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68,772 result(s) for "Reilly, T."
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High Fat Diet-Induced CD8+ T Cells in Adipose Tissue Mediate Macrophages to Sustain Low-Grade Chronic Inflammation
Obesity in the United States and worldwide reached epidemic proportions within the last 20 years. Obesity is a very powerful health determinant or indicator that facilitates the development and progression of several metabolic diseases, insulin resistance, and low-grade chronic inflammation. Low-grade chronic inflammation in adipose tissue (AT) is marked by the accumulation of T cells, macrophages, and other immune cells and increased production of proinflammatory cytokines. During the onset of obesity but before the influx of macrophages, the AT is infiltrated by T cells that are strongly implicated in the initiation of obesity-associated inflammation. In comparing mice fed a high-fat diet (HFD) with those fed a normal diet (ND), we observed in HFD epididymal AT induction and infiltration of activated T cells, an accumulation and polarization of macrophages, and an increase in populations of activated CD4 + T cells and CD8 + T cells that express CXCR3 or killer cell lectin-like receptor subfamily G member 1 (KLRG1). Levels of inflammatory cytokines and leptin and the results of in vitro co-culture experiments revealed interactions among HFD- and ND-induced CD8 + T cells, macrophages, and adipocytes. Our findings suggest that obese tissues activate and induce both CD4 + and CD8 + CD69 + T cells and augment the expression of CXCR3 receptors, which promotes the recruitment and numbers of pro-inflammatory M1 macrophages to maintain low-grade chronic inflammation. The results support the hypothesis that CXCR3-expressing CD8 + T cells play an essential role in the initiation and maintenance of adipose tissue inflammation.
Making hard decisions with DecisionTools
Teaching the fundamental ideas of decision analysis, this text avoids an overly technical explanation of the mathematics used in management science. This new version incorporates and implements the powerful Decision Tools Suite, a toolkit for risk and decision analysis.
Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity
Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue. Blockade of CB1 attenuated DIO, inflammatory cytokines and trafficking of M1 macrophages into adipose tissue. Decreased inflammatory tone was associated with a lower intestinal permeability and decreased metabolic endotoxemia as evidenced by reduced plasma LPS level, and improved hyperglycemia and insulin resistance. 16S rRNA metagenomics sequencing revealed that CB1 blockade dramatically increased relative abundance of Akkermansia muciniphila and decreased Lanchnospiraceae and Erysipelotrichaceae in the gut. Together, the current study suggests that blocking of CB1 ameliorates Diet-Induced Obesity and metabolic disorder by modulating macrophage inflammatory mediators, and that this effect is associated with alterations in gut microbiota and their metabolites.
Fully recyclable and tough thermoplastic elastomers from simple bio-sourced δ-valerolactones
While a large number of chemically recyclable thermoplastics have been developed in recent years, technologically important thermoplastic elastomers (TPEs) that are not only bio-based and fully recyclable but also exhibit mechanical properties that can rival or even exceed those petroleum-based, non-recyclable polyolefin TPEs are critically lacking. The key challenge in developing chemically circular, bio-based, high-performance TPEs rests on the complexity of TPE’s block copolymer (BCP) structure involving block segments of different suitable monomers required to induce self-assembled morphologies responsible for performance as well as the control and monomer compatibility in their synthesis and the selectivity in their depolymerization. Here we demonstrate the utilization of bio-sourced δ-valerolactone (δVL) and its simple α-alkyl-substituted derivatives to produce all δVL-based polyester tri-BCP TPEs, which exhibit not only complete (closed-loop) chemical recyclability but also excellent toughness that is 2.5–3.8 times higher than commercial polyolefin-based TPEs. The visualized cylindrical morphology formed via crystallization-driven self-assembly in the new all δVL tri-BCP is postulated to contribute to the excellent TPE property. While a large number of chemically recyclable thermoplastics have been developed in recent years, technologically bio-based and fully recyclable thermoplastic elastomers (TPEs) with excellent mechanical properties are lacking. Here the authors demonstrate an all δvalerolactone-based polyester tri-BCP TPEs, which exhibit not only closed-loop chemical recyclability but also exceptional toughness.
Winter torpor expression varies in four bat species with differential susceptibility to white-nose syndrome
Studies examining the overwintering behaviors of North American hibernating bats are limited to a handful of species. We deployed temperature-sensitive transmitters on four species of bat that exhibit differences in their susceptibility to white nose syndrome (WNS; Myotis grisescens , M. leibii , M. sodalis, and Perimyotis subflavus ) to determine if these differences are correlated with behavior exhibited during hibernation (i.e., torpor expression and arousal frequency). Mean torpor skin temperature (T sk ) and torpor bout duration varied significantly among species ( P  ≤ 0.024), but arousal T sk and duration did not ( P  ≥ 0.057). One of the species with low susceptibility to WNS, M. leibii , had significantly shorter torpor bout durations (37.67 ± 26.89 h) than M. sodalis (260.67 ± 41.33 h), the species with medium susceptibility to WNS. Myotis leibii also had significantly higher torpor T sk (18.57 °C ± 0.20) than M. grisescens (13.33 °C ± 0.60), a second species with low WNS susceptibility. The high susceptibility species, Perimyotis subflavus, exhibited low torpor T sk (14.42 °C ± 0.36) but short torpor bouts (72.36 ± 32.16 h). We demonstrate that the four cavernicolous species examined exhibit a wide range in torpid skin temperature and torpor bout duration. Information from this study may improve WNS management in multispecies hibernacula or individual species management by providing insight into how some species may differ in their techniques for overwinter survival.
Movement Intention After Parietal Cortex Stimulation in Humans
Parietal and premotor cortex regions are serious contenders for bringing motor intentions and motor responses into awareness. We used electrical stimulation in seven patients undergoing awake brain surgery. Stimulating the right inferior parietal regions triggered a strong intention and desire to move the contralateral hand, arm, or foot, whereas stimulating the left inferior parietal region provoked the intention to move the lips and to talk. When stimulation intensity was increased in parietal areas, participants believed they had really performed these movements, although no electromyographic activity was detected. Stimulation of the premotor region triggered overt mouth and contralateral limb movements. Yet, patients firmly denied that they had moved. Conscious intention and motor awareness thus arise from increased parietal activity before movement execution.
A new tool for the assessment of speech understanding and spatial hearing difficulties in children: the Kid-SSQ questionnaire
Purpose To develop and validate a new questionnaire, the Kid-SSQ, for the rapid screening of hearing abilities in children with hearing impairment, aged 7–17 years. Methods The questionnaire was constructed from two existing, validated versions of the ‘Speech, Spatial and Qualities of Hearing’ - (SSQ) questionnaire (pediatric form and adult short-form). The 12 selected items included auditory aspects from three subscales: speech perception, spatial hearing, and qualities of hearing. This new short form was then validated in 154 children with cochlear implants (100 bilaterally, and 54 unilaterally implanted children). Construct validity was assessed by testing relationships between Kid-SSQ scores and objective clinical parameters (e.g., age at test, pure-tone audiometry-PTA threshold, speech reception threshold-SRT, duration of binaural experience). Results Completion time was acceptable for use with children (less than 10 min) and the non-response rate was less than 1%. Good internal consistency was obtained (Cronbach’s α  = 0.78), with a stable internal structure corresponding to the 3 intended subscales. External validity showed the specificity of each subscale: speech subscale scores were significantly predicted ( r  = 0.32, p  < 0.001) by both 2 kHz PTA threshold ( β  = 0.33, p  < 0.001) and SRT ( β  = − 0.23, p  < 0.001). Children with more binaural experience showed significantly higher scores on the spatial subscale than children with less binaural experience ( F (1,98) = 5.1, p  < 0.03) and the qualities of hearing subscale scores significantly depended on both age and SRT ( r  = 0.32, p  < 0.001). Conclusions The Kid-SSQ questionnaire is a robust and clinically useful questionnaire for self-assessment of difficulties in various auditory domains.
Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer
Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia.