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Background: Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism. Objectives: We aimed to further investigate the molecular background of patients with SCA8 diagnosis. Methods: Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing. Results: Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non‐SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05). Conclusions: The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction. [ABSTRACT FROM AUTHOR]

Serial crystallography has emerged as an important tool for structural studies of integral membrane proteins. The ability to collect data from micrometre-sized weakly diffracting crystals at room temperature with minimal radiation damage has opened many new opportunities in time-resolved studies and drug discovery. However, the production of integral membrane protein microcrystals in lipidic cubic phase at the desired crystal density and quantity is challenging. This paper introduces VIALS (versatile approach to high-density microcrystals in lipidic cubic phase for serial crystallography), a simple, fast and efficient method for preparing hundreds of microlitres of high-density microcrystals suitable for serial X-ray diffraction experiments at both synchrotron and free-electron laser sources. The method is also of great benefit for rational structure-based drug design as it facilitates in situ crystal soaking and rapid determination of many cocrystal structures. Using the VIALS approach, room-temperature structures are reported of (i) the archaerhodopsin-3 protein in its dark-adapted state and 110 ns photocycle intermediate, determined to 2.2 and 1.7 Å, respectively, and (ii) the human A2A adenosine receptor in complex with two different ligands determined to a resolution of 3.5 Å. [ABSTRACT FROM AUTHOR]

Background and Aims: Extracellular vesicles (EVs) have emerged as a potential source of circulating biomarkers in liver disease. We evaluated circulating AV+ EpCAM+ CD133+ EVs as a potential biomarker of the transition from simple steatosis to steatohepatitis. Methods: EpCAM and CD133 liver proteins and EpCAM+ CD133+ EVs levels were analysed in 31 C57BL/6J mice fed with a chow or high fat, high cholesterol and carbohydrates diet (HFHCC) for 52 weeks. The hepatic origin of MVs was addressed using AlbCrexmT/mG mice fed a Western (WD) or Dual diet for 23 weeks. Besides, we assessed plasma MVs in 130 biopsy‐proven NAFLD patients. Results: Hepatic expression of EpCAM and CD133 and EpCAM+ CD133+ EVs increased during disease progression in HFHCC mice. GFP+ MVs were higher in AlbCrexmT/mG mice fed a WD (5.2% vs 12.1%) or a Dual diet (0.5% vs 7.3%). Most GFP+ MVs were also positive for EpCAM and CD133 (98.3% and 92.9% respectively), suggesting their hepatic origin. In 71 biopsy‐proven NAFLD patients, EpCAM+ CD133+ EVs were significantly higher in those with steatohepatitis compare to those with simple steatosis (286.4 ± 61.9 vs 758.4 ± 82.3; p < 0.001). Patients with ballooning 367 ± 40.6 vs 532.0 ± 45.1; p = 0.01 and lobular inflammation (321.1 ± 74.1 vs 721.4 ± 80.1; p = 0.001), showed higher levels of these EVs. These findings were replicated in an independent cohort. Conclusions: Circulating levels of EpCAM+ CD133+ MVs in clinical and experimental NAFLD were increased in the presence of steatohepatitis, showing high potential as a non‐invasive biomarker for the evaluation and management of these patients. [ABSTRACT FROM AUTHOR]

Background: Autosomal dominant spinocerebellar ataxia 36 (SCA36) is caused by hexanucleotide repeat expansion in the NOP56 gene. Objectives: To assess frequency, clinical and genetic features of SCA36 in Eastern Spain. Methods: NOP56 expansion was tested in a cohort of undiagnosed cerebellar ataxia families (n = 84). Clinical characterization and haplotype studies were performed. Results: SCA36 was identified in 37 individuals from 16 unrelated families. It represented 5.4% of hereditary ataxia patients. The majority were originally from the same region and displayed a shared haplotype. Mean age at onset was 52.5 years. Non‐ataxic features included: hypoacusis (67.9%), pyramidal signs (46.4%), lingual fasciculations/atrophy (25%), dystonia (17.8%), and parkinsonism with evidence of dopaminergic denervation (10.7%). Conclusions: SCA36 is a frequent cause of hereditary ataxia in Eastern Spain, and is associated with a strong founder effect. SCA36 analysis should be considered prior to other studies, especially in AD presentations. Parkinsonism reported here broadens SCA36 clinical spectrum. [ABSTRACT FROM AUTHOR]

Background: Viral lower respiratory tract infections (LRTI) are the leading cause of hospitalization in children. In Catalonia (Spain), information is scarce about the burden of viral LRTIs in paediatric hospitalizations. The aim of this study is to describe epidemiological, clinical, virological and economic features of paediatric hospitalizations due to viral LRTI. Methods: From October 2012 to December 2020, children aged <16 years admitted to a tertiary paediatric hospital in Catalonia (Spain) with confirmed viral LRTI were included in the study. Virus seasonality, prevalence, age and sex distribution, clinical characteristics, hospital costs and bed occupancy rates were determined. Results: A total of 3,325 children were included (57.17% male, 9.44% with comorbidities) accounting for 4056 hospitalizations (32.47% ≤ 12 months): 53.87% with wheezing/asthma, 37.85% with bronchiolitis and 8.28% with pneumonia. The most common virus was respiratory syncytial virus (RSV) (52.59%). Influenza A was associated with pneumonia (odds ratio [OR] 7.75) and caused longer hospitalizations (7 ± 31.58 days), while RSV was associated with bronchiolitis (OR 6.62) and was the most frequent reason for admission to the paediatric intensive care unit (PICU) (11.23%) and for respiratory support (78.76%). Male sex, age ≤12 months, chronic conditions and bronchiolitis significantly increased the odds of PICU admission. From October to May, viral LRTIs accounted for 12.36% of overall hospital bed days. The total hospitalization cost during the study period was €16,603,415. Conclusions: Viral LRTIs are an important cause of morbidity, hospitalization and PICU admission in children. The clinical burden is associated with significant bed occupancy and health‐care costs, especially during seasonal periods. [ABSTRACT FROM AUTHOR]

Objective: Duchenne muscular dystrophy (DMD) exon 45–55 deletion (del45–55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. Methods: This cross‐sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. Results: The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index‐case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45–57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. Interpretation: We confirmed that del45–55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793–806 [ABSTRACT FROM AUTHOR]

Background: The single nucleotide polymorphism (SNP) (rs10401670) of the RETN gene has been associated with metabolic disorder in obese subjects and has scarcely been evaluated after dietary interventions. The present study aimed to analyse the effects of the rs10401670 RETN gene polymorphism on metabolic changes secondary to weight loss and secondary to a high‐fat hypocaloric diet with a Mediterranean dietary pattern. Methods: A Caucasian population comprising 284 obese patients without diabetes mellitus was analysed. Before and after 3 months of a high‐fat hypocaloric diet with a Mediterranean pattern, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. A statistical analysis was conducted for the combined CT and TT as a group and for wild‐type CC as a second group. Results: Decreases in weight, body mass index (BMI), fat mass, systolic blood pressure and waist circumference were similar in both genotypes groups. In T allele carriers, insulin, homeostatic model assessment for insulin resistance (HOMA‐IR), triglycerides and C‐reactive protein levels were decreased. The decrease in these parameters was statistically significant for triglycerides (−22.3 ± 9.3 mg dl–1: p = 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1: p = 0.03), insulin (−7.4 ± 2.9 mUI L–1: p = 0.03) and HOMA‐IR (−2.4 ± 1.0: p = 0.02). Leptin levels were decreased in both genotypes groups after the hypocaloric diet, as well as the anthropometric parameters BMI, weight, waist circumference and fat mass. Resistin and adiponectin levels remained unchanged in both groups. Conclusions: In the present study, we have detected a significant association between the T allele of this SNP and a better response of insulin resistance, triglycerides and C‐reactive protein compared to non T allele carriers after weight loss with a high‐fat hypocaloric diet and a Mediterranean diet. Key points: In T allele carriers of the rs10401670 variant, insulin, homeostatic model assessment for insulin resistance (HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.Leptin levels were decreased in both genotypes groups (carriers and non T allele carriers) after the hypocaloric diet, as well as the anthropometric parameters body mass index, weight, waist circumference and fat mass.Resistin and adiponectin levels remained unchanged in both groups. [ABSTRACT FROM AUTHOR]

Background & Aims: Non‐alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non‐alcoholic steatohepatitis (NASH) is largely unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain. Methods: This was an observational, retrospective, cross‐sectional, population‐based study with merged data from two Spanish datasets: a large (N = 12 246) population‐based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi‐centric biopsy‐proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy‐proven cohort. Results: From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval [95% CI]: 2.53‐11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13–8.75). In the biopsy‐proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2‐4). The estimated prevalence of NASH F2‐3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29–5.98) and 0.70% (95% CI 0.10–4.95) respectively. Conclusions: These estimations provide an accurate picture of the current prevalence of NASH‐related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available. [ABSTRACT FROM AUTHOR]

In macromolecular crystallography, radiation damage limits the amount of data that can be collected from a single crystal. It is often necessary to merge data sets from multiple crystals; for example, small‐wedge data collections from micro‐crystals, in situ room‐temperature data collections and data collection from membrane proteins in lipidic mesophases. Whilst the indexing and integration of individual data sets may be relatively straightforward with existing software, merging multiple data sets from small wedges presents new challenges. The identification of a consensus symmetry can be problematic, particularly in the presence of a potential indexing ambiguity. Furthermore, the presence of non‐isomorphous or poor‐quality data sets may reduce the overall quality of the final merged data set. To facilitate and help to optimize the scaling and merging of multiple data sets, a new program, xia2.multiplex, has been developed which takes data sets individually integrated with DIALS and performs symmetry analysis, scaling and merging of multi‐crystal data sets. xia2.multiplex also performs analysis of various pathologies that typically affect multi‐crystal data sets, including non‐isomorphism, radiation damage and preferential orientation. After the description of a number of use cases, the benefit of xia2.multiplex is demonstrated within a wider autoprocessing framework in facilitating a multi‐crystal experiment collected as part of in situ room‐temperature fragment‐screening experiments on the SARS‐CoV‐2 main protease. [ABSTRACT FROM AUTHOR]

Background and Aim: Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic‐associated fatty liver disease (MAFLD). Methods: Spanish multicenter study including 1893 biopsy‐proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow‐up (4.7 ± 3.8 years). Results: Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P =.0001). More than 70% of non‐NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P <.0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P =.015). Death and decompensated cirrhosis were similar between these. Conclusions: The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death. [ABSTRACT FROM AUTHOR]

The substrate‐binding protein YfeA (also known as YPO2439 or y1897) is a polyspecific metal‐binding protein that is crucial for nutrient acquisition and virulence in Yersinia pestis, the causative microbe of plague. YfeA folds into a monomeric c‐clamp like other substrate‐binding proteins and has two metal‐binding sites (sites 1 and 2). Site 2 is a bidentate surface site capable of binding Zn and Mn atoms and is a unique feature of YfeA. Occasionally, the site 2 residues of two YfeA molecules will cooperate with the histidine tag of a third YfeA molecule in coordinating the same metal and lead to metal‐dependent crystallographic packing. Here, three crystal structures of YfeA are presented at 1.85, 2.05 and 2.25 Å resolution. A comparison of the structures reveals that the metal can be displaced at five different locations ranging from ∼4 to ∼16 Å away from the canonical site 2. These observations reveal different configurations of site 2 that enable cooperative metal binding and demonstrate how site 2 is dynamic and freely available for inter‐protein metal coordination. [ABSTRACT FROM AUTHOR]

Benthic iron (Fe) fluxes from continental shelf sediments are an important source of Fe to the global ocean, yet the magnitude of these fluxes is not well constrained. Processing of Fe in sediments is of particular importance in the Arctic Ocean, which has a large shelf area and Fe limitation of primary productivity. In the Arctic fjords of Svalbard, glacial weathering delivers high volumes of Fe‐rich sediment to the fjord benthos. Benthic redox cycling of Fe proceeds through multiple pathways of reduction (i.e., dissimilatory iron reduction and reduction by hydrogen sulfide) and re‐oxidation. There are few estimates of the magnitude and controlling factors of the benthic Fe flux in Arctic fjords. We collected cores from two Svalbard fjords (Kongsfjorden and Lilliehöökfjorden), measured dissolved Fe2+ concentrations using a two‐dimensional sensor, and analyzed iron, manganese, carbon, and sulfur species to study benthic Fe fluxes. Benthic fluxes of Fe2+ vary throughout the fjords, with a "sweet spot" mid‐fjord controlled by the availability of organic carbon linked to sedimentation rates. The flux is also impacted by fjord circulation and sea ice cover, which influence overall mineralization rates in the sediment. Due to ongoing Arctic warming, we predict an increase in the benthic Fe2+ flux with reduced sea ice cover in some fjords and a decrease in the Fe2+ flux with the retreat of tidewater glaciers in other regions. Decreasing benthic Fe2+ fluxes in fjords may exacerbate Fe limitation of primary productivity in the Arctic Ocean. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) is a liver‐derived hormone with pleiotropic beneficial effects on metabolism. Paradoxically, FGF21 levels are elevated in metabolic diseases. Interventions that restore metabolic homeostasis reduce FGF21. Whether abnormalities in FGF21 secretion or resistance in peripheral tissues is the initiating factor in altering FGF21 levels and function in humans is unknown. A genetic approach is used to help resolve this paradox. The authors demonstrate that the primary event in dysmetabolic phenotypes is the elevation of FGF21 secretion. The latter is regulated by translational reprogramming in a genotype‐ and context‐dependent manner. To relate the findings to tissues outcomes, the minor (A) allele of rs838133 is shown to be associated with increased hepatic inflammation in patients with metabolic associated fatty liver disease. The results here highlight a dominant role for translation of the FGF21 protein to explain variations in blood levels that is at least partially inherited. These results provide a framework for translational reprogramming of FGF21 to treat metabolic diseases. [ABSTRACT FROM AUTHOR]

Epicatechin (EC) is a very abundant flavonoid in vegetable tissues that presents high antioxidant activity in living systems. The minimum inhibitory concentration (MIC) of (‐)EC was determined in three species of bacteria commonly associated with foodborne illness of plant origin: Listeria (L.) monocytogenes, Escherichia (E.) coli ‐serogroups O157: H7 and O111‐ and Bacillus (B.) cereus; two strains of probiotic‐type lactic acid bacteria (PT‐LAB) and two control strains. All 10 strains were assayed under three temperature conditions (30º, 10º, and 4ºC) and at each temperature under two pH conditions (6.7 and 5.5). Mean EC MIC values were generally lower at refrigeration (4º and 10ºC) temperatures and at standard pH (6.7). By inoculating with each of the strains separately, both melon juice (MJ) and MJ supplemented with EC (ECSMJ), at the accepted maximum sensorial limit, and storing them at 4ºC for 10 days; the final counts (CFU/mL) were lower for ECSMJ than for plain MJ both for pathogenic bacteria and for PT‐LAB. The presence of EC during refrigerated storage counteracted the ability of MJ as a growth medium for all the pathogenic bacteria. ECSMJ increased the antioxidant activity of MJ significantly to levels similar to those of EC alone. (‐) Epicathechin would be a promising ingredient for increasing the functional properties of "Piel de Sapo" MJ (phenolic compounds and antioxidant ability) while contributing to improving the safety of this type of juice during prolonged refrigerated storage at 4ºC. [ABSTRACT FROM AUTHOR]

Aim: To retrospectively analyse hospital outpatient treatment (HOT) withdrawal due to unacceptable toxicity at our hospital. Information regarding unacceptable toxicity leading to treatment withdrawal was recorded. Methods: HOT interruptions because of unacceptable toxicity were identified from the Register of Patients and Treatments (RPT) (January 2014 to December 2017). Information regarding the demographic and clinical characteristics of patients, adverse drug reactions (ADRs) and drug treatments was retrieved from electronic health records. Causality and previous knowledge of ADRs were assessed according to the Spanish Pharmacovigilance System algorithm. Information regarding HOT risk management plans (RMPs) and their classification as inverted black triangle medicines was obtained from the European Medicines Agency (EMA). Results: HOTs were withdrawn due to unacceptable toxicity in 136 (1.5%) registries corresponding to 135 (1.7%) patients. Fifty‐one different HOTs (38.6% of those registered) were involved in 240 ADR/HOT pairs: 24 (47%) were additional monitoring medicines and 37 (72.5%) were EMA RMPs. The most frequent medicines involved in ADRs were lenalidomide (30, 12.5%) (mainly neutropenia, thrombocytopenia and bicytopenia), bevacizumab (19, 7.9%) (mainly venous and pulmonary thromboembolism) and sunitinib (13, 5.4%) (mainly thromboembolic events, diarrhoea and worsening of chronic renal failure). Cytopenia (40, 17.3%), diarrhoea (15, 6.5%), asthenia (9, 3.9%) and neuropathy (6, 2.6%) were the most frequent ADRs. All ADRs were severe, 10 (6 patients) had been poorly described or were unknown and only 9 (5 patients) had been reported by spontaneous notification. Conclusions: Valuable information regarding severe and unknown ADRs was obtained from the RPT. Such registers are useful tools to complement spontaneous ADR notifications. [ABSTRACT FROM AUTHOR]

Members of the ATP‐binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP‐binding cassette in the nucleotide‐binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes. In recent years, it has become increasingly evident that the distinct TMD folds are best suited to categorize the multitude of ABC transporters. We therefore propose a new ABC transporter classification that is based on structural homology in the TMDs. [ABSTRACT FROM AUTHOR]

Background & Aims: Low‐grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients. Patients & Methods: Multicenter cross‐sectional study including consecutive patients with biopsy‐proven NAFLD. Demographic, metabolic and fibrosis‐related variables were collected. Circulating bacterial antigens were quantified in blood. Toll‐like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro. Results: Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI < 30 (63.4%) and 163 patients with BMI > 30 (77.3%) (P =.014). HOMA‐IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non‐obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro‐inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF‐α and IL‐6, in both BMI subgroups of patients. Age independently influenced TNF‐α and IL‐6 in non‐obese patients, and TNF‐α in obese patients. Conclusion: Serum circulating bacterial antigens as well as age were BMI‐independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients. [ABSTRACT FROM AUTHOR]

In this article, a new approach to experimental phasing for macromolecular crystallography (MX) at synchrotrons is introduced and described for the first time. It makes use of automated robotics applied to a multi‐crystal framework in which human intervention is reduced to a minimum. Hundreds of samples are automatically soaked in heavy‐atom solutions, using a Labcyte Inc. Echo 550 Liquid Handler, in a highly controlled and optimized fashion in order to generate derivatized and isomorphous crystals. Partial data sets obtained on MX beamlines using an in situ setup for data collection are processed with the aim of producing good‐quality anomalous signal leading to successful experimental phasing. [ABSTRACT FROM AUTHOR]

A retrospective study was conducted using 250 clinical records of brown trout (Salmo trutta L.) with saprolegniosis by Saprolegnia parasitica, which had been collected from 8 rivers and 1 fish farm in the province of León (Spain). A geographic information system (GIS) was used to obtain skin lesion distribution patterns in males and females. Lesions in wild brown trout affected 15.31 ± 13.33% of the body surface, with a mean of 12.76 ± 6.56 lesions per fish. In addition, 51.23% of wild trout presented lesions with necrosis of the skin or fins. The pattern obtained when not distinguishing between sexes indicated that saprolegniosis lesions are mainly located above the lateral line and most frequently affect the dorsal cephalic region, the adipose fin, the peduncle and the caudal fin. However, differences were observed between males and females. Farmed trout presented a lower percentage of affected body surface (2.06 ± 4.36) and a lower number of lesions with and without necrosis because they received preventive treatment for saprolegniosis. [ABSTRACT FROM AUTHOR]

We have developed electrochromic inks and electrolyte materials to enable mass production of flexible electrochromic displays (ECDs) and other optoelectronic devices by screen printing. Here we present a new screen‐printable ink incorporating electrochromic polymer, poly(3,4‐propylenedioxythiophene)bis(ethylhexyloxy), referred to here as ECP‐Magenta, and antimony‐doped tin oxide (ATO/TiO2) particles to facilitate electron transport. Their dispersion in a P(VDF‐co‐HFP) binder leads to the formation of a new electrochromic ink that is suitable for screen printing. This strategy opens the door to the preparation of similar electrochromic inks based on other organic or polymeric compounds. This approach is scalable and can applied to different fields. Ion gels (IGs) composed of P(VDF‐co‐HFP) and room temperature ionic liquids (RTILs) are promising solid‐state electrolytes with high ionic conductivity, flexibility, elasticity and eco‐friendliness. The electrochemical features of different ion gels were analyzed as a function of composition and nature of the ionic liquid. Hence, new formulations of IGs were developed, evaluated by Electrochemical Impedance Spectroscopy, Cyclic Voltammetry, before being incorporated into ECDs. The electrochromic performance of ECP‐Magenta ink combined with the RTIL‐based IG was evaluated by terms of spectroelectrochemistry showing that fully flexible ECD operating at voltages below 1 V can be screen‐printed. [ABSTRACT FROM AUTHOR]

Efficient sample delivery is an essential aspect of serial crystallography at both synchrotrons and X‐ray free‐electron lasers. Rastering fixed target chips through the X‐ray beam is an efficient method for serial delivery from the perspectives of both sample consumption and beam time usage. Here, an approach for loading fixed targets using acoustic drop ejection is presented that does not compromise crystal quality, can reduce sample consumption by more than an order of magnitude and allows serial diffraction to be collected from a larger proportion of the crystals in the slurry. [ABSTRACT FROM AUTHOR]

In the structural biology of bacterial substrate‐binding proteins (SBPs), a growing number of comparisons between substrate‐bound and substrate‐free forms of metal atom‐binding (cluster A‐I) SBPs have revealed minimal structural differences between forms. These observations contrast with SBPs that bind substrates such as amino acids or nucleic acids and may undergo >60° rigid‐body rotations. Substrate transfer in these SBPs is described by a Venus flytrap model, although this model may not apply to all SBPs. In this report, structures are presented of substrate‐free (apo) and reconstituted substrate‐bound (holo) YfeA, a polyspecific cluster A‐I SBP from Yersinia pestis. It is demonstrated that an apo cluster A‐I SBP can be purified by fractionation when co‐expressed with its cognate transporter, adding an alternative strategy to the mutagenesis or biochemical treatment used to generate other apo cluster A‐I SBPs. The apo YfeA structure contains 111 disordered protein atoms in a mobile helix located in the flexible carboxy‐terminal lobe. Metal binding triggers a 15‐fold reduction in the solvent‐accessible surface area of the metal‐binding site and reordering of the 111 protein atoms in the mobile helix. The flexible lobe undergoes a 13.6° rigid‐body rotation that is driven by a spring‐hammer metal‐binding mechanism. This asymmetric rigid‐body rotation may be unique to metal atom‐binding SBPs (i.e. clusters A‐I, A‐II and D‐IV). [ABSTRACT FROM AUTHOR]

The 1,2,3‐triazole has been successfully utilized as an amide bioisostere in multiple therapeutic contexts. Based on this precedent, triazole analogues derived from VX‐809 and VX‐770, prominent amide‐containing modulators of the cystic fibrosis transmembrane conductance regulator (CFTR), were synthesized and evaluated for CFTR modulation. Triazole 11, derived from VX‐809, displayed markedly reduced efficacy in F508del‐CFTR correction in cellular TECC assays in comparison to VX‐809. Surprisingly, triazole analogues derived from potentiator VX‐770 displayed no potentiation of F508del, G551D, or WT‐CFTR in cellular Ussing chamber assays. However, patch clamp analysis revealed that triazole 60 potentiates WT‐CFTR similarly to VX‐770. The efficacy of 60 in the cell‐free patch clamp experiment suggests that the loss of activity in the cellular assay could be due to the inability of VX‐770 triazole derivatives to reach the CFTR binding site. Moreover, in addition to the negative impact on biological activity, triazoles in both structural classes displayed decreased metabolic stability in human microsomes relative to the analogous amides. In contrast to the many studies that demonstrate the advantages of using the 1,2,3‐triazole, these findings highlight the negative impacts that can arise from replacement of the amide with the triazole and suggest that caution is warranted when considering use of the 1,2,3‐triazole as an amide bioisostere. Trying out the triazole as an amide bioisostere in CFTR modulators VX‐809 and VX‐770 revealed that triazole derivatives of VX‐809 and VX‐770 displayed significantly decreased efficacy or inactivity in cellular assays. In addition, triazole derivatives displayed decreased metabolic stability in hepatic microsomal assays. These findings represent an important counterpoint to the many successful uses of the triazole as an amide bioisostere. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy is a severe complication of both chronic and acute liver diseases. The term hepatic encephalopathy stems from the belief that hepatic insufficiency is its fundamental etiopathogenic factor. However, most clinical cases show liver failure along with mesenteric venous portal hypertension. This portal hypertension would explain the abnormal mechanical forces suffered by the digestive tract in the early stages of the disorder. These forces could regulate some gut biochemical pathological pathways in a process known as mechanotransduction. Thus, portal hypertension would begin with the establishment of a mechanotransduced afferent or sensory inflammatory gut‐brain pathway, resulting in functional and structural changes in the central nervous system. In this review, we will revisit the term "hepatic encephalopathy" in light of new results where portal hypertension occurs before liver failure and is accompanied by brain changes. Moreover, we will point out cellular links that can explain the microbiota, immune, gut, and brain axis disturbances found in this disorder. [ABSTRACT FROM AUTHOR]

The probiotic activity of 15 bacterial isolates that inhibit Saprolegnia parasitica in vitro was tested for the biocontrol of saprolegniosis in rainbow trout (Oncorhynchus mykiss Walbaum), adding the bacteria to tank water for 14 days at a concentration of 106 bacteria ml−1 water. Pseudomonas fluorescens LE89 and Pseudomonas fluorescens LE141 were effective in controlling experimental infection with S. parasitica since of the fish treated with LE89, 24.5% ± 16.27% (p < 0.05) became infected, as did 42.8% ± 8.41% (p < 0.05) of those treated with LE141. Given their protective effect when administered in water, their effect was also studied when administered in feed before and after experimental infection. Both bacterial isolates survived low pH levels and the action of bile, grew in skin and intestinal mucus, were resistant to several antibiotics and survived in feed; however, neither of the two isolates prevented S. parasitica infection when administered in feed. [ABSTRACT FROM AUTHOR]

Summary: Background: Metabolically healthy obesity (MHO) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non‐alcoholic fatty liver disease (NAFLD)‐related outcomes compared with non‐obese subjects with a few metabolic risks. Aim: To define the impact of the metabolic status on the NAFLD‐related outcomes, beyond the presence of obesity. Methods: We designed a multicentre cross‐sectional study, including 1058 biopsy‐proven NAFLD patients. Metabolically healthy status was strictly defined by the lack of metabolic risk factors (diabetes mellitus, low HDL, hypertriglyceridemia, arterial hypertension). Non‐alcoholic steatohepatitis (NASH) and significant fibrosis (F2‐F4) were identified by liver biopsy. Chronic kidney disease epidemiology collaboration equation was calculated for kidney function and the atherogenic index of plasma (AIP) for cardiovascular risk. Results: Metabolically healthy (OR 1.88; P = 0.050) and unhealthy obesity (OR 3.47: P < 0.0001), and unhealthy non‐obesity (OR 3.70; P < 0.0001) were independently associated with NASH together with homeostatic model assessment (HOMA), ALT, and platelets. Significant fibrosis was more frequently observed in the presence of adverse metabolic conditions in obese (OR 3.89; P = 0.003) and non‐obese patients (OR 3.92; P = 0.002), and independently associated with platelets, albumin, ALT, HOMA, and age. The number of metabolic factors determined the risk of NASH and significant fibrosis. Glomerular filtration rate was lower in unhealthy (91.7 ± 18) than healthy metabolism (95.6 ± 17) (P = 0.007). AIP was higher in adverse metabolic conditions (P = 0.0001). Metabolically unhealthy non‐obesity showed higher liver damage (NASH 55.8% vs 42.4%; P < 0.05; significant fibrosis 31.7% vs 11.4%; P < 0.0001) and cardiovascular risk (P < 0.0001) than healthy obesity. Conclusions: Metabolic unhealthy status showed a greater impact on NASH, significant fibrosis, kidney dysfunction, and atherogenic profile than obesity. However, metabolically healthy obesity was not a full healthy condition. We should focus our messages especially on patients with adverse metabolic conditions. [ABSTRACT FROM AUTHOR]

Biological chelating molecules called siderophores are used to sequester iron and maintain its ferric state. Bacterial substrate-binding proteins (SBPs) bind iron-siderophore complexes and deliver these complexes to ATP-binding cassette (ABC) transporters for import into the cytoplasm, where the iron can be transferred from the siderophore to catalytic enzymes. In Yersinia pestis, the causative agent of plague, the Yersinia iron-uptake (Yiu) ABC transporter has been shown to improve iron acquisition under iron-chelated conditions. The Yiu transporter has been proposed to be an iron-siderophore transporter; however, the precise siderophore substrate is unknown. Therefore, the precise role of the Yiu transporter in Y. pestis survival remains uncharacterized. To better understand the function of the Yiu transporter, the crystal structure of YiuA (YPO1310/y2875), an SBP which functions to present the iron-siderophore substrate to the transporter for import into the cytoplasm, was determined. The 2.20 and 1.77 Å resolution X-ray crystal structures reveal a basic triad binding motif at the YiuA canonical substrate-binding site, indicative of a metal-chelate binding site. Structural alignment and computational docking studies support the function of YiuA in binding chelated metal. Additionally, YiuA contains two mobile helices, helix 5 and helix 10, that undergo 2-3 Å shifts across crystal forms and demonstrate structural breathing of the c-clamp architecture. The flexibility in both c-clamp lobes suggest that YiuA substrate transfer resembles the Venus flytrap mechanism that has been proposed for other SBPs. [ABSTRACT FROM AUTHOR]

Burial of biogenic silica (bSitotal) in high sedimentation rate continental margins remains highly uncertain. Cosmogenic 32Si (t1/2~140 years) can be used to trace the fates of bSitotal postdeposition, including as opal (bSiopal) and diagenetically altered opal (bSialtered), the latter dominantly authigenic clay (bSiclay). To determine the magnitude and form of bSitotal storage in coastal sediments, conventional operational leaches targeting bSiopal and bSialtered (including bSiclay) were modified for large-scale samples necessary for measurement of 32Si. The 32Si activity was used to estimate total biogenic silica burial (bSitotal = bSiopal + bSialtered) in several depositional settings: Gulf of Papua, Gulf of Mexico, Long Island Sound, and in the previously studied Amazon-Guianas deltaic system. In subtropical and temperate regions, 32Si was detected in both traditional biogenic silica leaches (bSiopal) and residual authigenic clays. Traditional bSiopal and modified operational leaches designed to target the most reactive authigenic silicates (~bSialtered) consistently underestimate authigenic clay formation (bSiclay) and thus the magnitude of bSitotal burial in temperate coastal zones and subtropical deltas by 2-4-fold. In tropical deltas, 32Si activities in the residual fraction after removal of bSiopal demonstrate rapid and almost complete alteration of initial bSiopal to new forms, most likely bSiclay. Globally, 4.5-4.9 Tmol/yr Si may be trapped in marine nearshore deposits as rapidly formed clay (bSiclay), 100% of the 'missing silica sink' in the marine silica budget. [ABSTRACT FROM AUTHOR]

Corn residue removed from Midwestern farms is a large potential source of biomass for cellulosic bioenergy production in the US long-term harvesting of biomass, however, may lead to the degradation of soil quality unless management practices that compensate for the removal of biomass are used. In this study, biochar amendments and long-term crop rotations that include triticale and switchgrass with corn and soybeans were hypothesized to reduce the negative effects of biomass harvesting on soil quality. Chemical breakthrough curves, measured for intact soil cores indicate that crop rotations that include switchgrass or triticale increased both retardation and dispersivity relative to conventional rotations and biochar amendments decreased dispersivity relative to controls. Across all crop rotations, there was an increase in total soil C and N, soil C/N ratio, pH and gravity drained water content and a decrease in bulk density for soils treated with biochar relative to no-biochar controls. No significant effect of biochar age on soil physical properties was measured in 2014 but significant increases with biochar age were found for total soil C and N in 2016, suggesting a synergistic interaction (negative priming). Continuous switchgrass stands were found to build soil organic C and N, increase retention of plant available P and K and lower bulk density relative to the continuous corn cropping system. The results suggested that soil biochar amendments and crop rotations that included switchgrass helped mitigate some of the adverse effects of biomass harvesting on soil quality. [ABSTRACT FROM AUTHOR]

Glutathione peroxidase-like enzymes (GPXLs) constitute a family of eight peroxidases in Arabidopsis thaliana. In contrast to the eponymous selenocysteine glutathione peroxidases in mammalian cells that use glutathione as electron donor, GPXLs rely on cysteine instead of selenocysteine for activity and depend on the thioredoxin system for reduction. Although plant GPXLs have been implicated in important agronomic traits such as drought tolerance, photooxidative tolerance and immune responses, there remain major ambiguities regarding their subcellular localization. Because their site of action is a prerequisite for an understanding of their function, we investigated the localization of all eight GPXLs in stable Arabidopsis lines expressing N-terminal and C-terminal fusions with redox-sensitive green fluorescent protein 2 (roGFP2) using confocal microscopy. GPXL1 and GPXL7 were found in plastids, while GPXL2 and GPXL8 are cytosolic nuclear. The N-terminal target peptide of GPXL6 is sufficient to direct roGFP2 into mitochondria. Interestingly, GPXL3, GPXL4 and GPXL5 all appear to be membrane bound. GPXL3 was found exclusively in the secretory pathway where it is anchored by a single N-terminal transmembrane domain. GPXL4 and GPXL5 are anchored to the plasma membrane. Presence of an N-terminal myristoylation motif and genetic disruption of membrane association through targeted mutagenesis point to myristoylation as essential for membrane localization. [ABSTRACT FROM AUTHOR]

Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that YfeA is polyspecific and can alter its substrate specificity. In minimal-media experiments, YfeA crystals grown after iron supplementation showed a threefold increase in iron fluorescence emission over the iron fluorescence emission from YfeA crystals grown from nutrient-rich conditions, and YfeA crystals grown after manganese supplementation during overexpression showed a fivefold increase in manganese fluorescence emission over the manganese fluorescence emission from YfeA crystals grown from nutrient-rich conditions. In all experiments, the YfeA crystals produced the strongest fluorescence emission from zinc and could not be manipulated otherwise. Additionally, this report documents the discovery of a novel surface metal-binding site that prefers to chelate zinc but can also bind manganese. Flexibility across YfeA crystal forms in three loops and a helix near the buried metal-binding site suggest that a structural rearrangement is required for metal loading and unloading. [ABSTRACT FROM AUTHOR]

The effects of no-take marine reserve (NTMR) protection and changes in benthic habitat on fusiliers (family Caesionidae) were investigated at four small Philippine offshore islands on time scales of 10-31 years. Fusiliers are highly mobile, schooling, medium-sized planktivorous fish that generally feed 'off-reef.' For these reasons, and given the small size of the NTMRs (3.6-37.5 ha) in this study, it was predicted that fusilier density would be unlikely to show clear effects of NTMR protection, or to respond to changes in benthic habitat. In contrast to predictions, clear NTMR effects were observed on fusilier density at three of the four NTMRs, with durations of protection from 14 to 31 years. Furthermore, the study provided strong evidence that benthic variables, specifically cover of live hard coral and dead substratum, affect the density of fusiliers. This effect of benthic habitat on density was highlighted by several major environmental disturbances that caused shifts in the benthic habitat from live hard coral to dead substratum. For two of the three most abundant species of fusiliers individually, and for all three of them combined ( Pterocaesio pisang + Caesio caerulaurea + Pterocaesio digramma/tessellata), as live hard coral cover decreased, fish density decreased. It is hypothesized that these 'off-reef' daytime feeders may have such a strong association with live hard coral cover because they use this habitat as nocturnal sleeping sites. Multivariate analyses indicated that, across all sites and times sampled, cover of live hard coral and dead substratum accounted for 38% of the variation in fish assemblage structure. These results are important as there are very few reports in the published literature of strong effects of NTMR protection or changes in benthic habitat on the density and assemblage structure of fusiliers. [ABSTRACT FROM AUTHOR]

Background The main genetic variant described in NPY gene is rs16147 (G-399A) and it is located within the promoter region upstream of the gene for neropeptide Y ( NPY). We evaluate the effects of the rs16147 NPY gene polymorphism on metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adult obese patients. Methods A population of 82 obese patients was analysed in an interventional design of one arm. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for combined GA and AA as a group (minor allele group) and GG as second group (major allele group) (dominant model). Results In A allele carriers, the mean (SD) decrease in weight was −2.8 (2.2) kg [decrease in non A allele carriers −2.6 (1.1) kg, P > 0.05), body mass index was −1.2 (0.6) kg m−2 [decrease in non A allele carriers −1.1 (0.8) kg m−2, P > 0.05], fat mass was −1.7 (1.4) kg [decrease in non A allele carriers −1.9 (1.3) kg, P > 0.05], waist circumference was −5.5 (3.4) cm [decrease in non A allele carriers −3.7 (4.1) cm, P = 0.006], C-reactive protein (CRP) was −0.7 (0.6) mg dL−1 [decrease in non A allele carriers −0.1 (0.3) mg dL−1, P = 0.02], insulin was −1.5 (0.4) mUI L−1 [decrease in non A allele carriers −0.8 (2.0) mUI L−1, P = 0.001] and homeostasis model assessment-insulin resistance (HOMA-IR) was −0.4 (0.5) [decrease in non A allele carriers −0.2 (0.1), P = 0.005]. interleukin ( IL)-6 changes were significant in A allele carriers [−0.7 (0.2) pg mL−1] versus non A allele carriers [−0.1 (0.3) pg mL−1] ( P = 0.01). Conclusions We found that the rs164147 genotype affected the reduction of waist circumference, HOMA- IR, insulin, CRP and IL-6 levels in response to weight loss diet in obese subjects. [ABSTRACT FROM AUTHOR]

Paper has been used for a long time in the production of low-cost point-of-care (POC) detection devices, most of which rely on the detection of colored bands by the user. However, test strips rarely provide the quantitative detection of biomarkers in clinical samples. In contrast, electrochemical detection enables quantitative detection in paper-based immunoassays. Here, we demonstrate the production of a simple and economical lateral-flow electrode device using only screen printing. Contrary to previous work, this device is used to simplify the washing and detection of a short and sensitive immunomagnetic assay for myeloperoxidase (MPO) detection. As we show, after incubation of the sample with magnetic beads (MBs) and detection antibody (Ab) for only 5 min, the whole reaction mixture can be directly pipetted onto the strip. Washing and detection can then be performed, as the MBs are retained with the aid of a magnet, and minimal user intervention is needed. The obtained results reveal that MPO can be detected in 1 : 100 diluted serum with limits of detection and quantification of 0.18 and 0.62 ng mL−1, respectively, in less than 15 min. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis is one of the leading causes of death in HIV/ AIDS patients. Our aim was to in order to characterise the epidemiology, antifungal susceptibility pattern and virulence of 28 Cyptococcus sp. strains recovered from 12 AIDS patients during two years in a Spanish single institution. Antifungal susceptibility testing was performed according to the CLSI protocols. Clinical strains were molecularly characterised by serotyping, mating type, PCR fingerprinting (M13 and GACA4 microsatellites) and analysis of two rDNA regions ( IGS1 and ITS). Sequencing of the ERG11 gene was used to explore mechanisms of fluconazole resistance. Differences in virulence between species were studied in a Galleria mellonella infection model. Cryptococcus deneoformans and C. deneoformans x Cryptococcus neoformans hybrids were the most frequent variety (65%) followed by C. neoformans (35%). Strains were categorised according to 13 microsatellite genotypes and mixed infections could be detected in three patients. Twenty-nine per cent of the strains were fluconazole resistant. In one of the patients, the fluconazole resistance phenotype was associated with a point mutation in the ERG11 gene responsible for the amino acid substitution G470R. C. neoformans strains were able to kill G. mellonella larvae more efficiently than C. deneoformans and hybrids between both species. Precisely molecular characterisation of C. neoformans species is important for an accurate patient's management. [ABSTRACT FROM AUTHOR]

The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction ( STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary percutaneous coronary intervention ( PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging ( MRI) at 6 ± 2 days. Secondary endpoints were changes in left ventricular volumes and ejection fraction ( LVEF) at 130 ± 10 days post- PPCI and adverse events during the first year. No significant differences in baseline characteristics were observed between groups. MRI was performed in 108 patients (86.4%). Myocardial infarct size by MRI evaluated 6 ± 2 days post- PPCI, did not differ between melatonin and placebo groups ( P=.63). Infarct size assessed by MRI at 130 ± 10 days post- PPCI, performed in 91 patients (72.8%), did not show statistically significant differences between groups ( P=.27). The recovery of LVEF from 6 ± 2 to 130 ± 10 days post- PPCI was greater in the placebo group (60.0 ± 10.4% vs 53.1 ± 12.5%, P=.008). Both left ventricular end-diastolic and end-systolic volumes were lower in the placebo group ( P=.01). The incidence of adverse events at 1 year was comparable in both groups ( P=.150). Thus, in a nonrestricted STEMI population, intravenous and intracoronary melatonin was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution. Likewise, there is lack of toxicity of melatonin with the doses used. [ABSTRACT FROM AUTHOR]

Hydrological regimes are significant drivers of fisheries production in many African Lakes due to their influence on fish habitat and food availability, breeding success, and catchability. Lake Turkana, Kenya, will undergo substantial changes in hydrology due to water regulation and extraction along the Omo River in neighboring Ethiopia, which provides over 90% of its water. The objective of this study was to predict how the lake's fisheries, which provide an important livelihood and protein source in the region, will respond to hydrological change. While variations in fishing effort are poor predictors of fisheries catch in the lake, water levels and their fluctuations strongly influence fisheries production. Seasonal oscillations play a particularly important role, and with complete loss of these oscillations, the lake's predicted fisheries yield will decrease by over two thirds. The fishery is predicted to collapse at a lake level decline of 25 m, regardless of seasonal amplitude magnitude. The lake's total littoral habitat, where fisheries are currently concentrated, will increase in surface area with lake level declines of <25 m. However, the extent of productive, dynamic littoral habitat will decrease with dampening of the lake's seasonal oscillations. The most severe habitat loss will occur in the lake's Turkwel Sector, which hosts the region's highest human population densities, and North Sector, where inter-tribal conflict over resources is common and likely to be exacerbated by lake level decline. The continued ecological functioning of Lake Turkana necessitates immediate efforts to develop and apply a water resource management plan rooted in science. [ABSTRACT FROM AUTHOR]

Reworked and fluidized fine-grained deposits in energetic settings are a major modern-day feature of river deltas and estuaries. Similar environments were probably settings for microbial evolution on the early Earth. These sedimentary systems act as efficient biogeochemical reactors with high bacterial phylogenetic diversity and functional redundancy. They are temporally rather than spatially structured, with repeated cycling of redox conditions and successive stages of microbial metabolic processes. Intense reworking of the fluidized bed entrains bacteria from varied habitats providing new, diverse genetic materials to contribute to horizontal gene transfer events and the creation of new bacterial ecotypes. These vast mud environments may act as exporters and promoters of biosphere diversity and novel adaptations, potentially on a globally important scale. [ABSTRACT FROM AUTHOR]

Mucous gels are produced by benthic animals rapidly and in copious amounts, and consequently they are a possible priming substrate whose addition in modest amounts may affect sedimentary organic matter (SOM) remineralization. The priming effect of benthic infaunal mucus was tested using mucus of the common gastropod Neverita duplicata as model substrate. Its composition is typical of marine molluscan mucus, consisting primarily of water (> 96% by weight). Salt-free dry weight constitutes 0.7% of total mucus. Relationships between C, N, and S content show the presence of N-free and S-free fractions, indicative of mucopolysaccharides, that account for approximately half of the total C present. The C/N ratios of the N-containing fraction (6.1 and 8.75 for pedal and hypobranchial mucus, respectively) are indicative of a carbohydrate-protein complex. Relatively low C/S ratios for the S-containing fraction (21.8 and 10.5 for pedal and hypobranchial mucus, respectively) and positive staining with Alcian Blue dye are indicative of S-ester and alkyl- [ABSTRACT FROM AUTHOR]

The long-term impact of biochar on soil properties and agronomic outcomes is influenced by changes in the physical and chemical properties of biochars that occur with time (aging) in soil environments. Fresh biochars, however, are often used in studies because aged biochars are generally unavailable. Therefore, a need exists to develop a method for rapid aging of biochars in the laboratory. The objectives of this study were to compare the physicochemical properties of fresh, laboratory-aged (LA), and field-aged (FA) (≥3 yr) biochars and to assess the appropriateness of a laboratory aging procedure that combines acidification, oxidation, and incubations as a mimic to field aging in neutral or acidic soil environments. Twenty-two biochars produced by fast and slow pyrolysis, and gasification techniques from five different biomass feedstocks (hardwood, corn stover, soybean stover, macadamia nut shells, and switchgrass) were studied. In general, both laboratory and field aging caused similar increases in ash-free volatile matter (% w/w), cation and anion exchange capacities, specific surface area, and modifications in oxygen-containing surface functional groups of the biochars. However, ash content increased for FA (18-195%) and decreased for LA (22-74%) biochars, and pH decreased to a greater extent for LA (2.8-6.7 units) than for FA (1.6-3.8 units) biochars. The results demonstrate that the proposed laboratory aging procedure is effective for predicting the direction of changes in biochar properties on field aging. However, in the future we recommend using a less aggressive acid treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND Snails and slugs are terrestrial gastropods representing an important biotic stress that adversely affects crop yields. These pests are typically controlled with molluscicides, which produce pollution and toxicity and further induce the evolution of resistance mechanisms, making pest management even more challenging. In our work, we have assessed the efficacy of two different plant defence activators, menadione sodium bisulphite ( MSB) and 1,2,3-benzothiadiazole-7-thiocarboxylic acid S-methyl ester ( BTH), as inducers of resistance mechanisms of the model plant for defence, Solanum lycopersicum, against the generalist mollusc Theba grasseti (Helicidae). The study was designed to test the feeding behaviour and choice of snails, and also to analyse the expression profile of different genes specifically involved in defence against herbivores and wounds. RESULTS Our data suggest that, through the downregulation of the terpene volatile genes and the production of proteinase inhibitors, treated MSB plants may be less apparent to herbivores that use herbivore-induced plant volatiles for host location. By contrast, BTH was not effective in the treatment of the pest, probably owing to an antagonistic effect derived from the induction of both salicylic-acid-dependent and jasmonic-acid-dependent pathways. CONCLUSIONS This information is crucial to determine the genetic basis of the choice of terrestrial gastropod herbivores in tomato, providing valuable insight into how the plant defence activators could control herbivore pests in plants. Our work not only reports for the first time the interaction between tomato and a mollusc pest but also presents the action of two plant defence inductors that seems to produce opposed responses by inducing resistance mechanisms through different defence pathways. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]