MRI features indicative of permanent colon damage in ulcerative colitis: an exploratory study.

BACKGROUND AND AIMS: It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross sectional image. We aimed to characterize bowel damage in patients with ulcerative colitis using magnetic resonance imaging and determine its relation with duration of disease and the impact on patients' quality of life. METHODS: In this prospective study, subjects with ulcerative colitis in endoscopic remission underwent MRI without bowel cleansing and completed quality-of-life questionnaires. Subjects' magnetic resonance findings were analyzed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease (n=40) and in patients with Crohn's disease with no history of colonic involvement (n=12). Subjects with UC were stratified according to disease duration (<7 years vs. 7‒14 years vs. >14 years). RESULTS: We analyzed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 (92.7%) and 1 in 3 (7.3%)]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented of being affected by ulcerative colitis versus controls showed subjects with ulcerative colitis had decreased cross-sectional area (p≤0.0034) and perimeter (p≤0.0005), and increased wall thickness (p=0.026) in all segments. Colon damage, defined as wall thickness ≥3 mm, was seen in 22 (53.7%) subjects. Colon damage was not associated with disease duration or quality of life. CONCLUSIONS: Morphologic abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life.

Enhanced TrkA signaling impairs basal forebrain-dependent behavior.

Basal forebrain cholinergic neurons (BFCNs) modulate cognitive functions such as attention, learning and memory. The NGF/TrkA pathway plays an important role in the development and function of BFCNs, although two mouse models conditionally deleting TrkA expression in the central nervous system (CNS) have shown contradictory results. To shed light into this discrepancy, we used a mouse model with a gain-of-function in TrkA receptor signaling. Our results indicate that enhanced TrkA signaling did not alter hippocampal cholinergic innervation, general locomotion or anxiety-related behaviors, but it increases ChAT expression, the number of cholinergic neurons at early postnatal stages and, mutant mice showed impaired motor learning and memory functions. These data demonstrate that proper functioning of the cholinergic system in CNS requires a balanced NGF/TrkA signaling.

A Simple, Reproducible Procedure for Chemiluminescent Western Blot Quantification.

Western blotting is a universally used technique to identify specific proteins from a heterogeneous and complex mixture. However, there is no clear and common procedure to quantify the results obtained, resulting in variations due to the different software and protocols used in each laboratory. Here, we have developed a procedure based on the increase in chemiluminescent signal to obtain a representative value for each band to be quantified. Images were processed with ImageJ and subsequently compared using R software. The result is a linear regression model in which we use the slope of the signal increase within the combined linear range of detection to compare between samples. This approach allows to quantify and compare protein levels from different conditions in a simple and reproducible way. Graphical overview.

Mechanisms Controlling the Expression and Secretion of BDNF.

Brain-derived nerve factor (BDNF), through TrkB receptor activation, is an important modulator for many different physiological and pathological functions in the nervous system. Among them, BDNF plays a crucial role in the development and correct maintenance of brain circuits and synaptic plasticity as well as in neurodegenerative diseases. The proper functioning of the central nervous system depends on the available BDNF concentrations, which are tightly regulated at transcriptional and translational levels but also by its regulated secretion. In this review we summarize the new advances regarding the molecular players involved in BDNF release. In addition, we will address how changes of their levels or function in these proteins have a great impact in those functions modulated by BDNF under physiological and pathological conditions.

Embriogénesis, desarrollo larval y sobrevivencia post-asentamiento del coral Orbicella annularis (Scleractinia: Merulinidae)

Introducción: Las poblaciones del coral Orbicella annularis han mostrado bajo reclutamiento en el Caribe. Uno de los cuellos de botella demográficos es la alta mortalidad en las primeras etapas de desarrollo. El conocimiento detallado del ciclo y las tasas de supervivencia de estas fases nos permitirá ayudar en la recuperación de la población y la restauración de los arrecifes. Objetivo: Describir la embriogénesis y estadios larvarios obtenidos por fertilización asistida y medir las tasas de asentamiento y supervivencia de las larvas en sustratos artificiales, antes de ser trasplantadas al arrecife. Métodos: Seis días después de la luna llena de septiembre de 2021, se recolectaron bolsas de gametos de ocho colonias de O. annularis en el Parque Nacional Natural Los Corales del Rosario y San Bernardo, Colombia, y se llevaron al laboratorio. Se realizó fecundación cruzada, se siguió el desarrollo embrionario y larvario hasta el asentamiento larval y se registró supervivencia hasta el día 41. Las larvas se mantuvieron en tres tanques con agua de mar filtrada con 126 sustratos marcados, previamente acondicionados con algas coralináceas costrosas. Luego, los sustratos se trasplantaron al arrecife. Resultados: El inicio del desarrollo embrionario ocurrió 1.11 hAF (horas después de la fertilización), cuando las células mostraron signos de la primera división, y duró hasta 104.59 hAF cuando comenzaron a metamorfosearse. El asentamiento de larvas se observó al sexto día AF. Veintiún días después de la fecundación se encontraron zooxantelas. La supervivencia de las larvas después del asentamiento fue de 27.5 %. Conclusión: En este primer esfuerzo de propagación sexual utilizando O. annularis en Colombia, 1.4 % de larvas competentes completaron todo el proceso de desarrollo. Aunque la tasa de supervivencia fue baja, estos resultados se suman a los esfuerzos de restauración de corales en el Caribe en los que se ayuda a las especies a aumentar la supervivencia de los corales en sus primeras etapas de desarrollo.

Introduction: Populations of the coral Orbicella annularis have shown low recruitment in the Caribbean. One of the demographic bottlenecks is the high mortality in the early stages of development. Detailed knowledge of the cycle and survival rates of these phases will allow us to assist in population recovery and reef restoration. Objective: To describe the embryogenesis and larval stages obtained by assisted fertilization and measure the settlement and survival rates of larvae on artificial substrates, before being outplanted to the reef. Methods: Six days after the full moon in September 2021, gamete bundles were collected from eight O. annularis colonies in Los Corales del Rosario and San Bernardo National Natural Park, Colombia and brought to the laboratory. Cross fertilization was carried out and embryonic and larval development were followed until larval settlement and survival was recorded until day 41. The larvae were kept in three tanks with filtered sea water with 126 tagged substrates, previously conditioned with crustose coralline algae. The substrates were then outplanted to the reef. Results: The onset of embryonic development occurred 1.11 hAF (hours after fertilization), when cells showed signs of the first cleavage, and lasted until 104.59 hAF when they began to metamorphose. Larvae settlement was observed on the sixth day AF. Twenty-one days after fertilization, zooxanthellae were found. Post-settlement larval survival was 27.5 %. Conclusions: In this first sexual propagation effort using O. annularis in Colombia, 1.4 % of competent larvae completed the entire development process. Although low survival rate, these results add to coral restoration efforts in the Caribbean in which species are assisted to increase the survival of corals in their early stages of development.

Gastrointestinal manifestations of COVID-19 in a Colombian population. A cross-sectional study

Introduction: gastrointestinal involvement in COVID-19 occurs in approximately 20% of patients and may include nausea, vomiting, abdominal pain, diarrhea or abnormal liver function tests. In our country, the characteristics of gastrointestinal involvement in COVID-19 patients have not been studied. Objectives: to determine the prevalence of gastrointestinal and liver involvement in patients with COVID-19 treated at two hospitals in Bogotá, Colombia. To determine the association between COVID-19 gastrointestinal involvement and length of hospital stay, severity and mortality. Design and methodology: a cross-sectional study carried out at two hospitals in a hospital subnetwork in Bogotá, Colombia from February 2020 to March 2021. Results: a total of 1,176 patients with a positive reverse transcription polymerase chain reaction (RT-PCR) were included. Gastrointestinal manifestations occurred in 50% (95%CI 47-52%), with the most frequent being diarrhea in 18.4%, odynophagia in 17.6%, anorexia in 14.7% and abdominal pain in 8.8%. An association was found between diarrhea during hospitalization and prolonged hospitalization (OR 1.93 95%CI 1.19-3.13), and between gastrointestinal bleeding on admission and death (OR 3.13, 95%CI 1.1-9.1), among others. Abnormal liver function tests occurred in 46% (95%CI 43-49%) and were more frequent in patients with severe disease and those who died. Conclusions: the prevalence of gastrointestinal manifestations in patients with COVID-19 was 50%. Diarrhea was associated with a longer hospital stay, and gastrointestinal bleeding was associated with respiratory failure and death. Forty-six percent of patients had abnormal liver function tests, with elevated transaminases being the most frequent. Elevated aspartate transaminase (AST) on admission was associated with greater mortality. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2729).

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV.

A functional nerve growth factor NGF-Tropomyosin Receptor kinase A (TrkA) system is an essential requisite for the generation and maintenance of long-lasting thermal and mechanical hyperalgesia in adult mammals. Indeed, mutations in the gene encoding for TrkA are responsible for a rare condition, named Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), characterized by the loss of response to noxious stimuli, anhidrosis and cognitive impairment. However, to date, there is no available mouse model to properly understand how the NGF-TrkA system can lead to pathological phenotypes that are distinctive of HSAN IV. Here, we report the generation of a knock-in mouse line carrying the HSAN IV TrkAR649W mutation. First, by in vitro biochemical and biophysical analyses, we show that the pathological R649W mutation leads to kinase-inactive TrkA also affecting its membrane dynamics and trafficking. In agreement with the HSAN IV human phenotype, TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. Our results further uncover unexplored roles of TrkA in thermoregulation and sociability. In addition to accurately recapitulating the clinical manifestations of HSAN IV patients, our findings contribute to clarifying the involvement of the NGF-TrkA system in pain sensation.

ARMS/Kidins220 regulates nociception by controlling brain-derived neurotrophic factor secretion.

ABSTRACT: Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed. Here, we find that ARMS/Kidins220, a scaffold protein for Trk receptors, is a modulator of nociception. Male mice, with ARMS/Kidins220 reduction exclusively in TrkA-expressing cells, displayed hyperalgesia to heat, inflammatory, and capsaicin stimuli, but not to cold or mechanical stimuli. Simultaneous deletion of brain-derived neurotrophic factor (BDNF) reversed the effects of ARMS/Kidins220 knock down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from dorsal root ganglion. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.

An In-Silico Evaluation of Anthraquinones as Potential Inhibitors of DNA Gyrase B of Mycobacterium tuberculosis.

The World Health Organization reported that tuberculosis remains on the list of the top ten threats to public health worldwide. Among the main causes is the limited effectiveness of treatments due to the emergence of resistant strains of Mycobacterium tuberculosis. One of the main drug targets studied to combat M. tuberculosis is DNA gyrase, the only enzyme responsible for regulating DNA topology in this specie and considered essential in all bacteria. In this context, the present work tested the ability of 2824 anthraquinones retrieved from the PubChem database to act as competitive inhibitors through interaction with the ATP-binding pocket of DNA gyrase B of M. tuberculosis. Virtual screening results based on molecular docking identified 7122772 (N-(2-hydroxyethyl)-9,10-dioxoanthracene-2-sulfonamide) as the best-scored ligand. From this anthraquinone, a new derivative was designed harbouring an aminotriazole moiety, which exhibited higher binding energy calculated by molecular docking scoring and free energy calculation from molecular dynamics simulations. In addition, in these last analyses, this ligand showed to be stable in complex with the enzyme and further predictions indicated a low probability of cytotoxic and off-target effects, as well as an acceptable pharmacokinetic profile. Taken together, the presented results show a new synthetically accessible anthraquinone with promising potential to inhibit the GyrB of M. tuberculosis.

Survival study and factors associated with mortality in Chilean patients on peritoneal dialysis infected with SARS-CoV-2.

The Covid-19 pandemic has been responsible for millions of deaths worldwide. Patients with comorbidities- such as those on peritoneal dialysis (PD)- present higher morbidity and mortality than the general population. We prospectively evaluated all Chilean patients on PD (48 centres) and followed those who had Covid-19 from the beginning of the Covid-19 pandemic in Chile (March 2020) to January 2021 (start of vaccination campaign). We described demographic history, comorbidities, factors related to infection, need for hospitalisation and death due to Covid-19. During the study period, 106 adults on PD were infected by SARS-CoV-2, with a mean age of 53.1 (±16.3) and of which 53.9% were female. From that group, 54.8% required hospitalisation and 24.5% (n = 26) died due to Covid-19. Most of the patients (63.4%) were infected at home and 22.8% during hospitalisation for other reasons. There was a significant association for Covid-19 mortality with: being ≥60 years old, diabetes, time on PD ≥5 years, need for hospitalisation and hospital-acquired infection. At 90 days of follow-up, all deaths associated to Covid-19 occurred before 40 days. We conclude that patients on PD without Covid-19 vaccination have a high mortality and need for hospitalisation associated to Covid-19. To avoid this negative outcome, it is necessary to intensify strategies to avoid contagion, especially in those ≥60 years old, with diabetes and/or ≥5 years spent on PD.

Virtual screening, optimization and molecular dynamics analyses highlighting a pyrrolo[1,2-a]quinazoline derivative as a potential inhibitor of DNA gyrase B of Mycobacterium tuberculosis.

Tuberculosis is a disease that remains a significant threat to public health worldwide, and this is mainly due to the selection of strains increasingly resistant to Mycobacterium tuberculosis, its causative agent. One of the validated targets for the development of new antibiotics is DNA gyrase. This enzyme is a type II topoisomerase responsible for regulating DNA topology and, as it is essential in bacteria. Thus, to contribute to the search for new molecules with potential to act as competitive inhibitors at the active site of M. tuberculosis DNA gyrase B, the present work explored a dataset of 20,098 natural products that were filtered using the FAF-Drugs4 server to obtain a total of 5462 structures that were subsequently used in virtual screenings. The consensus score analysis between LeDock and Auto-Dock Vina software showed that ZINC000040309506 (pyrrolo[1,2-a]quinazoline derivative) exhibit the best binding energy with the enzyme. In addition, its subsequent optimization generated the derivative described as PQPNN, which show better binding energy in docking analysis, more stability in molecular dynamics simulations and improved pharmacokinetic and toxicological profiles, compared to the parent compound. Taken together, the pyrrolo[1,2-a]quinazoline derivative described for the first time in the present work shows promising potential to inhibit DNA gyrase B of M. tuberculosis.

Violencia de género contra mujeres indígenas del área rural del cantón tena, año 2021 / Gender-based violence against indigenous women in the rural area of the tena Canton, year 2021

El Ecuador es un estado laico, pluricultural y multiétnico, la población indígena está representada por el 27% de la población ecuatoriana. Las mujeres indígenas, se enfrentan a diversos tipos de violencia en su vida cotidiana, la cual representa una violación de derechos humanos, civiles, políticos, justicia y vivir una vida libre de violencia. Objetivo: Analizar los factores que inciden en la violencia de género contra las mujeres indígenas del área rural del Cantón Tena. Metodología: Es un estudio con enfoque cuali-cuantitativo, en la parte cualitativa se utilizó un diseño bibliográfico documental- analítico y en la parte cualitativa se realizó a través de un enfoque fenomenológico analítico. Para la parte cuantitativa se aplicó un instrumento de recolección cuantitativa validado, mientras tanto, la parte cualitativa se aplicó un cuestionario semi estructurado bajo la técnica de la entrevista. Los datos obtenidos de la encuesta fueron codificados y procesados en el programa spss2.0. Resultados: Se evidenció que los factores sociodemográficos representaron una relación directa con la alta incidencia de violencia contra las mujeres indígenas del cantón Tena. Los datos de la prueba piloto a 30 encuestadas, período agosto- septiembre 2021, fueron: la edad 20-45 años (87,67%); estado civil unión libre (63.33%); grado de instrucción secundaria (76,67%); ocupación ama de casa (100%); procedencia rural (100%), el tipo de violencia recibida la violencia psicológica (86,67%), física (56,67%), sexual (33,33%). Conclusiones: Se identificó que la totalidad de mujeres indígenas del área rural del cantón Tena recibieron violencia por parte de sus familiares, amigos y parejas y tenían un nivel educativo bajo y pobres(AU)

Ecuador is a secular, multicultural and multi-ethnic state, the indigenous population is represented by 27% of the Ecuadorian population. Indigenous women face various types of violence in their daily life, which represents a violation of human, civil, and political rights, justice and to live a life free of violence. Objective: To analyze the factors that influence gender violence against indigenous women in the rural area of Cantón Tena. Methodology: It is a study with a qualitative-quantitative approach, in the qualitative part a documentary-analytical bibliographic design was used and in the qualitative part it was carried out through an analytical phenomenological approach. For the quantitative part, a validated quantitative collection instrument was applied, meanwhile, the qualitative part was applied a semi-structured questionnaire under the interview technique. The data obtained from the survey were coded and processed in the spss2.0 program. Results: It was evidenced that sociodemographic factors represented a direct relationship with the high incidence of violence against indigenous women in the Tena Canton. The data from the pilot test on 30 respondents, period August-September 2021, were: age 20-45 years (87.67%); free union marital status (63.33%); grade of secondary education (76.67%); housewife occupation (100%); rural origin (100%), the type of violence received: psychological (86.67%), physical (56.67%), sexual (33.33%) violence. Conclusions: It was identified that all indigenous women in the rural area of the Tena canton received violence from their relatives, friends and partners and had a low and poor educational level(AU)

An in-silico analysis reveals 7,7'-bializarin as a promising DNA gyrase B inhibitor on Gram-positive and Gram-negative bacteria.

Bacterial diseases are considered by the World Health Organization to be one of the greatest threats to public health worldwide, mainly due to the increasingly frequent resistance to traditional antibiotics. Estimates from the World Bank indicate that the annual global economic impacts of antibiotic resistance will reach US$1.0-3.4 trillion by 2030. With this, the demand for studies aiming at the discovery of new antibiotics or molecules that may play a synergistic role within the spectrum of drug-resistant bacteria is of fundamental importance. In this in silico study, ligands generated from anthraquinones with established antibacterial activity were evaluated as potential inhibitors of the DNA gyrase subunit B of two species of Gram-positive and two Gram-negative bacteria. The main result of molecular docking-based virtual screening reveals several anthraquinones with remarkable binding energies, of which 7,7'-bializarin (ZINC000004783172) exhibited the highest value for all DNA gyrases subunit B studied and formed stable complexes, as evidenced by molecular dynamics simulations. Collectively, the results presented here reveal the potential of this molecule to bind tightly to the active site of DNA gyrases subunit B of Escherichia coli, Salmonella enterica (subtype typhi), Enterococcus faecalis, and Staphylococcus aureus, and therefore represents a promising candidate for further in vitro testing aimed at evaluating its antibacterial effect.

Relación del consumo de VO2pico y el porcentaje de masa muscular en adultos que habitan sobre 2600 M. S. N. M / relationship of vo2 max consumption and muscle mass amiong adults living in altitudes over 2600 MAMSL

Introducción: la reducción de la capacidad oxidativa del músculo con el envejecimiento parece jugar un papel importante en la vejez disminuyendo hasta 50%. En zonas elevadas sobre el nivel del mar se producen cambios en la dinámica del oxígeno arterial que se relacionan con el metabolismo del músculo y la sarcopenia. Objetivos: determinar si hay relación entre el VO2pico y el porcentaje de masa muscular, nivel de actividad física e IMC, en adultos que habitan en regiones superiores a 2600 metros sobre el nivel del mar. Metodología: estudio descriptivo de tipo transversal, se incluyeron participantes sin sarcopenia mayores de 50 años, con mínimo un año de residencia en Bogotá, Colombia. Se excluyeron participantes con terapia de reemplazo hormonal, tensión arterial elevada durante la prueba, enfermedad coronaria, valvular o trastornos de la conducción. Se determinó el nivel de actividad física aplicando la encuesta Ainsworthy col, la composición corporal con bioimpedanciometría y VO2pico mediante ergoespirometría. Resultados: la muestra fue de 21 participantes. La mitad de lapoblación mostró VO2pico de 23.7 ml/k/min, IMC de 27.2g/m2 y porcentaje de masa muscular de 35.5%; hay baja correlación entre VO2pico y el porcentaje de masa muscular. La mitad de la población saludable tiene un VO2pico de 28.9 ml/k/min, sedentaria saludable 23.7 ml/k/min y sedentaria riesgosa 21.6 ml/k/min. Conclusiones: el presente estudio mostró que hay baja correlación entre el porcentaje de masa muscular y el VO2pico, sin embargo estos resultados pudieron estar influenciados por el tamaño de la muestra y otros factores.

Introduction: the decrease of muscle oxidative capacity with aging appears to play an important role in old age and is observed to decline by 50%. Changes in arterial oxygen dynamics related to muscle metabolism and sarcopenia are evidenced in high altitudes. Objectives: to determine if there is a relationship between VO2max and muscle mass, physical activity and BMI, in adults living in altitudes over 2600 MAMSL. Methodology: descriptive cross-sectional study in older than 50 years subjects without sarcopenia, who had lived in Bogota, Colombia for at least one year. Subjects with hormone replacement therapy or high blood pressure during this test, coronary artery or valvular heart disease or conduction disorders, were excluded. Physical activity was determined applying the Ainsworthy et al. survey, body composition by bioelectrical impedance analysis and VO2max by ergospirometry. Results: sample size was 21 participants. Half of the population showed a VO2max of 23.7 ml/k/min, BMI of 27.2g/m2 and muscle mass of 35.5%. A low correlation between VO2max and muscle mass was evidenced. Half of the healthy population had a VO2max of 28.9 ml/k/min, healthy sedentary subjects 23.7 ml/k/min and sedentary subjects with risk factors 21.6 ml/k/min. Conclusions: this study showed a low correlation between muscle mass and VO2max. However, these results could have been influenced by the sample size and other factors.

TrkB deubiquitylation by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation.

Ubiquitylation of receptor tyrosine kinases (RTKs) regulates both the levels and functions of these receptors. The neurotrophin receptor TrkB (also known as NTRK2), a RTK, is ubiquitylated upon activation by brain-derived neurotrophic factor (BDNF) binding. Although TrkB ubiquitylation has been demonstrated, there is a lack of knowledge regarding the precise repertoire of proteins that regulates TrkB ubiquitylation. Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF- and TrkB-dependent neuronal differentiation. USP8 binds to the C-terminus of TrkB using its microtubule-interacting domain (MIT). Immunopurified USP8 deubiquitylates TrkB in vitro, whereas knockdown of USP8 results in enhanced ubiquitylation of TrkB upon BDNF treatment in neurons. As a consequence of USP8 depletion, TrkB levels and its activation are reduced. Moreover, USP8 protein regulates the differentiation and correct BDNF-dependent dendritic formation of hippocampal neurons in vitro and in vivo We conclude that USP8 positively regulates the levels and activation of TrkB, modulating BDNF-dependent neuronal differentiation.This article has an associated First Person interview with the first author of the paper.

Early life history of the Caribbean coral Orbicella faveolata (Scleractinia: Merulinidae) / Historia de vida temprana del coral caribeño Orbicella faveolata (Scleractinia: Merulinidae)

Introduction: Rehabilitation of hermatypic coral species that have declined in the Caribbean in recent decades is a priority. Production of sexual recruits is considered the best restoration method to aid affected populations. Objective: To gain knowledge of early life stages of Orbicella faveolata and to enhance production of new sexual recruits. Methods: Gamete bundles from the coral species O. faveolata were collected over two years (2018 and 2019) from Los Corales del Rosario y de San Bernardo Natural National Park, Cartagena, Colombia. Assisted fertilization, larval rearing, settlement (onto crustose coralline algae, CCA) and post settlement survival in laboratory conditions were monitored. Results: Embryonic and larval development were documented over 55 hours after the first cleavage, when larvae were fully developed and started pre-settlement behavior. Settlement began 7 days after first cleavage and after 37 days polyps had acquired zooxanthellae. Larval settlement was higher on Lythophyllum congestum and Titanoderma prototypum than in response to Porolithon pachydermum, Neogoniolithon sp., Hydrolithon sp., and Lythophyllum sp. Larvae did not settle on dead coral or on the negative control (sterilized seawater). After the first week post settlement survival was 59 % amongst O. faveolata recruits. During the second week, survival dropped to 42 %, and was further reduced to 0 % at the end of the third week. Conclusions: O. faveolata larvae require cues from certain CCA species to settle, they do not settle in absence of CCA. Increased larvae availability is possible through assisted fertilization in the laboratory, however, due to the high mortality in early post-settlement phases, additional research needs to be conducted in order to scale up larvae production and improve understanding of the cues that enhance settlement and the factors which cause post-settlement mortality.

Introducción: La rehabilitación de las especies de corales hermatípicos del Caribe que han disminuido en las últimas décadas es una prioridad. La producción de reclutas sexuales se considera el mejor método de restauración para ayudar a las poblaciones afectadas. Objetivo: Obtener conocimiento de las primeras etapas de la vida de O. faveolata y mejorar la producción de nuevos reclutas sexuales. Métodos: Por dos años (2018 y 2019), seis días después de luna llena en septiembre, se recolectaron paquetes gaméticos en arrecifes del Parque Nacional Natural Los Corales del Rosario y de San Bernardo, Cartagena, Colombia. Se siguió la fertilización asistida, la cría de larvas, el asentamiento y la supervivencia posterior al asentamiento en algas coralinas costrosas (ACC) en condiciones de laboratorio. Resultados: El desarrollo de embriones y larvas se documenta a lo largo de 55 h después del primer clivaje, cuando la larva está desarrollada completamente y comenzó el comportamiento previo al asentamiento. El asentamiento comienza 7 días después del primer clivaje y 37 días después, la mayoría de los pólipos presentan zooxantelas. El asentamiento larval fue más alto en Lythophyllum congestum y Titanoderma prototypum que en respuesta a Porolithon pachydermum, Neogoniolithon sp., Hydrolithon sp., y Lythophyllum sp. No hubo asentamiento sobre coral muerto ni en el control negativo (agua de mar esterilizada). La supervivencia bajó de un 59 % en la primera semana después del asentamiento, a 42 % durante la segunda semana y 0 % para el final de la tercera semana. Conclusiones: Las larvas de O. faveolata requieren señales de ciertas especies de ACC para asentarse, ellas no se asientan en ausencia de ACC. La disponibilidad de larvas es posible mediante la fertilización asistida en laboratorio. Sin embargo, debido a la alta mortalidad en las primeras fases posteriores al asentamiento, queda mucho por hacer para aumentar la producción de larvas y mejorar nuestro conocimiento y comprensión de las señales que mejoran el asentamiento y las que previenen o inhiben la supervivencia del recluta.

Push-pull driving of the Central America Forearc in the context of the Cocos-Caribbean-North America triple junction.

Different kinematic models have been proposed for the triple junction between the North American, Cocos and Caribbean plates. The two most commonly accepted hypotheses on its driving mechanism are (a) the North American drag of the forearc and (b) the Cocos Ridge subduction push. We present an updated GPS velocity field which is analyzed together with earthquake focal mechanisms and regional relief. The two hypotheses have been used to make kinematic predictions that are tested against the available data. An obliquity analysis is also presented to discuss the potential role of slip partitioning as driving mechanism. The North American drag model presents a better fit to the observations, although the Cocos Ridge push model explains the data in Costa Rica and Southern Nicaragua. Both mechanisms must be active, being the driving of the Central American forearc towards the NW analogous to a push-pull train. The forearc sliver moves towards the west-northwest at a rate of 12-14 mm/yr, being pinned to the North American plate in Chiapas and western Guatemala, where the strike-slip motion on the volcanic arc must be very small.

Early Downregulation of p75NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington's Disease Mice.

Deficits in striatal brain-derived neurotrophic factor (BDNF) delivery and/or BDNF/tropomyosin receptor kinase B (TrkB) signaling may contribute to neurotrophic support reduction and selective early degeneration of striatal medium spiny neurons in Huntington's disease (HD). Furthermore, we and others have demonstrated that TrkB/p75NTR imbalance in vitro increases the vulnerability of striatal neurons to excitotoxic insults and induces corticostriatal synaptic alterations. We have now expanded these studies by analyzing the consequences of BDNF/TrkB/p75NTR imbalance in the onset of motor behavior and striatal neuropathology in HD mice. Our findings demonstrate for the first time that the onset of motor coordination abnormalities, in a full-length knock-in HD mouse model (KI), correlates with the reduction of BDNF and TrkB levels, along with an increase in p75NTR expression. Genetic normalization of p75NTR expression in KI mutant mice delayed the onset of motor deficits and striatal neuropathology, as shown by restored levels of striatal-enriched proteins and dendritic spine density and reduced huntingtin aggregation. We found that the BDNF/TrkB/p75NTR imbalance led to abnormal BDNF signaling, manifested as a diminished activation of TrkB-phospholipase C-gamma pathway but upregulation of c-Jun kinase pathway. Moreover, we confirmed the contribution of the proper balance of BDNF/TrkB/p75NTR on HD pathology by a pharmacological approach using fingolimod. We observed that chronic infusion of fingolimod normalizes p75NTR levels, which is likely to improve motor coordination and striatal neuropathology in HD transgenic mice. We conclude that downregulation of p75NTR expression can delay disease progression suggesting that therapeutic approaches aimed to restore the balance between BDNF, TrkB, and p75NTR could be promising to prevent motor deficits in HD.

Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels.

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.SIGNIFICANCE STATEMENT BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD.

Reticulocyte hemoglobin content (MCHr) in the assessment of iron deficient erythropoiesis in inflammatory bowel disease.

BACKGROUND: In conditions associated with inflammation, biochemical parameters alone could be inadequate for assessing iron status. We investigated the potential utility of mean reticulocyte hemoglobin content (MCHr) in the assessment of the erythropoiesis status in inflammatory bowel disease (IBD). METHODS: We recruited 124 anemic outpatients with IBD. Serum iron, transferrin and ferritin were tested. Complete blood counts were performed on a CELL-DYN Sapphire analyzer (Abbott Diagnostics). Differences among groups were assessed using analysis of variance, considering P < 0.05 to be significant. Receiver operating characteristic analysis was used to assess the diagnostic performance of MCHr for detecting iron deficient erythropoiesis. The reference used as an indicator of insufficient iron availability was transferrin saturation <20%. RESULTS: Overall, 47.6% of the patients had iron deficiency anemia (IDA) and 31.5% anemia of chronic disease (ACD), while the others (20.9%) had mixed anemia. Patients with ACD or mixed anemia showed functional iron deficiency: normal or high ferritin and low MCHr. The area under curve was 0.858 (95% CI 0.742-0.942), considering a cut off 30.3 pg, the sensitivity was 82.2%, specificity 83.3%. CONCLUSIONS: MCHr provides information on iron availability in IBD patients. It is a reliable test to assess iron supply for erythropoiesis.