Broad-scale adaptive genetic variation in alpine plants is driven by temperature and precipitation.

Identifying adaptive genetic variation is a challenging task, in particular in non-model species for which genomic information is still limited or absent. Here, we studied distribution patterns of amplified fragment length polymorphisms (AFLPs) in response to environmental variation, in 13 alpine plant species consistently sampled across the entire European Alps. Multiple linear regressions were performed between AFLP allele frequencies per site as dependent variables and two categories of independent variables, namely Moran's eigenvector map MEM variables (to account for spatial and unaccounted environmental variation, and historical demographic processes) and environmental variables. These associations allowed the identification of 153 loci of ecological relevance. Univariate regressions between allele frequency and each environmental factor further showed that loci of ecological relevance were mainly correlated with MEM variables. We found that precipitation and temperature were the best environmental predictors, whereas topographic factors were rarely involved in environmental associations. Climatic factors, subject to rapid variation as a result of the current global warming, are known to strongly influence the fate of alpine plants. Our study shows, for the first time for a large number of species, that the same environmental variables are drivers of plant adaptation at the scale of a whole biome, here the European Alps.

Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design.

BACKGROUND: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. METHODS/DESIGN: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. DISCUSSION: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. TRIAL REGISTRATION: The TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

CPPD crystal deposition disease in patients with rheumatoid arthritis.

The aim of this study was to assess the frequency and the outcome of patients suffering from rheumatoid arthritis in which calcium pyrophosphate dihydrate (CPPD) crystal deposits were found to coexist in synovial fluid analysis. Such association was more frequent than previously believed with CPPD crystals found in 25.8% of 93 patients with rheumatoid arthritis. As a group, a trend toward a worse outcome was suggested by more frequent prostheses of the lower limb.

Verification at the protein level of the PIF4-mediated external coincidence model for the temperature-adaptive photoperiodic control of plant growth in Arabidopsis thaliana.

Plant circadian clock controls a wide variety of physiological and developmental events, which include the short-days (SDs)-specific promotion of the elongation of hypocotyls during de-etiolation and also the elongation of petioles during vegetative growth. In A. thaliana, the PIF4 gene encoding a phytochrome-interacting basic helix-loop-helix (bHLH) transcription factor plays crucial roles in this photoperiodic control of plant growth. According to the proposed external coincidence model, the PIF4 gene is transcribed precociously at the end of night specifically in SDs, under which conditions the protein product is stably accumulated, while PIF4 is expressed exclusively during the daytime in long days (LDs), under which conditions the protein product is degraded by the light-activated phyB and also the residual proteins are inactivated by the DELLA family of proteins. A number of previous reports provided solid evidence to support this coincidence model mainly at the transcriptional level of the PIF 4 and PIF4-traget genes. Nevertheless, the diurnal oscillation profiles of PIF4 proteins, which were postulated to be dependent on photoperiod and ambient temperature, have not yet been demonstrated. Here we present such crucial evidence on PIF4 protein level to further support the external coincidence model underlying the temperature-adaptive photoperiodic control of plant growth in A. thaliana.

Potential impact of climate change on vegetation in the European Alps: a review

Based on conclusions drawn from general climatic impact assessment in mountain regions, the review synthesizes results relevant to the European Alps published mainly from 1994 onward in the fields of population genetics, ecophysiology, phenology, phytogeography, modeling, paleoecology and vegetation dynamics. Other important factors of global change interacting synergistically with climatic factors are also mentioned, such as atmospheric CO2 concentration, eutrophication, ozone or changes in land-use. Topics addressed are general species distribution and populations (persistence, acclimation, genetic variability, dispersal, fragmentation, plant/animal interaction, species richness, conservation), potential response of vegetation (ecotonal shift - area, physiography - changes in the composition, structural changes), phenology, growth and productivity, and landscape. In conclusion, the European Alps appear to have a natural inertia and thus to tolerate an increase of 1-2 K of mean air temperature as far as plant species and ecosystems are concerned in general. However, the impact of land-use is very likely to negate this buffer in many areas. For a change of the order of 3 K or more, profound changes may be expected.

Metallogenic model of the Trepca Pb-Zn-Ag skarn deposit, Kosovo: Evidence from fluid inclusions, Rare Earth Elements, and stable isotope data

The Trepca Pb-Zn-Ag skarn deposit (29 Mt of ore at 3.45% Pb, 2.30% Zn, and 80 g/t Ag) is located in the Kopaonik block of the western Vardar zone, Kosovo. The mineralization, hosted by recrystallized limestone of Upper Triassic age, was structurally and lithologically controlled. Ore deposition is spatially and temporally related with the postcollisional magmatism of Oligocene age (23-26 Ma). The deposit was formed during two distinct mineralization stages: an early prograde closed-system and a later retrograde open-system stage. The prograde mineralization consisting mainly of pyroxenes (Hd(54-100)Jo(0-45)Di(0-45)) resulted from the interaction of magmatic fluids associated with Oligocene (23-26 Ma) postcollisional magmatism. Whereas there is no direct contact between magmatic rocks and the mineralization, the deposit is classified as a distal Pb-Zn-Ag skarn. Abundant pyroxene reflects low oxygen fugacity (<10(-31) bar) and anhydrous environment. Fluid inclusion data and mineral assemblage limit the prograde stage within a temperature range between 390 degrees and 475 degrees C. Formation pressure is estimated below 900 bars. Isotopic composition of aqueous fluid, inclusions hosted by hedenbergite (delta D = -108 to -130 parts per thousand; delta O-18 = 7.5-8.0 parts per thousand), Mn-enriched mineralogy and high REE content of the host carbonates at the contact with the skarn mineralization suggest that a magmatic fluid was modified during its infiltration through the country rocks. The retrograde mineral assemblage comprises ilvaite, magnetite, arsenopyrite, pyrrhotite, marcasite, pyrite, quartz, and various carbonates. Increases in oxygen and sulfur fugacities, as well as a hydrous character of mineralization, require an open-system model. The opening of the system is related to phreatomagmatic explosion and formation of the breccia. Arsenopyrite geothermometer limits the retrograde stage within the temperature range between 350 degrees and 380 degrees C and sulfur fugacity between 10(-8.8) and 10(-7.2) bars. The principal ore minerals, galena, sphalerite, pyrite, and minor chalcopyrite, were deposited from a moderately saline Ca-Na chloride fluid at around 350 degrees C. According to the isotopic composition of fluid inclusions hosted by sphalerite (delta D = -55 to -74 parts per thousand; delta O-18 = -9.6 to -13.6 parts per thousand), the fluid responsible for ore deposition was dominantly meteoric in origin. The delta S-31 values of the sulfides spanning between -5.5 and +10 parts per thousand point to a magmatic origin of sulfur. Ore deposition appears to have been largely contemporaneous with the retrograde stage of the skarn development. Postore stage accompanied the precipitation of significant amount of carbonates including the travertine deposits at the deposit surface. Mineralogical composition of travertine varies from calcite to siderite and all carbonates contain significant amounts of Mn. Decreased formation temperature and depletion in the REE content point to an influence of pH-neutralized cold ground water and dying magmatic system.

The cervical spine in calcium pyrophosphate dihydrate deposition disease. A prevalent case-control study.

OBJECTIVE: To test the hypothesis that calcium pyrophosphate dihydrate (CPPD) deposition disease is a risk factor for neck pain. METHODS: A prevalent case-control study was conducted to assess cervical calcifications and neck pain between patients with and without known peripheral CPPD deposition disease. CPPD cases were included if diagnosed with CPPD deposition disease of peripheral joints, and excluded if their chief complaint was neck pain. Controls were randomly selected among consecutive patients, hospitalized for conditions unrelated to CPPD deposition disease or neck pain, and matched to CPPD cases by age and sex. Cervical calcifications were assessed by lateral cervical radiographs and computed tomography scans of the upper cervical spine; neck pain and cervical function were appraised by a validated questionnaire. RESULTS: Cervical calcifications were found in 24 out of 35 patients (69%) in the CPPD group compared to 4 out of 35 patients (11%) in the control group (p < 0.001). Patients with CPPD deposition disease reported significantly more neck pain and discomfort than controls (p < 0.001), and were 5 times more likely to report any neck pain (odds ratio 5.5; 95% confidence interval: 1.9, 21.9). Among male patients, more extensive cervical calcified deposits correlated with more severe neck pain (rs = 0.58, p = 0.03). CONCLUSION: These results suggest that CPPD deposition disease frequently involves the cervical spine and may be associated with the development of neck pain.

Effect of a temperature increase in the non-noxious range on proton-evoked ASIC and TRPV1 activity.

Acid-sensing ion channels (ASICs) are neuronal H(+)-gated cation channels, and the transient receptor potential vanilloid 1 channel (TRPV1) is a multimodal cation channel activated by low pH, noxious heat, capsaicin, and voltage. ASICs and TRPV1 are present in sensory neurons. It has been shown that raising the temperature increases TRPV1 and decreases ASIC H(+)-gated current amplitudes. To understand the underlying mechanisms, we have analyzed ASIC and TRPV1 function in a recombinant expression system and in dorsal root ganglion (DRG) neurons at room and physiological temperature. We show that temperature in the range studied does not affect the pH dependence of ASIC and TRPV1 activation. A temperature increase induces, however, a small alkaline shift of the pH dependence of steady-state inactivation of ASIC1a, ASIC1b, and ASIC2a. The decrease in ASIC peak current amplitudes at higher temperatures is likely in part due to the observed accelerated open channel inactivation kinetics and for some ASIC types to the changed pH dependence of steady-state inactivation. The increase in H(+)-activated TRPV1 current at the higher temperature is at least in part due to a hyperpolarizing shift in its voltage dependence. The contribution of TRPV1 relative to ASICs to H(+)-gated currents in DRG neurons increases with higher temperature and acidity. Still, ASICs remain the principal pH sensors of DRG neurons at 35°C in the pH range ≥6.

Pitfalls in cefepime titration from human plasma: plasma- and temperature-related drug degradation in vitro.

While developing a high-pressure liquid chromatography assay for cefepime in plasma, we observed significant drug degradation at 20 and 37 degrees C but not at 4 degrees C. This plasma-related degradation persisted after protein removal. This warrants caution regarding cefepime assays for pharmacokinetic and pharmacodynamic studies of cefepime in vitro and in vivo.

Dissolution-reprecipitation of zircon at low-temperature, high-pressure conditions (Lanzo Massif, Italy)

An eclogite facies meta-plagiogranite from the Lanzo massif (western Alps, Italy) contains crystals of zircon intimately associated with allanite. Zircon displays different microtextures ranging from pristine, euhedral, and magmatic to fractured, porous varieties with mosaic zoning, and pervasive recrystallization into euhedral microcrystals. Fractures and voids in the recrystallized zircon microcrystals are mainly filled by high-pressure Na-rich pyroxene. Electron backscattered diffraction analysis revealed a similar crystallographic orientation for primary magmatic zircon crystals and microcrystals, with less than 2 degrees misorientation among neighboring microdomains. The textural change is coupled with chemical and isotopic modifications: recrystallized zircon domains contain significantly less Th and light- to mid-REE, but are richer in Sr than magmatic zircon crystals. Magmatic zircon preserves the protolith U-Pb age of 163.5 +/- 1.7 Ma, whereas zircon microcrystals have a mean age of 55 +/- 1 Ma. The coexisting allanite also contains inclusions of Na-rich pyroxene and has chemical features (elevated Sr and Ni contents and lack of Eu anomaly) indicating formation at high pressure. Despite being associated texturally with zircon, allanite yields a younger Th-Pb age of 46.5 +/- 3.0 Ma, suggesting that the Lanzo unit remained at relatively high pressure conditions for similar to 8 m.y. Zircon recrystallization proceeded with volume reduction and loss of material to an alkaline metamorphic fluid that acted as the agent for a coupled dissolution-reprecipitation process. Recrystallization occurred with minimum transport, in a low-strain environment, and was not significantly enhanced by metamictization. The source of the fluid for zircon recrystallization is most probably related to prograde devolatilization reactions in the surrounding serpentinite.

High protein intake reduces intrahepatocellular lipid deposition in humans.

BACKGROUND: High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown. OBJECTIVE: The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men. DESIGN: Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens. RESULTS: The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14). CONCLUSIONS: Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.

Geographical and altitudinal population genetic structure of two dung fly species with contrasting mobility and temperature preference.

Local adaptation of populations requires some degree of spatio-temporal isolation. Previous studies of the two dung fly species Scathophaga stercoraria and Sepsis cynipsea have revealed low levels of geographic and altitudinal genetic differentiation in quantitative life history and morphological traits, but instead high degrees of phenotypic plasticity. These patterns suggest that gene flow is extensive despite considerable geographic barriers and large spatio-temporal variation in selection on body size and related traits. In this study we addressed this hypothesis by investigating genetic differentiation of dung fly populations throughout Switzerland based on the same 10 electrophoretic loci in each species. Overall, we found no significant geographic differentiation of populations for either species. This is inconsistent with the higher rates of gene flow expected due to better flying capacity of the larger S. stercoraria. However, heterozygote deficiencies within populations indicated structuring on a finer scale, seen for several loci in S. cynipsea, and for the locus PGM (Phosphoglucomutase) in S. stercoraria. Additionally, S. cynipsea showed a tendency towards a greater gene diversity at higher altitudes, mediated primarily by the locus MDH (malate dehydrogenase), at which a second allele was only present in populations above 1000 m. This may be caused by increased environmental stress at higher altitudes in this warm-adapted species. MDH might thus be a candidate locus subject to thermal selection in this species, but this remains to be corroborated by direct evidence. In S. stercoraria, no altitudinal variation was found.

Magmatic-dominated fluid evolution in the Jurassic Nambija gold skarn deposits (southeastern Ecuador)

The Jurassic (approximately 145 Ma) Nambija oxidized gold skarns are hosted by the Triassic volcanosedimentary Piuntza unit in the sub-Andean zone of southeastern Ecuador. The skarns consist dominantly of granditic garnet (Ad(20-98)) with subordinate pyroxene (Di(46-92)Hd(17-42)Jo(0-19)) and epidote and are spatially associated with porphyritic quartz-diorite to granodiorite intrusions. Endoskarn is developed at the intrusion margins and grades inwards into a potassic alteration zone. Exoskarn has an outer K- and Na-enriched zone in the volcanosedimentary unit. Gold mineralization is associated with the weakly developed retrograde alteration of the exoskarn and occurs mainly in sulfide-poor vugs and milky quartz veins and veinlets in association with hematite. Fluid inclusion data for the main part of the prograde stage indicate the coexistence of high-temperature (500A degrees C to > 600A degrees C), high-salinity (up to 65 wt.% eq. NaCl), and moderate- to low-salinity aqueous-carbonic fluids interpreted to have been trapped at pressures around 100-120 MPa, corresponding to about 4-km depth. Lower-temperature (510-300A degrees C) and moderate- to low-salinity (23-2 wt.% eq. NaCl) aqueous fluids are recorded in garnet and epidote of the end of the prograde stage. The microthermometric data (Th from 513A degrees C to 318A degrees C and salinity from 1.0 to 23 wt.% eq. NaCl) and delta(18)O values between 6.2aEuro degrees and 11.5aEuro degrees for gold-bearing milky quartz from the retrograde stage suggest that the ore-forming fluid was dominantly magmatic. Pressures during the early retrograde stage were in the range of 50-100 MPa, in line with the evidence for CO(2) effervescence and probable local boiling. The dominance of magmatic low-saline to moderately saline oxidizing fluids during the retrograde stage is consistent with the depth of the skarn system, which could have delayed the ingression of external fluids until relatively low temperatures were reached. The resulting low water-to-rock ratios explain the weak retrograde alteration and the compositional variability of chlorite, essentially controlled by host rock compositions. Gold was precipitated at this stage as a result of cooling and pH increase related to CO(2) effervescence, which both result in destabilization of gold-bearing chloride complexes. Significant ingression of external fluids took place after gold deposition only, as recorded by delta(18)O values of 0.4aEuro degrees to 6.2aEuro degrees for fluids depositing quartz (below 350A degrees C) in sulfide-rich barren veins. Low-temperature (< 300A degrees C) meteoric fluids (delta(18)O(water) between -10.0aEuro degrees and -2.0aEuro degrees) are responsible for the precipitation of late comb quartz and calcite in cavities and veins and indicate mixing with cooler fluids of higher salinities (about 100A degrees C and 25 wt.% eq. NaCl). The latter are similar to low-temperature fluids (202-74.5A degrees C) with delta(18)O values of -0.5aEuro degrees to 3.1aEuro degrees and salinities in the range of 21.1 to 17.3 wt.% eq. CaCl(2), trapped in calcite of late veins and interpreted as basinal brines. Nambija represents a deep equivalent of the oxidized gold skarn class, the presence of CO(2) in the fluids being partly a consequence of the relatively deep setting at about 4-km depth. As in other Au-bearing skarn deposits, not only the prograde stage but also the gold-precipitating retrograde stage is dominated by fluids of magmatic origin.

A mechanism for localized lignin deposition in the endodermis.

The precise localization of extracellular matrix and cell wall components is of critical importance for multicellular organisms. Lignin is a major cell wall modification that often forms intricate subcellular patterns that are central to cellular function. Yet the mechanisms of lignin polymerization and the subcellular precision of its formation remain enigmatic. Here, we show that the Casparian strip, a lignin-based, paracellular diffusion barrier in plants, forms as a precise, median ring by the concerted action of a specific, localized NADPH oxidase, brought into proximity of localized peroxidases through the action of Casparian strip domain proteins (CASPs). Our findings in Arabidopsis provide a simple mechanistic model of how plant cells regulate lignin formation with subcellular precision. We speculate that scaffolding of NADPH oxidases to the downstream targets of the reactive oxygen species (ROS) that they produce might be a widespread mechanism to ensure specificity and subcellular precision of ROS action within the extracellular matrix.