Molecular bases of circadian rhythmicity in renal physiology and pathology.

The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental-social cues and physiological-behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time-dependent changes in renal pathology.

Verbal labels selectively bias brain responses to high-energy foods.

The influence of external factors on food preferences and choices is poorly understood. Knowing which and how food-external cues impact the sensory processing and cognitive valuation of food would provide a strong benefit toward a more integrative understanding of food intake behavior and potential means of interfering with deviant eating patterns to avoid detrimental health consequences for individuals in the long run. We investigated whether written labels with positive and negative (as opposed to 'neutral') valence differentially modulate the spatio-temporal brain dynamics in response to the subsequent viewing of high- and low-energetic food images. Electrical neuroimaging analyses were applied to visual evoked potentials (VEPs) from 20 normal-weight participants. VEPs and source estimations in response to high- and low- energy foods were differentially affected by the valence of preceding word labels over the ~260-300 ms post-stimulus period. These effects were only observed when high-energy foods were preceded by labels with positive valence. Neural sources in occipital as well as posterior, frontal, insular and cingulate regions were down-regulated. These findings favor cognitive-affective influences especially on the visual responses to high-energetic food cues, potentially indicating decreases in cognitive control and goal-adaptive behavior. Inverse correlations between insular activity and effectiveness in food classification further indicate that this down-regulation directly impacts food-related behavior.

Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.

Inflammasomes are caspase-1-activating multiprotein complexes. The mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome was identified as the sensor of Bacillus anthracis lethal toxin (LT) in mouse macrophages from sensitive strains such as BALB/c. Upon exposure to LT, the NLRP1b inflammasome activates caspase-1 to produce mature IL-1β and induce pyroptosis. Both processes are believed to depend on autoproteolysed caspase-1. In contrast to human NLRP1, mouse NLRP1b lacks an N-terminal pyrin domain (PYD), indicating that the assembly of the NLRP1b inflammasome does not require the adaptor apoptosis-associated speck-like protein containing a CARD (ASC). LT-induced NLRP1b inflammasome activation was shown to be impaired upon inhibition of potassium efflux, which is known to play a major role in NLRP3 inflammasome formation and ASC dimerization. We investigated whether NLRP3 and/or ASC were required for caspase-1 activation upon LT stimulation in the BALB/c background. The NLRP1b inflammasome activation was assessed in both macrophages and dendritic cells lacking either ASC or NLRP3. Upon LT treatment, the absence of NLRP3 did not alter the NLRP1b inflammasome activity. Surprisingly, the absence of ASC resulted in IL-1β cleavage and pyroptosis, despite the absence of caspase-1 autoprocessing activity. By reconstituting caspase-1/caspase-11(-/-) cells with a noncleavable or catalytically inactive mutant version of caspase-1, we directly demonstrated that noncleavable caspase-1 is fully active in response to the NLRP1b activator LT, whereas it is nonfunctional in response to the NLRP3 activator nigericin. Taken together, these results establish variable requirements for caspase-1 cleavage depending on the pathogen and the responding NLR.

Cadmium-free quantum dots in aqueous solution: potential for fingermark detection, synthesis and an application to the detection of fingermarks in blood on non-porous surfaces

The use of quantum dots (QDs) in the area of fingermark detection is currently receiving a lot of attention in the forensic literature. Most of the research efforts have been devoted to cadmium telluride (CdTe) quantum dots often applied as powders to the surfaces of interests. Both the use of cadmium and the nano size of these particles raise important issues in terms of health and safety. This paper proposes to replace CdTe QDs by zinc sulphide QDs doped with copper (ZnS:Cu) to address these issues. Zinc sulphide-copper doped QDs were successfully synthesized, characterized in terms of size and optical properties and optimized to be applied for the detection of impressions left in blood, where CdTe QDs proved to be efficient. Effectiveness of detection was assessed in comparison with CdTe QDs and Acid Yellow 7 (AY7, an effective blood reagent), using two series of depletive blood fingermarks from four donors prepared on four non-porous substrates, i.e. glass, transparent polypropylene, black polyethylene and aluminium foil. The marks were cut in half and processed separately with both reagents, leading to two comparison series (ZnS:Cu vs. CdTe, and ZnS:Cu vs. AY7). ZnS:Cu proved to be better than AY7 and at least as efficient as CdTe on most substrates. Consequently, copper-doped ZnS QDs constitute a valid substitute for cadmium-based QDs to detect blood marks on non-porous substrates and offer a safer alternative for routine use.

Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium.

Background The association between dietary patterns and head and neck cancer has rarely been addressed. Patients and methods We used individual-level pooled data from five case-control studies (2452 cases and 5013 controls) participating in the International Head and Neck Cancer Epidemiology consortium. A posteriori dietary patterns were identified through a principal component factor analysis carried out on 24 nutrients derived from study-specific food-frequency questionnaires. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional logistic regression models on quintiles of factor scores. Results We identified three major dietary patterns named 'animal products and cereals', 'antioxidant vitamins and fiber', and 'fats'. The 'antioxidant vitamins and fiber' pattern was inversely related to oral and pharyngeal cancer (OR = 0.57, 95% CI 0.43-0.76 for the highest versus the lowest score quintile). The 'animal products and cereals' pattern was positively associated with laryngeal cancer (OR = 1.54, 95% CI 1.12-2.11), whereas the 'fats' pattern was inversely associated with oral and pharyngeal cancer (OR = 0.78, 95% CI 0.63-0.97) and positively associated with laryngeal cancer (OR = 1.69, 95% CI 1.22-2.34). Conclusions These findings suggest that diets rich in animal products, cereals, and fats are positively related to laryngeal cancer, and those rich in fruit and vegetables inversely related to oral and pharyngeal cancer.

Total and exogenous carbohydrate oxidation in obese prepubertal children.

The aim was to explore whether the origin of carbohydrate oxidation (exogenous compared with endogenous carbohydrate) after consumption of a mixed meal was influenced by obesity in children. Ten obese prepubertal children 8 y of age (44.2 +/- 3.6 kg) were studied over 9.5 h and compared with eight normal-weight, matched control children (28.5 +/- 1.6 kg). They were fed a mixed meal containing naturally enriched [13C]carbohydrate (cane sugar and popcorn) providing 55% of the daily energy requirement as measured by 24-h resting metabolic rate. Total carbohydrate oxidation was calculated by indirect calorimetry (hood system) whereas exogenous carbohydrate oxidation was estimated from carbon dioxide production (VCO2), the isotopic enrichment of breath 13CO2, and the abundance of [13C]carbohydrate in the meal ingested. The time course of 13CO2 in breath-measured over 570 min-followed a similar pattern in both groups. Although total carbohydrate oxidation was not significantly different among the two groups, exogenous carbohydrate utilization was significantly greater (P < 0.03) and endogenous carbohydrate oxidation was significantly lower (P < 0.05) in obese compared with control children. In addition, the rate of exogenous carbohydrate oxidation expressed as a proportion of total carbohydrate oxidation was positively related to the body fat of the children (r = 0.68, P < 0.01). The study suggests that in the postprandial phase, a smaller proportion of carbohydrate oxidation is accounted for by glycogen breakdown in obese children. The sparing of endogenous glycogen may result from decreased glycogen turnover already present at an early age.

Growth and demise of Permian biogenic chert along northwest Pangea: evidence for end-Permian collapse of thermohaline circulation

The Permian Chert Event (PCE) was a 30 Ma long episode of unusual chert accumulation along the northwest margin of Pangea, and possibly worldwide. The onset of the PCE occurred at about the Sakmarian-Artinskian boundary in the Sverdrup Basin, Canadian Arctic, where it coincides with a maximum flooding event, the ending of high-frequency/high-amplitude shelf cyclicity, the onset of massive biogenic chert deposition in deep-water distal areas, and a long-term shift from warm- to cool-water carbonate sedimentation in shallow-water proximal areas. A similar and coeval shift is observed from the Barents Sea to the northwestern USA. A landward and southward expansion of silica factories occurred during the Middle and Late Permian at which time warm-water carbonate producers disappeared completely from the northwest margin of Pangea. Biotically impoverished and increasingly narrow cold-water carbonate factories (characterised by non-cemented bioclasts of sponges, bryozoans, echinoderms and brachiopods) were then progressively replaced by silica factories. By Late Permian time, little carbonate sediments accumulated in the Barents Sea and in the Sverdrup Basin. where the deep- to shallow-water sedimentary spectrum was occupied by siliceous sponge spicules. By that time, biogenic silica sedimentation was common throughout the world. Silica factories collapsed in the Late Permian, abruptly bringing the PCE to an end. In northwest Pangea, the end- Permian collapse of the PCE was associated with a major transgression and with a return to much warmer oceanic and continental climatic conditions. Chert deposition resumed in the distal oceanic areas during the early Middle Triassic (Anisian) after a 8-10 Ma interruption (Early Triassic Chert Gap). The conditions necessary for the onset, expansion and zenith of the PCE were provided by the thermohaline circulation of nutrient-rich cold waters along the northwestern and western margin of Pangea, and possibly throughout the world oceans. These conditions provided an efficient transportation mechanism that constantly replenished the supply of silica in the area, created a nutrient- and oxygen-rich environment favouring siliceous biogenic productivity. established cold sea-floor conditions, hindering silica dissolution, while increasing calcium carbonate solubility, and provided conditions adverse to organic and inorganic carbonate production, The northwest margin of Pangea was, for nearly 30 Ma. bathed by cold waters presumably derived from the seasonal melting of northern sea ice, the assumed engine for thermohaline circulation. This process started near the Sakmarian-Artinskian boundary. intensified throughout Middle and Late Permian time and ceased suddenly in latest Permian time, It led to oceanic conditions much colder than normally expected from the palaeolatitudes. and the influence of cold northerly-derived water was felt as far south southern Nevada. The demise of silica factories was caused by the rapid breakdown of these conditions and the establishment of a much warmer marine environment accompanied by sluggish circulation and perhaps a reduced input of dissolved silica to the ocean. Complete thawing of northern sea ice would have ended thermohaline circulation and led to warm and sluggish oceanic conditions inimical to the production. accumulation and preservation of biogenic silica.

Cellules gliales et douleur chronique: du laboratoire a l'espoir clinique [Glial cells and chronic pain: from the laboratory to clinical hope].

Despite their high prevalence, associated disability and seemingly rich pharmacopeia, the various forms of chronic pain remain frequently intractable. The past decade witnessed the rise of a concept stating that non-neuronal cells of the central nervous system, astrocytes and microglia, are crucial elements in pathological pain. This review gathers and summarizes the experimental data underpinning this theory in animal models and addresses their pertinence in humans. The potential opportunities and constraints of glial inhibition are exposed and compared to more moderate strategies of selective modulation. This therapeutic hope is particularly highlighted in our discussion of the first completed clinical trials employing glial inhibitors in the treatment of chronic pain.

Cell wall maturation of Arabidopsis trichomes is dependent on exocyst subunit EXO70H4 and involves callose deposition.

Arabidopsis (Arabidopsis thaliana) leaf trichomes are single-cell structures with a well-studied development, but little is understood about their function. Developmental studies focused mainly on the early shaping stages, and little attention has been paid to the maturation stage. We focused on the EXO70H4 exocyst subunit, one of the most up-regulated genes in the mature trichome. We uncovered EXO70H4-dependent development of the secondary cell wall layer, highly autofluorescent and callose rich, deposited only in the upper part of the trichome. The boundary is formed between the apical and the basal parts of mature trichome by a callose ring that is also deposited in an EXO70H4-dependent manner. We call this structure the Ortmannian ring (OR). Both the secondary cell wall layer and the OR are absent in the exo70H4 mutants. Ecophysiological aspects of the trichome cell wall thickening include interference with antiherbivore defense and heavy metal accumulation. Ultraviolet B light induces EXO70H4 transcription in a CONSTITUTIVE PHOTOMORPHOGENIC1-dependent way, resulting in stimulation of trichome cell wall thickening and the OR biogenesis. EXO70H4-dependent trichome cell wall hardening is a unique phenomenon, which may be conserved among a variety of the land plants. Our analyses support a concept that Arabidopsis trichome is an excellent model to study molecular mechanisms of secondary cell wall deposition.

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease.

Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exists in two isoforms: KHK-A and KHK-C, generated through mutually exclusive alternative splicing of KHK pre-mRNAs. KHK-C displays superior affinity for fructose compared with KHK-A and is produced primarily in the liver, thus restricting fructose metabolism almost exclusively to this organ. Here we show that myocardial hypoxia actuates fructose metabolism in human and mouse models of pathological cardiac hypertrophy through hypoxia-inducible factor 1α (HIF1α) activation of SF3B1 and SF3B1-mediated splice switching of KHK-A to KHK-C. Heart-specific depletion of SF3B1 or genetic ablation of Khk, but not Khk-A alone, in mice, suppresses pathological stress-induced fructose metabolism, growth and contractile dysfunction, thus defining signalling components and molecular underpinnings of a fructose metabolism regulatory system crucial for pathological growth.