The rockefeller university

Cancer immunotherapy represents a promising treatment approach for malignant gliomas but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified cluster of differentiation (CD)70 as a novel immunosuppressive ligand and glioma target. Normal tissues derived from 52 different organs and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression. The association between CD70 and patients' overall survival and its impact on T-cell death was also evaluated. Human and mouse CD70-specific chimeric antigen receptors (CARs) were tested respectively against human primary GBMs and murine glioma lines. The antitumor efficacies of these CARs were also examined in orthotopic xenograft and syngeneic models. CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death. To explore the potential for therapeutic targeting of this newly identified immunosuppressive axis in GBM tumors, we demonstrate that both human and mouse CD70-specific CAR T cells recognize primary CD70+ GBM tumors in vitro and mediate the regression of established GBM in xenograft and syngeneic models without illicit effect. These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.

Although the surge in research into the neuroscience of resilience is relatively new, it has been able to elucidate the brain structures that underlie resilience and identify strategies for supporting brain health and mental health across the lifespan. Despite advances, neuroscientists need the input of social work clinicians and clinical researchers to continue to move the field forward. This article provides a narrative review of the recent literature on the neuroscience of resilience with the goal of informing social workers and social work researchers about the state of knowledge in this field. We restricted our review to research in the past 20 years on resilience to stress and trauma, including only those papers that relate to neuroscience or mental functioning. We summarize recent developments in the neuroscience of resiliencenotably the neural circuitry and physiology that underlie resilience in humans and animals. We go on to identify a number of interventions likely to promote resilience and resilient brain function, including parenting and community-based interventions for children and adolescents, hardiness training, meditation and mindfulness approaches, and aerobic exercise. Recommendations are made for future cross-disciplinary work.

The mammalian brain is a densely interconnected network that consists of millions to billions of neurons. Decoding how information is represented and processed by this neural circuitry requires the ability to capture and manipulate the dynamics of large populations at high speed and high resolution over a large area of the brain. Although the use of optical approaches by the neuroscience community has rapidly increased over the past two decades, most microscopy approaches are unable to record the activity of all neurons comprising a functional network across the mammalian brain at relevant temporal and spatial resolutions. In this review, we survey the recent development in optical technologies for Ca2+ imaging in this regard and provide an overview of the strengths and limitations of each modality and its potential for scalability. We provide guidance from the perspective of a biological user driven by the typical biological applications and sample conditions. We also discuss the potential for future advances and synergies that could be obtained through hybrid approaches or other modalities.

Neurons in Caenorhabditis elegans and other nematodes have been thought to lack classical action potentials. Unexpectedly, we observe membrane potential spikes with defining characteristics of action potentials in C. elegans AWA olfactory neurons recorded under current-clamp conditions. Ion substitution experiments, mutant analysis, pharmacology, and modeling indicate thatAWA fires calcium spikes, which are initiated by EGL-19 voltage-gated CaV1 calcium channels and terminated by SHK-1 Shaker-type potassium channels. AWA action potentials result in characteristic signals in calcium imaging experiments. These calcium signals are also observed when intact animals are exposed to odors, suggesting that natural odor stimuli induce AWA spiking. The stimuli that elicit action potentials match AWA's specialized function in climbing odor gradients. Our results provide evidence that C. elegans neurons can encode information through regenerative all-or-none action potentials, expand the computational repertoire of its nervous system, and inform future modeling of its neural coding and network dynamics.

Hidradenitis Suppurativa (HS) is a chronic debilitating skin condition that impairs the productivity and the quality of patients` lives. HS has recently drawn lots of attention among scholars to further expand their knowledge but it still loads with uncertainties and gaps to be explored. This publication addresses these uncertainties, and provides a road-map for researchers, scholars and clinicians from different disciplines for their future studies about HS. This is a proceeding report of the first Symposium on Hidradenitis Suppurativa Advances (SHSA), and it reviews the scientific sessions about the epidemiology, pathophysiology, presentations, and management of HS. This symposium was a great opportunity for experts in the HS field to exchange their knowledge, and improve their mutual understanding of this disease.

Oil palm (Elaeis guineensis Jacq.) is the leading oil-producing crops and the most important edible oil resource worldwide. DNA markers and genetic linkage maps are essential resources for marker-assisted selection to accelerate genetic improvement. We conducted RAD-seq on an Illumina NextSeq500 to discover genome-wide SNPs, and used the SNPs to construct a linkage map for an oil palm (Tenera) population derived from a cross between a Deli Dura and an AVROS Pisifera. The RAD-seq produced 1,076 million single-end reads across the breeding population containing 155 trees. Mining this dataset detected 510,251 loci. After filtering out loci with low accuracy and more than 20% missing data, 11,394 SNPs were retained. Using these SNPs, in combination with 188 anchor SNPs and 123 microsatellites, we constructed a linkage map containing 10,023 markers covering 16 chromosomes. The map length is 2,938.2 cM with an average marker space of 0.29 cM. The large number of SNPs will supply ample choices of DNA markers in analysing the genetic diversity, population structure and evolution of oil palm. This high-density linkage map will contribute to mapping quantitative trait loci (QTL) for important traits, thus accelerating oil palm genetic improvement.

Aim: To determine whether specific dopaminergic system gene variants are associated with opioid dependence. Patients & methods: Subjects included 153 healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent. Genotypes of 90 variants in 13 genes were examined. Results: The most significant results were obtained for DA beta-hydroxylase variants, rs2073837 and rs1611131, which were associated with protection from addiction (q = 0.0172, 0.0415, respectively) and the functional TH variant, rs2070762, was associated with more risk (q = 0.0387). The three variants also showed a combined effect that remained significant after correction for multiple testing (p(final) = 0.0039). Conclusion: These data offer support that dopaminergic gene variants have a role in opioid dependence and warrant further study.

The prevalence of affective disorders such as depression and anxiety is particularly high in patients with autoimmune diseases, including inflammatory skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. A dys-regulated immune response has been linked to the precipitation of depression in many patient populations. However, studies examining the extent to which the underlying skin disease inflammatory processes contribute to depression and a subsequent decline in quality of life are limited. The published literature over the past 5 years was reviewed for evidence of a relationship between depression and inflammatory processes in the context of skin pathology. The findings, particularly the evidence from interventional clinical trials of targeted anti-cytokine therapies, suggest that pro-inflammatory cytokines associated with several skin diseases may be causally linked with the coexistent depressive symptomology. (C) 2018 S. Karger AG, Basel

Thiovulum majus self-organize on glass surfaces into active two-dimensional crystals of rotating cells. Unlike classical crystals, these bacterial crystallites continuously rotate and reorganize as the power of rotating cells is dissipated by the surrounding flow. In this article, we describe the earliest stage of crystallization, the attraction of two bacteria into a hydrodynamically-bound dimer. This process occurs in three steps. First a free-swimming cell collides with the wall and becomes hydrodynamically bound to the two-dimensional surface. We present a simple model to understand how viscous forces localize cells near the chamber walls. Next, the cell diffuses over the surface for an average of 63 +/- 6 s before escaping to the bulk fluid. The diffusion coefficient D-eff = 7.98 +/- 0.1 mu m(2) s(-1) of these 8.5 mu m diameter cells corresponds to a temperature of (4.16 +/- 0.05) x 10(4) K, and thus cannot be explained by equilibrium fluctuations. Finally, two cells coalesce into a rotating dimer when the convergent flow created by each cell overwhelms their active Brownian motion. This occurs when cells diffuse to within a distance of 13.3 +/- 0.2 mu m of each other.

A search for supersymmetry is presented based on proton-proton collision events containing identified hadronically decaying top quarks, no leptons, and an imbalance p(T)(miss) in transverse momentum. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). Search regions are defined in terms of the multiplicity of bottom quark jet and top quark candidates, the p(T)(miss) , the scalar sum of jet transverse momenta, and themT2 mass variable. No statistically significant excess of events is observed relative to the expectation from the standard model. Lower limits on the masses of supersymmetric particles are determined at 95% confidence level in the context of simplified models with top quark production. For a model with direct top squark pair production followed by the decay of each top squark to a top quark and a neutralino, top squark masses up to 1020 GeVand neutralino masses up to 430 GeVare excluded. For amodel with pair production of gluinos followed by the decay of each gluino to a top quark-antiquark pair and a neutralino, gluino masses up to 2040 GeVand neutralino masses up to 1150 GeVare excluded. These limits extend previous results.