Pyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we investigated mechanisms underlying CA1 PC differentiation and the development of this inhibitory circuit motif.
View Article and Find Full Text PDFChildhood neuroblastoma with MYCN amplification is classified as high risk and often relapses after intensive treatments. Immune checkpoint blockade therapy against the PD-1/L1 axis shows limited efficacy in patients with neuroblastoma, and the cancer intrinsic immune regulatory network is poorly understood. Here, we leverage genome-wide CRISPR/Cas9 screens and identify H2AFY as a resistance gene to the clinically approved PD-1 blocking antibody nivolumab.
View Article and Find Full Text PDFMelanin is an amorphous, highly heterogeneous polymer found across all kingdoms of life. Although the properties of melanin can greatly vary, most forms are insoluble and strongly absorb light, appearing dark brown to black. Here, we describe a water-soluble form of melanin (peptidomelanin) secreted by the spores of (strain: melanoliber) during germination.
View Article and Find Full Text PDFWhile many computational methods accurately predict destabilizing mutations, identifying stabilizing mutations has remained a challenge, because of their relative rarity. We tested ΔΔG predictions from computational predictors such as Rosetta, ThermoMPNN, RaSP, and DeepDDG, using 82 mutants of the bacterial toxin CcdB as a test case. On this dataset, the best computational predictor is ThermoMPNN, which identifies stabilizing mutations with a precision of 68%.
View Article and Find Full Text PDFAutism spectrum disorder (ASD) presents with diverse cognitive and behavioral abnormalities beginning during early development. Although the neural circuit mechanisms remain unclear, recent work suggests pathology in cortical inhibitory interneurons (INs) plays a crucial role. However, we lack fundamental information regarding changes in the physiology of synapses to and from INs in ASD.
View Article and Find Full Text PDFis a high confidence risk gene for autism spectrum disorder that encodes a subunit of a chromatin remodeling complex expressed in neuronal progenitors. Haploinsufficiency causes a broad range of social, behavioral, and intellectual disability phenotypes, including Coffin-Siris syndrome. Recent work using transgenic mouse models suggests pathology is due to deficits in proliferation, survival, and synaptic development of cortical neurons.
View Article and Find Full Text PDFIn our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice.
View Article and Find Full Text PDFImmune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC).
View Article and Find Full Text PDFThe microalgal-based production of fucoxanthin has emerged as an imperative research endeavor due to its antioxidant, and anticancer properties. In this study, three brown marine microalgae, namely Skeletonema costatum, Chaetoceros gracilis, and Pavlova sp., were screened for fucoxanthin production.
View Article and Find Full Text PDFPyramidal cells (PCs) in CA1 hippocampus can be classified by their radial position as deep or superficial and organize into subtype-specific circuits necessary for differential information processing. Specifically, superficial PCs receive fewer inhibitory synapses from parvalbumin (PV)-expressing interneurons than deep PCs, resulting in weaker feedforward inhibition of input from CA3 Schaffer collaterals. Using mice, we investigated mechanisms underlying PC differentiation and the development of this inhibitory circuit motif.
View Article and Find Full Text PDFSalt stress is a recognized annihilating abiotic stress that has a significant impact on agricultural and horticulture crop productivity. Plant development faces three distinct dangers as a result of salt stress: oxidative stress, osmotic stress, and ionic toxicity. It has been shown that plants can forecast diurnal patterns using the circadian clock; moreover, they can manage their defensive mechanism for the detoxification of reactive oxygen species (ROS).
View Article and Find Full Text PDFMegaselia scalaris, commonly known as the scuttle fly, is a cosmopolitan species in the family Phoridae. It is an easily cultured fly species that is an emerging model organism in the fields of genetics and developmental biology. Its affinity for carrion and its predictable life cycle makes it useful in the field of forensic science for estimating the post-mortem interval (PMI) of human remains.
View Article and Find Full Text PDFNatural astaxanthin is synthesized by diverse organisms including: bacteria, fungi, microalgae, and plants involving complex cellular processes, which depend on numerous interrelated parameters. Nonetheless, existing knowledge regarding astaxanthin biosynthesis and the conditions influencing astaxanthin accumulation is fairly limited. Thus, manipulation of the growth conditions to achieve desired biomass and astaxanthin yields can be a complicated process requiring cost-intensive and time-consuming experiment-based research.
View Article and Find Full Text PDFNeutrosophic multicriteria is a method of decision-making that uses indeterminacy to combine several criteria or elements, frequently with incomplete or ambiguous information, to find a solution. The neutrosophic multicriteria analysis enables the assessment of qualitative and subjective aspects and can assist in resolving conflicting goals and preferences. In the Neutrosophic Multi-Attribute Group Decision Making (NMAGDM) problems, all the information provided by the decision makers (DMs) is expressed as single value neutrosophic triangular and trapezoidal numbers examined in this study which can provide more flexibility and accuracy in capturing uncertainty and aggregating preferences.
View Article and Find Full Text PDFPlastics have become an essential part of life. When it enters the environment, it migrates and breaks down to form smaller size fragments, which are called microplastics (MPs). Compared with plastics, MPs are detrimental to the environment and pose a severe threat to human health.
View Article and Find Full Text PDFUnderstanding the mechanisms and kinetics of membrane damage is of interest to researchers in several overlapping fields of biology. In this study, we describe the development and validation of a simple 32PO43- release radioassay used to track nanometer-scale damage to the bacterial cell membrane. Nanoscale membrane damage will result in the release of small cytoplasmic molecules, such as amino acids, sugars, and osmolytes.
View Article and Find Full Text PDFIn this study, Aurantiochytrium sp. CJ6 was cultivated heterotrophically on a waste resource, sorghum distillery residue (SDR) hydrolysate without adding any nitrogen sources. Mild sulfuric acid treatment released sugars that supported the growth of CJ6.
View Article and Find Full Text PDFInflammatory mediators released by cancer cells promote the induction of immune suppression and tolerance in myeloid cells. IL-1 receptor-associated kinase-3 (IRAK3) is a pseudokinase that inhibits IL-1/TLR signaling, but its role in patients treated with immune checkpoint blockade (ICB) therapy remains unclear. Using RNA-Seq data from the IMvigor210 trial, we found that tumors with high IRAK3 expressions showed enriched antiinflammatory pathways and worse clinical response to ICB therapy.
View Article and Find Full Text PDFCiprofloxacin (CIP) is a commonly used antibiotic for the treatment of infectious diseases in humans and as a prophylactic agent in the livestock industry, leading to the environmental discharge of significant amounts of CIP. CIP is stable in aquatic systems leading to its pseudo-persistence. Constant exposure to these antibiotics results in the generation of antibiotic-resistant pathogens and potential toxicity/hypersensitivity in humans.
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