Advances in the Treatment of Primary Brain Tumors: The Realm of Immunotherapy

Central nervous system (CNS) tumors, although rare, represent a group of neoplasms that have a disproportionate morbidity and mortality. Despite advances in our understanding of tumor pathogenesis coupled with improvements in therapeutic options, overall survival for primary brain tumors remains dismal. Although challenging, newer approaches such as brachytherapy, immunotherapy, and electric field generators are currently being evaluated in the clinical setting with promising results. The field of immunotherapy in neurooncology is still in its infancy, but several advances have already been made, including the development of tumor vaccines, utilization of immune checkpoint inhibitors, and activation of tumor dendritic cells to stimulate the host’s immune system. Recent advances in noninvasive electric fields have been applied to the treatment of glioblastoma multiforme (GBM) with encouraging clinical outcome. In this chapter, we will review the latest advances in the treatment of glioblastoma multiforme with a focus on immunotherapy

Pathologic Thr 175 tau phosphorylation in CTE and CTE with ALS

Objective To investigate whether chronic traumatic encephalopathy (CTE) and CTE with amyotrophic lateral sclerosis (CTE-ALS) exhibit features previously observed in other tauopathies of pathologic phosphorylation of microtubule-associated protein tau at Thr 175 (pThr 175 tau) and Thr 231 (pThr 231 tau), and glycogen synthase kinase-3β (GSK3β) activation, and whether these pathologic features are a consequence of traumatic brain injury (TBI). Methods Tau isoform expression was assayed by western blot in 6 stage III CTE cases. We also used immunohistochemistry to analyze 5 cases each of CTE, CTE-ALS, and 5 controls for expression of activated GSK3β, pThr 175 tau, pThr 231 tau, and oligomerized tau within spinal cord tissue and hippocampus. Using a rat model of moderate TBI, we assessed tau pathology and phospho-GSK3β expression at 3 months postinjury. Results CTE and CTE-ALS are characterized by the presence of all 6 tau isoforms in both soluble and insoluble tau isolates. Activated GSK3β, pThr 175 tau, pThr 231 tau, and oligomerized tau protein expression was observed in hippocampal neurons and spinal motor neurons. We observed tau neuronal pathology (fibrillar inclusions and axonal damage) and increased levels of pThr 175 tau and activated GSK3β in moderate TBI rats. Conclusions Pathologic phosphorylation of tau at Thr 175 and Thr 231 and activation of GSK3β are features of the tauopathy of CTE and CTE-ALS. These features can be replicated in an animal model of moderate TBI

Inference of protein function and protein linkages in Mycobacterium tuberculosis based on prokaryotic genome organization: a combined computational approach

The genome of Mycobacterium tuberculosis was analyzed using recently developed computational approaches to infer protein function and protein linkages. We evaluated and employed a method to infer genes likely to belong to the same operon, as judged by the nucleotide distance between genes in the same genomic orientation, and combined this method with those of the Rosetta Stone, Phylogenetic Profile and conserved Gene Neighbor computational methods for the inference of protein function

MotomiRs: miRNAs in Motor Neuron Function and Disease

MiRNAs are key regulators of the mammalian transcriptome that have been increasingly linked to degenerative diseases of the motor neurons. Although many of the miRNAs currently incriminated as participants in the pathogenesis of these diseases are also important to the normal development and function of motor neurons, at present there is no knowledge of the complete miRNA profile of motor neurons. In this review, we examine the current understanding with respect to miRNAs that are specifically required for motor neuron development, function and viability, and provide evidence that these should be considered as a functional network of miRNAs which we have collectively termed MotomiRs. We will also summarize those MotomiRs currently known to be associated with both amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), and discuss their potential use as biomarkers

Role of appetitive phenotype trajectory groups on child body weight during a family-based treatment for children with overweight or obesity.

ObjectiveEmerging evidence suggests that individual appetitive traits may usefully explain patterns of weight loss in behavioral weight loss treatments for children. The objective of this study was to identify trajectories of child appetitive traits and the impact on child weight changes over time.MethodsSecondary data analyses of a randomized noninferiority trial conducted between 2011 and 2015 evaluated children's appetitive traits and weight loss. Children with overweight and obesity (mean age = 10.4; mean BMI z = 2.0; 67% girls; 32% Hispanic) and their parent (mean age = 42.9; mean BMI = 31.9; 87% women; 31% Hispanic) participated in weight loss programs and completed assessments at baseline, 3, 6,12, and 24 months. Repeated assessments of child appetitive traits, including satiety responsiveness, food responsiveness and emotional eating, were used to identify parsimonious grouping of change trajectories. Linear mixed-effects models were used to identify the impact of group trajectory on child BMIz change over time.ResultsOne hundred fifty children and their parent enrolled in the study. The three-group trajectory model was the most parsimonious and included a high satiety responsive group (HighSR; 47.4%), a high food responsive group (HighFR; 34.6%), and a high emotional eating group (HighEE; 18.0%). Children in all trajectories lost weight at approximately the same rate during treatment, however, only the HighSR group maintained their weight loss during follow-ups, while the HighFR and HighEE groups regained weight (adjusted p-value < 0.05).ConclusionsDistinct trajectories of child appetitive traits were associated with differential weight loss maintenance. Identified high-risk subgroups may suggest opportunities for targeted intervention and maintenance programs

Field-scale remediation of atrazine-contaminated soil using recombinant Escherichia coli expressing atrazine chlorohydrolase

We performed the first field-scale atrazine remediation study in the United States using chemically killed, recombinant organisms. This field study compared biostimulation methods for enhancing atrazine degradation with a novel bioaugmentation protocol using a killed and stabilized whole-cell suspension of recombinant Escherichia coli engineered to overproduce atrazine chlorohyrolase, AtzA. AtzA dechlorinates atrazine, producing non-toxic and non-phytotoxic hydroxyatrazine. Soil contaminated by an accidental spill of atrazine (up to 29 000 p.p.m.) supported significant populations of indigenous microorganisms capable of atrazine catabolism. Laboratory experiments indicated that supplementing soil with carbon inhibited atrazine biodegradation, but inorganic phosphate stimulated atrazine biodegradation. A subsequent field-scale study consisting of nine (0.75m3) treatment plots was designed to test four treatment protocols in triplicate. Control plots contained moistened soil; biostimulation plots received 300 p.p.m. phosphate; bioaugmentation plots received 0.5% (w/w) killed, recombinant E. coli cells encapsulating AtzA; and combination plots received phosphate plus the enzyme-containing cells. After 8 weeks, atrazine levels declined 52% in plots containing killed recombinant E. coli cells, and 77% in combination plots. In contrast, atrazine levels in control and biostimulation plots did not decline significantly. These data indicate that genetically engineered bacteria overexpressing catabolic genes significantly increased degradation in this soil heavily contaminated with atrazine

SRG/eROSITA X-ray shadowing study of giant molecular clouds

SRG/eROSITA is situated in a halo orbit around L2 where the highly variable solar wind charge exchange (SWCX) emission from Earth's magnetosheath is expected to be negligible. The soft X-ray foreground emissions from the local hot bubble (LHB) and the remaining heliospheric SWCX emissions could be studied in unprecedented detail with eROSITA All-Sky Survey (eRASS) data in a 6-month cadence and better spectral resolution than ROSAT. We aim to use eRASS data of the sight lines towards three giant molecular clouds away from the Galactic plane to isolate and study the soft X-ray diffuse foreground emission. These X-ray shadows will serve as calibration baselines for the future three-dimensional structural study of the LHB. We conducted spectral analysis on the diffuse X-ray spectra of these clouds from the first four eRASSs to estimate and separate the heliospheric SWCX contribution from the LHB emission. We find the density of the LHB to be independent of the sight line with $n_e \sim 4 \times 10^{-3}\,$cm$^{-3}$, but not the temperature. We report a lower temperature of $kT_{\mathrm{LHB}}=0.084\pm0.004\,$keV towards Chamaeleon$~$II & III (Cha$~$II & III) than Ophiuchus (Oph) and Corona Australis (CrA), in which we measured $0.102\pm0.006$ and $0.112\pm0.009\,$keV, respectively. We measured the emission measure of the LHB to be $\sim 2\times10^{-3}\,$cm$^{-6}\,$pc at medium Galactic latitudes ($|b| \sim 20^{\circ}$). A monotonic increase in the SWCX contribution has been observed since the start of 2020, coincidental with the beginning of solar cycle 25. For Oph, SWCX has dominated the LHB in the $0.3$-$0.7\,$keV band intensity since eRASS2. We observed lower SWCX contributions in Cha$~$II & III and CrA, consistent with the expected decreasing solar wind ion density at high heliographic latitudes.Comment: 22 pages, 15 figures. Accepted for publication in A&

Evaluating The Roles Of Visual Openness And Edge Effects On Nest-Site Selection And Reproductive Success In Grassland Birds

In some species, habitat edges (ecotones) affect nest-site selection and nesting success. Openness, or how visually open a habitat is, has recently been shown to influence grassland bird density and may affect nest-site selection, possibly by reducing the risk of predation on adults, nests, or both. Because edge and openness are correlated, it is possible that effects of openness have been overlooked or inappropriately ascribed to edge effects. We tested the roles of edges and visual openness in nest-site selection and nesting success of two grassland passerines, the Bobolink (Dolichonyx oryzivorus) and Savannah Sparrow (Passerculus sandwichensis), in the Champlain Valley, Vermont. We also evaluated the sensitivity of our results to alternative definitions of edge on our landscape. Bobolink (n = 580) and Savannah Sparrow nests (n = 922) were located on seven hay fields and three pastures from 2002 to 2010. Both species avoided placing nests near edges and in less open habitat compared with expectations based on random placement. When the effects of openness and edge were separated, less open habitats were still avoided, but edge responses were less clear. These results were robust to different definitions of habitat edge. We found no strong relationships between either openness or edges and reproductive success (numbers of eggs and fledglings, percentage of eggs producing fledglings, and nest success), although there may be an edge-specific openness effect on timing of reproduction (clutch completion date). Our results support openness as an important factor in nest-site selection by grassland birds

Measurement crosstalk between two phase qubits coupled by a coplanar waveguide

We analyze the measurement crosstalk between two flux-biased phase qubits coupled by a resonant coplanar waveguide cavity. After the first qubit is measured, the superconducting phase can undergo damped oscillations resulting in an a.c. voltage that produces a frequency chirped noise signal whose frequency crosses that of the cavity. We show experimentally that the coplanar waveguide cavity acts as a bandpass filter that can significantly reduce the crosstalk signal seen by the second qubit when its frequency is far from the cavity's resonant frequency. We present a simple classical description of the qubit behavior that agrees well with the experimental data. These results suggest that measurement crosstalk between superconducting phase qubits can be reduced by use of linear or possibly nonlinear resonant cavities as coupling elements.Comment: 4 pages, 3 figure