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Abstract Background Autism spectrum disorder (ASD) is characterized by repetitive behaviors, deficits in communication, and overall impaired social interaction. Of all the integrin subunit mutations, mutations in integrin β3 (Itgb3) may be the most closely associated with ASD. Integrin β3 is required for normal structural plasticity of dendrites and synapses specifically in excitatory cortical and hippocampal circuitry. However, the behavioral consequences of Itgb3 function in the forebrain have not been assessed. We tested the hypothesis that behaviors that are typically abnormal in ASD—such as self-grooming and sociability behaviors—are disrupted with conditional Itgb3 loss of function in forebrain circuitry in male and female mice. Methods We generated male and female conditional knockouts (cKO) and conditional heterozygotes (cHET) of Itgb3 in excitatory neurons and glia that were derived from Emx1-expressing forebrain cells during development. We used several different assays to determine whether male and female cKO and cHET mice have repetitive self-grooming behaviors, anxiety-like behaviors, abnormal locomotion, compulsive-like behaviors, or abnormal social behaviors, when compared to male and female wildtype (WT) mice. Results Our findings indicate that only self-grooming and sociability are altered in cKO, but not cHET or WT mice, suggesting that Itgb3 is specifically required in forebrain Emx1-expressing cells for normal repetitive self-grooming and social behaviors. Furthermore, in cKO (but not cHET or WT), we observed an interaction effect for sex and self-grooming environment and an interaction effect for sex and sociability test chamber. Limitations While this study demonstrated a role for forebrain Itgb3 in specific repetitive and social behaviors, it was unable to determine whether forebrain Itgb3 is required for a preference for social novelty, whether cHET are haploinsufficient with respect to repetitive self-grooming and social behaviors, or the nature of the interaction effect for sex and environment/chamber in affected behaviors of cKO. Conclusions Together, these findings strengthen the idea that Itgb3 has a specific role in shaping forebrain circuitry that is relevant to endophenotypes of autism spectrum disorder.

Survivors of preterm birth struggle with multitudes of disabilities due to improper in utero programming of various tissues and organ systems contributing to adult-onset diseases at a very early stage of their lives. Therefore, the persistent rates of low birth weight (birth weight < 2,500 grams), as well as rates of neonatal and maternal morbidities and mortalities, need to be addressed. Active research throughout the years has provided us with multiple theories regarding the risk factors, initiators, biomarkers, and clinical manifestations of spontaneous preterm birth. Fetal organs, like the placenta and fetal membranes, and maternal tissues and organs, like the decidua, myometrium, and cervix, have all been shown to uniquely respond to specific exogenous or endogenous risk factors. These uniquely contribute to dynamic changes at the molecular and cellular levels to effect preterm labor pathways leading to delivery. Multiple intervention targets in these different tissues and organs have been successfully tested in preclinical trials to reduce the individual impacts on promoting preterm birth. However, these preclinical trial data have not been effectively translated into developing biomarkers of high-risk individuals for an early diagnosis of the disease. This becomes more evident when examining the current global rate of preterm birth, which remains staggeringly high despite years of research. We postulate that studying each tissue and organ in silos, as how the majority of research has been conducted in the past years, is unlikely to address the network interaction between various systems leading to a synchronized activity during either term or preterm labor and delivery. To address current limitations, this review proposes an integrated approach to studying various tissues and organs involved in the maintenance of normal pregnancy, promotion of normal parturition, and more importantly, contributions towards preterm birth. We also stress the need for biological models that allows for concomitant observation and analysis of interactions, rather than focusing on these tissues and organ in silos.

The importance of Na+/H+ antiporters in salt tolerance in plants has been demonstrated in many studies, but much less is known about their protective role during drought stress. To study their possible contribution to water deficit tolerance, two closely related soybean Na+/H+ antiporters belonging to the intracellular NHX exchanger protein family, GmNHX3 and GmNHX1, were evaluated in transgenic Arabidopsis thaliana. A. thaliana plants ectopically expressing GmNHX3 or GmNHX1 displayed a more drought-tolerant phenotype compared to wild-type plants, which was accompanied by an increase in relative water content and chlorophyll content during stress conditions. Both GmHNX1 and GmHNX3 transgenic lines accumulated higher amounts of Na+ and K+ cations, showed increased antioxidant enzyme activities and less membrane damage due to lipid peroxidation under water deficit, as compared to non-transformed plants. Furthermore, plants expressing GmNHX3 showed an increased sensitivity to abscisic acid as deduced from stomatal closure and seed germination inhibition studies. Finally, a significant up-regulation of abiotic stress-related genes was observed in both transgenic lines compared to wild-type plants in response to abscisic acid and mannitol treatments. These results demonstrate that GmNHX3 and GmNHX1 antiporters confer protection during drought stress in A. thaliana and hence are potential genetic targets to improve drought tolerance in soybean and other crops.

Abstract Background Bladder cancer cells orchestrate tumour progression by pro-inflammatory cytokines. Cytokines modulate the local tumour microenvironment and increase the susceptibility of tumour distant tissues for metastasis. Here, we investigated the impact of human bladder cancer cell derived factors on the ability to modulate and activate human vascular endothelial cells. Methods The pro-inflammatory and pro-coagulatory potential of four different bladder cancer cell lines was accessed by qRT-PCR arrays and ELISA. Modulation and activation of endothelial cells was studied in microfluidic devices. Clinical relevance of our findings was confirmed by immune histology in tissue samples of bladder cancer patients and public transcriptome data. Results The unbalanced ratio between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1ra) in the secretome of bladder cancer cells converted the quiescent vascular endothelium into a pro-adhesive, pro-inflammatory, and pro-coagulatory surface. Microfluidic experiments showed that tumour cell induced endothelial cell activation promoted leukocyte recruitment and platelet adhesion. Human bladder cancer tissue analysis confirmed that loss of IL-1ra and elevated IL-1 expression was associated with enhanced cancer progression. Conclusions Our data indicate that IL-1 and IL-1ra were dysregulated in bladder cancer and could facilitate tumour dissemination through endothelial cell activation. Targeting the IL-1/IL-1ra axis might attenuate tumour-mediated inflammation and metastasis formation.

Abstract Dysfunctional dendritic arborization is a key feature of many developmental neurological disorders. Across various human brain regions, basal dendritic complexity is known to increase along a caudal-to-rostral gradient. We recently discovered that basal dendritic complexity of layer II/III cortical pyramidal neurons in the mouse increases along a caudomedial-to-rostrolateral gradient spanning multiple regions, but at the time, no molecules were known to regulate that exquisite pattern. Integrin subunits have been implicated in dendritic development, and the subunit with the strongest associations with autism spectrum disorder and intellectual disability is integrin β3 (Itgb3). In mice, global knockout of Itgb3 leads to autistic-like neuroanatomy and behavior. Here, we tested the hypothesis that Itgb3 is required for increasing dendritic complexity along the recently discovered tangential gradient among layer II/III cortical pyramidal neurons. We targeted a subset of layer II/III cortical pyramidal neurons for Itgb3 loss-of-function via Cre-loxP-mediated excision of Itgb3. We tracked the rostrocaudal and mediolateral position of the targeted neurons and reconstructed their dendritic arbors. In contrast to controls, the basal dendritic complexity of Itgb3 mutant neurons was not related to their cortical position. Basal dendritic complexity of mutant and control neurons differed because of overall changes in branch number across multiple branch orders (primary, secondary, etc.), rather than any changes in the average length at those branch orders. Furthermore, dendritic spine density was related to cortical position in control but not mutant neurons. Thus, the autism susceptibility gene Itgb3 is required for establishing a tangential pattern of basal dendritic complexity among layer II/III cortical pyramidal neurons, suggesting an early role for this molecule in the developing brain.

In this paper, we present the sine-Gordon expansion method to prepare the mixed dark bright wave patterns to the nonlinear partial differential equations arising in mathematical physics. Then, we apply the proposed method for a credible recourse of two nonlinear physical models: the modified Vakhnenko-Parkes and modified α-equation. These exact solutions comprise the hyperbolic, trigonometric, rational and exponential function with few licentious parameter. The analytical solutions have different physical structures and they are graphically analyzed in order to show their dynamical behavior by means of 2D, 3D and contour plots.

Fragile X syndrome (FXS) is the most common form of intellectual disability that arises from the dysfunction of a single gene—Fmr1. The main neuroanatomical correlate of FXS is elevated dendritic spine density on cortical pyramidal neurons, which has been modeled in Fmr1-/Y mice. However, the cell-autonomous contribution of Fmr1 on cortical dendritic spine density has not been assessed. Even less is known about the role of Fmr1 in heterozygous female mosaic mice, which are a putative model for human Fmr1 full mutation carriers (i.e., are heterozygous for the full Fmr1-silencing mutation). In this neuroanatomical study, spine density in cortical pyramidal neurons of Fmr1+/− and Fmr1-/Y mice was studied at multiple subcellular compartments, layers, and brain regions. Spine density in Fmr1+/− mice is higher than WT but lower than Fmr1-/Y. Not all subcellular compartments in layer V Fmr1+/− and Fmr1-/Y cortical pyramidal neurons are equally affected: the apical dendrite, a key subcellular compartment, is principally affected over basal dendrites. Within apical dendrites, spine density is differentially affected across branch orders. Finally, identification of FMRP-positive and FMRP-negative neurons within Fmr1+/− permitted the study of the cell-autonomous effect of Fmr1 on spine density. Surprisingly, layer V cortical pyramidal spine density between FMRP-positive and FMRP-negative neurons does not differ, suggesting that the regulation of the primary neuroanatomical defect of FXS—elevated spine density—is non-cell-autonomous.

In this paper, we study the extraction of some analytical solutions to the nonlinear perturbed sine-Gordon equation with the long Josephson junction properties. The model studied was formed to observe the long Josephson junction properties separated by two superconductors. Moreover, it is also used to explain the Josephson effect arising in the highly nonlinear nature of the Josephson junctions. This provides the shunt inductances to realize a Josephson left-handed transmission line. A powerful scheme is used to extract the complex function solutions. These complex results are used to explain deeper properties of Josephson effects in the frame of impedance. Various simulations of solutions obtained in this paper are also reported.

Cassava is an important staple food for low-income countries. However, its cooking characteristics are especially affected by genotype. In this study, two groups of genotypes, namely hard to cook (HTC) and easy to cook (ETC), were harvested at different times (9 and 15 months), and evaluated by NMR coupled to chemometrics. Additionally, lignin of these materials was studied by 1H-13C HSQC NMR. The carbohydrates were the most important class of compounds to differentiate the cassava genotypes. The correlation of NMR with cooking time and starch content showed that the higher content of primary metabolites, mostly glucose, can be associated with longer cooking times and reduction of starch, corroborating the metabolic pathways analysis. Furthermore, it was observed that the lignin from cell walls did not differentiate the cooking performance of the genotypes.

This research paper focuses on the application of the tanh function method to find the soliton solutions of the (2+1)-dimensional nonlinear electrical transmission line model. Materials used to form a transmitting line are very important to transmit electric charge. In this sense, we find some new voltage behaviors such as dark, trigonometric, and complex function solutions. Choosing some suitable values of parameters, we present some various surfaces of results obtained in this paper. These results play an important role in telecommunications lines used to stand for wave propagations.

This paper aimed to study the use of peracetic acid (PAA) to disinfect the wastewater. In this perspective, the consume of PAA and its efficiency to deactivate total coliforms microorganisms and E.coli was investigated and under different conditions of total suspended solids (TSS) and pH. The tests of disinfection with PAA demonstrate that content of TSS over than 50 mg/L led to an increase of up to 50% in the consume of disinfectant to the microbial inactivation. The efficiency for inactivation of PAA related to E.coli was also damaged in PH conditions greater than 8. The time of contact had greater influence in the disinfection in dosages up to 5mg/L of PAA.

Preeclampsia is one of the major hypertensive diseases of pregnancy. Genetic factors contribute to abnormal placentation. The inadequate transformation of cytotrophoblasts causes failure of maternal spiral arteries’ remodeling and results in narrow, atherotic-prone vessels, leading to relative placental ischemia. This study aims to explore the possibility of identifying dysregulated gene networks that may offer a potential target in the possible prevention of preeclampsia. We performed a weighted gene correlated network analysis (WGCNA) on a subset of gene expression profiles of placental tissues from severe preeclamptic pregnancies. We identified a gene module (number of genes = 402, GS = 0.35, p = 0.02) enriched for several G-protein-coupled receptor (GPCR)-related genes with significant protein–protein molecular interaction (number of genes = 38, FDR = 0.0007) that may play key roles in preeclampsia. Some genes are noted to play key roles in preeclampsia, including LPAR4/5, CRLR, NPY, TACR1/2, and SFRP4/5, whose functions generally relate to angiogenesis and vasodilation or vasoconstriction. Other upregulated genes, including olfactory and orexigenic genes, serve limited functions in the disease pathogenesis. Altogether, this study shows the utility of WGCNA in exploring possible new gene targets, and additionally reinforces the feasibility of targeting GPCRs that may offer intervention against development and disease progression among severe preeclampsia patients.

La Triple Cuenta de Resultados busca incorporar los impactos ambientales y sociales que genera una organización a su información financiera. Esta incorporación se da mediante diversos reportes, entre ellos los reportes de sostenibilidad permiten comunicar el impacto económico, social y medioambiental que una organización ejerce sobre su entorno y comunidad, pudiendo medir a través de variables o indicadores la incidencia positiva o negativa en estas áreas. Los Estados, y todas sus empresas públicas y administraciones deberían ser pioneros y jugar un papel decisivo a la hora de desarrollar, legitimar y consolidar modelos de Triple Balance a través de diferentes reportes. Sin embargo, No se tiene evidencia sobre cómo los estados están incorporando la TCR en sus reportes, en cuántas de sus empresas y con qué propósitos. El objetivo de este estudio es precisamente ser capaz de describir qué tipo de reportes elaboran las empresas públicas uruguayas y cuál es su contenido. Se determina cuántas empresas públicas reportan sobre sostenibilidad, cómo hacen visibles dichos reportes, qué tipo de informe publican y con qué frecuencia. Asimismo se vincula la información obtenida en dichos reportes con los principios del Pacto Global de Naciones Unidas, los Objetivos de Desarrollo Sostenible así como los Principios y Estándares del GRI. Se emplearon como fuente de información los sitios web de las empresas públicas uruguayas, se efectuó una revisión de Reportes de sostenibilidad en la base de datos del Global Reporting Initiative (GRI) y en el sitio web de Responsabilidad Social Empresaria (DERES) de Uruguay. Como resultado se obtuvo que al menos el 86% de las empresas públicas uruguayas presentan reportes de características variopintas, no encontrándose uniformidad entre estos. Sin embargo, se ha notado una evolución en la preparación de los reportes, adoptando denominaciones más adecuadas, incorporando contenidos, así como aumentando la cantidad y calidad de la información. Sin embargo, en dichos reportes no necesariamente se identifican de manera específica temas como la RSE, los principios del Pacto Global, los ODS, los principios y estándares GRI, con lo cual existe información relevante para comunicar a los grupos de interés que no queda referenciada en los informes. Asimismo, son escasas las empresas públicas que elaboran propiamente Reportes de sostenibilidad y ninguna presenta un Reporte integrado.

Multidrug resistance (MDR) is the main challenge in the treatment of chronic myeloid leukemia (CML), and P-glycoprotein (P-gp) overexpression is an important mechanism involved in this resistance process. However, some compounds can selectively affect MDR cells, inducing collateral sensitivity (CS), which may be dependent on P-gp. The aim of this study was to investigate the effect of piperine, a phytochemical from black pepper, on CS induction in CML MDR cells, and the mechanisms involved. The results indicate that piperine induced CS, being more cytotoxic to K562-derived MDR cells (Lucena-1 and FEPS) than to K562, the parental CML cell. CS was confirmed by analysis of cell metabolic activity and viability, cell morphology and apoptosis. P-gp was partially required for CS induction. To investigate a P-gp independent mechanism, we analyzed the possibility that poly (ADP-ribose) polymerase-1 (PARP-1) could be involved in piperine cytotoxic effects. It was previously shown that only MDR FEPS cells present a high level of 24 kDa fragment of PARP-1, which could protect these cells against cell death. In the present study, piperine was able to decrease the 24 kDa fragment of PARP-1 in MDR FEPS cells. We conclude that piperine targets selectively MDR cells, inducing CS, through a mechanism that might be dependent or not on P-gp.

Architectonic heterogeneity in neurons is thought to be important for equipping the mammalian cerebral cortex with an adaptable network that can organize the manifold totality of information it receives. To this end, the dendritic arbors of supragranular pyramidal neurons, even those of the same class, are known to vary substantially. This diversity of dendritic morphology appears to have a rostrocaudal configuration in some brain regions of various species. For example, in humans and non-human primates, neurons in more rostral visual association areas (e.g., V4) tend to have more complex dendritic arbors than those in the caudal primary visual cortex. A rostrocaudal configuration is not so clear in any region of the mouse, which is increasingly being used as a model for neurodevelopmental disorders that arise from dysfunctional cerebral cortical circuits. Therefore, in this study we investigated the complexity of dendritic arbors of neurons distributed throughout a broad area of the mouse cerebral cortex. We reduced selection bias by labeling neurons restricted to become supragranular pyramidal neurons using in utero electroporation. While we observed that the simple rostrocaudal position, cortical depth, or even functional region of a neuron was not directly related to its dendritic morphology, a model that instead included a caudomedial-to-rostrolateral gradient accounted for a significant amount of the observed dendritic morphological variance. In other words, rostrolateral neurons from our data set were generally more complex when compared to caudomedial neurons. Furthermore, dividing the cortex into a visual area and a non-visual area maintained the power of the relationship between caudomedial-to-rostrolateral position and dendritic complexity. Our observations therefore support the idea that dendritic morphology of mouse supragranular excitatory pyramidal neurons across much of the tangential plane of the cerebral cortex is partly shaped by a developmental gradient spanning several functional regions.