cells in the spinal cord for pain control under injury conditions (e.g. nerve injury). We will also discuss possible signaling mechanisms in particular MAP kinase pathways that are critical for glia control of pain. Investigating signaling mechanisms in microglia may lead to more effective management of devastating chronic pain.

ENaC and its regulatory proteins as drug targets for blood pressure control.

Hypertension is a serious medical problem affecting millions of people worldwide. A key protein regulating blood pressure is the Epithelial Na(+) Channel (ENaC). In accord, loss of function mutations in ENaC (PHA1) cause hypotension, whereas gain of function mutations (Liddle syndrome) result in hypertension. The region mutated in Liddle syndrome, called the PY motif (L/PPxY), serves as a binding site for the ubiquitin ligase Nedd4-2, a C2-WW-Hect E3 ubiquitin ligase. Nedd4-2 binds the ENaC-PY motif via it WW domains, ubiquitylates the channel and targets it for endocytosis, a process impaired in Liddle syndrome due to poor binding of the channel to Nedd4-2. This leads to accumulation of active channels at the cell surface and increased Na(+) (and fluid) absorption in the distal nephron, resulting in elevated blood volume and blood pressure. Compounds that destabilize cell surface ENaC, or enhance Nedd4-2 activity in the kidney, could potentially serve as drug targets for hypertension. In addition, recent discoveries of regulation of activation of ENaC by proteases such as furin, prostasin and elastase, which cleave the extracellular domain of this channel leading to it activation, as well as the identification of inhibitors that block the activity of these proteases, provide further avenues for drug targeting of ENaC and the control of blood pressure.

The degradation of HFR1, a putative bHLH class transcription factor involved in light signaling, is regulated by phosphorylation and requires COP1.

All developmental transitions throughout the life cycle of a plant are influenced by light. In Arabidopsis, multiple photoreceptors including the UV-A/blue-sensing cryptochromes (cry1-2) and the red/far-red responsive phytochromes (phyA-E) monitor the ambient light conditions. Light-regulated protein stability is a major control point of photomorphogenesis. The ubiquitin E3 ligase COP1 (constitutively photomorphogenic 1) regulates the stability of several light-signaling components. HFR1 (long hypocotyl in far-red light) is a putative transcription factor with a bHLH domain acting downstream of both phyA and the cryptochromes. HFR1 is closely related to PIF1, PIF3, and PIF4 (phytochrome interacting factor 1, 3 and 4), but in contrast to the latter three, there is no evidence for a direct interaction between HFR1 and the phytochromes. Here, we show that the protein abundance of HFR1 is tightly controlled by light. HFR1 is an unstable phosphoprotein, particularly in the dark. The proteasome and COP1 are required in vivo to degrade phosphorylated HFR1. In addition, HFR1 can interact with COP1, consistent with the idea of COP1 directly mediating HFR1 degradation. We identify a domain, conserved among several bHLH class proteins involved in light signaling , as a determinant of HFR1 stability. Our physiological experiments indicate that the control of HFR1 protein abundance is important for a normal de-etiolation response.

Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis.

PURPOSE OF REVIEW: The control of glucose and energy homeostasis, including feeding behaviour, is tightly regulated by gut-derived peptidic and nonpeptidic endocrine mediators, autonomic nervous signals, as well as nutrients such as glucose. We will review recent findings on the role of the gastrointestinal tract innervation and of portal vein glucose sensors; we will review selected data on the action of gastrointestinally released hormones. RECENT FINDINGS: The involvement of mechanosensory vagal afferents in postprandial meal termination has been clarified using mouse models with selective impairments of genes required for development of mechanosensory fibres. These activate central glucogen-like peptide-1/glucogen-like peptide-2 containing ascending pathways linking the visceroceptive brainstem neurons to hypothalamic nuclei. Mucosal terminals comprise the chemosensory vagal afferents responsive to postprandially released gastrointestinal hormones. The mechanism by which the hepatoportal glucose sensor stimulates glucose utilization by muscles was demonstrated, using genetically modified mice, to be insulin-independent but to require GLUT4 and AMP-kinase. This sensor is a key site of glucogen-like peptide-1 action and plays a critical role in triggering first phase insulin secretion. PeptideYY and ghrelin target intracerebral receptors as they are bidirectionally transported across the blood brain barrier. The anorectic functions of peripherally released peptideYY may however be mediated both via vagal afferents and intracerebral Y2 receptors in the brainstem and arcuate nucleus. SUMMARY: These recent findings demonstrate that the use of improved anatomical and physiological techniques and animal models with targeted gene modifications lead to an improved understanding of the complex role of gastrointestinal signals in the control of energy homeostasis.

Risk Factors for Anal Cancer in Persons Infected With HIV: A Nested Case-Control Study in the Swiss HIV Cohort Study.

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = â^?, 95% CI: 4.64, â^?) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. â0/00¥500 cells/μL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice.

Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4) is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG) in melanopsin-deficient (Opn4(-/-)) mice under various light-dark (LD) schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz) and gamma (40-70 Hz) activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/-) mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/-) mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN) and in sleep-active ventrolateral preoptic (VLPO) neurons was importantly reduced in Opn4(-/-) mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/-) mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/-) mice for most of the (subjective) dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/-) mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of other light-encoding pathways such as rod and cones. Our study, furthermore, demonstrates that lack of melanopsin alters sleep homeostasis. These findings call for a reevaluation of the role of light on mammalian physiology and behavior.

The role of queen pheromones in social insects: queen control or queen signal?

Queens and workers in social insect colonies can differ in reproductive goals such as colony-level sex allocation and production of males by workers. That the presence of queen(s) often seems to affect worker behaviour in situations of potential conflict has given rise to the idea of queen control over reproduction. In small colonies queen control is possible via direct aggression against workers, but in large colonies queens cannot be effectively aggressive towards all the workers. This, plus evidence that queen-produced chemicals affect worker behaviour, has led to the conclusion that physical intimidation has been replaced by pheromonal queen control, whereby queen(s) chemically manipulate workers into behaving in ways that increase the queen's fitness at the worker's expense. It is argued in this paper, however, that pheromonal queen control has never conclusively been demonstrated and is evolutionarily difficult to justify. Proposed examples of pheromonal control are more likely to be honest signals, with workers' responses increasing their own inclusive fitness. A series of experimental and field studies in which positive results would give prima facie evidence for pheromonal queen control is suggested. Finally, three terms are defined: (1) pheromonal queen control for workers or subordinate queens being chemically manipulated into acting against their own best interests; (2) pheromonal queen signal for situations where workers or subordinate queens react to queen pheromones in ways that increase their, and possibly the queens', inclusive fitness; and (3) pheromonal queen effect where changes in the workers' or subordinate queens' behaviour have an unknown consequence on their inclusive fitness.

Prevalence, awareness, treatment and control of high blood pressure in a Swiss city general population: the CoLaus study.

BACKGROUND: This study is aimed to assess the prevalence of awareness, treatment and control of high blood pressure (HBP) and associated factors in a Swiss city. DESIGN: Population-based cross-sectional study of 6182 participants (52.5% women) aged 35-75 years living in Lausanne, Switzerland. METHODS: HBP was defined as blood pressure >/=140/90 mmHg or current antihypertensive medication. RESULTS: The overall prevalence of HBP was 36% (95% confidence interval: 35-38%). Among participants with HBP, 63% were aware of it. Among participants aware of HBP, 78% were treated, and among those treated, 48% were controlled (BP <140/90 mmHg). In multivariate analysis, HBP prevalence was associated with older age, male sex, low educational level, high alcohol intake, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP awareness was associated with older age, female sex, awareness of diabetes or dyslipidaemia, obesity and parental history of myocardial infarction. HBP control was associated with younger age, higher educational level and no alcohol intake. Alone or in combination, sartans were the most often prescribed antihypertensive medication category (41%), followed by diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium channel blockers. Only 31% of participants treated for HBP were taking >/=2 antihypertensive medications. CONCLUSION: Although more than half of all participants with HBP were aware and more than three-quarters of them received a pharmacological treatment, less than half of those treated were adequately controlled.

Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications.

Because of the emergence of dried blood spots (DBS) as an attractive alternative to conventional venous plasma sampling in many pharmaceutical companies and clinical laboratories, different analytical approaches have been developed to enable automated handling of DBS samples without any pretreatment. Associated with selective and sensitive MS-MS detection, these procedures give good results in the rapid identification and quantification of drugs (generally less than 3 min total run time), which is desirable because of the high throughput requirements of analytical laboratories. The objective of this review is to describe the analytical concepts of current direct DBS techniques and to present their advantages and disadvantages, with particular focus on automation capacity and commercial availability. Finally, an overview of the different biomedical applications in which these concepts could be of major interest will be presented.

Glucose control after severe brain injury.

PURPOSE OF REVIEW: A substantial body of evidence supports the use of intensive insulin therapy in general critical care practice, particularly in surgical intensive care unit patients. The impact of intensive insulin therapy on the outcome of critically ill neurological patients, however, is still controversial. While avoidance of hyperglycemia is recommended in neurointensive care, no recommendations exist regarding the optimal target for systemic glucose control after severe brain injury. RECENT FINDINGS: An increase in brain metabolic demand leading to a deficiency in cerebral extracellular glucose has been observed in critically ill neurological patients and correlates with poor outcome. In this setting, a reduction of systemic glucose below 6 mmol/l with exogenous insulin has been found to exacerbate brain metabolic distress. Recent studies have confirmed these findings while showing intensive insulin therapy to have no substantial benefit on the outcome of critically ill neurological patients. SUMMARY: Questions persist regarding the optimal target for glucose control after severe brain injury. Further studies are needed to analyze the impact of intensive insulin therapy on brain glucose metabolism and outcome of critically ill neurological patients. According to the available evidence, a less restrictive target for systemic glucose control (6-10 mmol/l) may be more appropriate.

Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease.

Variation in the 3' untranslated region (3'UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative to those alleles that escape its binding. The HLA-C 3'UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3'UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease.