The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

The Pediatric Cell Atlas:Defining the Growth Phase of Human Development at Single-Cell Resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Removal of Azo Dye from Synthetic Wastewater Using Immobilized Nano-Diatomite Within Calcium Alginate

Introduction: The presence of organic dyes, discharged by textile industries, in aqueous environments can cause detrimental effects on aquatic life and subsequently human health. Therefore, the decolorization of aquatic environments is mandatory to protect the environment. For this reason, in the present study, nano-sized diatomite was immobilized within calcium alginate as a nanocomposite adsorbent for removing organic azo dye (Direct blue 15) from aqueous solutions.  Methods: First of all, Iranian diatomite was grinded in a planetary ball mill equipped with tungsten carbide cup for 20 h to achieve nanoparticles of the diatomite. For the immobilization of nanostructured diatomite, a 2% sodium alginate solution was used. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infra-red (FT-IR) spectroscopy were used to characterize immobilized nano-diatomite. Fifty milliliter Erlenmeyer flasks were used as batch flow mode experimental reactors. Working solutions were prepared by the dilution of stock solution (1 g/L) to desired concentrations. The effect of different operational parameters including contact time, initial pH, adsorbent dosage and initial dye concentration along with kinetic and isotherm of the adsorption were evaluated. After each experiment, the residual concentration of the dyes was measured spectrophotometrically. Results: As results, the adsorption of organic dye increased with increasing contact time and adsorbent dosage, while increasing initial dye concentrations resulted in decreasing the adsorption. The adsorption of DB-15 was favored at basic PH. The immobilization of diatomite led to enhancing the adsorption of  DB-15 compared to diatomite alone. According to the obtained correlation coefficient, the adsorption of DB-15 obeyed pseudo-second order kinetic model and Langmuir isotherm model. The maximum adsorption capacity of diatomite/alginate nanocomposite for the adsorption of DB-15 were found about 33.22 mg/g. Conclusion: The results of this study showed that the diatomite/alginate nanocomposite can be used effectively for treating colored effluents containing azo dyes. Because of its high efficiency, availability of diatomite mines in our country, it can be used as an economic adsorbent for the decolorization of textile effluents

The E3 ubiquitin ligase Cul4b promotes CD4+ T cell expansion by aiding the repair of damaged DNA.

The capacity for T cells to become activated and clonally expand during pathogen invasion is pivotal for protective immunity. Our understanding of how T cell receptor (TCR) signaling prepares cells for this rapid expansion remains limited. Here we provide evidence that the E3 ubiquitin ligase Cullin-4b (Cul4b) regulates this process. The abundance of total and neddylated Cul4b increased following TCR stimulation. Disruption of Cul4b resulted in impaired proliferation and survival of activated T cells. Additionally, Cul4b-deficient CD4+ T cells accumulated DNA damage. In T cells, Cul4b preferentially associated with the substrate receptor DCAF1, and Cul4b and DCAF1 were found to interact with proteins that promote the sensing or repair of damaged DNA. While Cul4b-deficient CD4+ T cells showed evidence of DNA damage sensing, downstream phosphorylation of SMC1A did not occur. These findings reveal an essential role for Cul4b in promoting the repair of damaged DNA to allow survival and expansion of activated T cells

An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation

The unfolded protein response plays an evolutionarily conserved role in homeostasis, and its dysregulation often leads to human disease, including diabetes and cancer. IRE1α is a major transducer that conveys endoplasmic reticulum stress via biochemical signals, yet major gaps persist in our understanding of how the detection of stress is converted to one of several molecular outcomes. It is known that, upon sensing unfolded proteins via its endoplasmic reticulum luminal domain, IRE1α dimerizes and then oligomerizes (often visualized as clustering). Once assembled, the kinase domain trans-autophosphorylates a neighboring IRE1α, inducing a conformational change that activates the RNase effector domain. However, the full details of how the signal is transmitted are not known. Here, we describe a previously unrecognized role for helix αK, located between the kinase and RNase domains of IRE1α, in conveying this critical conformational change. Using constructs containing mutations within this interdomain helix, we show that distinct substitutions affect oligomerization, kinase activity, and the RNase activity of IRE1α differentially. Furthermore, using both biochemical and computational methods, we found that different residues at position 827 specify distinct conformations at distal sites of the protein, such as in the RNase domain. Of importance, an RNase-inactive mutant, L827P, can still dimerize with wildtype monomers, but this mutation inactivates the wildtype molecule and renders leukemic cells more susceptible to stress. We surmise that helix αK is a conduit for the activation of IRE1α in response to stress