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Measurements in seven sites in the Campus of the University of the Balearic Islands (UIB; Mallorca, Spain) during an experimental campaign to study the contribution of local surface heterogeneities on the surface energy budget at one point have been used to characterize the differences in extreme daily temperatures between the sites during a summer month. Absolute temperature differences in this month reached up to 1.92 (with a median of 0.73) and 2.02 (median of 1.21)°C for daily maximum and minimum, respectively. Higher differences in the minimum temperature can be attributed to the stably stratified and weak turbulent conditions at night that enhance local differences in the surface energy fluxes, especially in an area with strong variability of the surface characteristics like the UIB Campus. Instead, during daytime, maximum temperature differences are smoothed due to the convection and the horizontal advection due to the sea‐breeze. Two sites with longer records allowed to study the seasonal variations of these differences, which were substantially lower in the colder months. These results suggest that relocation of observatories, even at distances as short as 200 m, may introduce important inhomogeneities in the temperature series. Therefore, raw values of series from nearby stations should not be used to infill missing data in other series without adequate statistical adjustments. [ABSTRACT FROM AUTHOR]

The homogenization of climate observational series is a needed process before undertaking confidently any study of their internal variability, since changes in the observation methods or in the surroundings of the observatories, for instance, can introduce biases in the data of the same order of magnitude than the underlying climate variations and trends. Many methods have been proposed in the past to remove the unwanted perturbations from the climatic series, and some of them have been implemented in software packages freely available on the Internet. The Spanish project MULTITEST was intended to test their performance in an automatic way with synthetic monthly series of air temperature and atmospheric precipitation, to update inter‐comparison results from former projects, especially those of the COST Action ES0601. Several networks representing different climates and station densities were used to test a variety of homogenization packages on hundreds of random samples. Results were evaluated mainly in the form of root mean squared errors and errors in the trend of the series, showing that ACMANT, followed by Climatol, minimized these errors. However, other packages performed also relatively well, even outperforming them when there were simultaneous biases of the same sign in most or all the test series. [ABSTRACT FROM AUTHOR]

The aim of time series homogenization is to remove nonclimatic effects, such as changes in station location, instrumentation, observation practices, and so on, from observed data. Statistical homogenization usually reduces the nonclimatic effects but does not remove them completely. In the Spanish "MULTITEST" project, the efficiencies of automatic homogenization methods were tested on large benchmark datasets of a wide range of statistical properties. In this study, test results for nine versions, based on five homogenization methods—the adapted Caussinus-Mestre algorithm for the homogenization of networks of climatic time series (ACMANT), "Climatol," multiple analysis of series for homogenization (MASH), the pairwise homogenization algorithm (PHA), and "RHtests"—are presented and evaluated. The tests were executed with 12 synthetic/surrogate monthly temperature test datasets containing 100–500 networks with 5–40 time series in each. Residual centered root-mean-square errors and residual trend biases were calculated both for individual station series and for network mean series. The results show that a larger fraction of the nonclimatic biases can be removed from station series than from network-mean series. The largest error reduction is found for the long-term linear trends of individual time series in datasets with a high signal-to-noise ratio (SNR), where the mean residual error is only 14%–36% of the raw data error. When the SNR is low, most of the results still indicate error reductions, although with smaller ratios than for large SNR. In general, ACMANT gave the most accurate homogenization results. In the accuracy of individual time series ACMANT is closely followed by Climatol, and for the accurate calculation of mean climatic trends over large geographical regions both PHA and ACMANT are recommended. [ABSTRACT FROM AUTHOR]

The Mid-Atlantic region of the USA has experienced increasing annual precipitation amounts in recent decades, along with more frequent extreme events of greater magnitude. Unlike many US regions that have suffered increasing drought conditions from higher evapotranspiration demand, positive trends in the Mid-Atlantic accumulated precipitation are greater than the recent increases in reference evapotranspiration. The temporal correlation between precipitation events and soil moisture capacity is essential for determining how the nature of drought has changed in the region. This analysis has shown that soil moisture scarcity has declined in nine of ten subregions of the Mid-Atlantic that were analyzed from 1985 to 2019. Two algorithms were deployed to draw this conclusion: Climatol enabled the use of the FAO-56 Penman-Monteith equation on daily observation station data for which complete records were unavailable, and the second algorithm calculated soil moisture levels on a daily basis, more accurately capturing drought conditions than common methods using weekly or monthly summaries. Although the declining drought trends were not statistically significant, a result of more extreme events and higher evapotranspiration rates, the inclusion of direct data from an expanded set of locations provides greater clarity from the trends, allowing policymakers and landowners to anticipate changes in future Mid-Atlantic irrigation water demand. [ABSTRACT FROM AUTHOR]

With regard to the climatology included in the monography on Cabrera published in 1993, the subsequent operation of two new climatological stations in the main island (Cabrera), one with temperature data, in addition to those of rainfall, and the other with complete data, including wind and humidity, has allowed to complete the previous climatology with much more local information. From here the behaviour of Cabrera has been evaluated as a factor of its own climate, with the result that the effects associated with the presence of the island, on the wind, the temperature and the precipitation are not negligible, but they are much more moderate than those that generate larger islands, such as Menorca or Eivissa and, of course, Mallorca. Cabrera is situated, climatically speaking, halfway between what would be a costal islet and a larger island. About the climate of Cabrera, it can be added that it is quite windy and maritime, fully representative of the Mediterranean area where the archipelago is located, with strong seasonality, changing from a warm and dry summer to a period with temperate temperature and variable rainfall, with an also alternate wind regime, from predominance of eastern winds in summer to predominance of western winds in winter. The climate of Cabrera is not clearly arid, but it is not far from aridity. [ABSTRACT FROM AUTHOR]

Bacterial antibiotic resistance is one of the main healthcare problems currently. Apart from reducing antibiotic efficacy, it has awakened the interest of scientists due to its association with bacterial fitness and virulence. Interestingly, antibiotic resistance can be a source of both increased fitness and decreased fitness, even though the molecular basis of these relationships remains unknown. The aim of this work is to define the effects of sub‐MIC concentrations of cefotaxime, an antibiotic extensively used in clinical practice, on the physiology and virulence of Yersinia ruckeri and to determine the importance of these sub‐MIC concentrations for the selection of antibiotic‐resistant mutants in the aquatic environment. Results indicated that exposure to sub‐MIC concentrations of cefotaxime selected Y. ruckeri populations with irreversible alterations in the physiology, such as slow growth, aggregation in liquid cultures and modification of the colony morphology. These bacteria also displayed changes in the OMPs and LPS profiles and a full attenuation of virulence. An overexpression of the envelope stress regulator RpoE was also detected after exposure to the antibiotic. In conclusion, exposure to cefotaxime selected, at high frequency, Y. ruckeri strains that survive the antibiotic stress at the expense of a fitness cost and the loss of virulence. [ABSTRACT FROM AUTHOR]

Among pollution remediation technologies, advanced oxidation processes (AOPs) are genuinely efficient since they are based on the production of strong, non-selective oxidants, mainly hydroxyl radicals (·OH), by a set of physicochemical methods. The biological counterparts of AOPs, which may be referred to as advanced bio-oxidation processes (ABOPs), have begun to be investigated since the mechanisms of induction of ·OH production in fungi are known. To contribute to the development of ABOPs, advanced oxidation of a wide number of dyes by the white-rot fungus Pleurotus eryngii, via a quinone redox cycling (QRC) process based on Fenton's reagent formation, has been described for the first time. The fungus was incubated with 2,6-dimethoxy-1,4-benzoquinone (DBQ) and Fe3+-oxalate, with and without Mn2+, leading to different ·OH production rates, around twice higher with Mn2+. Thanks to this process, the degradative capacity of the fungus increased, not only oxidising dyes it was not otherwise able to, but also increasing the decolorization rate of 20 dyes by more than 7 times in Mn2+ incubations. In terms of process efficacy, it is noteworthy that with Mn2+ the degradation of the dyes reached values of 90–100% in 2–4 h, which are like those described in some AOPs based on the Fenton reaction. [ABSTRACT FROM AUTHOR]

Plasma membrane integrity is essential for cell life. Any major break on it immediately induces the death of the affected cell. Different molecules were described as disrupting this cell structure and thus showing antitumor activity. We have previously defined that elisidepsin (Irvalec®, PM02734) inserts and self-organizes in the plasma membrane of tumor cells, inducing a rapid loss of membrane integrity, cell permeabilization and necrotic death. Here we show that, in sensitive HCT-116 colorectal cells, all these effects are consequence of the interaction of elisidepsin with glycosylceramides in the cell membrane. Of note, an elisidepsin-resistant subline (HCT-116-Irv) presented reduced levels of glycosylceramides and no accumulation of elisidepsin in the plasma membrane. Consequently, drug treatment did not induce the characteristic necrotic cell death. Furthermore, GM95, a mutant derivative from B16 mouse melanoma cells lacking ceramide glucosyltransferase (UGCG) activity and thus the synthesis of glycosylceramides, was also resistant to elisidepsin. Over-expression of UGCG gene in these deficient cells restored glycosylceramides synthesis, rendering them sensitive to elisidepsin, at a similar level than parental B16 cells. These results indicate that glycosylceramides act as membrane targets of elisidepsin, facilitating its insertion in the plasma membrane and the subsequent membrane permeabilization that leads to drug-induced cell death. They also indicate that cell membrane lipids are a plausible target for antineoplastic therapy. [ABSTRACT FROM AUTHOR]

Ligninases and hemicellulases are crucial as accessory enzymes to increase the enzymatic hydrolysis of lignocellulose, boosting sugars production from which biofuels and bioproducts could be obtained. In order to find new sources of these accessory enzymes, this study evaluates the potential of laccase and mannanase enzymes from Streptomyces ipomoeae for improving the conventional hydrolysis with commercial cellulases of steam-pretreated softwood. For that, different laccase treatment and mannanase supplementation strategies were performed. S. ipomoeae laccase increased both glucose and xylose production (17.8% and 9.3%, respectively), which was attributed to a removal of phenols of 29%. Moreover, the combination of laccase and alkaline extraction produced a lignin reduction of 16.2%, improving the glucose and xylose production by almost 41.3% and 44.9%, respectively. On the other hand, the supplementation of S. ipomoeae mannanase to the hydrolysis 24 h before the addition of cellulases increased the glucose (18.4%), xylose (12.3%), and mannose (47.2%) production. [ABSTRACT FROM AUTHOR]

This article reports on an exploratory study aimed to identify which ways of marking required and optional fields help older people fill in web forms correctly. Drawing on a pilot study and selective attention research in ageing, modified versions of widely used forms were created, in which standard asterisks were replaced with one of three alternatives: large asterisks (double standard size), textual labels and a simple binary classification of fields. Older novice computer users participated in this study (N = 88). The quantitative results were independent of the type of form and showed that the method of denoting required fields had a significant effect on the number of errors (measured as required fields not being filled (p < 0.05)). The participants made fewer errors in the binary classification than in the others (p < 0.05), while the differences between standard asterisks, large asterisks and labels were not significant (p > 0.05). The qualitative findings revealed that the participants felt overloaded with information when using every method except the binary classification. These results challenge widespread design solutions for older people (e.g. enlarging elements) and suggest that reducing selective attention demands can help us meet their accessibility needs. [ABSTRACT FROM PUBLISHER]

Irvalec is a marine-derived antitumor agent currently undergoing phase II clinical trials. In vitro, Irvalec induces a rapid loss of membrane integrity in tumor cells, accompanied of a significant Ca2+ influx, perturbations of membrane conductivity, severe swelling and the formation of giant membranous vesicles. All these effects are not observed in Irvalec-resistant cells, or are significantly delayed by pretreating the cells with Zn2+. Using fluorescent derivatives of Irvalec it was demonstrated that the compound rapidly interacts with the plasma membrane of tumor cells promoting lipid bilayer restructuration. Also, FRET experiments demonstrated that Irvalec molecules localize in the cell membrane close enough to each other as to suggest that the compound could self-organize, forming supramolecular structures that likely trigger cell death by necrosis through the disruption of membrane integrity. [ABSTRACT FROM AUTHOR]

A newly identified extracellular laccase produced by Streptomyces ipomoea CECT 3341 (SilA) was cloned and overexpressed, and its physicochemical characteristics assessed together with its capability to decolorize and detoxify an azotype dye. Molecular analysis of the deduced sequence revealed that SilA contains a TAT-type signal peptide at the N-terminus and only two cupredoxine domains; this is consistent with reports describing two other Streptomyces laccases but contrasts with most laccases, which contain three cupredoxine domains. The heterologous expression and purification of SilA revealed that the homodimer is the only active form of the enzyme. Its stability at high pH and temperature, together with its resistance to high concentrations of NaCl and to typical laccase inhibitors such as sodium azide confirmed the unique properties of this novel laccase. The range of substrates that SilA is able to oxidize was found to be pH-dependent; at alkaline pH, SilA oxidized a wide range of phenolic compounds, including the syringyl and guayacil moieties derived from lignin. The oxidative potential of this enzyme to use phenolic compounds as natural redox mediators was shown through the coordinated action of SilA and acetosyringone (as mediator), which resulted in the complete detoxification of the azo-type dye Orange II. [ABSTRACT FROM AUTHOR]

Homogenised climatological series and gridded data are the basis for climate monitoring and climate change detection. Considering this, monthly mean temperatures from 122 Croatian stations were homogenised, and high-resolution monthly gridded data were developed for the 1981–2018 period. Homogenisation needs to be performed on stations from the same climate region; therefore, hierarchical clustering is introduced to define those climate regions in Croatia. The breaks of homogeneity were detected by the standard normal homogeneity test on 54 stations. Regression kriging was applied to produce monthly grids for each month in the analysed period. The quality of the interpolation assessed by leave-one-out cross-validation resulted in a root mean square error of 0.7 °C. The quality of spatial interpolation is supplemented with normalised error maps. The derived homogenised station data and monthly grids are necessary for national climate monitoring, the production of climate normals and the estimation of trends. After 1999, average annual anomalies from the 30-year climate standard normal 1981–2010 were positive and up to 1.4 °C warmer than the average and only occasionally negative. The measured amount, sign and significance of the trend were accurately captured on the trend maps calculated from the monthly maps. Significant strong warming was observed and mapped over the entire Croatian territory in April, June, July, August and November. It was stronger inland than on the coast. Annual trends were significant and ranged from 0.3 °C/decade to 0.7 °C/decade. There was no observational evidence of enhanced elevation-dependent warming over elevations from 750 to 1594 m. [ABSTRACT FROM AUTHOR]

The European project INDECIS* (Integrated approach for the development across Europe of user oriented climate indicators for GFCS high-priority sectors: agriculture, disaster risk reduction, energy, health, water and tourism) needs quality controlled and homogenized daily series of several essential climate variables to produce climate indices for their target economical sectors. Work Package 3 is the project team dedicated to provide these high quality series from their raw versions stored at the European Climate Assessment and Dataset (ECA&D).As a first step, a benchmarking exercise was designed in order to test available methodologies on two target areas: Southern Sweden and Slovenia. After considering other alternatives, the Royal Netherlands Meteorological Institute (KNMI) Regional Atmospheric Climate Model (RACMO) version 2 driven by Hadley Global Environment Model 2 - Earth System (MOHC-HadGEM2-ES) was selected as benchmark homogeneous data-set because of its high spatial resolution (0.11°), daily time step and a correspondence of the output variables with the studied ECA&D variables.Relocation inhomogeneities and other perturbations were then applied to the homogeneous data-set to compile different benchmark flavors with varied difficulties. These benchmarks were released to be used by developers and users of homogenization packages in order to test their performances when applied to daily climatic series, not only of extreme temperatures and precipitation as has been customary in past benchmarking efforts, but also of cloud cover, wind speed, relative humidity, sea level pressure, sunshine duration and snow depth.The performance of the applied methodologies are evaluated by comparing errors in the corrected series, their trends and monthly indices relevant to the project objectives. The discussion includes considerations about the difficulties found when homogenizing the different variables and prospects for the homogenization of the complete set of ECA&D series, which will be used by the rest of the INDECIS teams.-----* Project INDECIS is part of ERA4CS, an ERA-NET initiated by JPI Climate, and funded by FORMAS (SE), DLR (DE), BMWFW (AT), IFD (DK), MINECO (ES), ANR (FR) with co-funding by the European Union (Grant 690462). [ABSTRACT FROM AUTHOR]

Meteorological observations may be affected by events unrelated to spatio-temporal variability specific to weather phenomena (errors in transmitting or measuring). Independent of natural weather and climate variability and change, the shifts in the measuring instruments, and changes in the location or the surroundings of the stations can influence meteorological measurements. Findings of meteorological and climatic studies may be altered when they are based on data sets that contain inhomogeneities; therefore, in order to reduce or eliminate the false signals from the climatic data series, methods of homogenisation were developed.In this work, the homogenisation and data filling of the hourly air temperature data, measured on the territory and in the immediate vicinity of Romania, were performed using the R package climatol: Climate Tools (Series Homogenization and Derived Products). Four data sources have been used: Romanian National Meteorological Administration Network, Romanian National Air Quality Monitoring Network, Regional Basic Synoptic Networks and Meteorological Aerodrome Report Network.By using the climatol homogenization method, values related to unrealistic changes in the natural meteorological and climatic system were identified and corrected. Also, missing data were filled by considering the similarities between the data from each station and the reference series (records from the stations which are best correlated with the values of the analysed station). Comparing the homogenization results with the initial (non-homogenized) data revealed that by removing the breakpoints and correcting the analysed series, the statistical properties of the homogenized data set do not differ significantly from those computed from raw data. The main result of this study is a homogenized hourly air temperature dataset at country scale which combines data from several networks of measurements. This work was supported by a grant of Ministry of Research and Innovation, CNCS - UEFISCDI, project number PN-III-P1-1.1-PD-2016-1579, within PNCDI III. [ABSTRACT FROM AUTHOR]

A dense monthly precipitation dataset of Ireland and Northern Ireland was homogenized with several modern homogenization methods. The efficiency of these homogenizations was tested by examining the similarity of homogenization results both in the real data homogenization and in the homogenization of a simulated dataset. The analysis of homogenization results shows that the real dataset is characterized by a large number of, but mostly small, non‐climatic biases, and a moderate reduction of such biases can be achieved with homogenization. Finally, a combination of the ACMANT and Climatol homogenization results was applied to improve the data accuracy before the trend calculations. These two methods were selected for their proven high accuracy, missing data tolerance and ability to complete time series via the infilling of missing values before the trend calculations. Metadata were used within the Climatol method. To facilitate this analysis the study area was split into smaller climatic regions by using the Ward clustering method. Five climatic zones consistent with the known spatial patterns of precipitation in Ireland were established. Linear regression fitting and the Mann‐Kendall test were applied. Low frequency fluctuations were also examined by applying a Gaussian filter. The results show that the precipitation amount generally increases in the study area, particularly in the northwestern region. The most significant increasing trends for the whole study period (1941–2010) are found for late winter and spring precipitation, as well as for the annual totals. In the period from the early 1970s the increase of precipitation is general in all seasons of the year except in winter, but the statistical significance of this increase is weak. [ABSTRACT FROM AUTHOR]

Time series homogenization for 299 of the available precipitation records for the island of Ireland (IENet) was performed. Four modern relative homogenization methods, that is, HOMER, ACMANT, CLIMATOL and AHOPS were applied to this network of station series where contiguous intact monthly records range from 30 to 70 years within the base period 1941–2010. Break detection results are compared between homogenization methods, and coincidences with available documentary information (metadata) were analysed. The lowest (highest) number of breaks were detected with HOMER (ACMANT). Large differences of break frequency were found, namely ACMANT and AHOPS detected 8 times as many breaks than HOMER, while the break frequency with CLIMATOL was intermediate. Also, the ratio of series classified to be homogeneous varies widely between the methods. It is 85% with HOMER, 60% with CLIMATOL, 31% with AHOPS, while only 22% with ACMANT. In a further experiment, all the available time series for Ireland and Northern Ireland, (910 series) were used with ACMANT and CLIMATOL to explore the stability of break frequency for the same 299 series examined in the base experiment. While overall break frequency slightly increased (by 6–13%), the break positions notably changed for individual time series. The number of breaks changed for 59% (23%) of the series with ACMANT (CLIMATOL). For the breaks detected coincidentally by at least three methods including ACMANT and CLIMATOL in the base experiment, the second experiment confirmed the break positions in 86–87% of the breaks. The consequences of these results in relation to the reliability of statistical homogenization are discussed. Sometimes markedly different step functions provide comparable good approaches. However, the accuracy of homogenized time series cannot be related directly to the instability of break detection results. [ABSTRACT FROM AUTHOR]

Daily and sub‐daily homogenization of climate variables have been intensively investigated in the last decades, but to the best of our knowledge, this is the first study on homogenization of hourly temperature in Romania. This paper describes the creation of a homogenized hourly air temperature data set at a country scale by combining data from four independent meteorological networks. The air temperature measurements for the period 2009 and 2017 were obtained from the following networks: Romanian National Meteorological Administration (ANM), National Network for Monitoring Air Quality (RNMCA), Regional Basic Synoptic Network (RBSN), and Meteorological Terminal Aviation Routine Weather Report network (METAR). The climatological limits, persistence, temporal variation (step test), and spatial consistency were the quality control tests used to isolate the errors due to malfunctioning of the temperature sensors, data coding or transmission. The Climatol homogenization method was successfully applied for identifying and correcting any suspicious values. The missing data were filled by considering the similarities between each station and the reference series. Comparing the output with the original data, it is apparent that the removal of the break points, correction and homogenization resulted in a new data set with statistical properties very similar to the raw data, but more reliable for climate research due to the increased homogeneity. Eventually, the procedure can be implemented in operational use for collecting more data from other networks. [ABSTRACT FROM AUTHOR]

Central banks, blamed when countries and regions fail to grow, are continually subject to political pressures as well as closely scrutinized by analysts and financial markets. Misunderstandings may occur because of the tasks these agencies are charged with, which center on price stability and control over inflation. Central banks may be credited with generously achieving their goal, given the inflation record of the last three decades. In 2004, average world inflation fell below 4 percent, compared with over 40 percent in 1990. Nonetheless, the challenges to monetary policy in coming years suggest a complex management task. [ABSTRACT FROM AUTHOR]

Background: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of metabolism characterized by recurrent metabolic crises caused by fasting, intercurrent illness and excessive physical exercise. Non ketotic hypoglycemia is normally the cause of primary symptoms but without an immediate treatment the illness can evolve into a worsening metabolic state resembling the Reye's syndrome that may cause the patient's death. We report a case with some clinical and therapeutic features not previously described. Case presentation: Patient with HMG-CoA lyase deficiency whom after diagnosis at 2 years of age was re- admitted 12 years later, after severe metabolic decompensation following consumption of alcohol. Despite a quick correction of hypoglycemia, within the following few hours, the patient fell into a coma. Suspecting intracranial hypertension (ICH), the patient required mechanical ventilation. Although liver cytolysis was minimal, hyperamoniemia reached 1394 µmol/L, returning to normal, a few hours after administering sodium phenylacetate and sodium benzoate, whose use has not been reported in these patients. Brain edema was evidenced in the computed tomography and by the magnetic resonance imaging that determined that the edema was cytotoxic, as quantified with the restriction of diffusion in the apparent diffusion coefficient map. During the recovery of the ICH, we belatedly, detected vasospasm moderate-severe that was treated with nimodipine. Currently, the patient maintains clinical normality. Conclusions: The alcohol consumption must be avoided in patients with HMG-CoA lyase deficiency. In our patient hyperamoniemia was effectively treated with sodium phenylacetate and sodium benzoate. Magnetic resonance imaging showed and quantified the cytotoxic brain edema. Belatedly, a cerebral vasospasm was an additional mechanism of cerebral injury. None of these observations has been previously reported. [ABSTRACT FROM AUTHOR]

Using observations and model simulations from the 5th and 6th phases of the Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively), this study evaluated changes in monthly, seasonal, and annual precipitation over Bolivia from 1950 to 2019. Results demonstrate that observed precipitation is characterized by strong interannual and decadal variability. However, long‐term precipitation trends were not identified on the annual scale. Similarly, changes in seasonal precipitation were almost nonsignificant (p >.05) for the study period. Spatially, albeit with its complex orography, no substantial regional variations in observed precipitation trends can be identified across Bolivia. In contrast, long‐term precipitation trends, based on CMIP5 and CMIP6 models, suggest a dominance of negative trends, mainly during austral winter (JJA) (−10%) and spring (SON) (−15%). These negative trends were more pronounced in the lowlands of Bolivia (−20%). Overall, these contradictory results highlight the need for validating precipitation trend outputs from model simulations, especially in areas of complex topography like Bolivia. [ABSTRACT FROM AUTHOR]

Using observations and model simulations from the 5th and 6th phases of the Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively), this study evaluated changes in monthly, seasonal, and annual precipitation over Bolivia from 1950 to 2019. Results demonstrate that observed precipitation is characterized by strong interannual and decadal variability. However, long‐term precipitation trends were not identified on the annual scale. Similarly, changes in seasonal precipitation were almost nonsignificant (p >.05) for the study period. Spatially, albeit with its complex orography, no substantial regional variations in observed precipitation trends can be identified across Bolivia. In contrast, long‐term precipitation trends, based on CMIP5 and CMIP6 models, suggest a dominance of negative trends, mainly during austral winter (JJA) (−10%) and spring (SON) (−15%). These negative trends were more pronounced in the lowlands of Bolivia (−20%). Overall, these contradictory results highlight the need for validating precipitation trend outputs from model simulations, especially in areas of complex topography like Bolivia. [ABSTRACT FROM AUTHOR]

Abstract: Yersinia ruckeri is the causative agent of enteric redmouth disease or yersiniosis, which affects mainly salmonids. This microorganism has been consistently causing economic losses in the aquaculture industry since its first description; but the early development of a vaccine allowed a relative control of the disease. This might be the reason why the specific pathogenicity mechanisms of this bacterium remained elusive until recently, when the results obtained with traditional microbiology have been complemented with those provided by molecular biology. The data obtained by using these novel techniques, which are the main subject of this review, have started to shed light on the virulence of this pathogen. Thus, iron acquisition by the siderophore ruckerbactin, proteolytic and haemolytic activities, and resistance to immune mechanisms, were proved to be involved in the virulence of this bacterium. Additionally, these data will, in the long term, help clarify the controversial taxonomic status of this microorganism and allow the development of novel ways to prevent outbreaks, which is particularly interesting nowadays, given that commercial vaccines seem to be ineffective against some new isolates. [Copyright &y& Elsevier]

The article cites a study of the virulence factor of yersinia ruckeri that causes redmouth disease or yersiniosis in fish. It investigates the virulence mechanisms of gene encoding a putative proteins involved in the secretion and activation of a haemolysin. It highlights that the decisive role of iron and temperature as environmental factors that regulates and coordinate the expression of gene encoding.

Abstract: This paper reports the development of genetic tools in Lactococcus garvieae, an important Gram-positive bacterial pathogen affecting both fish and mammals. The vector pGKV210, a broad host range vector, was introduced by electroporation into L. garvieae UNIUD074. The maximal frequency obtained was transformants/μg of DNA. Moreover, this effect is highly reproducible and appears to be constant, since all L. garvieae strains tested were transformed. Once the optimal transformation procedure was established, it was used to generate isogenic and transposition mutants. Insertional mutagenesis of the L. garvieae SA9H10L gene, similar to a Streptococcus pyogenes gene encoding the M protein (emm64), was carried out using the conditional replication plasmid pORI19. Transposition mutagenesis using the streptococcal temperature-sensitive suicide vector pTV408 to deliver Tn917 into the chromosome of L. garvieae was also achieved at a frequency of ca. 10−4. Transposon flanking DNA sequences were obtained by plasmid rescue in Escherichia coli and their sequencing analysis demonstrated that the transposon was inserted at different chromosomal loci. Tn917 also made it possible to select a mutant in the operon involved in mannitol fermentation in this microorganism. The results obtained in the present study lay the foundation for future research on the virulence mechanisms of L. garvieae. [Copyright &y& Elsevier]

Plitidepsin (PLD, Aplidin®), a cyclic depsipeptide originally isolated from the marine tunicate Aplidium albicans , has been recently approved by Australian regulatory authorities for the treatment of multiple myeloma patients. Plitidepsin binds to eEF1A2 and induces oxidative stress, Rac1 activation and JNK1 phosphorylation, triggering a rapid apoptotic program in tumor cells. Since oxidative stress is one of the known sources of endoplasmic reticulum stress, we investigated whether PLD was inducing a bona fide ER stress in HeLa cells and whether this process was essential in the mechanism of action of the compound. Indeed, PLD activated an ER stress-induced unfolded protein response (UPR), including the alternative splicing of XBP1, the proteolytic processing of ATF6 and the phosphorylation of eIF2α and JNK. Interestingly, though PLD induced a strong phosphorylation of eIF2α in all the analyzed cell lines, it did not elicit an increased expression of ATF4 and CHOP, a transcription factor involved in launching UPR-mediated apoptosis. On the contrary, a clear reduction of CHOP protein levels was observed after PLD treatment, most probably due to both the lack of transactivation by ATF4 and its rapid degradation by the ubiquitin/proteasome machinery. Using fibroblasts devoid of each one of the four possible kinases involved in eIF2α phosphorylation, we observed that only PKR was involved in the response to PLD treatment and, accordingly, PKR−/− fibroblasts are shown to be resistant to the apoptogenic activity of the compound. Furthermore, eIF2α phosphorylation itself was shown to be irrelevant for the induction of cell death by PLD. Instead, we reveal that PLD induces an increase in the levels of misfolded proteins while simultaneously inhibiting the autophagic flux. These two effects combined prevent PLD-treated cells from reducing proteotoxic stress and lead to apoptosis. Other anti-myeloma drugs like bortezomib, which target the proteasome, also inhibit the degradation of misfolded proteins through alternate pathways and a synergistic anticancer effect of the PLD plus bortezomib combination has been previously disclosed. The present results extend this synergy to in vivo experiments and provide a mechanistic rationale for this synergy. [ABSTRACT FROM AUTHOR]

A new high‐resolution (5 km) gridded daily precipitation dataset for Tunisia between 1979 and 2015 is introduced. This product combines 960 rain gauges with the SAFRAN analysis to produce the precipitation gridded data. A validation approach on two different datasets reveals that the SAFRAN analysis outperforms other standard interpolation methods such as Inverse Distance, Nearest Neighbors, Ordinary Kriging or Residual Kriging with altitude. When compared to EOBS, a widely used gridded dataset over Europe, a strong negative bias in EOBS precipitation is found. However due to the aridity and the low density of rain gauges in south Tunisia, results in this region must be analyzed with care. The SAFRAN product could be useful for various purposes such as climate model evaluation, climate studies, hydrological modelling to support the planning and management of surface water resources in Tunisia. [ABSTRACT FROM AUTHOR]

Daily time series from the Climate Prediction Center (CPC) Africa Rainfall Climatology version 2.0 (ARC2), Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS) and Tropical Applications of Meteorology using SATellite (TAMSAT) African Rainfall Climatology And Time series version 2 (TARCAT) high-resolution long-term satellite rainfall products are exploited to study the spatial and temporal variability of East Africa (EA, 5S–20N, 28–52E) rainfall between 1983 and 2015. Time series of selected rainfall indices from the joint CCl/CLIVAR/JCOMM Expert Team on Climate Change Detection and Indices are computed at yearly and seasonal scales. Rainfall climatology and spatial patterns of variability are extracted via the analysis of the total rainfall amount (PRCPTOT), the simple daily intensity (SDII), the number of precipitating days (R1), the number of consecutive dry and wet days (CDD and CWD), and the number of very heavy precipitating days (R20). Our results show that the spatial patterns of such trends depend on the selected rainfall product, as much as on the geographic areas characterized by statistically significant trends for a specific rainfall index. Nevertheless, indications of rainfall trends were extracted especially at the seasonal scale. Increasing trends were identified for the October–November–December PRCPTOT, R1, and SDII indices over eastern EA, with the exception of Kenya. In March–April–May, rainfall is decreasing over a large part of EA, as demonstrated by negative trends of PRCPTOT, R1, CWD, and R20, even if a complete convergence of all satellite products is not achieved. [ABSTRACT FROM AUTHOR]

Using clustering analysis for the sea level pressure field of the ERA-Interim reanalysis between 1979 and 2016, five synoptic pressure patterns have been obtained for the Drake area and Antarctic Peninsula (AP) region (458-758S, 208-1208W), and the resulting daily series has been made available to the scientific community. The five patterns have been named according to their most important features as follows: low over the Weddell Sea (LWS), low over the Amundsen and Bellingshausen Seas (LAB), low over the Drake Passage (LDP), zonal flow over the Drake Passage (ZDP), and ridge over the Antarctic Peninsula (RAP). Each atmospheric pattern is described after analyzing its development and evolution. A frequency analysis shows that the five atmospheric patterns present a similar annual frequency but a large seasonal variability. The transitions from one pattern to another tend to follow a cycle in which synoptic atmospheric waves are displaced eastward by a quarter wavelength. Four of the five atmospheric patterns (all except RAP) are very influenced by the southern annular mode (SAM); however, only LAB and LWS are influenced to some degree by ENSO. The occurrence of the LAB pattern presents a positive trend showing agreement with other studies that indicate an enhancement of the Amundsen-Bellingshausen Seas low. Finally, atmospheric circulation patterns have been related to the airmass advection and precipitation in Livingston Island, showing the potential application for studying the changes in the surface mass balance on the AP cryosphere. [ABSTRACT FROM AUTHOR]

Retrorectal cystic hamartomas, or tailgut cysts, are complex congenital cystic lesions which arise from embryologic tissues. Fewer than 200 cases have been reported worldwide, with women outnumbering men by 3:1. They are asymptomatic in 50% of the cases; the remainder present with back pain or mass effect as the most common symptoms. Malignant transformation rarely occurs. Guided biopsy is controversial, while surgery is the therapy of choice. We report the case of a 31‑year‑old woman complaining about perineal and vague lower abdominal pain, who was submitted to magnetic resonance imaging, which revealed a multilocular cystic, well‑circumscribed retrorectal mass. Subsequently, laparoscopic excision was successfully accomplished. Operative time was 175 min. Intra‑.and post‑operative course was uneventful. Hospital stay was 75 h. While any malignancy suspicion should lead to open surgery, given the risk of rupture, we support the benefits of laparoscopy may also be applied [ABSTRACT FROM AUTHOR]

Flavobacterium psychrophilum is a Gram-negative fish pathogen that causes important economic losses in aquaculture worldwide. Although the genome of this bacterium has been determined, the function and relative importance of genes in relation to virulence remain to be established. To investigate their respective contribution to the bacterial pathogenesis, effective tools for gene inactivation are required. In the present study, a markerless gene deletion system has been successfully developed for the first time in this bacterium. Using this method, the F. psychrophilum fcpB gene, encoding a predicted cysteine protease homologous to Streptococcus pyogenes streptopain, was deleted. The developed system involved the construction of a conjugative plasmid that harbors the flanking sequences of the fcpB gene and an I-SceI meganuclease restriction site. Once this plasmid was integrated in the genome by homologous recombination, the merodiploid was resolved by the introduction of a plasmid expressing I-SceI under the control of the fpp2 F. psychrophilum inducible promoter. The resulting deleted fcpB mutant presented a decrease in extracellular proteolytic activity compared to the parental strain. However, there were not significant differences between their LD50 in an intramuscularly challenged rainbow trout infection model. The mutagenesis approach developed in this work represents an improvement over the gene inactivation tools existing hitherto for this “fastidious” bacterium. Unlike transposon mutagenesis and gene disruption, gene markerless deletion has less potential for polar effects and allows the mutation of virtually any non-essential gene or gene clusters. [ABSTRACT FROM AUTHOR]

Background The heat sensitive factor (HSF) of the fish pathogen Yersinia ruckeri was previously identified as an unusual band on SDS-PAGE. According to this, Y. ruckeri strains were classified in HSF+ and HSF- in terms of the presence/absence of the factor. Experiments carried out by injection challenge with HSF+ strains caused high mortalities in rainbow trout. In contrast, HSF- strains did not cause mortality. In conclusion, HSF appeared to be a relevant virulence factor in Y. ruckeri. Results We report here the identification and study of the gene coding for the enzyme involved in the production of HSF. Culture media containing SDS and Coomassie brilliant blue dye was used to screen a mini-Tn5 Km2 mutant library of Y. ruckeri 150. Blue colonies lacking a surrounding creamy deposit, a phenotype described in former studies as HSF-, were identified. DNA sequence analysis of a selected mutant revealed that this had a transposon interruption in a chromosome-located gene which codes for a heat sensitive alkyl sulphatase of 78.7 kDa (YraS; Yersinia ruckeri alkyl sulphatase) which is able to degrade SDS to 1- dodecanol. As it was expected, the introduction of the yraS gene into an HSF- strain turned this into HSF+. Surprisingly, although the protein allows Y. ruckeri to degrade SDS, the bacterium could not use this compound as the sole carbon source. Moreover, the yraS mutant showed a similar level of SDS resistance to the parental strain. It was the interruption of the acrA gene which made Y. ruckeri sensitive to this compound. LD50 experiments showed a similar virulence of the yraS mutant and parental strain. Conclusions The HSF of Y. ruckeri is the product of the alkyl sulphatase YraS, able to degrade SDS to 1- dodecanol. This degradation is not linked to the utilization of SDS as a carbon source and surprisingly, the enzyme is not involved in bacterial virulence or in the high SDS resistance displayed by the bacterium. This role is played by the AcrAB-TolC system. [ABSTRACT FROM AUTHOR]

Bacterial cold water disease ( BCWD) is a globally distributed freshwater fish disease caused by the Gram-negative bacterium F lavobacterium psychrophilum. It is a particularly devastating infection in fry salmonids and may lead to high levels of mortality. In spite of its economic impact on fish farms, neither the biology of the bacterium nor the bacterium-host interactions are well understood. This review provides a synopsis of the major problems related to critical remaining questions about research into the use of vaccines against F. psychrophilum and the development of a commercial vaccine against this disease. Studies using sera from convalescent rainbow trout have shown the antigenic properties of different proteins such as OmpH, OmpA and FspA, as well as low and high molecular mass lipopolysaccharide of F . psychrophilum, which are potential candidates for subunit vaccines. Inactivated F . psychrophilum bacterins have been successfully tested as vaccines under laboratory conditions by both immersion and intraperitoneal routes. However, the efficacy and the practical usefulness of these preparations still have to be proved. The use of attenuated and wild-type strains to immunize fish showed that these systems offer high levels of protection. Nevertheless, their application clashes with the regulations for environmental protection in many countries. In conclusion, protective vaccines against BCWD are theoretically possible, but substantial efforts still have to be made in order to permit the development of a commercial vaccine. [ABSTRACT FROM AUTHOR]

In an attempt to dissect the virulence mechanisms of Yersinia ruckeri two adjacent genes, yrpA and yrpB, encoding putative peptidases belonging to the U32 family, were analyzed. Similar genes, with the same genetic organization were identified in genomic analysis of human-pathogenic yersiniae. RT-PCR studies indicated that these genes form an operon in Y. ruckeri. Transcriptional studies using an yrpB::lacZY fusion showed high levels of expression of these genes in the presence of peptone in the culture medium, as well as under oxygen-limited conditions. These two factors had a synergic effect on gene induction when both were present simultaneously during bacterial incubation, which indicates the important role that environmental conditions in the fish gut can play in the regulation of specific genes. LD50 experiments using an yrpA insertional mutant strain demonstrated the participation of this gene in the virulence of Y. ruckeri. [ABSTRACT FROM AUTHOR]

Abstract: The study of the fish pathogen Flavobacterium psychrophilum has been drastically hampered by the difficulty to perform genetic manipulation of this organism. Although recent publications described the successful transfer of genetic material into this bacterium by transformation and conjugation, additional tools are still needed. This paper reports the construction of vector pCP23-G, which permits for the first time to monitor transcriptional regulation in this pathogen by using a promoterless gfpmut3 gene as a reporter. Additionally, use of pCP23-G enabled the trancriptional analysis of three putative promoter regions of F. psychrophilum, corresponding to genes fpp2–fpp1, pdhB and gldJ, under different growth conditions. Overall, the construction of pCP23-G facilitates genetic analysis in F. psychrophilum, by enabling the determination of gene expression both in vitro and in vivo. Furthermore, this would also open the possibility for studies on the location of this bacterium in the fish tissues. [Copyright &y& Elsevier]

Abstract: Elisidepsin is a marine-derived anti-tumor agent with unique mechanism of action. It has been suggested to induce necrosis associated with severe membrane damage. Since indirect evidence points to the involvement of ErbB receptor tyrosine kinases and lipid rafts in the mechanism of action of elisidepsin, we investigated the effect of the drug on the distribution of ErbB proteins and systematically compared the elisidepsin sensitivity of cell lines overexpressing ErbB receptors. Stable expression of a single member of the ErbB family (ErbB1-3) or co-transfection of ErbB2 and ErbB3 did not modify the elisidepsin sensitivity of CHO and A431 cells. However, elisidepsin induced the redistribution of ErbB3 and two GPI-anchored proteins (transfected GPI-anchored eGFP and placental alkaline phosphatase) from the plasma membrane to intracellular vesicles without comparable effects on ErbB1 and ErbB2. Elisidepsin increased the binding of a conformational sensitive anti-ErbB3 antibody without modifying the binding of other ErbB2 or ErbB3 antibodies, and it decreased the homoassociation of both ErbB2 and ErbB3. We also found that elisidepsin decreased the fluorescence anisotropy of a membrane specific fluorescent probe and induced a blue shift in the emission spectrum of Laurdan pointing to significant changes in the order of the plasma membrane possibly associated with the formation of liquid ordered domains. Although the distribution of ErbB proteins is preferentially altered by elisidepsin, our data question their role in determining sensitivity to the drug. We assume that induction of liquid ordered domains is the primary action of elisidepsin leading to all the other observed changes. [Copyright &y& Elsevier]

Application of in vivo expression technology (WET) to Yersinia ruckeri, an important fish pathogen, allowed the identification of two adjacent genes that represent a novel bacterial system involved in the uptake and degradation of L-cysteine. Analysis of the translational products of both genes showed permease domains (open reading frame 1 [ORF1]) and amino acid position identities (ORF2) with the L-cysteine desulfidase from Methanocaldococcus jannaschii, a new type of enzyme involved in the breakdown of L-cysteine. The operon was named cdsAB (cysteine desulfidase) and is found widely in anaerobic and facultative bacteria. cdsAB promoter analysis using LacZY gene fusion showed highest induction in the presence of L-cysteine. Two cdsA and cdsB mutant strains were generated. The limited toxic effect and the low utilization of L-cysteine observed in the cdsA mutant, together with radiolabeled experiments, strongly suggested that CdsA is an L-cysteine permease. Fifty percent lethal dose (LD50) and competence index experiments showed that both the cdsA and cdsB loci were involved in the pathogenesis of the bacteria. In conclusion, this study has shown for the first time in bacteria the existence of an L-cysteine uptake system that together with an additional L-cysteine desulfidase-encoding gene constitutes a novel operon involved in bacterial virulence. [ABSTRACT FROM AUTHOR]

A three-gene operon, named yctCBA (Yersinia citrate transporter), induced by citrate and repressed by glucose was identified from a previously selected in vivo-induced (ivi) clone in the fish pathogen Yersinia ruckeri. Interestingly, despite being an ivi clone, the drastic growth reduction of the yctC mutant in the presence of citrate, and the relatively high content of this compound in rainbow trout serum, the operon was not required for virulence. [ABSTRACT FROM AUTHOR]

The article focuses on Flavobacterium psychrophilum, a psychrotrophic fish-pathogenic bacterium that causes cold water disease (CWD) in salmonids. It is said that Tn4351 mutagenesis was used to isolate a mutant named FP1033, which recovered the parental phenotype in the presence of iron. The presence of a tonB cluster of genes composed of exbB, exbD1 and exbD2, and tonB loci is shown by the analysis of the DNA surrounding the transposon insertion. It is mentioned that the genes are transcribed as an operon and that FP1033 has a decreased virulence and conferred a high level of protection in rainbow trout fry after vaccination.

The article presents a study on the genes required for Lactococcus garvieae survival in fish host. This paper focuses on the pathogenic mechanisms of the bacterium Lactococcus garvieae as it is considered to be an emergent pathogen in aquaculture. It is also being associated with mastitis in domestic animals, human endocarditis, and septicaemia. Mutagenesis was used in identification of virulence factors establishing a basis of pathogen-host interactions. More mutants are identified and their pathogenesis may provide intervention for the development of therapies.

Simple Summary: Trabectedin and lurbinectedin are two potent onco-therapeutic drugs for the treatment of advanced soft tissue sarcomas. Here we show that, in addition to cancer cells, these molecules exert important effects on macrophages and tissue-associated macrophages altering metabolic functions, such as respiration and cell viability. Interestingly, the macrophages from one-fourth of healthy individuals exhibit apoptotic cell death when treated with these drugs at therapeutic doses. These data are relevant to understand the action of these molecules in the context of chemotherapy of oncologic patients. Background: Tumor-associated macrophages (TAMs) play a crucial role in suppressing the immunosurveillance function of the immune system that prevents tumor growth. Indeed, macrophages can also be targeted by different chemotherapeutic agents improving the action over immune checkpoints to fight cancer. Here we describe the effect of trabectedin and lurbinectedin on human macrophage cell viability and function. Methods: Blood monocytes from healthy donors were differentiated into macrophages and exposed to different stimuli promoting functional polarization and differentiation into tumor-associated macrophages. Cells were challenged with the chemotherapeutic drugs and the effects on cell viability and function were analyzed. Results: Human macrophages exhibit at least two different profiles in response to these drugs. One-fourth of the blood donors assayed (164 individuals) were extremely sensitive to trabectedin and lurbinectedin, which promoted apoptotic cell death. Macrophages from other individuals retained viability but responded to the drugs increasing reactive oxygen production and showing a rapid intracellular calcium rise and a loss of mitochondrial oxygen consumption. Cell-membrane exposure of programmed-death ligand 1 (PD-L1) significantly decreased after treatment with therapeutic doses of these drugs, including changes in the gene expression profile of hypoxia-inducible factor 1 alpha (HIF-1α)-dependent genes, among other. Conclusions: The results provide evidence of additional onco-therapeutic actions for these drugs. [ABSTRACT FROM AUTHOR]

In the past years, several long-term (20+ years) reprocessed GNSS tropospheric delay and water vapor time series datasets have been produced and are available for climate studies. It includes worldwide datasets (e.g. the International GNSS Service 'IGS troposphere repro 1'), pan-European datasets (e.g. the EUREF Permanent Network 'EPN troposphere repro 2'), but also regional datasets. At the same time, several individual groups studied these reprocessed GNSS tropospheric delay and water vapor time series and found evidence for remaining inhomogeneities due to e.g. instrumental changes, environmental changes, etc. These inhomogeneities impact e.g. the calculation of the long-term water vapor trend (and its associated error), hence preventing a correct and precise interpretation of the dataset in terms of climate change. The homogenization of these datasets is thus mandatory prior any proper usage for studying the climate.In that context, several of these groups joined their efforts within the sub-WG "Data Homogenization" of the COST Action ES1206 "Advanced Global Navigation Satellite Systems tropospheric products for monitoring severe weather events and climate" (GNSS4SWEC), focusing first on the IGS repro 1 tropospheric dataset as a case study. The COST Action being ended, this work is now continued in the framework of the IAG WG 4.3.8 "GNSS Tropospheric Products for Climate".Amongst their activities, the working group (1) inventoried the existing homogenization tools that could be applied on the GNSS tropospheric delay and water vapor time series, (2) produced synthetic datasets (based on the true characteristics of the IGS repro 1 and ERA-Interim datasets, but with known offsets included) in order to (3) benchmark (blindly) the performance, weakness and advantages of each of these methods (via e.g. statistical scores and CRMEs, trend differences), and (4) finally assessed different methods for computing trends and their uncertainties in these time series.This presentation will summarize the working group activities, focusing on the most recent developments and achievements towards the homogenization of GNSS-based tropospheric delay and water vapor time series. [ABSTRACT FROM AUTHOR]

This work describes the draft genome sequence of Lactococcus garvieae IPLA 31405, isolated from a traditional Spanish cheese. The genome contains a lactose-galactose operon, a bacteriocin locus, two integrated phages, a transposon harboring an active tet(M) gene, and two theta-type plasmid replicons. Genes encoding virulence factors were not recorded. [ABSTRACT FROM AUTHOR]

Lactococcus garvieae is the etiological agent of lactococcosis disease, affecting many cultured fish species worldwide. In addition, this bacterium is currently considered a potential zoonotic microorganism since it is known to cause several opportunistic human infections. Here we present the draft genome sequence of the L. garvieae strain UNIUD074. [ABSTRACT FROM AUTHOR]