199 research outputs found
Connected at a Distance: Experiences and Efforts Within a Synchronous, Online Mathematics Specialist Program
Online learning offers flexibility and convenience to students regardless of their proximity to a traditional campus. However, online programs can also feel isolating. Beth, a mathematics specialist candidate, completed a graduate program while living 7000 miles and seven time zones away from her instructor and peers. Through intentional planning by instructors, Beth found community by making personal connections, celebrating life experiences, and sharing a passion for mathematics education with her peers. Furthermore, Beth felt empowered to take academic risks and expose professional vulnerabilities in the learning community. The instructors within the program valued learning as a social construct and therefore designed opportunities for candidates to make ongoing personal and professional connections. In this mathematics specialist program, participants and instructors each took responsibility for forming and sustaining the online community. Although the examples shared in this manuscript are one student’s experiences in a specific context, mathematics leaders may be able to extend the idea of forging connections into other virtual contexts. Specifically, we value and highlight the importance of creating an environment that recognizes the learner as a whole person with competing personal and professional priorities
Coagulation, Microenvironment and Liver Fibrosis
Fibrosis is the main consequence of any kind of chronic liver damage. Coagulation and thrombin generation are crucial in the physiological response to tissue injury; however, the inappropriate and uncontrolled activation of coagulation cascade may lead to fibrosis development due to the involvement of several cellular types and biochemical pathways in response to thrombin generation. In the liver, hepatic stellate cells and sinusoidal endothelial cells orchestrate fibrogenic response to chronic damage. Thrombin interacts with these cytotypes mainly through protease-activated receptors (PARs), which are expressed by endothelium, platelets and hepatic stellate cells. This review focuses on the impact of coagulation in liver fibrogenesis, describes receptors and pathways involved and explores the potential antifibrotic properties of drugs active in hemostasis in studies with cells, animal models of liver damage and humans
Components of SurA Required for Outer Membrane Biogenesis in Uropathogenic Escherichia coli
Background: SurA is a periplasmic peptidyl-prolyl isomerase (PPIase) and chaperone of Escherichia coli and other Gramnegative bacteria. In contrast to other PPIases, SurA appears to have a distinct role in chaperoning newly synthesized porins destined for insertion into the outer membrane. Previous studies have indicated that the chaperone activity of SurA rests in its ‘‘core module’ ’ (the N- plus C-terminal domains), based on in vivo envelope phenotypes and in vitro binding and protection of non-native substrates. Methodology/Principal Findings: In this study, we determined the components of SurA required for chaperone activity using in vivo phenotypes relevant to disease causation by uropathogenic E. coli (UPEC), namely membrane resistance to permeation by antimicrobials and maturation of the type 1 pilus usher FimD. FimD is a SurA-dependent, integral outer membrane protein through which heteropolymeric type 1 pili, which confer bladder epithelial binding and invasion capacity upon uropathogenic E. coli, are assembled and extruded. Consistent with prior results, the in vivo chaperone activity of SurA in UPEC rested primarily in the core module. However, the PPIase domains I and II were not expendable for wild-type resistance to novobiocin in broth culture. Steady-state levels of FimD were substantially restored in the UPEC surA mutant complemented with the SurA N- plus C-terminal domains. The addition of PPIase domain I augmented FimD maturation into the outer membrane, consistent with a model in which domain I enhances stability of and/or substrat
Quantum Interference: From Kaons to Neutrinos (with Quantum Beats in between)
Using the vehicle of resolving an apparent paradox, a discussion of quantum
interference is presented. The understanding of a number of different physical
phenomena can be unified, in this context. These range from the neutral kaon
system to massive neutrinos, not to mention quantum beats, Rydberg wave
packets, and neutron gravity.Comment: 12 pages, LaTeX, 3 figure
Genistein supplementation and cardiac function in postmenopausal women with metabolic syndrome: Results from a pilot strain-echo study
Genistein, a soy-derived isoflavone,may improve cardiovascular risk profile in postmenopausal women with metabolic syndrome (MetS), but few literature data on its cardiac effects in humans are available. The aim of this sub-study of a randomized double-blind case-control study was to analyze the effect on cardiac function of one-year genistein dietary supplementation in 22 post-menopausal patients with MetS. Participants received 54 mg/day of genistein (n = 11) or placebo (n = 11) in combination with a Mediterranean-style diet and regular exercise. Left ventricular (LV) systolic function was assessed as the primary endpoint, according to conventional and strain-echocardiography measurements. Also, left atrial (LA) morphofunctional indices were investigated at baseline and at the final visit. Results were expressed as median with interquartile range (IQ). A significant improvement of LV ejection fraction (20.3 (IQ 12.5) vs. -1.67 (IQ 24.8); p = 0.040)), and LA area fractional change (11.1 (IQ 22.6) vs. 2.8 (9.5); p = 0.034)) were observed in genistein patients compared to the controls, following 12 months of treatment. In addition, body surface area indexed LA systolic volume and peak LA longitudinal strain significantly changed from basal to the end of the study in genistein-treated patients. One-year supplementation with 54 mg/day of pure genistein improved both LV ejection fraction and LA remodeling and function in postmenopausal women with MetS
17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.
In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the non-feminizing estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p \u3c 0.0001, log-rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang-Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex-specific aspects of aging
SS-31 and NMN: Two paths to improve metabolism and function in aged hearts
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts. After treatment with the drugs, individually or Combined, heart function was examined by echocardiography. SS-31 partially reversed an age-related decline in diastolic function while NMN fully reversed an age-related deficiency in systolic function at a higher workload. Metabolomic analysis revealed that both NMN and the Combined treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NA
Daidzein Prevents the Increase in CD4+CD28null T Cells and B Lymphopoesis in Ovariectomized Mice: A Key Mechanism for Anti-Osteoclastogenic Effect
Estrogen deficiency leads to an upregulation of TNF-α producing T cells and B-lymphopoesis which augments osteoclastogenesis. Estrogen deficiency also increases the population of premature senescent CD4+CD28null T cells which secrete a higher amount of TNF-α thus leading to enhanced osteoclastogenesis. Isoflavonoids like daidzein and genistein are found mostly in soybeans, legumes, and peas. These share structural similarity with 17β-stradiol (E2) and have osteoprotective role. This study explores the effect of daidzein (Daid) on the proliferation of TNF-α producing T cells, premature senescent T cells and B cell lymphopoesis under estrogen deficient conditions. For this study adult Balb/c mice were treated with Daid at 10 mg/kg body weight dose by oral gavage daily post ovariectomy (Ovx). After six weeks animals were autopsied and bone marrow and spleen cells were collected for FACS analysis. Blood serum was collected for ELISA. It was observed that Ovx mice treated with Daid for six weeks show reduction in Ovx induced expansion of CD4+ T cells in bone marrow and spleen when analysed by flow cytometry. Estrogen deficiency led to increased prevalence of TNF-α secreting CD4+CD28null T cells, however, treatment with Daid increased the percentage of CD4+CD28+ T cells. Co-culture of CD4+CD28null T cells and bone marrow resulted in enhanced osteoclastogenesis as evident by increased tartarate resistant acid phosphatase (TRAP) expression, an osteoclast marker. However, treatment with Daid resulted in reduced osteoclastogenesis in CD4+CD28null T cells and bone marrow cell co-culture. Daid also regulated B lymphopoesis and decreased mRNA levels of RANKL in B220+ cells. Taken together, we propose that one of the mechanisms by which Daid prevents bone loss is by reversing the detrimental immune changes as a result of estrogen deficiency
Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase
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