Biocontrol and plant growth promoting traits of two avocado rhizobacteria are orchestrated by the emission of diffusible and volatile compounds.

Avocado (Persea americana Mill.) is a tree crop of great social and economic importance. However, the crop productivity is hindered by fast-spreading diseases, which calls for the search of new biocontrol alternatives to mitigate the impact of avocado phytopathogens. Our objectives were to evaluate the antimicrobial activity of diffusible and volatile organic compounds (VOCs) produced by two avocado rhizobacteria (Bacillus A8a and HA) against phytopathogens Fusarium solani, Fusarium kuroshium, and Phytophthora cinnamomi, and assess their plant growth promoting effect in Arabidopsis thaliana. We found that, in vitro, VOCs emitted by both bacterial strains inhibited mycelial growth of the tested pathogens by at least 20%. Identification of bacterial VOCs by gas chromatography coupled to mass spectrometry (GC-MS) showed a predominance of ketones, alcohols and nitrogenous compounds, previously reported for their antimicrobial activity. Bacterial organic extracts obtained with ethyl acetate significantly reduced mycelial growth of F. solani, F. kuroshium, and P. cinnamomi, the highest inhibition being displayed by those from strain A8a (32, 77, and 100% inhibition, respectively). Tentative identifications carried out by liquid chromatography coupled to accurate mass spectrometry of diffusible metabolites in the bacterial extracts, evidenced the presence of some polyketides such as macrolactins and difficidin, hybrid peptides including bacillaene, and non-ribosomal peptides such as bacilysin, which have also been described in Bacillus spp. for antimicrobial activities. The plant growth regulator indole-3-acetic acid was also identified in the bacterial extracts. In vitro assays showed that VOCs from strain HA and diffusible compounds from strain A8a modified root development and increased fresh weight of A. thaliana. These compounds differentially activated several hormonal signaling pathways involved in development and defense responses in A. thaliana, such as auxin, jasmonic acid (JA) and salicylic acid (SA); genetic analyses suggested that developmental stimulation of the root system architecture by strain A8a was mediated by the auxin signaling pathway. Furthermore, both strains were able to enhance plant growth and decreased the symptoms of Fusarium wilt in A. thaliana when soil-inoculated. Collectively, our results evidence the potential of these two rhizobacterial strains and their metabolites as biocontrol agents of avocado pathogens and as biofertilizers.

Caracterización clínica y microbiológica de los eventos de peritonitis asociada a diálisis peritoneal en un hospital de Chile. Un análisis retrospectivo / Clinical and microbiological characterization of Peritoneal Dialysis-Associated Peritonitis events in a hospital in Chile. A retrospective analysis

INTRODUCCIÓN: Las infecciones asociadas a diálisis peritoneal constituyen una de las causas de morbimortalidad más importante en estos pacientes y la terapia antimicrobiana empírica y dirigida adecuada es fundamental para mejorar el resultado, por lo que es importante establecer la microbiología local. OBJETIVO: Revisar la experiencia clínica de cinco años del Hospital Carlos Van Buren de Valparaíso, Chile, describiendo las características clínicas y microbiológicas de los pacientes con episodios de peritonitis asociada a diálisis peritoneal. METODOLOGÍA De forma retrospectiva se accedió a los registros clínicos de aquellos pacientes mayores de 18 años que presentaron al menos un evento de peritonitis asociada a diálisis peritoneal. RESULTADOS: De un total de 26 episodios, 62% de los pacientes fueron de sexo femenino, con un promedio de edad de 53 años. La principal comorbilidad fue la hipertensión arterial (100%), y el dolor abdominal fue el síntoma más frecuente (85%), con una mortalidad general de 7,7%. En el laboratorio la leucocitosis, la proteína C reactiva (PCR) y la velocidad de hemosedimentación (VHS) fueron los hallazgos más importantes. Predominaron las cocáceas grampositivas (54%), seguido de bacilos gramnegativos no fermentadores y Enterobacterales en igual proporción (11,5% cada grupo). Casos aislados de Candida albicans y Pasteurella canis fueron identificados, y en 15% de los casos el cultivo resultó negativo. CONCLUSIÓN: Se pudo conocer las características clínicas y microbiológicas locales de esta patología, para así redefinir las directrices de manejo en la institución.

BACKGROUND: Infections associated with peritoneal dialysis are one of the most important causes of morbidity and mortality in these patients, and adequate empirical and targeted antimicrobial therapy are essential to improve the outcome, so it is important to establish the local microbiology. AIM: To review the clinical experience of 5 years at the Carlos Van Buren Hospital in Valparaíso, Chile, in order to know the clinical and microbiological characteristics of patients with episodes of peritonitis associated with peritoneal dialysis. METHODS: Retrospectively, the clinical records of those patients over 18 years of age who presented at least one peritonitis event associated with peritoneal dialysis were accessed. RESULTS: Of a total of 26 episodes, 62% of the patients were female, with a mean age of 53 years. The main comorbidity was arterial hypertension (100%), and abdominal pain was the most frequent symptom (85%), with an overall mortality of 7.7%. In the laboratory parameters, leukocytosis, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were the most important findings. Gram-positive cocci (54%) predominated, followed by Gram-negative non-fermenting and enterobacterial bacilli in the same proportion (11.5% each group). Isolated cases of Candida albicans and Pasteurella canis were identified, and in 15% of the cases the culture was negative. CONCLUSION: It was possible to know the local clinical and microbiological characteristics of this pathology, in order to redefine management guidelines for our institution.

Effect of Process Parameters and Postprocessing on Mechanical Properties of Additive Manufacturing Polylactic Acid Obtained by Fused Deposition Modeling.

The aim of this article is to study the influence of some printing parameters and postprocessing on mechanical properties of polylactic acid samples manufactured by fused deposition modeling with a 3D printer. The effects of different building orientations, concentric infill, and postprocessing by annealing were analyzed. In this sense, uniaxial tensile and three-point bending tests were performed to determine the ultimate strength, modulus of elasticity, and elongation at break. Among all printing parameters of interest, the print orientation can be considered one of the most important, being fundamental in the mechanical behavior. Once samples were fabricated, annealing processes were also considered, close to the T g, in order to study the effects on mechanical properties. In the modified print orientation, the average values for the E and the σ TS are 3337.15-3337.92 and 36.42-37.62 MPa, compared with default printing with the E and the σ TS that are 2541.63-2692.34 and 28.81-28.89 MPa, respectively. In the annealed samples, the values for the Ef and the σf are 2337.73 and 63.96 MPa, compared with the reference samples with the Ef and the σf values of 2164.40 and 59.66 MPa, respectively. Hence, the print orientation and postprocessing must be taken into account as important factors for the final properties of the desired product.

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators.

Coronaviruses (CoVs) of genera α, ß, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.

Molecular Heterogeneity in Pediatric Malignant Rhabdoid Tumors in Patients With Multi-Organ Involvement.

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with SMARCB1 germline alterations. Here we present data from seven RTs from three pediatric patients who all had multi-organ involvement. The tumors were analyzed using a multimodal molecular approach, which included exome sequencing of tumor and germline comparator and RNA sequencing and DNA array-based methylation profiling of tumors. SMARCB1 germline alterations were identified in all patients and in all tumors. We observed a second hit in SMARCB1 via chr22 loss of heterozygosity. By methylation profiling, all tumors were classified as rhabdoid tumors with a corresponding subclassification within the MYC, TYR, or SHH AT/RT subgroups. Using RNA-seq gene expression clustering, we recapitulated the classification of known AT/RT subgroups. Synchronous brain and kidney tumors from the same patient showed different patterns of either copy number variants, single-nucleotide variants, and/or genome-wide DNA methylation, suggestive of non-clonal origin. Furthermore, we demonstrated that a lung and abdominal metastasis from two patients shared overlapping molecular features with the patient's primary kidney tumor, indicating the likely origin of the metastasis. In addition to the SMARCB1 events, we identified other whole-chromosome events and single-nucleotide variants in tumors, but none were found to be prognostic, diagnostic, or offer therapeutic potential for rhabdoid tumors. While our findings are of biological interest, there may also be clinical value in comprehensive molecular profiling in patients with multiple rhabdoid tumors, particularly given the potential prognostic and therapeutic implications for different rhabdoid tumor subgroups demonstrated in recent clinical trials and other large cohort studies.

Nature of viruses and pandemics: Coronaviruses.

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.

Microbiota Perturbation or Elimination Can Inhibit Normal Development and Elicit a Starvation-Like Response in an Omnivorous Model Invertebrate.

Omnivorous animals, including humans, harbor diverse, species-rich gut communities that impact their growth, development, and homeostasis. Model invertebrates are broadly accessible experimental platforms that enable linking specific species or species groups to host phenotypes, yet often their specialized diets and distinct gut microbiota make them less comparable to human and other mammalian and gut communities. The omnivorous cockroach Periplaneta americana harbors ∼4 × 102 bacterial genera within its digestive tract and is enriched with taxa commonly found in omnivorous mammals (i.e., Proteobacteria, Bacteroidetes, and Firmicutes). These features make P. americana a valuable platform for identifying microbe-mediated host phenotypes with potential translations to mammals. Rearing P. americana insects under germfree conditions resulted in prolonging development time by ∼30% and an up to ∼8% reduction in body size along three dimensions. Germfree rearing resulted in downregulation of gene networks involved in growth, energy homeostasis, and nutrient availability. Reintroduction of a defined microbiota comprised of a subset of P. americana commensals to germfree insects did not recover normal growth and developmental phenotypes or transcriptional profiles observed in conventionally reared insects. These results are in contrast with specialist-feeding model insects (e.g., Drosophila), where introduction of a single endemic bacterial species to germfree condition-reared specimens recovered normal host phenotypes. These data suggest that understanding microbe-mediated host outcomes in animals with species-rich communities should include models that typically maintain similarly diverse microbiomes. The dramatic transcriptional, developmental, and morphological phenotypes linked to gut microbiome status in this study illustrates how microbes are key players in animal growth and evolution. IMPORTANCE Broadly accessible model organisms are essential for illustrating how microbes are engaged in the growth, development, and evolution of animals. We report that germfree rearing of omnivorous Periplaneta americana cockroaches resulted in growth defects and severely disrupted gene networks that regulate development, which highlights the importance of gut microbiota in these host processes. Absence of gut microbiota elicited a starvation-like transcriptional response in which growth and development were inhibited while nutrient scavenging was enhanced. Additionally, reintroduction of a subset of cockroach gut bacterial commensals did not broadly recover normal expression patterns, illustrating that a particular microbiome composition may be necessary for normal host development. Invertebrate microbiota model systems that enable disentangling complex, species-rich communities are essential for linking microbial taxa to specific host phenotypes.

Asociación de la violencia obstétrica, control prenatal y embarazo no planeado con la prematurez / Association of obstetric violence, prenatal control, and unplanned pregnancy with prematurity

Resumen La prematurez (PM) neonatal es un problema mayor de salud pública en el mundo, debido a su frecuencia de presentación y los años de vida potencialmente perdidos; además, es la principal causa de muerte en menores de cinco años. Entre las consecuencias negativas de la PM están las discapacidades del aprendizaje, visual y auditiva. Múltiples son los factores asociados a la PM; algunos pueden ser detectados y modificados de forma oportuna en las consultas prenatales y también, en las preconcepcionales. Por otro lado, la PM no es solamente responsabilidad del prestador de los servicios de salud, sino también del sistema de salud, el cual, debe otorgar los recursos mínimos necesarios para monitorear y mantener a la embarazada en un estado óptimo de salud para evitarla, y en caso de presentarse, debe contar con la infraestructura hospitalaria básica que permita la viabilidad del producto y evitar su muerte. Aunado a lo anterior, se debe de considerar la responsabilidad de la paciente y su pareja, debido a que en ellos recae la obligación de llevar un estilo de vida saludable y acudir a las consultas preconcepcionales y control prenatal.

Abstract Neonatal prematurity (MP) is a major public health problem in the world, due to its presentation frequency and the years of life potentially lost; In addition, it is the main cause of death in children under five years of age. Among the negative consequences of MP are learning, visual and hearing disabilities. There are multiple factors associated with MP; some can be detected and modified in a timely manner in prenatal consultations and in preconception. On the other hand, MP is not only responsibility of the health service provider, but also of the health system, which must grant the minimum resources necessary to monitor and maintain the pregnant woman in an optimal state of health to avoid it, and if it occurs, the hospital must have the basic infrastructure that allows the viability of the product and prevents its death. In addition, the responsibility of the patient and her partner must be considered since they are obliged to lead a healthy lifestyle and attend preconception consultations and prenatal care.

Multiple concurrent and convergent stages of genome reduction in bacterial symbionts across a stink bug family.

Nutritional symbioses between bacteria and insects are prevalent and diverse, allowing insects to expand their feeding strategies and niches. A common consequence of long-term associations is a considerable reduction in symbiont genome size likely influenced by the radical shift in selective pressures as a result of the less variable environment within the host. While several of these cases can be found across distinct insect species, most examples provide a limited view of a single or few stages of the process of genome reduction. Stink bugs (Pentatomidae) contain inherited gamma-proteobacterial symbionts in a modified organ in their midgut and are an example of a long-term nutritional symbiosis, but multiple cases of new symbiont acquisition throughout the history of the family have been described. We sequenced the genomes of 11 symbionts of stink bugs with sizes that ranged from equal to those of their free-living relatives to less than 20%. Comparative genomics of these and previously sequenced symbionts revealed initial stages of genome reduction including an initial pseudogenization before genome reduction, followed by multiple stages of progressive degeneration of existing metabolic pathways likely to impact host interactions such as cell wall component biosynthesis. Amino acid biosynthesis pathways were retained in a similar manner as in other nutritional symbionts. Stink bug symbionts display convergent genome reduction events showing progressive changes from a free-living bacterium to a host-dependent symbiont. This system can therefore be used to study convergent genome evolution of symbiosis at a scale not previously available.

ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies.

Cardiovascular disease (CVD) is the leading cause of mortality in the world, with most CVD-related deaths resulting from myocardial infarction or stroke. The main underlying cause of thrombosis and cardiovascular events is atherosclerosis, an inflammatory disease that can remain asymptomatic for long periods. There is an urgent need for therapeutic and diagnostic options in this area. Atherosclerotic plaques contain autoantibodies1,2, and there is a connection between atherosclerosis and autoimmunity3. However, the immunogenic trigger and the effects of the autoantibody response during atherosclerosis are not well understood3-5. Here we performed high-throughput single-cell analysis of the atherosclerosis-associated antibody repertoire. Antibody gene sequencing of more than 1,700 B cells from atherogenic Ldlr-/- and control mice identified 56 antibodies expressed by in-vivo-expanded clones of B lymphocytes in the context of atherosclerosis. One-third of the expanded antibodies were reactive against atherosclerotic plaques, indicating that various antigens in the lesion can trigger antibody responses. Deep proteomics analysis identified ALDH4A1, a mitochondrial dehydrogenase involved in proline metabolism, as a target antigen of one of these autoantibodies, A12. ALDH4A1 distribution is altered during atherosclerosis, and circulating ALDH4A1 is increased in mice and humans with atherosclerosis, supporting the potential use of ALDH4A1 as a disease biomarker. Infusion of A12 antibodies into Ldlr-/- mice delayed plaque formation and reduced circulating free cholesterol and LDL, suggesting that anti-ALDH4A1 antibodies can protect against atherosclerosis progression and might have therapeutic potential in CVD.

Esophageal deviation with vacuum suction and mechanical deflection during ablation of atrial fibrillation: First in man evaluation.

Deviation of the esophagus during atrial fibrillation (AF) ablation can reduce esophageal injury. This study reports upon a novel esophageal retractor that utilizes vacuum suction and mechanical deflection to deviate the esophagus. The device was used in seven patients undergoing cryoballoon AF ablation. The esophagus was deviated 31.9 ± 4.4 mm to the right and 28.2 ± 5.9 mm to the left. Endoscopy at 4.4 ± 1.5 days postablation showed no esophageal injury. This study demonstrates the safe and effective deviation of the esophagus without a trailing edge with an esophageal retractor utilizing vacuum suction and mechanical deflection.

Infección respiratoria aguda por coronavirus Sars-CoV-2 en personal de salud: implementación de un programa de detección precoz y seguimiento de casos en un hospital universitario / A surveillance system to detect COVID-19 infections in health care workers: experience in 209 cases

Background: Healthcare personnel are a high-risk group for acquiring COVID-19 disease. They represent 4 to 20% of the total number of cases reported in different geographical areas. Aim: To describe an epidemiological surveillance strategy to detect symptoms compatible with SARS-CoV-2 infection and early case detection among healthcare personnel at a university hospital. Patients and Methods: We assessed 209 healthcare workers reporting symptoms suggestive of COVID-19 in a telephone counseling system. After a structured evaluation, the suggestions ranged from having a SARS-CoV-2 nasopharyngeal swab PCR test, consulting in the emergency room or at outpatient clinic or returning to work. Results: In 61% of assessed workers a coronavirus SARS-CoV-2 nasopharyngeal swab PCR was requested and 28 (22%) were positive. In a multivariate analysis, the clinical variables associated with a positive PCR test were the presence of fever, sudden loss of smell or taste, and a history of contact with a COVID-19 positive case. Conclusions: The telephone symptom monitoring program allowed the early detection of a significant number of healthcare officials with acute respiratory infection due to coronavirus SARS-CoV-2, it is easy to implement and has a low cost.

[A surveillance system to detect COVID-19 infections in health care workers. Experience in 209 cases]. / Infección respiratoria aguda por coronavirus Sars-CoV-2 en personal de salud. Implementación de un programa de detección precoz y seguimiento de casos en un hospital universitario.

BACKGROUND: Healthcare personnel are a high-risk group for acquiring COVID-19 disease. They represent 4 to 20% of the total number of cases reported in different geographical areas. AIM: To describe an epidemiological surveillance strategy to detect symptoms compatible with SARS-CoV-2 infection and early case detection among healthcare personnel at a university hospital. PATIENTS AND METHODS: We assessed 209 healthcare workers reporting symptoms suggestive of COVID-19 in a telephone counseling system. After a structured evaluation, the suggestions ranged from having a SARS-CoV-2 nasopharyngeal swab PCR test, consulting in the emergency room or at outpatient clinic or returning to work. RESULTS: In 61% of assessed workers a coronavirus SARS-CoV-2 nasopharyngeal swab PCR was requested and 28 (22%) were positive. In a multivariate analysis, the clinical variables associated with a positive PCR test were the presence of fever, sudden loss of smell or taste, and a history of contact with a COVID-19 positive case. CONCLUSIONS: The telephone symptom monitoring program allowed the early detection of a significant number of healthcare officials with acute respiratory infection due to coronavirus SARS-CoV-2, it is easy to implement and has a low cost.

Hepatectomía derecha y hemicolectomía derecha por necrosis hepática y perforación cólica causadas por Entamoeba histolytica / Right hepatectomy and right hemicolectomy for liver necrosis and colonic perforation caused by Entamoeba histolytica

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CONSTITUTIVE TRIPLE RESPONSE1 and PIN2 act in a coordinate manner to support the indeterminate root growth and meristem cell proliferating activity in Arabidopsis seedlings.

The plant hormone ethylene induces auxin biosynthesis and transport and modulates root growth and branching. However, its function on root stem cells and the identity of interacting factors for the control of meristem activity remains unclear. Genetic analysis for primary root growth in wild-type (WT) Arabidopsis thaliana seedlings and ethylene-related mutants showed that the loss-of-function of CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) inhibits cell division and elongation. This phenotype is associated with an increase in the expression of the auxin transporter PIN2 and a drastic decrease in the expression of key factors for stem cell niche maintenance such as PLETHORA1, SHORT ROOT and SCARECROW. While the root stem cell niche is affected in ctr1 mutants, its maintenance is severely compromised in the ctr1-1eir1-1(pin2) double mutant, in which an evident loss of proliferative capacity of the meristematic cells leads to a fully differentiated root meristem shortly after germination. Root traits affected in ctr1-1 mutants could be restored in ctr1-1ein2-1 double mutants. These results reveal that ethylene perception via CTR1 and EIN2 in the root modulates the proliferative capacity of root stem cells via affecting the expression of genes involved in the two major pathways, AUX-PIN-PLT and SCR-SHR, which are key factors for proper root stem cell niche maintenance.

Bullying entre adolescentes, una problemática creciente / Bullying among adolescents, an growing problem

El bullying en la actualidad es un verdadero problema de salud creciente que ha ganado espacio,pero sin embargo es poco denunciado, a pesar de existir leyes en el Ecuador que lo estipulan como delito;la forma de maltrato en la actualidad se ha intensificado debido a la utilización de redes sociales y discriminación de clase. En Ambato, en una unidad educativa privada, se realizó el presente estudio transversal descriptivo en jóvenes de 13 a 18 años deedad, mediante la aplicación de una encuesta, y los resultados mostraron que el 49 % de adolescentes admite ser acosado, identificándosea la provocación, el maltrato verbal como formas frecuentes de intimidación, seguido del maltrato físico y psicológico; el lugar donde se produce el mayor número de intimidaciones es fuera de la unidad educativa y en ausencia del docente; el adolescente intimidado en alto porcentaje no comparte su problema, lo que hace que esta modalidad de intimidación no sea resuelta deforma inmediata y no se tome el correctivo necesario, tanto para el acosador como para el intimidado,lo cual en el futuro traerá graves consecuencias, dentro de las cuales se pueden citar trastornos psicológicos, de conducta, bajo rendimiento escolar, distimia y en el peor de los casos llegar a autolisis. Por todo aquello es necesario realizar campañas de concienciación dirigidas a docentes, padres de familia y estudiantes, con el fin de detectar y corregir a tiempo esta problemática social, evitando consecuencias fatales.

Bullying is in the actuality a real and silent health problem, that has gained ground, however it is little denounced, despite of the existence of laws in Ecuador that report it as a crime, the way to abuse today has been intensified due to the use of social networks and class discrimination. In Ambato, in a private education unit, was made this descriptive cross-sectional study in teenagers between 13-18 years old, and the results showed that 49 % of teenagers admit being bullied, as the main factor was identified the provocation, and as more frequent the verbal abuse, followed by physical and psychological abuse; the place the most number of intimidations where made is in the around of the educational unit and in the absence of teachers; the teenager who is bullied in high percentage does not share their problem, what makes this type of intimidation not be resolved immediately and they do not take the necessary corrective measures, for both the bully as the aggressed, this will bring serious consequences in the future within which we can cite psychological disorders, behavioral, poor school performance, dysthymias and in the worst of case to the autolysis, For this reason, it is necessary to conduct awareness campaigns aimed at teachers, parents and students, in order to detect and correct as soon as possible this social problem, avoiding fatal consequences.

Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy.

Virtually all patients of the rare inflammatory eye disease birdshot chorioretinopathy (BSCR) carry the HLA-A*29:02 allele. BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. To investigate the relationship between both risk factors we employed label-free quantitative mass spectrometry to characterize the effects of ERAP2 on the A*29:02-bound peptidome. An ERAP2-negative cell line was transduced with lentiviral constructs containing GFP-ERAP2 or GFP alone, and the A*29:02 peptidomes from both transduced cells were compared. A similar analysis was performed with two additional A*29:02-positive, ERAP1-concordant, cell lines expressing or not ERAP2. In both comparisons the presence of ERAP2 affected the following features of the A*29:02 peptidome: 1) Length, with increased amounts of peptides >9-mers, and 2) N-terminal residues, with less ERAP2-susceptible and more hydrophobic ones. The paradoxical effects on peptide length suggest that unproductive binding to ERAP2 might protect some peptides from ERAP1 over-trimming. The influence on N-terminal residues can be explained by a direct effect of ERAP2 on trimming, without ruling out and improved processing in concert with ERAP1. The alterations in the A*29:02 peptidome suggest that the association of ERAP2 with BSCR is through its effects on peptide processing. These differ from those on the ankylosing spondylitis-associated HLA-B*27. Thus, ERAP2 alters the peptidome of distinct HLA molecules as a function of their specific binding preferences, influencing different pathological outcomes in an allele-dependent way.

Ranking the Contribution of Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) Polymorphisms to Shaping the HLA-B*27 Peptidome.

The Endoplasmic reticulum aminopeptidase I (ERAP1) trims peptides to their optimal size for binding to Major Histocompatibility Complex class I proteins. The natural polymorphism of this enzyme is associated with ankylosing spondylitis (AS) in epistasis with the major risk factor for this disease, HLA-B*27, suggesting a direct relationship between AS and HLA-B*27-bound peptides. Three polymorphisms that affect peptide trimming protect from AS: K528R, D575N/R725Q, and Q730E. We characterized and ranked the effects of each mutation, and their various combinations, by quantitative comparisons of the HLA-B*27 peptidomes from cells expressing distinct ERAP1 variants. Five features were examined: peptide length, N-terminal flanking residues, N-terminal residues of the natural ligands, internal sequences and affinity for B*27:05. Polymorphism at residue 528 showed the largest influence, affecting all five features regardless of peptide length. D575N/R725Q showed a much smaller effect. Yet, when co-occurring with K528R, it further decreased ERAP1 activity. Polymorphism at residue 730 showed a significant influence on peptide length, because of distinct effects on trimming of nonamers compared with longer peptides. Accordingly, multiple features were affected by the Q730E mutation in a length-dependent way. The alterations induced in the B*27:05 peptidome by natural ERAP1 variants with different K528R/Q730E combinations reflected separate and additive effects of both mutations. Thus, the influence of ERAP1 on HLA-B*27 is very diverse at the population level, because of the multiplicity and complexity of ERAP1 variants, and to the distinct effects of their co-occurring polymorphisms, leading to significant modulation of disease risk among HLA-B*27-positive individuals.

Cladogenesis and Genomic Streamlining in Extracellular Endosymbionts of Tropical Stink Bugs.

Phytophagous stink bugs are globally distributed and many harbor vertically inherited bacterial symbionts that are extracellular, yet little is known about how the symbiont's genomes have evolved under this transmission strategy. Genome reduction is common in insect intracellular symbionts but limited genome sampling of the extracellular symbionts of distantly related stink bugs has precluded inferring patterns of extracellular symbiont genome evolution. To address this knowledge gap, we completely sequenced the genomes of the uncultivable bacterial symbionts of four neotropical stink bugs of the Edessa genus. Phylogenetic and comparative analyses indicated that the symbionts form a clade within the Pantoea genus and their genomes are highly reduced (∼0.8 Mb). Furthermore, genome synteny analysis and a jackknife approach for phylogenetic reconstruction, which corrected for long branch attraction artifacts, indicated that the Edessa symbionts were the result of a single symbiotic event that was distinct from the symbiosis event giving rise to Candidatus "Pantoea carbekii," the extracellular symbiont of the invasive pentatomid stink bug, Halyomorpha halys. Metabolic functions inferred from the Edessa symbiont genomes suggests a shift in genomic composition characteristic of its lifestyle in that they retained many host-supportive functions while undergoing dramatic gene loss and establishing a stable relationship with their host insects. Given the undersampled nature of extracellular insect symbionts, this study is the first comparative analysis of these symbiont genomes from four distinct Edessa stink bug species. Finally, we propose the candidate name "Candidatus Pantoea edessiphila" for the species of these symbionts with strain designations according to their host species.