Case report on activated PI3K-delta syndrome.

BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) [OMIM 615513] is an inborn error of immunity with autosomal dominant inheritance caused by a pathogenic variant in the PIK3CD gene. The prevalence ratio of APDS is < 1: 1,000,000 newborns. The main clinical features of APDS are sinopulmonary infections, benign lymphoproliferation, autoinflammatory disease, and a major risk of lymphoid neoplasms. CLINICAL CASE: A 17-year-old female with a history of pneumonia at 9 months of age subsequently developed recurrent respiratory tract infections, bronchiectasis, perforated otitis media, unilateral tonsillar lymphoid hyperplasia, pansinusitis, recurrent oral candidiasis, and chronic rhinitis. Laboratory studies reported persistent leukopenia and lymphopenia, low CD4 lymphocyte subpopulation, and persistently elevated immunoglobulin M immunoglobulin studies with values up to 692 mg/dL. An inborn error of immunity next-generation sequencing and multiplex ligation-dependent probe amplification analysis detected a heterozygous pathogenic variant in the PIK3CD gene, compatible with APDS. Treatment with monthly injectable gamma globulin and prophylactic antibiotics was started, allowing better control of the infectious processes. CONCLUSION: This is the second case of APDS reported in Mexico in the literature. It is important to be aware of this condition to make a timely diagnosis, which requires a high clinical suspicion and immunological and genetic studies to provide adequate treatment and prevent complications.

INTRODUCCIÓN: El síndrome de la Fosfoinositida 3-cinasa delta activado (Activated Phosphoinositide 3-kinase δ síndrome, APDS) [OMIM 615513] es un error innato de la inmunidad con patrón de herencia autosómica dominante causada por una variante patogénica heterocigota del gen PIK3CD. Su prevalencia es < 1: 1,000,000 nacidos vivos. Las principales manifestaciones clínicas son infecciones sinopulmonares, linfoproliferación benigna, autoinmunidad y aumento del riesgo de malignización linfoide. CASO CLÍNICO: Femenino de 17 años de vida con antecedentes de neumonía a los 9 meses de edad, posteriormente infecciones de vías respiratorias recurrentes, bronquiectasias, otitis media perforada, hiperplasia linfoide de amigdala unilateral, pansinusitis, candidiasis oral recurrente y rinitis crónica. Los estudios de laboratorio reportaron leuco linfopenia persistente, subpoblación linfocitaria con CD4 baja y estudios de inmunoglobulinas con IgM persistentemente elevada con valor de hasta 692 mg/dl. Se realizó estudio molecular de secuenciación de siguiente generación (NGS por sus siglas en inglés Next-Generation Sequencing) y amplificación de sondas dependientes de ligandos múltiples (MLPA por sus siglas en inglés Multiplex Ligation-dependent Probe Amplification) dirigido a errores innatos de la inmunidad que detectó una variante patogénica en estado heterocigoto en el gen PIK3CD, compatible con APDS. Se inició tratamiento con gammaglobulina intravenosa mensual y antibiótico profiláctico, permitiendo mejor control de los procesos infecciosos. CONCLUSIONES: Este es el segundo caso reportado en la literatura de APDS en México, por lo que es importante su conocimiento para poder realizar un diagnóstico oportuno, para el cual se requiere una alta sospecha clínica, además de estudios inmunológicos y genéticos, con la finalidad de otorgar el tratamiento adecuado y prevenir complicaciones.

[20q11.2 microdeletion syndrome: a phenotypic spectrum expansion. Case report]. / Síndrome de microdeleción 20q11.2: ampliación del espectro fenotípico. Reporte de un caso.

Background: 20q11.2 microdeletion syndrome [ORPHA: 444051] is a rare disease, since 16 patients have been reported in literature worldwide. Prevalence ratio is < 1:1,000,000 individuals. Haploinsufficiency on GDF5, SAMHD1 and EPB41L1 genes is important due to phenotypic manifestations in patients. Clinical features can be grouped into craniofacial abnormalities, limb abnormalities, neurological and perinatal disorders. The aim of this report is to present a clinical case of 20q11.21-q11.23 microdeletion, to describe clinical manifestations found, to compare them with features reported in literature, and to contribute to the phenotypic spectrum expansion. Clinical case: 5-year-old female patient who presented hypotonia, psychomotor retardation, microcephaly, facial dysmorphia, pectus excavatum, thoracolumbar scoliosis, right hip subluxation, camptodactyly and clinodactyly. Karyotype test was normal and SNP microarray test reported deletion of chromosomal region 20q11.21-q11.23. Conclusions: It was presented a 20q11.2 microdeletion syndrome confirmed case that shares the features reported in literature, in addition to previously unreported features, such as blepharoptosis, pectus excavatum, scoliosis and hip dysplasia. Interdisciplinary management is important to improve the patient's condition (in her 3 spheres), in order to achieve her best possible health status.

Introducción: el síndrome de microdeleción 20q11.2 [ORPHA: 444051] es una enfermedad rara, pues se han reportado 16 casos a nivel mundial. Su prevalencia se estima en < 1:1,000,000 de nacidos vivos. Induce haploinsuficiencia en los genes GDF5, SAMHD1 y EPB41L1, los cuales son de importancia clínica por las manifestaciones fenotípicas. Se caracteriza por anomalías craneofaciales, anomalías de extremidades, alteraciones neurológicas y perinatales. El objetivo de este reporte es presentar un caso de microdeleción 20q11.21-q11.23, describir las manifestaciones clínicas encontradas, compararlo con lo reportado en la literatura y colaborar en la ampliación del espectro fenotípico. Caso clínico: paciente del sexo femenino de 5 años que presentó hipotonía, retraso psicomotor, microcefalia, dismorfias faciales, pectus excavatum, escoliosis toracolumbar, subluxación de cadera derecha, camptodactilia y clinodactilia. La prueba de cariotipo se reportó sin alteraciones y el ensayo de microarreglo de polimorfismos de un nucleótido (SNP) reportó deleción de la región cromosómica 20q11.21-q11.23. Conclusiones: se presentó un caso confirmado de síndrome de microdeleción 20q11.2 que comparte las características reportadas en la literatura, además de características no reportadas previamente, como ptosis palpebral, pectus excavatum, escoliosis y displasia del desarrollo de cadera. Es importante el manejo interdisciplinario para buscar mejoría en la condición de la paciente (en sus 3 esferas), a fin de alcanzar el mejor estado de salud posible.

Green synthesis of ethyl cinnamates under microwave irradiation: photophysical properties, cytotoxicity, and cell bioimaging.

A simple and green method for the synthesis of six ethyl cinnamates was performed via Horner-Wadsworth-Emmons reaction under microwave irradiation. The photoluminescent properties of all compounds in ethyl acetate solutions were evaluated demonstrating that all compounds exhibit fluorescence. Five compounds exhibited blue emissions in the 369-442 nm range, and another compound exhibited blue-green emission at 504 nm. This last compound showed the largest Stokes shift (134 nm), and the highest quantum yield (17.8%). Two compounds showed extinction coefficient values (ε) higher than 30 000 M-1 cm-1, which are appropriate for cell bioimaging applications. In this sense, cytotoxicity assays were performed using Vero cells at different concentrations; the results showed that these compounds were not cytotoxic at the highest concentration tested (20 µg mL-1). Finally, the analysis by fluorescence microscopy for localization and cellular staining using Vero cells demonstrated that the compounds stained the cytoplasm and the nuclei in a selective way.

A biostimulant yeast, Hanseniaspora opuntiae, modifies Arabidopsis thaliana root architecture and improves the plant defense response against Botrytis cinerea.

MAIN CONCLUSION: The biostimulant Hanseniaspora opuntiae regulates Arabidopsis thaliana root development and resistance to Botrytis cinerea. Beneficial microbes can increase plant nutrient accessibility and uptake, promote abiotic stress tolerance, and enhance disease resistance, while pathogenic microorganisms cause plant disease, affecting cellular homeostasis and leading to cell death in the most critical cases. Commonly, plants use specialized pattern recognition receptors to perceive beneficial or pathogen microorganisms. Although bacteria have been the most studied plant-associated beneficial microbes, the analysis of yeasts is receiving less attention. This study assessed the role of Hanseniaspora opuntiae, a fermentative yeast isolated from cacao musts, during Arabidopsis thaliana growth, development, and defense response to fungal pathogens. We evaluated the A. thaliana-H. opuntiae interaction using direct and indirect in vitro systems. Arabidopsis growth was significantly increased seven days post-inoculation with H. opuntiae during indirect interaction. Moreover, we observed that H. opuntiae cells had a strong auxin-like effect in A. thaliana root development during in vitro interaction. We show that 3-methyl-1-butanol and ethanol are the main volatile compounds produced by H. opuntiae. Subsequently, it was determined that A. thaliana plants inoculated with H. opuntiae have a long-lasting and systemic effect against Botrytis cinerea infection, but independently of auxin, ethylene, salicylic acid, or jasmonic acid pathways. Our results demonstrate that H. opuntiae is an important biostimulant that acts by regulating plant development and pathogen resistance through different hormone-related responses.

Effect of Spirulina in Bread Formulated with Wheat Flours of Different Alveograph Strength.

Consumers within the EU are increasingly asking for natural and healthier food products, which are additive-free and environmentally friendly. The aim of this study was to assess the effects of Spirulina (Arthrospira sp.) in bread formulated with four wheat flours with different alveograph strengths. The flours used were Manitoba Flour (00/251), Ground-force wholemeal (Whole/126), Standard Bakery Flour (0/W105), and Organic Bakery Flour (2/W66). Powdered Spirulina biomass was used as a new ingredient with a high nutritional profile and bioactive compounds; incorporation was made at two levels: 1.5% and 2.5% of the flour amount. The same bread recipe was used for all formulations, but for the 1.5 and 2.5% variations, 6 g and 10 g of Spirulina were added, respectively. Antioxidant capacity increased with increasing microalgal biomass. The visual and taste attributes of the breads with microalgae underwent noticeable changes compared to their counterparts without microalgae. Biomass addition significantly (p < 0.05) affected bread weight and volume, and different trends were found based on the type of wheat flour. Spirulina-containing breads showed a greener coloration while the microalgae concentration was augmented. The moisture and texture were slightly affected by the addition of the biomass at both levels. The 2.5% concentration samples were well accepted in most cases by consumers, emphasizing the salty flavor as a pleasant feature. No significant sensory differences were observed between samples, and the acceptability index was always higher than 72%. The results show that Spirulina could be an environmentally friendly ingredient for the reformulation of nutritionally enhanced bread with a good texture that is well-accepted by consumers.

Involvement of small molecules and metabolites in regulation of biomolecular condensate properties.

Biomolecular condensate (BMCs) formation facilitates the grouping of molecules, including proteins, nucleic acids, and small molecules, creating specific microenvironments with particular functions. They are often assembled through liquid-liquid phase separation (LLPS), a phenomenon that arises when specific proteins, nucleic acids, and small molecules demix from the aqueous environment into another phase with different physiochemical properties. BMCs assemble and disassemble in response to external and internal stimuli such as temperature, molecule concentration, ionic strength, pH, and cellular redox state. Likewise, the nature of the regulatory stimuli may affect the lifespan, morphology, and content of BMCs. In humans, compelling evidence points to the critical role of BMCs in diseases. By contrast, the link between BMC formation, stress resistance, and cell survival has not been revealed in plants. Recent studies have pointed out the nascent roles of small molecules in the assembly and dynamics of BMCs; however, this is still an emerging field of study. This review briefly highlights the most significant efforts to identify the molecular mechanisms between small molecules and BMC formation and regulation in plants and other organisms. We then discuss (i) how small molecules exert control over the BMC assembly and dynamics in plants and (ii) how small molecules can influence the formation and material properties of plant BMCs. Finally, we propose novel alternatives that might help to understand the relationship between chemicals and condensation dynamics and their possible application to plant biotechnology.

Morphology Effect of Photoconverted Silver Nanoparticles on the Performance of Surface-Enhanced Raman Spectroscopy Substrates.

Nowadays, surface-enhanced Raman spectroscopy (SERS) substrates are of great interest for many researchers, aiming to fabricate substrates with high sensitivity and low fabrication costs. In this study, we photoconverted Ag nanoparticles by using a simple and affordable red-green-blue light-emitting diode photoreactor. The obtained dispersions were transformed into a paste of nanoparticles and used to fabricate SERS substrates by a simple drop-casting process under controlled humidity conditions. The performance of these substrates was tested using p-aminothiophenol as a Raman probe. The results indicate that the particle shape has an influence on the Raman intensities and substrate sensitivity, showing a significant enhancement as the number of faces and vertices in the particle increases.

Congenital Zika syndrome.

In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.

En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.

Congenital Zika syndrome / Síndrome congénito por virus Zika

Abstract In February 2016, the World Health Organization declared Zika virus (ZIKV) infection a public health emergency of international concern because it caused congenital Zika syndrome (CZS). The CZS is considered a specific pattern of birth defects caused by ZIKV infection, which is transmitted by the bite of the Aedes aegypti mosquito. The CZS clinical manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular alterations, congenital contractures, early hypertonia, and pyramidal as well as extrapyramidal symptoms. The ZIKV has gained great importance because it has affected a large percentage of the population worldwide during the last few years, despite the measures implemented by international organizations. The pathophysiology and non-vectorial transmission routes of the virus are still under study. The diagnosis is made upon suspicion of ZIKV infection, the patient's clinical manifestations, and it is confirmed by molecular laboratory tests demonstrating the presence of viral particles. Unfortunately, there is no specific treatment or vaccine for this condition; however, patients receive multidisciplinary care and constant monitoring. Therefore, the strategies that have been implemented are directed toward preventive measures and vector control.

Resumen En febrero de 2016, la Organización Mundial de la Salud declaró a la infección por virus Zika una emergencia de salud pública de importancia internacional por ser la causa del síndrome congénito por virus Zika. Este síndrome es considerado un patrón específico de defectos al nacimiento causados por la infección por virus Zika, que se transmite por la picadura del mosquito vector Aedes aegypti y cuyas manifestaciones clínicas son amplias e inespecíficas, entre las que destacan microcefalia, calcificaciones subcorticales, alteraciones oculares, contracturas congénitas, hipertonía temprana y síntomas de afectación piramidal y extrapiramidal. Este virus ha tomado gran importancia debido a que durante los últimos años ha afectado a un gran porcentaje de la población en todo el mundo, a pesar de las medidas implementadas por organizaciones internacionales. La fisiopatología y las vías de transmisión no vectorial de la infección aún siguen en estudio. El diagnóstico se realiza ante la sospecha por las manifestaciones clínicas del paciente, y se confirma mediante pruebas moleculares de laboratorio en las que se demuestre la presencia de partículas virales. Desafortunadamente, no existe aún un tratamiento ni una vacuna específica para este padecimiento; sin embargo, los pacientes reciben cuidados multidisciplinarios y monitorización constante. Las estrategias que se han implementado se dirigen hacia medidas preventivas de la infección y el control de los vectores.

Affinity Purification Protocol Starting with a Small Molecule as Bait.

Protein-metabolite interactions (PMIs) are fundamental for several biological processes. Even though PMI studies have increased in recent years, our knowledge is still limited. The screening of PMIs using small molecules as bait will broaden our ability to uncover novel PMIs, setting the basis for establishing their biological relevance. Here, we describe a protocol that allows the identification of multiple protein partners for one ligand. This protocol describes a straightforward methodology that can be adapted to a wide variety of organisms.

Exploring the Nutritional Potential of Microalgae in the Formulation of Bakery Products.

Microalgae have positioned themselves as an innovative and sustainable source of bioactive compounds and high nutritional value. The selection of a suitable food carrier is important to ease its consumption, and to preserve bioactivity through food processing. The aim of this study was to assess the suitability of different microalgae in baked products. Crackers and grissini were produced following a specific formulation, with percentages ranging from 1.5 to 3.5% of flour substituted with Spirulina, Chlorella, and Tetraselmis dry biomass in the formulas. Physico-chemical, nutritional, and sensorial characterization was carried out. The incorporation of microalgae led to increased nutritional values, including antioxidant capacity (AOX), total phenolic content (TPC) and protein content with an amino acids' identification and quantification. Grissini with Chlorella at 3.5% and crackers with Spirulina at 1.5% levels, showed a higher overall acceptance within the panelists. For amino acid content, Spirulina crackers were shown to be rich in alanine, aspartate, and tryptophan, while Chlorella grissini stood out for being particularly rich in isoleucine, leucine, lysine, and valine. Thus, Spirulina and Chlorella could be a sustainable ingredient to formulate baked goods with an enhanced nutrimental matrix without altering their acceptability to consumers.

Valorization of Local Legumes and Nuts as Key Components of the Mediterranean Diet.

Legumes and nuts are components of high importance in the diet of many countries, mainly those in the Mediterranean region. They are also very versatile and culturally diverse foods found all over the world, acting as a basic protein source in certain countries. Their genetic diversity is needed to sustain the food supply and security for humans and livestock, especially because of the current loss of habitats, species, and genetic diversity worldwide, but also because of the ever present need to feed the increasing human population. Even though both legumes and nuts are considered as high-protein food and environmentally friendly crops, developed countries have lower consumption rates when compared to Asia or Africa. With a view to increasing the consumption of legumes and nuts, the objective of this review is to present the advantages on the use of autochthonous varieties from different countries around the world, thus providing a boost to the local market in the area. The consumption of these varieties could be helped by their use in ready-to-eat foods (RTE), which are now on the rise thanks to today's fast-paced lifestyles and the search for more nutritious and sustainable foods. The versatility of legumes and nuts covers a wide range of possibilities through their use in plant-based dairy analogues, providing alternative-protein and maximal amounts of nutrients and bioactive compounds, potential plant-based flours for bakery and pasta, and added-value traditional RTE meals. For this reason, information about legume and nut nutrition could possibly increase its acceptance with consumers.

LEAfing through literature: late embryogenesis abundant proteins coming of age-achievements and perspectives.

To deal with increasingly severe periods of dehydration related to global climate change, it becomes increasingly important to understand the complex strategies many organisms have developed to cope with dehydration and desiccation. While it is undisputed that late embryogenesis abundant (LEA) proteins play a key role in the tolerance of plants and many anhydrobiotic organisms to water limitation, the molecular mechanisms are not well understood. In this review, we summarize current knowledge of the physiological roles of LEA proteins and discuss their potential molecular functions. As these are ultimately linked to conformational changes in the presence of binding partners, post-translational modifications, or water deprivation, we provide a detailed summary of current knowledge on the structure-function relationship of LEA proteins, including their disordered state in solution, coil to helix transitions, self-assembly, and their recently discovered ability to undergo liquid-liquid phase separation. We point out the promising potential of LEA proteins in biotechnological and agronomic applications, and summarize recent advances. We identify the most relevant open questions and discuss major challenges in establishing a solid understanding of how these intriguing molecules accomplish their tasks as cellular sentinels at the limits of surviving water scarcity.

Attomolar detection of 4-aminothiophenol by SERS using silver nanodendrites decorated with gold nanoparticles.

In the present work we report a simple, fast, reproducible and cheap methodology for surface enhanced Raman spectroscopy (SERS) substrate fabrication of silver dendritic nanostructures (prepared by electrodeposition) decorated with gold nanospheres by electrophoretic deposition. This is the first report where a metal dendritic nanostructure has been decorated with another type of metal nanoparticles by this technique. The decorated nanostructures were used directly as SERS substrate using 4-aminothiophenol (4-ATP) as analyte. The objective of the decoration is to create more hot-spots in order to detect the analyte in a lower concentration. Decorated nanodendrites had a detection limit one million times lower than bare silver nanodendrites and all the substrates showed an increase in the Raman intensity at concentrations below 1 nM; because this concentration corresponds to the threshold for the formation of a monolayer resulting in a triple mechanism of intensity increase, namely electric field, chemical factor and hot-spots. 4-ATP was detected in attomolar concentration, which is below 1 ppq, corresponding to an analytical enhancement factor in the order of 1015.