Receptor crosstalk improves concentration sensing of multiple ligands

Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems leading to crosstalk between different receptors. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of non-cognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the non-cognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing

Phenotypic delay in the evolution of bacterial antibiotic resistance: mechanistic models and their implications

Phenotypic delay-the time delay between genetic mutation and expression of the corresponding phenotype-is generally neglected in evolutionary models, yet recent work suggests that it may be more common than previously assumed. Here, we use computer simulations and theory to investigate the significance of phenotypic delay for the evolution of bacterial resistance to antibiotics. We consider three mechanisms which could potentially cause phenotypic delay: effective polyploidy, dilution of antibiotic-sensitive molecules and accumulation of resistance-enhancing molecules. We find that the accumulation of resistant molecules is relevant only within a narrow parameter range, but both the dilution of sensitive molecules and effective polyploidy can cause phenotypic delay over a wide range of parameters. We further investigate whether these mechanisms could affect population survival under drug treatment and thereby explain observed discrepancies in mutation rates estimated by Luria-Delbrück fluctuation tests. While the effective polyploidy mechanism does not affect population survival, the dilution of sensitive molecules leads both to decreased probability of survival under drug treatment and underestimation of mutation rates in fluctuation tests. The dilution mechanism also changes the shape of the Luria-Delbrück distribution of mutant numbers, and we show that this modified distribution provides an improved fit to previously published experimental data

A computational model for microbial colonisation of an antifouling surface

Biofouling of marine surfaces such as ship hulls is a major industrial problem. Antifouling (AF) paints delay the onset of biofouling by releasing biocidal chemicals. We present a computational model for microbial colonization of a biocide-releasing AF surface. Our model accounts for random arrival from the ocean of microorganisms with different biocide resistance levels, biocide-dependent proliferation or killing, and a transition to a biofilm state. Our computer simulations support a picture in which biocide-resistant microorganisms initially form a loosely attached layer that eventually transitions to a growing biofilm. Once the growing biofilm is established, immigrating microorganisms are shielded from the biocide, allowing more biocide-susceptible strains to proliferate. In our model, colonization of the AF surface is highly stochastic. The waiting time before the biofilm establishes is exponentially distributed, suggesting a Poisson process. The waiting time depends exponentially on both the concentration of biocide at the surface and the rate of arrival of resistant microorganisms from the ocean. Taken together our results suggest that biofouling of AF surfaces may be intrinsically stochastic and hence unpredictable, but immigration of more biocide-resistant species, as well as the biological transition to biofilm physiology, may be important factors controlling the time to biofilm establishment

Interpersonal theory of suicide and stressful life events in a clinical sample of adolescents in Spain

Aims The interpersonal theory of suicide (ITPS) provides a theoretical model for suicidal behaviour. It includes two interpersonal variables, thwarted belongingness (TB) and perceived burdensomeness (PB). This study tested the relationship between ITPS interpersonal variables and suicide risk (presence/absence of suicidal ideation and suicide attempts throughout life) in a clinical sample of Spanish adolescents. We also assessed the potential mediation effect of these variables in the well-established relationship between stressful life events (SLE) and suicide risk. Methods We recruited 147 adolescents aged 11–17 from the Child and Adolescent Mental Health Outpatient Services of the Jiménez Díaz Foundation (Madrid, Spain). Different questionnaires were administered to assess suicidal behaviour and SLE (SITBI, The Stressful Life Events Scale) and to calculate proxy measures for ITPS interpersonal factors (SDQ, STAXI-NA, CDI). Results TB and PB significantly correlated with suicide risk. PB played a mediating role in the relationship between SLE and suicide risk: adolescents reporting SLE were more likely to enact suicide behaviours when they experienced higher PB. Patients scoring higher PB were more likely to receive more intense treatment but tended to abandon intervention promptly. Conclusions ITPS seems useful for predicting suicide risk in an adolescent clinical sample. The results suggest an important role for PB in the SLE-suicide risk relationship and may impact the treatment process. Our exploratory findings should be addressed in future studies.2022-2

The European Eel NCCβ Gene Encodes a Thiazide-Resistant Na-Cl Cotransporter

The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCβ is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCβ from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCβ is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCβ is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCβ exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter

Bioestimulación láser en semillas y plantas

Different lasers have proven to be potentially useful to certain parameters of radiation and could benefit the establishment of planting in adverse conditions by UV-B radiation, drought, cold, salinity, pollution by cadmium, etc. This literature review shows the possible applications of lasers in recent years, as seed treatment and plants, emphasizing the use of He-Ne lasers, Ar, neodymium-YAG, CO2 and laser diodes. It is clear that applications of lasers to parameters specific irradiation of seeds and plants have become increasingly important because of the need to increase food production globally by methods that protect the environment and help to combat the effects of climate change and biodiversity conservation, improving the quality of human and animal life. Thus, in the International Year of “Light and light-based technologies,” it was important to become aware of possible potential use of laser light in agriculture because it could contribute to sustainable development and offering solutions to problems diverse. Advances that have found various scientists in the world provide evidence, thus, in the coming years could have a boom in its application in agriculture as an element “biostimulator” of seeds, seedlings and plants.Diversos láseres han demostrado ser potencialmente útiles a determinados parámetros de irradiación y podrían beneficiar el establecimiento de siembra en condiciones adversas por radiación UV-B, sequía, frío, salinidad, contaminación por cadmio, etc. Esta revisión de literatura científica exhibe las aplicaciones posibles de los láseres en los últimos años, como tratamiento de semillas y plantas, destacando el uso de los láseres de He-Ne, Ar, Neodimio-YAG, CO2 y los diodos láser. Es evidente que las aplicaciones de láseres a parámetros de irradiación específicos en semillas y plantas han adquirido cada vez mayor importancia debido a la necesidad de incrementar la producción de alimentos a nivel global mediante métodos que protejan el medio ambiente y contribuyan a combatir los efectos del cambio climático y a la conservación de la biodiversidad, mejorando la calidad de vida humana y animal. De esta manera, en este Año Internacional de “la Luz y las tecnologías basadas en la luz”, fue importante tomar conciencia del posible uso potencial de la luz láser en la agricultura, ya que podría coadyuvar a un desarrollo sostenible y ofrecer soluciones a problemáticas diversas. Los avances encontrados por diversos científicos lo evidencian y en los próximos años podría tener un auge en su aplicación en la agricultura como un elemento “bioestimulador” de semillas, plántulas y plantas

Algoritmo de organización de la gestión del conocimiento para la innovación. Caso municipios de Ciego de Ávila, Cuba

Se diseñó un algoritmo de organización de la gestión del conocimiento para la innova- ción en un municipio. El aporte fundamental radica en la secuencia metodológica de pasos que deben seguirse, donde la sistematización, tanto del conocimiento, como de la innovación, permite cubrir las brechas cognoscitivas en correspondencia con las ne- cesidades locales, hasta cubrir las brechas estratégicas del desarrollo. El método pri n- cipal utilizado en el estudio es la investigación-acción. La creación del algoritmo de ges- tión del conocimiento favoreció la articulación entre la universidad, la innovación y el desarrollo local. Además, las bases de datos e información y la participación organizada de los actores locales crecieron de forma sostenida en los municipios

The decline of dengue in the Americas in 2017: discussion of multiple hypotheses

OBJECTIVE: Since the 1980s, dengue incidence has increased 30-fold. However, in 2017, there was a noticeable reduction in reported dengue incidence cases within the Americas, including severe and fatal cases. Understanding the mechanism underlying dengue's incidence and decline in the Americas is vital for public health planning. We aimed to provide plausible explanations for the decline in 2017. METHODS: An expert panel of representatives from scientific and academic institutions, Ministry of Health officials from Latin America and PAHO/WHO staff met in October 2017 to propose hypotheses. The meeting employed six moderated plenary discussions in which participants reviewed epidemiological evidence, suggested explanatory hypotheses, offered their expert opinions on each and developed a consensus. RESULTS: The expert group established that in 2017, there was a generalised decreased incidence, severity and number of deaths due to dengue in the Americas, accompanied by a reduction in reported cases of both Zika and chikungunya virus infections, with no change in distribution among age groups affected. This decline was determined to be unlikely due to changes in epidemiological surveillance systems, as similar designs of surveillance systems exist across the region. Although sudden surveillance disruption is possible at a country or regional level, it is unlikely to occur in all countries simultaneously. Retrospective modelling with epidemiological, immunological and entomological information is needed. Host or immunological factors may have influenced the decline in dengue cases at the population level through immunity; however, herd protection requires additional evidence. Uncertainty remains regarding the effect on the outcome of sequential infections of different dengue virus (DENV) types and Zika virus (ZIKV), and vice versa. Future studies were recommended that examine the epidemiological effect of prior DENV infection on Zika incidence and severity, the epidemiological effect of prior Zika virus infection on dengue incidence and severity, immune correlates based on new-generation ELISA assays, and impact of prior DENV/other arbovirus infection on ZIKV immune response in relation to number of infections and the duration of antibodies in relation to interval of protection. Follow-up studies should also investigate whether increased vector control intensification activities contributed to the decline in transmission of one or more of these arboviruses. Additionally, proposed studies should focus on the potential role of vector competence when simultaneously exposed to various arboviruses, and on entomological surveillance and its impact on circulating vector species, with a goal of applying specific measures that mitigate seasonal occurrence or outbreaks. CONCLUSIONS: Multifactorial events may have accounted for the decline in dengue seen in 2017. Differing elements might explain the reduction in dengue including elements of immunity, increased vector control, and even vector and\or viruses changes or adaptations. Most of the results of this expert consensus group meeting are hypothetical and based on limited evidence. Further studies are needed