Bayesian inference of relative fitness on high-throughput pooled competition assays.

The tracking of lineage frequencies via DNA barcode sequencing enables the quantification of microbial fitness. However, experimental noise coming from biotic and abiotic sources complicates the computation of a reliable inference. We present a Bayesian pipeline to infer relative microbial fitness from high-throughput lineage tracking assays. Our model accounts for multiple sources of noise and propagates uncertainties throughout all parameters in a systematic way. Furthermore, using modern variational inference methods based on automatic differentiation, we are able to scale the inference to a large number of unique barcodes. We extend this core model to analyze multi-environment assays, replicate experiments, and barcodes linked to genotypes. On simulations, our method recovers known parameters within posterior credible intervals. This work provides a generalizable Bayesian framework to analyze lineage tracking experiments. The accompanying open-source software library enables the adoption of principled statistical methods in experimental evolution.

Bayesian inference of relative fitness on high-throughput pooled competition assays.

The tracking of lineage frequencies via DNA barcode sequencing enables the quantification of microbial fitness. However, experimental noise coming from biotic and abiotic sources complicates the computation of a reliable inference. We present a Bayesian pipeline to infer relative microbial fitness from high-throughput lineage tracking assays. Our model accounts for multiple sources of noise and propagates uncertainties throughout all parameters in a systematic way. Furthermore, using modern variational inference methods based on automatic differentiation, we are able to scale the inference to a large number of unique barcodes. We extend this core model to analyze multi-environment assays, replicate experiments, and barcodes linked to genotypes. On simulations, our method recovers known parameters within posterior credible intervals. This work provides a generalizable Bayesian framework to analyze lineage tracking experiments. The accompanying open-source software library enables the adoption of principled statistical methods in experimental evolution.

Diagnosis and management of temporomandibular joint synovial chondromatosis: A systematic review.

The aim of this study was to systematically review the diagnosis and management of temporomandibular joint synovial chondromatosis (TMJ-SC). Using a systematic study design based on the PRISMA guideline, the researchers implemented and analyzed a cohort of relevant publications indexed by PubMed, Embase, Medline, and LILACS between January 1990 and December 2022. The outcomes of interest were demographics of the primary studies, and Clinical, radiological, and therapeutic data associated with TMJ-SC. The study samples included 8 studies presenting 121 TMJ-SC cases (73.6% female; 100% unilateral; 53.7% left-sided; mean age, 43.3 ± SD 5,80 [range, 21-81]. Non-specific symptoms were mostly reported, including TMJ pain, noise and local inflammation, and/or malocclusion. Radiographically, loose bodies, masses with low-signal foci, and calcification were common charateristics. Until now, there has been no internationally accepted consensus on diagnosis and management of TMJ-SC. Arthroscopic surgery should be performed on masses confined to the superior TMJ space, while open arthroplasty is indicated in cases with the extra-articular extension. A combination of both treatment methods may be necessary, when the lesion locates extending beyond the medial groove of the condyle.

Physical Activity and Life Satisfaction: An Empirical Study in a Population of Senior Citizens.

Objective: The specialised literature indicates that the two key aspects in active ageing are performing physical activity and life satisfaction. Regarding physical activity, this not only improves physical aspects of senior citizens, but also has a positive impact on mental well-being and satisfaction with one's own life. The aim is to demonstrate the relationship between these two variables to explain healthy ageing. Method: In a sample of 300 senior citizen subjects, the influence of various sociodemographic variables (age, sex, institutionalisation, and level of education) on the performance of physical activity and life satisfaction, is analysed. The research design is a non-experimental study with two unique cross-sectional and correlational measurement groups. Results: An analysis of the results indicates that people with a higher level of education present differences in physical and motivational reserves. Furthermore, age and institutionalisation have an impact on physical reserves. Analysis using structural equation models allows key relationships between the variables analysed to be predicted, which can guide the implementation of active ageing. Conclusion: Motivational reserves affect healthy cognitive ageing through their positive impact on cognitive and physical reserves.

Reconciling kinetic and thermodynamic models of bacterial transcription.

The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on thermodynamic and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the thermodynamic models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.

First-principles prediction of the information processing capacity of a simple genetic circuit.

Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hypothesized to have consequences for how cells are able to survive in changing environments. Recent work has explored the use of information theory as a framework to understand the accuracy with which cells can ascertain the state of their surroundings. Yet the predictive power of these approaches is limited and has not been rigorously tested using precision measurements. To that end, we generate a minimal model for a simple genetic circuit in which all parameter values for the model come from independently published data sets. We then predict the information processing capacity of the genetic circuit for a suite of biophysical parameters such as protein copy number and protein-DNA affinity. We compare these parameter-free predictions with an experimental determination of protein expression distributions and the resulting information processing capacity of E. coli cells. We find that our minimal model captures the scaling of the cell-to-cell variability in the data and the inferred information processing capacity of our simple genetic circuit up to a systematic deviation.

Predictive shifts in free energy couple mutations to their phenotypic consequences.

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find that the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of Escherichia coli, probing several mutations in the DNA binding and inducer binding domains. We find that the change in gene expression due to a point mutation can be captured by modifying only the model parameters that describe the respective domain of the wild-type protein. These parameters appear to be insulated, with mutations in the DNA binding domain altering only the DNA affinity and those in the inducer binding domain altering only the allosteric parameters. Changing these subsets of parameters tunes the free energy of the system in a way that is concordant with theoretical expectations. Finally, we show that the induction profiles and resulting free energies associated with pairwise double mutants can be predicted with quantitative accuracy given knowledge of the single mutants, providing an avenue for identifying and quantifying epistatic interactions.

Figure 1 Theory Meets Figure 2 Experiments in the Study of Gene Expression.

It is tempting to believe that we now own the genome. The ability to read and rewrite it at will has ushered in a stunning period in the history of science. Nonetheless, there is an Achilles' heel exposed by all of the genomic data that has accrued: We still do not know how to interpret them. Many genes are subject to sophisticated programs of transcriptional regulation, mediated by DNA sequences that harbor binding sites for transcription factors, which can up- or down-regulate gene expression depending upon environmental conditions. This gives rise to an input-output function describing how the level of expression depends upon the parameters of the regulated gene-for instance, on the number and type of binding sites in its regulatory sequence. In recent years, the ability to make precision measurements of expression, coupled with the ability to make increasingly sophisticated theoretical predictions, has enabled an explicit dialogue between theory and experiment that holds the promise of covering this genomic Achilles' heel. The goal is to reach a predictive understanding of transcriptional regulation that makes it possible to calculate gene expression levels from DNA regulatory sequence. This review focuses on the canonical simple repression motif to ask how well the models that have been used to characterize it actually work. We consider a hierarchy of increasingly sophisticated experiments in which the minimal parameter set learned at one level is applied to make quantitative predictions at the next. We show that these careful quantitative dissections provide a template for a predictive understanding of the many more complex regulatory arrangements found across all domains of life.

Measuring the Energetic Costs of Embryonic Development.

What are the thermodynamic costs of development? In this issue of Developmental Cell, Rodenfels et al. (2019) demonstrate that the high energetic cost of coordinated cell division that is regulated by phospho-signaling gives rise to a measurable periodicity in the heat dissipated during zebrafish embryogenesis.

Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study.

The protein alpha-synuclein (α-Syn) has been linked to neuroinflammatory conditions. We investigated whether the presence of α-Syn in peripheral tissues is a surrogate of brain inflammatory status in a small group of relapsing-remitting multiple sclerosis (RRMS) patients in a pilot cross-sectional study. Skin biopsies and peripheral blood were sampled from 34 healthy controls and 23 MS patients for measurement of α-Syn levels. Within the RRMS group 15 patients were in remission, and 8 patients were in the relapsing phase. The protein α-Syn was evaluated by means of immunohistochemistry and flow cytometry in skin and nucleated blood cells, respectively. In the skin, α-Syn levels were lower in relapsing MS than in the other groups, both in positive area (p = .021) and staining intensity (p = .004). In blood, the percentage of α-Syn-positive lymphocytes and monocytes were not statistically different between study groups. Moreover, the use of systemic steroids did not affect α-Syn positivity in MS-relapse patients. Finally, epidermic Langerhans cells did not stain positively for α-Syn. Overall, the levels of α-Syn positivity were lower in inflammatory relapse of RRMS patients when measured in peripheral tissues. We discuss the role of α-Syn levels in inflammation according to the obtained results.

Control y evaluación de la microalbuminuria en una población del estado de Nayarit, México. Estudio realizado mediante la automedición a préstamo de la presión arterial / Control and evaluation of microalbuminuria in a population of the state of Nayarit, Mexico. Study conducted by self-measurement on loan of blood pressure

Resumen: ANTECEDENTES Existen antecedentes de que el control estricto de las cifras de presión arterial puede repercutir favorablemente evitando la aparición de microalbuminuria y, por tanto, previniendo la nefropatía, asimismo, disminuye significativamente los desenlaces fatales por enfermedad cardiovascular y cerebrovascular. OBJETIVO Demostrar que el control estricto de las cifras tensionales puede disminuir la microalbuminuria. MATERIAL Y METODO Estudio observacional y descriptivo efectuado de enero a diciembre de 2017, en el que se evaluaron pacientes con diagnóstico establecido de diabetes mellitus tipo 2, hipertensión arterial sistémica o ambas; la selección fue aleatoria. A estos pacientes se les incorporó en un protocolo de automedición a préstamo de la presión arterial. No se incluyeron pacientes con insuficiencia renal crónica. RESULTADOS Se incluyeron 200 pacientes en quienes se midió la correlación entre múltiples variables y la existencia de microalbuminuria. Se encontró correlación estadísticamente significativa al segmentar a los pacientes según la clasificación de ACC/AHA 2017 y posterior al ajuste de la dosis de antihipertensivo con valor de p = 0.00001. CONCLUSIONES Con estos hallazgos podría plantearse el ajuste del tratamiento con base en las cifras tensionales del paciente, sin importar si el tratamiento es con IECAS o ARA II.

Abstract: BACKGROUND There are precedents that the strict control of the blood pressure figures can have a favorable impact avoiding the development of microalbuminuria, and therefore preventing the appearance of nephropathy, as well as significantly reducing fatal outcomes due to cardiovascular and cerebrovascular disease. OBJECTIVE To show that strict control of tension figures can impact decreasing the microalbuminuria. MATERIAL AND METHOD An observational and descriptive study was done from January to December 2017 with patients with an established diagnosis of type 2 diabetes mellitus and/or systemic hypertension, with random selection. These patients were incorporated into a Self-Commissioning Protocol to loan blood pressure. Patients with chronic kidney disease were not included. RESULTS There were included 200 patients. The correlation between multiple variables and the presence of microalbuminuria was measured finding a statistically significant correlation when segmenting patients according to the ACC/AHA 2017 classification and after adjusting the antihypertensive dose with p = 0.00001. CONCLUSIONS Treatment should be adjusted based on the patient's blood pressure, regardless of whether the treatment is with IECAS or ARA II.

Tuning Transcriptional Regulation through Signaling: A Predictive Theory of Allosteric Induction.

Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general theory of allosteric transcriptional regulation using the Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous simple repression motif in bacteria by first predicting the behavior of strains that span a large range of repressor copy numbers and DNA binding strengths and then constructing and measuring their response. Our model not only accurately captures the induction profiles of these strains, but also enables us to derive analytic expressions for key properties such as the dynamic range and [EC50]. Finally, we derive an expression for the free energy of allosteric repressors that enables us to collapse our experimental data onto a single master curve that captures the diverse phenomenology of the induction profiles.

The Presence of Alpha-Synuclein in Skin from Melanoma and Patients with Parkinson's Disease.

BACKGROUND: The misfolding and prion-like propagation of the protein α-synuclein (α-syn) is the leading molecular signature in Parkinson's disease (PD). There is a significant coincidence of PD and melanoma that may suggest a shared pathophysiology. This study compared the presence of α-syn in neural crest-derived tissues, such as nevi, melanoma, skin tags, and skin biopsies from patients with PD and healthy controls. METHODS: Biopsies from participants with PD were obtained from patients from a tertiary referral center for dermatology and neurology in Mexico and a private dermatopathology center in Florida between January 2015 and March 2016. Biopsies from 7 patients with melanoma, 15 with nevi, 9 with skin tags, 8 with PD, and 9 skin biopsies from healthy volunteers were analyzed for immunohistochemical determination of α-syn and tyrosinase. All analyses were performed by pathologists who were blinded with respect to the clinical diagnosis. RESULTS: In healthy controls, positive α-syn status was restricted to scattered cells in the basal layer of the epidermis and accounted for 1 ± 0.8% of the analyzed area. In patients with PD, there was increased staining for α-syn PD (3.3 ± 2.3%), with a higher percentage of positive cells in nevi (7.7 ± 5.5%) and melanoma (13.6 ± 3.5%). There was no increased staining in skin tags compared with healthy controls. CONCLUSION: Patients with PD and melanoma have increased staining for α-syn in their skin. The authors propose that neurons and melanocytes, both derived from neuroectodermal cells, may share protein synthesis and regulation pathways that become dysfunctional in PD and melanoma.

Emotion-Bracelet: A Web Service for Expressing Emotions through an Electronic Interface.

The mechanisms to communicate emotions have dramatically changed in the last 10 years with social networks, where users massively communicate their emotional states by using the Internet. However, people with socialization problems have difficulty expressing their emotions verbally or interpreting the environment and providing an appropriate emotional response. In this paper, a novel solution called the Emotion-Bracelet is presented that combines a hardware device and a software system. The proposed approach identifies the polarity and emotional intensity of texts published on a social network site by performing real-time processing using a web service. It also shows emotions with a LED matrix using five emoticons that represent positive, very positive, negative, very negative, and neutral states. The Emotion-Bracelet is designed to help people express their emotions in a non-intrusive way, thereby expanding the social aspect of human emotions.

An in vivo metabolic approach for deciphering the product specificity of glycerate kinase proves that both E. coli's glycerate kinases generate 2-phosphoglycerate.

Apart from addressing humanity's growing demand for fuels, pharmaceuticals, plastics and other value added chemicals, metabolic engineering of microbes can serve as a powerful tool to address questions concerning the characteristics of cellular metabolism. Along these lines, we developed an in vivo metabolic strategy that conclusively identifies the product specificity of glycerate kinase. By deleting E. coli's phosphoglycerate mutases, we divide its central metabolism into an 'upper' and 'lower' metabolism, each requiring its own carbon source for the bacterium to grow. Glycerate can serve to replace the upper or lower carbon source depending on the product of glycerate kinase. Using this strategy we show that while glycerate kinase from Arabidopsis thaliana produces 3-phosphoglycerate, both E. coli's enzymes generate 2-phosphoglycerate. This strategy represents a general approach to decipher enzyme specificity under physiological conditions.

Residualidad del temefos en depósitos domésticos y su efectividad en el control de larvas de Aedes aegypti en Honduras / Residual temephos in domestic deposits and its effectiveness in controlling Aedes aegypti larvae in Honduras

Se realizó un estudio experimental en 4 viviendas de la colonia Villa Nueva de Tegucigalpa, en Honduras, a fin de evaluar la efectividad y residualidad del temefos a 1 % (Abate®) en el control de larvas de Aedes aegypti, desde octubre del 2007 hasta abril del 2008. Para ello se llevaron a cabo bioensayos en el campo y en el laboratorio; los de campo se efectuaron en 9 depósitos de agua de uso doméstico, como pilas y barriles, que fueron inspeccionados inicialmente para detectar la presencia de larvas; entonces se aplicó el temefos a los que fueron positivos --acorde con su capacidad en litros--, y se utilizaron como grupo de control los que resultaron negativos. Asimismo, se efectuaron observaciones a las 24 horas de aplicado el tratamiento, y luego semanalmente por más de 4 meses (anotadas en un registro diseñado a los efectos), a fin de comprobar la existencia de larvas y, además, medir los valores de cloro disuelto, el pH y la temperatura del agua. Por su parte, los bioensayos de laboratorio se realizaron con el agua de la pila abatizada, y se determinaron los porcentajes de mortalidad de las larvas a las 24 horas de tratar el líquido. Se evidenció la efectividad del Abate® y una residualidad de más de 100 días, a pesar de la influencia de los factores ambientales, sociales y antropogénicos.

An experimental study was carried out in 4 homes of Villa Nueva community of Tegucigalpa, in Honduras, to evaluate the effectiveness and residual 1% temephos (Abate®) in controlling Aedes aegypti larvae from October 2007 to April 2008. Field and laboratory bioassays were performed; those from the field were made in 9 water tanks for domestic use, such as "pila" and barrels, which were initially inspected for the presence of larvae, so that if they were positive, temephos was applied --according to its capacity in liters--, and if they were negative, then they were used as a control group. Furthermore, observations were made at 24 hours after applying the treatment, and then weekly for about 4 months (which were compiled in a register) in order to check the presence of larvae and measure the values of dissolved chlorine, pH and water temperature. On the other hand, the laboratory bioassays was made in the Abate-treated water from "pila", and the percentages of larvae mortality were determined at 24 hours of treating the liquid. Effectiveness of the Abate® and its residual level of more than 100 days were evidenced, in spite of the influence of environmental, social and anthropogenic factors.

Boccia: Factor de integración social y su significado en mujeres y hombres adscritos a la liga de parálisis cerebral de Bogotá / Boccia: Factor of social integration and its meaning for women and men members of Bogotá cerebral palsy league

Antecedentes. El Boccia es un deporte que debido a sus características técnicas y metodológicas y a que es mixto, de precisión y estrategia, permite la participación de individuos con diversos tipos de limitaciones físicas, permitiendo de esta forma la integración social de los mismos, en un contexto de equidad, por lo cual ha tenido una gran acogida a nivel mundial siendo catalogado como el deporte bandera de la Asociación Internacional de Deportes y Recreación para personas con Parálisis Cerebral (CP-ISRA). Objetivo. Explorar los posibles significados que para mujeres y hombres en situación de discapacidad, tiene la práctica del Boccia como factor de integración social. Método. Esta investigación optó por el enfoque Cualitativo etnográfico, a través de las narrativas y experiencias de los protagonistas en este caso mujeres y hombres que hacen parte de la liga de Parálisis Cerebral de Bogotá- Boccia. Para estos efectos se utilizaron instrumentos como las entrevistas semiestructuradas, grupos focales y narrativas visuales. Resultados. El documento presenta un análisis de la percepción y los alcances de la práctica de un deporte como el Boccia en la integración social de los individuos desde las categorías de los conceptos de solidaridad, autonomía, reconocimiento de la diversidad, participación, universalidad, equidad, corresponsabilidad, efectividad, poder, libertad e identidad. Conclusión. Se concluye que los significados otorgados al Boccia como factor de integración social, por parte de los participantes en la Liga, en general se enmarcan de manera positiva en las categorías conceptuales propuestas para su análisis. Sin embargo, existe aún un alto desconocimiento de la discapacidad y de aceptación de las diferencias que se convierte en un factor limitante para una adecuada integración social.

Background. The Boccia is a sport that due of their technical and methodological characteristics and that It is a mixed sport that requires precision and strategy and includes both genders within a context of equity, allows the participation of individuals with various types of physical limitations. These features have allowed the sport to be accepted by the International Association of Sports and Recreation for People with Cerebral Palsy (CP-ISRA). Objective. To explore the possible meanings of Boccia for women and men with disability, as a factor of social integration. Method. This is a qualitative ethnographic research, through the narratives and experiences of the protagonists in this case women and men who were part of the Cerebral Palsy League of Bogotá-Boccia. For this purpose, were used tools such as structured interviews, focus groups, and visual narratives. Results. The paper presents an analysis of the perception and the effect of practice Boccia in the social integration of individuals with disabilities conditions. The analysis is developed from the concepts of solidarity, autonomy, recognition of diversity, participation, universality, equity, responsibility, effectiveness, power, freedom and identity. Conclusion. It was concluded that the meaning given to Boccia as a factor of social integration, by participating in the league, are framed positively framed on the concepts proposed for the analysis. However, there is still great ignorance about disability and diversity acceptance that becomes a limiting factor for adequate social integration.

Transfusion-associated Chagas disease (American trypanosomiasis) in Mexico: implications for transfusion medicine in the United States.

BACKGROUND: Trypanosoma cruzi, the protozoan cause of Chagas disease, causes life-long infection and is easily transmitted by blood transfusion. Our goals were to determine the prevalence of Chagas disease among donors in five Mexican blood banks, to look for evidence of transmission of T. cruzi by transfusion, and to evaluate two serologic assays for Chagas disease. STUDY DESIGN AND METHODS: Blood samples from donors were tested initially with the Abbott Chagas EIA or the Meridian Chagas' IgG ELISA. Samples giving readings that were at least 50% of the cutoffs were run in a confirmatory radioimmune precipitation assay (RIPA), as were samples from recipients of blood products from RIPA-positive donors. RESULTS: The overall prevalence of Chagas disease was 1/133 (55/7,296; 0.75%). In addition, 4 of 9 surviving recipients of blood products from T. cruzi-infected donors were in turn infected. Using the manufacturers' recommended cutoffs, the sensitivity and specificity of the Abbott test were 92.0% (23/25) and 99.8% (2,865/2,872) respectively, and the corresponding values for the Meridian assay were 70.0% (21/30) and 100.0% (4,369/4,369). CONCLUSIONS: These findings indicate clearly that transfusion-associated transmission of T. cruzi is occurring in the study areas. Serologic testing of blood donors for Chagas disease should be performed there and in the rest of Mexico. The two screening assays evaluated may lack the accuracy necessary for blood donor testing when used as suggested by the manufacturers.

Comparación de hidralazina y alfa metildopa en la hipertensión durante el embarazo / Comparison with hydralazyn and alfa metildopa in hypertension during pregnancy

Estudiamos 30 pacientes con pre-eclampsia severa, manejados 15 de ellos con metildopa y los otros 15 con Hidralazina, en el Hospital Materno Infantil San Lorenzo en Los Mina D. N. Nuestro trabajo ofrece evidencia de superioridad de la Hidrazalina sobre la metildopa, pues la respuesta hipotensora es algo más rápida y el medicamento produce menos efectos colaterales indeseables. Ambos medicamentos son efectivos en reducir la presión arterial