From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

Bacteriophages potentiate the effect of antibiotics by eradication of persister cells and killing of biofilm-forming cells.

Persister cells and biofilms are associated with chronic urinary infections which are more critical when generated by multi-drug resistant bacteria. In this context, joint administration of phages and antibiotics has been proposed as an alternative approach, since it may decrease the probability to generate resistant mutants to both agents. In this work, we exposed cultures of uropathogenic Escherichia coli conjunctly to antibiotics and phages. We determined that MLP2 combined with antibiotics eradicates persister cells. Similarly, MLP1 and MLP3 impact viability of biofilm-forming cells when administered with ampicillin. Our findings suggest a feasible prophylactic and therapeutic use of these non-transducing phages.

Interactions of Vibrio phages and their hosts in aquatic environments.

Bacteriophages (phages) are viruses that specifically infect bacteria. These viruses were discovered a century ago and have been used as a model system in microbial genetics and molecular biology. In order to survive, bacteria have to quickly adapt to phage challenges in their natural settings. In turn, phages continuously develop/evolve mechanisms for battling host defenses. A deeper understanding of the arms race between bacteria and phages is essential for the rational design of phage-based prophylaxis and therapies to prevent and treat bacterial infections. Vibrio species and their phages (vibriophages) are a suitable model to study these interactions. Phages are highly ubiquitous in aquatic environments and Vibrio are waterborne bacteria that must survive the constant attack by phages for successful transmission to their hosts. Here, we review relevant literature from the past two years to delve into the molecular interactions of Vibrio species and their phages in aquatic niches.

Role of Bacteriophages in the Evolution of Pathogenic Vibrios and Lessons for Phage Therapy.

Viruses of bacteria, i.e., bacteriophages (or phages for short), were discovered over a century ago and have played a major role as a model system for the establishment of the fields of microbial genetics and molecular biology. Despite the relative simplicity of phages, microbiologists are continually discovering new aspects of their biology including mechanisms for battling host defenses. In turn, novel mechanisms of host defense against phages are being discovered at a rapid clip. A deeper understanding of the arms race between bacteria and phages will continue to reveal novel molecular mechanisms and will be important for the rational design of phage-based prophylaxis and therapies to prevent and treat bacterial infections, respectively. Here we delve into the molecular interactions of Vibrio species and phages.

Active and passive chlorophyll fluorescence measurements at canopy level on potato crops. Evidence of similitude of diurnal cycles of apparent fluorescence yields.

We performed active and passive measurements of diurnal cycles of chlorophyll fluorescence on potato crops at canopy level in outdoors conditions for 26 days. Active measurements of the stationary fluorescence yield (Fs) were performed using Ledflex, a fluorescence micro-LIDAR described in Moya et al. (Photosynth Res 142:1-15, 2019), capable of remote measurements of chlorophyll fluorescence under full sun-light in the wavelength range from 650 to 800 nm. Passive measurements of solar-induced fluorescence (SIF) fluxes were performed with Spectroflex, an instrument based on the method of filling-in in the O2A and O2B absorption bands at 760 nm (F760) and 687 nm (F687), respectively.Diurnal cycles of Fs showed significant variations throughout the day, directly attributed to changes in photosystem II yield. Contrasting patterns were observed according to illumination conditions. Under cloudy sky, Fs varied in parallel with photosynthetically active radiation (PAR). By contrast, during clear sky days, the diurnal cycle of Fs showed a "M" shape pattern with a minimum around noon.F687 and F760 showed different patterns, according to illumination conditions. Under low irradiance associated with cloudy conditions, F687 and F760 followed similar diurnal patterns, in parallel with PAR. Under high irradiance associated with clear sky we observed an increase of the F760/F687 ratio, which we attributed to the contributions in the 760 nm emission of photosystem I fluorescence from deeper layers of the leaves, on one end, and by the decrease of 687 nm emission as a result of red fluorescence re-absorption, on the other end.We defined an approach to derive a proxy of fluorescence yield (FYSIF) from SIF measurements as a linear combination of F687 and F760 normalized by vegetation radiance, where the coefficients of the linear combination were derived from the spectral transmittance of Ledflex. We demonstrated a close relationship between diurnal cycles of FYSIF and Fs, which outperformed other approaches based on normalization by incident light.

Active in situ and passive airborne fluorescence measurements for water stress detection on a fescue field.

Ledflex is a fluorometer adapted to measure chlorophyll fluorescence at the canopy level. It has been described in detail by Moya et al. (2019), Photosynthesis Research. https://doi.org/10.1007/s11120-019-00642-9 . We used this instrument to determine the effect of water stress on the fluorescence of a fescue field under extreme temperature and light conditions through a 12 days campaign during summer in a Mediterranean area. The fescue field formed part of a lysimeter station in "las Tiesas," near Albacete-Spain. In addition to the fluorescence data, the surface temperature was measured using infrared radiometers. Furthermore, "Airflex," a passive fluorometer measuring the filling-in of the atmospheric oxygen absorption band at 760 nm, was installed in an ultralight plane and flown during the most critical days of the campaign. We observed with the Ledflex fluorometer a considerable decrease of about 53% of the stationary chlorophyll fluorescence level at noon under water stress, which was well correlated with the surface temperature difference between the stressed and control plots. Airflex data also showed a decrease in far-red solar-induced fluorescence upon water stress in agreement with surface temperature data and active fluorescence measurements after correction for PS I contribution. Notwithstanding, the results from airborne remote sensing are not as precise as in situ active data.

Isolation and Characterization of Novel Lytic Phages Infecting Multidrug-Resistant Escherichia coli.

Urinary tract infections (UTIs) are the second most frequent bacterial infections worldwide, with Escherichia coli being the main causative agent. The increase of antibiotic-resistance determinants among isolates from clinical samples, including UTIs, makes the development of novel therapeutic strategies a necessity. In this context, the use of bacteriophages as a therapeutic alternative has been proposed, due to their ability to efficiently kill bacteria. In this work, we isolated and characterized three novel bacteriophages, microbes laboratory phage 1 (MLP1), MLP2, and MLP3, belonging to the Chaseviridae, Myoviridae, and Podoviridae families, respectively. These phages efficiently infect and kill laboratory reference strains and multidrug-resistant clinical E. coli isolates from patients with diagnosed UTIs. Interestingly, these phages are also able to infect intestinal pathogenic Escherichia coli strains, such as enteroaggregative E. coli and diffusely adherent E. coli. Our data show that the MLP phages recognize different regions of the lipopolysaccharide (LPS) molecule, an important virulence factor in bacteria that is also highly variable among different E. coli strains. Altogether, our results suggest that these phages may represent an interesting alternative for the treatment of antibiotic-resistant E. coli. IMPORTANCE Urinary tract infections affect approximately 150 million people annually. The current antibiotic resistance crisis demands the development of novel therapeutic alternatives. Our results show that three novel phages, MLP1, MLP2, and MLP3 are able to infect both laboratory and multidrug-resistant clinical isolates of Escherichia coli. Since these phages (i) efficiently kill antibiotic-resistant clinical isolates of uropathogenic Escherichia coli (UPEC), (ii) recognize different portions of the LPS molecule, and (iii) are able to efficiently infect intestinal pathogenic Escherichia coli hosts, we believe that these novel phages are good candidates to be used as a therapeutic alternative to treat antibiotic-resistant E. coli strains generating urinary tract and/or intestinal infections.

Importancia de un modelo de nefroprevención adaptado para Colombia

La enfermedad renal crónica es una afección que, dados sus altos niveles de incidencia y prevalencia, constituye un importante problema de salud pública a nivel mundial. Esta entidad se encuentra dentro de las principales causas de muerte tanto en Colombia como en el mundo y representa una gran carga social y económica, similar a la de otras enfermedades crónicas no trasmisibles como la hipertensión arterial y la diabetes mellitus. Actualmente, los gobiernos han realizado esfuerzos para moderar sus estadísticas; sin embargo, estos no han sido lo suficientemente sólidos para mantener bajo control el efecto que ejercen dichas patologías en la salud de las personas, por lo cual se hace imprescindible fortalecer las acciones que fomenten su prevención y control. En el presente artículo se realiza una revisión narrativa de la literatura, partiendo de la información disponible en las diferentes bases de datos, con el objetivo de resaltar la importancia de implementar un modelo de nefroprevención adaptado para Colombia que permita prevenir y detectar oportunamente los factores de riesgo cardiovasculares y renales, y que además facilite el diagnóstico precoz de la enfermedad renal crónica en aras de disminuir su progresión y sus consecuencias potencialmente letales.

Chronic kidney disease is a condition that, given its high levels of incidence and prevalence, constitutes a major public health problem worldwide. This entity is among the leading causes of death both in Colombia and in the world, and represents a great social an economic burden, similar to that of other chronic non-communicable diseases such as arterial hypertension and diabetes mellitus. Currently, governments have made efforts to moderate their statistics; however, these have not been solid enough to keep under control the effect that these pathologies have on the health of the individuals, for which it is indispensable to strengthen actions that promote their prevention and control. In the present article, a narrative literature review is carried out, based on the information available in the different databases, with the purpose of highlighting the importance of implementing a nephroprevention model adapted for Colombia that allows to timely prevent and detect the cardiovascular and renal risk factors, and also facilitate the early diagnosis of chronic kidney disease in order to slow its progression and its potentially lethal consequences.

The Role of Glycosyltransferases in Colorectal Cancer.

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), ß1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-ß) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell-cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells.

MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis.

BACKGROUND: In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. METHODS: We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. RESULTS: We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. CONCLUSION: The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.

Concordancia de tres escalas de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2 / Concordance of three scales of cardiovascular risk in women with diabetes mellitus type 2

Resumen Introducción: establecer estimadores del riesgo cardiovasculares (RCV) que permitan tener igual concordancia dentro del subconjunto de la población es importante para diseñar terapias que briden ventajas a cada subpoblación. Objetivo: comparar las escalas Framingham, SCORE/REGICOR y ACC/AHA en una corte de mujeres con diabetes. Materiales y métodos: se realizó un estudio descriptivo transversal en donde se compararon las escalas Framingham, SCORE/REGICOR y ACC/AHA para identificar los niveles de riesgo cardiovascular en mujeres con diabetes mellitus tipo 2. Los datos se recopilaron entre 2014 y 2016 en pacientes del Centro Endocrinológico del Caribe ubicado en Barranquilla, Colombia. Se consideraron variables sociodemográficas, antropométricas y clínicas. Resultados: el 100% de la muestra (n=107) eran mujeres con una edad media de 58,5±13,646 años. Según la escala Framingham el 72,9% (n=78) se clasificó como de riesgo bajo; el 21,5% (23), intermedio, y el 5,6% (n=6), alto. Con la escala SCORE/REGICOR el 57,0% (n=61) estuvo en riesgo bajo; el 42,1% (n=45), en moderado, y el 0,9% (n=1), en alto. Finalmente, mediante la escala ACC/ AHA el 35,5% (n=38) se clasificó en riesgo bajo y el 64,5% (n=69), en elevado. Conclusiones: en el presente estudio se observó una baja concordancia al comparar las escalas de riesgo cardíaco analizadas (Framingham, SCORE/REGICOR y ACC/AHA) en mujeres colombianas con diabetes mellitus tipo dos y se observó además que la edad y el colesterol total fueron los valores que más afectaron la variación entre las escalas comparadas.

Abstract Introduction: Establishing cardiovascular risk (CVR) estimators that allow for equal concordance within the subset of the population is important for establishing therapy that provide advantages for each subpopulation. In this article we focus on buying CVR scale in women with type 2 diabetes mellitus. Objective: Compare between the Framingham, SCORE/REGICOR and ACC/AHA scales in a court of women with diabetes. Methods: The data collected were between 2014 and 2016 from the population of the Caribbean Endocrinological Center, Barranquilla, Colombia, considering the sociodemographic, anthropometric, and clinical variables. In this study, it was possible to establish comparisons between the Framingham, SCORE/REGICOR and ACC/AHA scales to identify cardiovascular risk levels in women with T2DM. Results: 100% of the sample (n = 107) were women with a mean age of 58.5 ± 13,646 years, 78 (72.9%) were classified as low risk, 23 (21.5%) intermediate and 6 ( 5.6%) high with the scale The SCORE/REGICOR scale showed 61 (57.0%) at low risk, 45 (42.1%) moderate and 1 (0.9%) high; while ACC / AHA 38 (35.5%) is classified as low risk and 69 (64.5%) as high. Conclusions: In the present study, a low concordance was observed when comparing the cardiac risk scales (Framingham, SCORE/REGICOR and ACC/AHA) in Colombian women with type two diabetes and it was also observed that age and total cholesterol were the values that more affected variation between the comparative cardiovascular risk scale.

El impacto de la educación en ciencias biológicas en pacientes con enfermedad renal en un contexto de epidemia por COVID-19 / The impact of education in biological science in patients with kidney disease in the context of a covid-19 epidemic

Resumen La educación en ciencias biológicas juega un papel importante a la hora de entender los sistemas vivos y ecosistemas que nos rodea en contexto de una epidemia de tipo zoonótico como SARS-CoV-2 y cumple un papel importante para el autocuidado en pacientes con enfermedad renal que son una población en alto riesgo según datos epidemiológicos. El presente trabajo pretende describir la asociación entre la educación en ciencia biológica y la epidemia por COVID-19. La educación en ciencias biológicas es un componente importante supeditado al autocuidado para que muchos pacientes con enfermedad renal puedan entender la importancia de tener una mejor adherencia al régimen terapéutico y el régimen alimenticio, y en el caso puntual de la epidemia por COVID-19 puede permitir que ellos tomen las medidas preventivas que eviten su exposición al patógeno.

Abstract Biologic education plays an important role in understanding the living systems and ecosystems that it does not surround in the context of a zoonotic-like epidemic such as SARS-CoV-2 may have an important role for self-care in patients with kidney disease that they are a population at high risk according to epidemiological data. That is why the present work aims to describe the association between education in biological science in patients with kidney disease in the context of a covid-19 epidemic. Biological science education is an important component subject to self-care so that many patients with kidney disease allowing them to understand, the importance of having a better adhere to the therapeutic regimen, dietary regimen and in the specific case of the epidemic by COVID-19 may allow them to take preventive measures to avoid their exposure to the pathogen.

Compromiso renal y digestivo en infecciones por COVID-19 / Renal and digestive engagement in COVID-19 infections

Resumen La infección por el síndrome respiratorio agudo severo (SARS-CoV-2) ha causado una de las emergencias epidemiológicas más grandes de los últimos 10 años y sus efectos patológicos son aún estudiados. Por lo anterior, resulta importante describir los mecanismos asociados al compromiso renal y digestivo en la infección por SARS-CoV-2. Los mecanismos patológicos en tejido renal y en intestino causados por la infección por SARS-CoV-2 son propios del tropismo viral por células de estos sistemas y de los mecanismos citopáticos de etapa lítica de la infección, con una liberación continua de viriones que favorece la generación de un entorno inflamatorio con la consecuente secreción descontrolada de citoquinas proinflamatorias que conducen a la infección entérica del intestino y a las alteraciones en el riñón.

Abstract Infection with Severe Acute Respiratory Syndrome (SARS-CoV-2) has caused one of the largest epidemiological emergencies in the last 10 years and its pathological effects are still studied. Due to the aforementioned, it is important to describe the mechanisms associated with renal and digestive compromise in SARS-CoV-2 infection. The pathological mechanisms in kidney tissue and in the intestine caused by SARS-CoV-2 infection are characteristic of the viral tropism by cells of these systems and of the lymphocytic mechanisms of the lytic stage of the infection, with a continuous release of virions that favors the generation of an inflammatory environment with the consequent uncontrolled secretion of proinflammatory cytokines that lead to enteric infection of the intestine and alterations in the kidney.

Prophage-Dependent Neighbor Predation Fosters Horizontal Gene Transfer by Natural Transformation.

Natural transformation is a broadly conserved mechanism of horizontal gene transfer (HGT) in bacteria that can shape their evolution through the acquisition of genes that promote virulence, antibiotic resistance, and other traits. Recent work has established that neighbor predation via type VI secretion systems, bacteriocins, and virulent phages plays an important role in promoting HGT. Here, we demonstrate that in chitin estuary microcosms, Vibrio cholerae K139 lysogens exhibit prophage-dependent neighbor predation of nonlysogens to enhance HGT. Through predation of nonlysogens, K139 lysogens also have a fitness advantage under these microcosm conditions. The ecological strategy revealed by our work provides a better understanding of the evolutionary mechanisms used by bacteria to adapt in their natural setting and contributes to our understanding of the selective pressures that may drive prophage maintenance in bacterial genomes.IMPORTANCE Prophages are nearly ubiquitous in bacterial species. These integrated phage elements have previously been implicated in horizontal gene transfer (HGT) largely through their ability to carry out transduction (generalized or specialized). Here, we show that prophage-encoded viral particles promote neighbor predation leading to enhanced HGT by natural transformation in the waterborne pathogen Vibrio cholerae Our findings contribute to a comprehensive understanding of the dynamic forces involved in prophage maintenance which ultimately drive the evolution of naturally competent bacteria in their natural environment.

Epidemiology and Toxicology of Ciguatera Poisoning in the Colombian Caribbean.

Ciguatera is a food intoxication caused by the consumption of primarily coral fish; these species exist in large numbers in the seas that surround the Colombian territory. The underreported diagnosis of this clinical entity has been widely highlighted due to multiple factors, such as, among others, ignorance by the primary care practitioner consulted for this condition as well as clinical similarity to secondary gastroenteric symptoms and common food poisonings of bacterial, parasitic or viral etiology. Eventually, it was found that people affected by ciguatoxins had trips to coastal areas hours before the onset of symptoms. Thanks to multiple studies over the years, it has been possible to identify the relation between toxigenic dinoflagellates and seagrasses, as well as its incorporation into the food chain, starting by fish primarily inhabiting reef ecosystems and culminating in the intake of these by humans. Identifying the epidemiological link, its cardinal symptoms and affected systems, such as gastrointestinal, the peripheral nervous system and, fortunately with a low frequency, the cardiovascular system, leads to a purely clinical diagnostic impression without necessitating further complementary studies; in addition, what would also help fight ciguatera poisoning is performing an adequate treatment of the symptoms right from the start, without underestimating or overlooking any associated complications.

Radiation Interception, Conversion and Partitioning Efficiency in Potato Landraces: How Far Are We from the Optimum?

Crop efficiencies associated with intercepted radiation, conversion into biomass and allocation to edible organs are essential for yield improvement strategies that would enhance genetic properties to maximize carbon gain without increasing crop inputs. The production of 20 potato landraces-never studied before-was analyzed for radiation interception ( ε i ), conversion ( ε c ) and partitioning ( ε p ) efficiencies. Additionally, other physiological traits related to senescence delay (normalized difference vegetation index (NDVI) s l p ), tuberization precocity ( t u ), photosynthetic performance and dry tuber yield per plant (TY) were also assessed. Vegetation reflectance was remotely acquired and the efficiencies estimated through a process-based model parameterized by a time-series of airborne imageries. The combination of ε i and ε c , closely associated with an early tuber maturity and a NDVI s l p explained 39% of the variability grouping the most productive genotypes. TY was closely correlated to senescence delay (r P e a r s o n = 0.74), indicating the usefulness of remote sensing methods for potato yield diversity characterization. About 89% of TY was explained by the first three principal components, associated mainly to t u , ε c and ε i , respectively. When comparing potato with other major crops, its ε p is very close to the theoretical maximum. These findings suggest that there is room for improving ε i and ε c to enhance potato production.

Development of an Open-Source Thermal Image Processing Software for Improving Irrigation Management in Potato Crops (Solanum tuberosum L.).

Accurate determination of plant water status is mandatory to optimize irrigation scheduling and thus maximize yield. Infrared thermography (IRT) can be used as a proxy for detecting stomatal closure as a measure of plant water stress. In this study, an open-source software (Thermal Image Processor (TIPCIP)) that includes image processing techniques such as thermal-visible image segmentation and morphological operations was developed to estimate the crop water stress index (CWSI) in potato crops. Results were compared to the CWSI derived from thermocouples where a high correlation was found ( r P e a r s o n = 0.84). To evaluate the effectiveness of the software, two experiments were implemented. TIPCIP-based canopy temperature was used to estimate CWSI throughout the growing season, in a humid environment. Two treatments with different irrigation timings were established based on CWSI thresholds: 0.4 (T2) and 0.7 (T3), and compared against a control (T1, irrigated when soil moisture achieved 70% of field capacity). As a result, T2 showed no significant reduction in fresh tuber yield (34.5 ± 3.72 and 44.3 ± 2.66 t ha - 1 ), allowing a total water saving of 341.6 ± 63.65 and 515.7 ± 37.73 m 3 ha - 1 in the first and second experiment, respectively. The findings have encouraged the initiation of experiments to automate the use of the CWSI for precision irrigation using either UAVs in large settings or by adapting TIPCIP to process data from smartphone-based IRT sensors for applications in smallholder settings.