A nutrient limitation mosaic in the eastern tropical Indian Ocean

The Indian Ocean accounts for about one fifth of global ocean net primary production but remains undersampled relative to other major ocean basins. The eastern tropical Indian Ocean is characterized by extremely low concentrations of both macronutrients and the micronutrient iron. We measured concentrations of dissolved and particulate trace metals (Fe, Mn, Zn, Pb) in the upper ocean along the GO-SHIP IO9N transect (28˚S to 17˚N, mostly along the 95˚E meridian) during a cruise in April 2016. Cellular quotas (metal/C) of Fe, Mn, Co, Ni, Cu, and Zn were measured in small eukaryotic flagellates (2–7 μm). Deckboard bottle incubation experiments were conducted at one station in each of three putative biogeochemical regions: southern Indian Ocean gyre (SIO, 28-10˚S); equatorial Indian Ocean (EqIO, 10˚S - 5˚N); Bay of Bengal (BoB, 5-17˚N). Nitrate and phosphate were below detection limits in surface waters across the transect. Dissolved and particulate Fe were <0.2 nM south of 10˚N and lowest in the EqIO. Cellular Fe/C quotas were approximately 6 μmoL/mol and did not vary along the transect, nor did cellular Mn/C or Co/C quotas. Cellular Ni/C and Zn/C quotas were significantly higher at the southern terminus. Nutrient addition experiments indicated that N was the primary limiting nutrient for autotrophs using chlorophyll a as a proxy, but biomass measurements of specific phytoplankton groups pointed to a more complex nutrient limitation mosaic. Prochlorococcus was limited by N in the EqIO but by multiple nutrients (N, P, and/or Fe) in the BoB. Synechococcus was limited by N in the EqIO and BoB, while small (<20 μm) eukaryotic phytoplankton were limited by N in the EqIO and by multiple nutrients in the BoB. Stoichiometric comparisons of cells and underlying source waters indicate a gradient of N and Fe stress along the transect. These data demonstrate that autotroph communities are poised near multiple nutrient limitation horizons in extremely oligotrophic waters far from micronutrient sources

Therapeutic target-site variability in α1-antitrypsin characterized at high resolution

The intrinsic propensity of [alpha]1-antitrypsin to undergo conformational transitions from its metastable native state to hyperstable forms provides a motive force for its antiprotease function. However, aberrant conformational change can also occur via an intermolecular linkage that results in polymerization. This has both loss-of-function and gain-of-function effects that lead to deficiency of the protein in human circulation, emphysema and hepatic cirrhosis. One of the most promising therapeutic strategies being developed to treat this disease targets small molecules to an allosteric site in the [alpha]1-antitrypsin molecule. Partial filling of this site impedes polymerization without abolishing function. Drug development can be improved by optimizing data on the structure and dynamics of this site. A new 1.8 Å resolution structure of [alpha]1-antitrypsin demonstrates structural variability within this site, with associated fluctuations in its upper and lower entrance grooves and ligand-binding characteristics around the innermost stable enclosed hydrophobic recess. These data will allow a broader selection of chemotypes and derivatives to be tested in silico and in vitro when screening and developing compounds to modulate conformational change to block the pathological mechanism while preserving function

Picophytoplankton biomass distribution in the global ocean

The smallest marine phytoplankton, collectively termed picophytoplankton, have been routinely enumerated by flow cytometry since the late 1980s during cruises throughout most of the world ocean. We compiled a database of 40 946 data points, with separate abundance entries for Prochlorococcus, Synechococcus and picoeukaryotes. We use average conversion factors for each of the three groups to convert the abundance data to carbon biomass. After gridding with 1? spacing, the database covers 2.4% of the ocean surface area, with the best data coverage in the North Atlantic, the South Pacific and North Indian basins, and at least some data in all other basins. The average picophytoplankton biomass is 12 ± 22 µg Cl-1 or 1.9 g Cm-2. We estimate a total global picophytoplankton biomass of 0.53–1.32 Pg C (17–39% Prochlorococcus, 12–15% Synechococcus and 49–69% picoeukaryotes), with an intermediate/best estimate of 0.74 Pg C. Future efforts in this area of research should focus on reporting calibrated cell size and collecting data in undersampled regions

Population Size, Sex and Purifying Selection: Comparative Genomics of Two Sister Taxa of the Wild Yeast Saccharomyces paradoxus

This study uses population genomic data to estimate demographic and selection parameters in two sister lineages of the wild yeast Saccharomyces paradoxus and compare their evolution. We first estimate nucleotide and recombinational diversities in each of the two lineages to infer their population size and frequency of sex and then analyze the rate of mutation accumulation since divergence from their inferred common ancestor to estimate the generation time and efficacy of selection. We find that one of the lineages has significantly higher silent nucleotide diversity and lower linkage disequilibrium, indicating a larger population with more frequent sexual generations. The same lineage also shows shorter generation time and higher efficacy of purifying selection, the latter consistent with the finding of larger population size and more frequent sex. Similar analyses are also performed on the ancestries of individual strains within lineages and we find significant differences between strains implying variation in rates of mitotic cell divisions. Our sample includes some strains originating in the Chernobyl nuclear-accident exclusion zone, which has been subjected to high levels of radiation for nearly 30 years now. We find no evidence, however, for increased rates of mutation. Finally, there is a positive correlation between rates of mutation accumulation and length of growing period, as measured by latitude of the place of origin of strains. Our study illustrates the power of genomic analyses in estimating population and life history parameters and testing predictions based on population genetic theory

Decoupling of net community and export production on submesoscales in the Sargasso Sea

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 29 (2015): 1266–1282, doi:10.1002/2014GB004913.Determinations of the net community production (NCP) in the upper ocean and the particle export production (EP) should balance over long time and large spatial scales. However, recent modeling studies suggest that a horizontal decoupling of flux-regulating processes on submesoscales (≤10 km) could lead to imbalances between individual determinations of NCP and EP. Here we sampled mixed-layer biogeochemical parameters and proxies for NCP and EP during 10, high-spatial resolution (~2 km) surface transects across strong physical gradients in the Sargasso Sea. We observed strong biogeochemical and carbon flux variability in nearly all transects. Spatial coherence among measured biogeochemical parameters within transects was common but rarely did the same parameters covary consistently across transects. Spatial variability was greater in parameters associated with higher trophic levels, such as chlorophyll in >5.0 µm particles, and variability in EP exceeded that of NCP in nearly all cases. Within sampling transects, coincident EP and NCP determinations were uncorrelated. However, when averaged over each transect (30 to 40 km in length), we found NCP and EP to be significantly and positively correlated (R = 0.72, p = 0.04). Transect-averaged EP determinations were slightly smaller than similar NCP values (Type-II regression slope of 0.93, standard deviation = 0.32) but not significantly different from a 1:1 relationship. The results show the importance of appropriate sampling scales when deriving carbon flux budgets from upper ocean observations.NASA Ocean Carbon and Biogeochemistry program Grant Number: NNX11AL94G; WHOI Postdoctoral Scholar fellowship; NASA ACE Grant Number: NNX12AJ25G; NSF Grant Number: OCE-07523662016-02-2

Decoupling of Net Community Production and Export Production at Submesoscale Fronts in the Sargasso Sea

Determinations of the net community production (NCP) in the upper ocean and the particle export production (EP) should balance over long time and large spatial scales. However, recent modeling studies suggest that a horizontal decoupling of flux-regulating processes on submesoscales (≤10 km) could lead to imbalances between individual determinations of NCP and EP. Here we sampled mixed-layer biogeochemical parameters and proxies for NCP and EP during 10, high-spatial resolution (~2 km) surface transects across strong physical gradients in the Sargasso Sea. We observed strong biogeochemical and carbon flux variability in nearly all transects. Spatial coherence among measured biogeochemical parameters within transects was common but rarely did the same parameters covary consistently across transects. Spatial variability was greater in parameters associated with higher trophic levels, such as chlorophyll in \u3e5.0 µm particles, and variability in EP exceeded that of NCP in nearly all cases. Within sampling transects, coincident EP and NCP determinations were uncorrelated. However, when averaged over each transect (30 to 40 km in length), we found NCP and EP to be significantly and positively correlated (R = 0.72, p = 0.04). Transect-averaged EP determinations were slightly smaller than similar NCP values (Type-II regression slope of 0.93, standard deviation = 0.32) but not significantly different from a 1:1 relationship. The results show the importance of appropriate sampling scales when deriving carbon flux budgets from upper ocean observations

Fit-Fat Index is better associated with heart rate variability compared to fitness and fatness alone as indicators of cardiometabolic human health

ObjectivesCardiorespiratory fitness and fatness indicators have been related to heart rate variability (HRV) parameters. The Fit-Fat Index (FFI) is a single index combining cardiorespiratory fitness and fatness indicators. To the best of our knowledge, no studies have previously analyzed whether FFI are related to cardiac autonomic nervous system activity assessed through HRV parameters. This study aimed (i) to examine the association of cardiorespiratory fitness, fatness indicators, and FFI with HRV parameters; and (ii) to report what of the different fatness indicators included in FFI is better associated with HRV parameters in sedentary adults. MethodsOne hundred and fifty healthy adults (74 women; 76 men), aged between 18 and 65 years old, participated in this cross-sectional study. We measured cardiorespiratory fitness (maximal oxygen consumption) and fatness indicators (waist-to-height ratio [WHR], fat mass percentage [FM%] and visceral adipose tissue [VAT]). Three FFIs were calculated as the quotient between cardiorespiratory fitness and one out of three possible fatness indicators: Fit-Fat Index calculated waist-to-height ratio (FFIWHR), Fit-Fat Index calculated with FM% (FFIFM%), and Fit-Fat Index calculated with VAT (FFIVAT). HRV parameters were measured in resting conditions using a Polar RS800CX. ResultsFFI(WTHR), FFIFM% and FFIVAT were related to different HRV parameters (beta ranges between -0.507 and 0.529; R-2 ranges between 0.096 and 0.275; all p < .001) and the association was stronger with HRV parameters than the isolated fitness or fatness indicators (beta ranges between -0.483 and 0.518; R-2 ranges between 0.071 and 0.263; all p < .001). FFIVAT was the index more consistently associated with HRV parameters (beta ranges between -0.507 and 0.529; R-2 ranges between 0.235 and 0.275; all p < .001). ConclusionOur study suggests that compound FFIs are better predictors of HRV parameters than either cardiorespiratory fitness or fatness indicators alone. The FFIVAT was the best index in terms of its association to HRV.Spanish Ministry of Education FPU16/02760, FPU14/04172United States Department of Health & Human Services National Institutes of Health (NIH) - USA U01 TR00200

Melanoma in congenital melanocytic naevi

Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence, and therefore over clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that risk in childhood is related to the severity of the congenital phenotype, not only cutaneous but neuroradiological. New understanding of the genetics of CMN offers the possibility of improvement in diagnosis of melanoma, identification of those at highest risk, and new treatment options. We review the world literature and our centre's experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from our prospective cohort. Management strategies are proposed for presentation of suspected melanoma of the skin and the CNS in patients with CMN, including use of oral MEK inhibitors in NRAS-mutated tumours. This article is protected by copyright. All rights reserved

Assessment of autonomous nerve system through non-linear heart rate variability outcomes in sedentary healthy adults

Background: Heart rate variability (HRV) is a psycho-physiological phenomenon with broad health implications. Different data analysis methods have been used to assess the autonomic nervous system activity, but the validation of new indexes that accurately describe its balance through non-invasive methods (i.e., HRV analysis) is of clinical interest. This study aimed: (i) to evaluate the association of the Stress Score (SS) and the Sympathetic/Parasympathetic Ratio (S/PS) with time domain and frequency domain analysis of HRV, and (ii) to set reference values of SS and S/PS in sedentary healthy adults. Methods: A total of 156 sedentary healthy adults (38.4 ± 15.57 years old, 81 women), aged were involved in this study. HRV was measured for 15 min in a supine position at rest. SS and S/PS were calculated from the non-linear HRV analyses based on Poincare Plot. Results: Stress Score showed a non-linear negative power-law relationship with SDNN (β = −0.969; R2 = 0.963; P < 0.001), RMSSD (β = −0.867; R2 = 0.722; P < 0.001), high frequency (β = −0.834; R2 = 0.752; P =< 0.001), low frequency (β = −0.627; R2 = 0.330; P < 0.001), SD1 (β = −0.867; R2 = 0.722; P < 0.001) and SD2 (β = −1.000; R2 > 0.999; P < 0.001). There was observed a negative cubic relationship between SS with PNN50 (β = −1.972; R2 = 0.644; P < 0.001). A linear regression model was conducted between SS with Ratio Low/High Frequency (β = 0.026; R2 < 0.001; P = 0.750). Non-linear power-law regression models were built between S/PS and SDNN (β = −0.990; R2 = 0.981; P < 0.001), RMSSD (β = −0.973; R2 = 0.939; P < 0.001), high frequency (β = −0.928; R2 = 0.970; P < 0.001), low frequency (β = −2.344; R2 = 0.557; P < 0.001), SD1 (β = −0.973; R2 = 0.939; P < 0.001) and SD2 (β = −0.611; R2 = 0.908; P < 0.001). A non-linear negative regression model was built between S/PS and PNN50 (β = −3.412; R2 = 0.868; P < 0.001). A linear regression model was conducted between S/PS and SD2/SD1 (β = 0.075; R2 = 0.006; P < 0.001). Conclusion: Our results support the use of SS as a sympathetic activity marker, and S/PS as an indicator of the sympathetic and parasympathetic activity of the autonomic nervous system in sedentary healthy adults.Spanish Government FPU14/04172 FPU15/03960University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of ExcellenceUnit of Excellence on Exercise and Health (UCEES

Proteomic Analysis of Pichindé virus

The arenaviruses include a number of important pathogens including Lassa virus and Junin virus. Presently, the only treatment is supportive care and the antiviral Ribavirin. In the event of an epidemic, patient triage may be required to more effectively manage resources; the development of prognostic biomarker signatures, correlating with disease severity, would allow rational triage. Using a pair of arenaviruses, which cause mild or severe disease, we analyzed extracts from infected cells using SELDI mass spectrometry to characterize potential biomarker profiles. EDGE analysis was used to analyze longitudinal expression differences. Extracts from infected guinea pigs revealed protein peaks which could discriminate between mild or severe infection, and between times post-infection. Tandem mass-spectrometry identified several peaks, including the transcriptional regulator prothymosin-α. Further investigation revealed differences in secretion of this peptide. These data show proof of concept that proteomic profiling of host markers could be used as prognostic markers of infectious disease