Astrocytes in the brain release transmitters that actively modulate neuronal excitability and synaptic efficacy. Astrocytes also release vasoactive agents that contribute to neurovascular coupling. ...As reviewed in this article, Müller cells, the principal retinal glial cells, modulate neuronal activity and blood flow in the retina. Stimulated Müller cells release ATP which, following its conversion to adenosine by ectoenzymes, hyperpolarizes retinal ganglion cells by activation of A1 adenosine receptors. This results in the opening of G protein-coupled inwardly rectifying potassium (GIRK) channels and small conductance Ca2+-activated K+ (SK) channels. Tonic release of ATP also contributes to the generation of tone in the retinal vasculature by activation of P2X receptors on vascular smooth muscle cells. Vascular tone is lost when glial cells are poisoned with the gliotoxin fluorocitrate. The glial release of vasoactive metabolites of arachidonic acid, including prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs), contributes to neurovascular coupling in the retina. Neurovascular coupling is reduced when neuronal stimulation of glial cells is interrupted and when the synthesis of arachidonic acid metabolites is blocked. Neurovascular coupling is compromised in diabetic retinopathy owing to the loss of glial-mediated vasodilation. This loss can be reversed by inhibiting inducible nitric oxide synthase. It is likely that future research will reveal additional important functions of the release of transmitters from glial cells.
The retinal vasculature supplies cells of the inner and middle layers of the retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles producing blood flow increases, a response ...termed functional hyperemia. Despite recent advances, the neurovascular coupling mechanisms mediating the functional hyperemia response in the retina remain unclear. In this review, the retinal functional hyperemia response is described, and the cellular mechanisms that may mediate the response are assessed. These neurovascular coupling mechanisms include neuronal stimulation of glial cells, leading to the release of vasoactive arachidonic acid metabolites onto blood vessels, release of potassium from glial cells onto vessels, and production and release of nitric oxide (NO), lactate, and adenosine from neurons and glia. The modulation of neurovascular coupling by oxygen and NO are described, and changes in functional hyperemia that occur with aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed. Finally, outstanding questions concerning retinal blood flow in health and disease are discussed.
While the link between servant leadership and organizational citizenship behavior (OCB) has been established, the individual-level mechanisms underlying this relationship and its boundary conditions ...remain poorly understood. In this study, we investigate the salience of the mediating mechanisms of leader-member exchange (LMX) and psychological empowerment in explaining the process by which servant leaders elicit discretionary OCB among followers. We also examine the role of followers' proactive personality in moderating the indirect effects of servant leadership on OCB through LMX and psychological empowerment. Analysis of survey data collected from 446 supervisor-subordinate dyads in a large Chinese stateowned enterprise suggests that while servant leadership is positively related to subordinate OCB through LMX, psychological empowerment does not explain any additional variance in OCB above that accounted for by LMX. Moderated mediation tests confirm the moderating effect of proactive personality through LMX. By providing a nuanced understanding of how and when servant leadership leads followers to go above and beyond their job role, our study assists organizations in deciding how to develop and utilize servant leaders in their organizations.
Photometric redshifts are essential in studies of both galaxy evolution and cosmology, as they enable analyses of objects too numerous or faint for spectroscopy. The Rubin Observatory,
Euclid
, and
...Roman Space Telescope
will soon provide a new generation of imaging surveys with unprecedented area coverage, wavelength range, and depth. To take full advantage of these data sets, further progress in photometric redshift methods is needed. In this review, we focus on the greatest common challenges and prospects for improvement in applications of photometric redshifts to the next generation of surveys:
Gains in performance (i.e., the precision of redshift estimates for individual galaxies) could greatly enhance studies of galaxy evolution and some probes of cosmology.
Improvements in characterization (i.e., the accurate recovery of redshift distributions of galaxies in the presence of uncertainty on individual redshifts) are urgently needed for cosmological measurements with next-generation surveys.
To achieve both of these goals, improvements in the scope and treatment of the samples of spectroscopic redshifts that make high-fidelity photometric redshifts possible will also be needed. For the full potential of the next generation of surveys to be reached, the characterization of redshift distributions must improve by roughly an order of magnitude compared with the current state of the art, requiring progress on a wide variety of fronts. We conclude by presenting a speculative evaluation of how photometric redshift methods and the collection of the necessary spectroscopic samples may improve by the time near-future surveys are completed.
Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity
or surgery
, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be ...at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors
. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6C
monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6C
monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.
•The maximum information entropy inference method is described.•The relation of the method to explicitly mechanistic approaches is clarified.•A theory of macroecology based on the maximum entropy ...principle is summarized.•Successes and gaps of the theory are described, and future extensions are suggested.
The maximum information entropy (MaxEnt) principle is a successful method of statistical inference that has recently been applied to ecology. Here, we show how MaxEnt can accurately predict patterns such as species–area relationships (SARs) and abundance distributions in macroecology and be a foundation for ecological theory. We discuss the conceptual foundation of the principle, why it often produces accurate predictions of probability distributions in science despite not incorporating explicit mechanisms, and how mismatches between predictions and data can shed light on driving mechanisms in ecology. We also review possible future extensions of the maximum entropy theory of ecology (METE), a potentially important foundation for future developments in ecological theory.
Breast cancer statistics, 2019 DeSantis, Carol E.; Ma, Jiemin; Gaudet, Mia M. ...
CA: a cancer journal for clinicians,
November/December 2019, Letnik:
69, Številka:
6
Journal Article
Recenzirano
Odprti dostop
This article is the American Cancer Society’s biennial update on female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Over the most ...recent 5‐year period (2012‐2016), the breast cancer incidence rate increased slightly by 0.3% per year, largely because of rising rates of local stage and hormone receptor‐positive disease. In contrast, the breast cancer death rate continues to decline, dropping 40% from 1989 to 2017 and translating to 375,900 breast cancer deaths averted. Notably, the pace of the decline has slowed from an annual decrease of 1.9% during 1998 through 2011 to 1.3% during 2011 through 2017, largely driven by the trend in white women. Consequently, the black–white disparity in breast cancer mortality has remained stable since 2011 after widening over the past 3 decades. Nevertheless, the death rate remains 40% higher in blacks (28.4 vs 20.3 deaths per 100,000) despite a lower incidence rate (126.7 vs 130.8); this disparity is magnified among black women aged <50 years, who have a death rate double that of whites. In the most recent 5‐year period (2013‐2017), the death rate declined in Hispanics (2.1% per year), blacks (1.5%), whites (1.0%), and Asians/Pacific Islanders (0.8%) but was stable in American Indians/Alaska Natives. However, by state, breast cancer mortality rates are no longer declining in Nebraska overall; in Colorado and Wisconsin in black women; and in Nebraska, Texas, and Virginia in white women. Breast cancer was the leading cause of cancer death in women (surpassing lung cancer) in four Southern and two Midwestern states among blacks and in Utah among whites during 2016‐2017. Declines in breast cancer mortality could be accelerated by expanding access to high‐quality prevention, early detection, and treatment services to all women.
We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina ...and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored.
Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from ...active neurons evoke Ca(2+) increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K(+) from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca(2+) signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow.
PDF
