University of Chile

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably will have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The standard Einstein-Maxwell equations in 2+1 spacetime dimensions, with a negative cosmological constant, admit a black hole solution. The 2+1 black hole---characterized by mass, angular momentum, and charge, defined by flux integrals at infinity---is quite similar to its 3+1 counterpart. Anti--de Sitter space appears as a negative energy state separated by a mass gap from the continuous black hole spectrum. Evaluation of the partition function yields that the entropy is equal to twice the perimeter length of the horizon.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

BACKGROUND/AIMS: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological features used in adult women may be normal pubertal physiological events. Hence, international pediatric and adolescent specialty societies have defined criteria that have sufficient evidence to be used for the diagnosis of PCOS in adolescents. METHODS: The literature has been reviewed and evidence graded to address a series of questions regarding the diagnosis of PCOS during adolescence including the following: clinical and biochemical evidence of hyperandrogenism, criteria for oligo-anovulation and polycystic ovary morphology, diagnostic criteria to exclude other causes of hyperandrogenism and amenorrhea, role of insulin resistance, and intervention. RESULTS AND CONCLUSION: Features of PCOS overlap normal pubertal development. Hence, caution should be taken before diagnosing PCOS without longitudinal evaluation. However, treatment may be indicated even in the absence of a definitive diagnosis. While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls.

The increasing interest in integrating intermittent renewable energy sources into microgrids presents major challenges from the viewpoints of reliable operation and control. In this paper, the major issues and challenges in microgrid control are discussed, and a review of state-of-the-art control strategies and trends is presented; a general overview of the main control principles (e.g., droop control, model predictive control, multi-agent systems) is also included. The paper classifies microgrid control strategies into three levels: primary, secondary, and tertiary, where primary and secondary levels are associated with the operation of the microgrid itself, and tertiary level pertains to the coordinated operation of the microgrid and the host grid. Each control level is discussed in detail in view of the relevant existing technical literature.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

We survey the current techniques to cope with the problem of string matching that allows errors. This is becoming a more and more relevant issue for many fast growing areas such as information retrieval and computational biology. We focus on online searching and mostly on edit distance, explaining the problem and its relevance, its statistical behavior, its history and current developments, and the central ideas of the algorithms and their complexities. We present a number of experiments to compare the performance of the different algorithms and show which are the best choices. We conclude with some directions for future work and open problems.

We analyze the information credibility of news propagated through Twitter, a popular microblogging service. Previous research has shown that most of the messages posted on Twitter are truthful, but the service is also used to spread misinformation and false rumors, often unintentionally.

An edited volume containing data structures and algorithms for information retrieved including a disk with examples written in C. For programmers and students interested in parsing text, automated indexing, its the first collection in book form of the basic data structures and algorithms that are critical to the storage and retrieval of documents.

The Sloan Digital Sky Survey (SDSS) is an imaging and spectroscopic survey that will eventually cover approximately one-quarter of the celestial sphere and collect spectra of ~106 galaxies, 100,000 quasars, 30,000 stars, and 30,000 serendipity targets. In 2001 June, the SDSS released to the general astronomical community its early data release, roughly 462 deg2 of imaging data including almost 14 million detected objects and 54,008 follow-up spectra. The imaging data were collected in drift-scan mode in five bandpasses (u, g, r, i, and z); our 95% completeness limits for stars are 22.0, 22.2, 22.2, 21.3, and 20.5, respectively. The photometric calibration is reproducible to 5%, 3%, 3%, 3%, and 5%, respectively. The spectra are flux- and wavelength-calibrated, with 4096 pixels from 3800 to 9200 A at R~1800. We present the means by which these data are distributed to the astronomical community, descriptions of the hardware used to obtain the data, the software used for processing the data, the measured quantities for each observed object, and an overview of the properties of this data set.

The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity.

Potato (Solanum tuberosum L.) is the world’s most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop. The genome of the potato (Solanum tuberosum L.), a staple crop vital to food security, has been sequenced. The Potato Genome Sequencing Consortium sequenced a homozygous doubled-monoploid potato clone as well as a heterozygous diploid clone. Genome analysis reveals traces of at least two genome duplication events and genes specific to Asterids, a large clade of flowering plants of which the potato is the first to be sequenced. Gene presence/absence variants and other potentially deleterious mutations are frequent and may be the cause of inbreeding depression. The genome sequence will facilitate genetic improvements in the potato with a view to improving yield and to increasing disease and stress resistance of this crop, which is a now a significant component of worldwide food production and is becoming increasingly important in the developing world.

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

In this paper, we analyze the activity of single fibers in the optic nerve of a frog. Our method is to find what sort of stimulus causes the largest activity in one nerve fiber and then what is the exciting aspect of that stimulus such that variations in everything else cause little change in the response. It has been known for the past 20 years that each fiber is connected not to a few rods and cones in the retina but to very many over a fair area. Our results show that for the most part within that area, it is not the light intensity itself but rather the pattern of local variation of intensity that is the exciting factor. There are four types of fibers, each type concerned with a different sort of pattern. Each type is uniformly distributed over the whole retina of the frog. Thus, there are four distinct parallel distributed channels whereby the frog's eye informs his brain about the visual image in terms of local pattern independent of average illumination. We describe the patterns and show the functional and anatomical separation of the channels. This work has been done on the frog, and our interpretation applies only to the frog.

Aims. We present cosmological constraints from a joint analysis of type Ia supernova (SN Ia) observations obtained by the SDSS-II and SNLS collaborations. The dataset includes several low-redshift samples (z< 0.1), all three seasons from the SDSS-II (0.05 <z< 0.4), and three years from SNLS (0.2 <z< 1), and it totals 740 spectroscopically confirmed type Ia supernovae with high-quality light curves.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

The geometry of the spinning black holes of standard Einstein theory in 2+1 dimensions, with a negative cosmological constant, and without couplings to matter, is analyzed in detail. It is shown that the black hole arises from identifications of points of anti--de Sitter space by a discrete subgroup of SO(2,2). The generic black hole is a smooth manifold in the metric sense. The surface r=0 is not a curvature singularity but, rather, a singularity in the causal structure. Continuing past it would introduce closed timelike lines. However, simple examples show the regularity of the metric at r=0 to be unstable: couplings to matter bring in a curvature singularity there. Kruskal coordinates and Penrose diagrams are exhibited. Special attention is given to the limiting cases of (i) the spinless hole of zero mass, which differs from anti--de Sitter space and plays the role of the vacuum, and (ii) the spinning hole of maximal angular momentum. A thorough classification of the elements of the Lie algebra of SO(2,2) is given in an appendix.