Osteocalcin deficient mice (OC-/-), on a mixed 129/BL6J background, were reported to show glucose intolerance, insulin insensitivity and reduced insulin secretion at 1-6 mos of age. This is controversial as two studie...
Osteocalcin deficient mice (OC-/-), on a mixed 129/BL6J background, were reported to show glucose intolerance, insulin insensitivity and reduced insulin secretion at 1-6 mos of age. This is controversial as two studies in OC-/- mice on different backgrounds (C3H/BL6 (5-6 mos.) and C57BL/6N (5 and 9 mos.)) found no effect on glucose metabolism. To determine the role of OC in glucose metabolism we conducted glucose tolerance tests (GTT), insulin tolerances tests (ITT) and glucose stimulated insulin secretion (GSIS) on 6 and 9.5 month-old male OC-/- and OC+/+ mice on a pure C57BL/6J background and fed a normal chow diet. All results were analyzed with a two-way repeated measures ANOVA. The GTT results showed no effect on males at 6 months of age but glucose intolerance was significantly increased (p < 0.05) in male OC-/- mice at 9.5 months of age. The ITT results indicated significantly increased insulin resistance in male OC-/- mice. Glucose stimulated insulin secretion (GSIS) showed insulin significantly (p < 0.05) reduced in OC-/- at several time points. Mouse Osteocalcin injected into OC-/- mice decreased the glucose level. Our results confirm the role of OC in glucose metabolism and insulin sensitivity and demonstrate a role in insulin secretion in older male mice on a C57BL/6J background. Differences in background, age, or experimental procedures could explain controversial results. A delayed onset of the effect of OC on glucose metabolism at 9.5 months in male C57BL/6J mice highlights the importance of background on phenotype. Consideration of genetic background and age may be beneficial for human studies on osteocalcin and glucose homeostasis and may be relevant to the elderly where osteocalcin is reduced.
Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous *** recent years,BDNF has received considerable attention f...
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Discovered in pig brains in 1982,the brain-derived neurotrophic factor(BDNF)is one of the most studied and characterized neurotrophins in the central nervous *** recent years,BDNF has received considerable attention for its importance in the development and maintenance of normal brain *** is because BDNF plays an important role in crucial functions of the nervous system,such as the survival,differentiation,and maturation of neurons and glial cells as well as the actions of neuroprotection in adverse conditions,such as glutamatergic overstimulation,cerebral ischemia,hypoglycemia,and neurotoxicity(Kowiański et al.,2018).
While today, it might seem absurd to hear anyone claim that stress does not alter all aspects of the human experience, including behavioral, cognitive, affective, and physiological processes. Dr. Janice Kiecolt-Glaser...
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While today, it might seem absurd to hear anyone claim that stress does not alter all aspects of the human experience, including behavioral, cognitive, affective, and physiological processes. Dr. Janice Kiecolt-Glaser started her career at a time when stress was primarily considered a neuroendocrine response with cardiovascular repercussions. She was part of a small group of innovative scientists who began to push the boundaries of stress research - many contemporary immunologists and virologist disputed their early results in 1980s and 90s - and, yet, they persevered by connecting psychological stress to altered immune function via stress-related neuroendocrine changes. As a clinical psychologist, she focused mainly on human research studies to advance the field of psychoneuroimmunology throughout her career. Her research demonstrates how adversity and psychosocial aspects of human experience alter physiological functioning, primarily immune, and health or, in other words, the embodiment of our lived experiences. This short review is a contextualized synthesis of Dr. Kiecolt-Glaser's key contributions to the fields of psychoneuroimmunology and health psychology and her influence on my present day thinking and research approaches, as well as potential steps forward in our postpandemic world.
The mechanism of perchlorate resistance of the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 was investigated by assessing whether the pathways associated with its desiccation tolerance might play a role again...
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The mechanism of perchlorate resistance of the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 was investigated by assessing whether the pathways associated with its desiccation tolerance might play a role against the destabilizing effects of this chaotropic agent. During 3 weeks of growth in the presence of 2.4 mM perchlorate, an upregulation of trehalose and sucrose biosynthetic pathways was detected. This suggested that in response to the water stress triggered by perchlorate salts, these two compatible solutes play a role in the stabilization of macromolecules and membranes as they do in response to dehydration. During the perchlorate exposure, the production of oxidizing species was observed by using an oxidant-sensing fluorochrome and determining the expression of the antioxidant defense genes, namely superoxide dismutases and catalases, while the presence of oxidative DNA damage was highlighted by the over-expression of genes of the base excision repair. The involvement of desiccation-tolerance mechanisms in the perchlorate resistance of this desert cyanobacterium is interesting since, so far, chaotropic-tolerant bacteria have been identified among halophiles. Hence, it is anticipated that desert microorganisms might possess an unrevealed capability of adapting to perchlorate concentrations exceeding those naturally occurring in dry environments. Furthermore, in the endeavor of supporting future human outposts on Mars, the identified mechanisms might contribute to enhance the perchlorate resistance of microorganisms relevant for biologically driven utilization of the perchlorate-rich soil of the red planet.
Endometrosis in mares is a disease resulting from chronic inflammation characterized by peri glandular fibrosis. There is no effective treatment so far, which opens the door for exploring the use of stem cells as a ca...
Endometrosis in mares is a disease resulting from chronic inflammation characterized by peri glandular fibrosis. There is no effective treatment so far, which opens the door for exploring the use of stem cells as a candidate. Transforming growth factor beta (TGF beta ) is crucial for the establishment and progression of fibrosis in mare's endometrosis. We aimed to develop regenerative approaches to treat endometrosis by using mesenchymal stem cells (MSC), for which understanding the effect of TGF beta on exogenous MSC is crucial. We isolated and characterized equine adipose MSC from six donors. Cells were pooled and exposed to 10 ng/ml of TGF beta for 0, 4, and 24 h, after which cells were analyzed for proliferation, migration, mesodermal differentiation, expression of fibrosis-related mRNAs, and prostaglandin E2 secretion. At 24 h of exposition to TGF beta , there was a progressive increase in the contraction of the monolayer, leading to nodular structures, while cell viability did not change. Exposure to TGF beta impaired adipogenic and osteogenic differentiation after 4 h of treatment, which was more marked at 24 h, represented by a decrease in Oil red and Alizarin red staining, as well as a significant drop (p < 0.05) in the expression of key gene regulators of differentiation processes ( PPARG for adipose and RUNX2 for osteogenic differentiation). TGF beta increased chondrogenic differentiation as shown by the upsurge in size of the resulting 3D cell pellet and intensity of Alcian Blue staining, as well as the significant up-regulation of SOX9 expression (p < 0.05) at 4 h, which reached a maximum peak at 24 h (p < 0.01), indicative of up-regulation of glycosaminoglycan synthesis. Preconditioning MSC with TGF beta led to a significant increase (p < 0.05) in the expression of myofibroblast gene markers aSMA, COL1A1, and TGF beta at 24 h exposition time. In contrast, the expression of COL3A1 did not change with respect to the control but registered a significant d
alpha-Hydroxytropolones (alpha HTs) have potent antiviral activity against herpes simplex virus-1 and -2 (HSV-1 and HSV-2) in cell culture, including against acyclovir-resistant mutants, and as a result have the poten...
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alpha-Hydroxytropolones (alpha HTs) have potent antiviral activity against herpes simplex virus-1 and -2 (HSV-1 and HSV-2) in cell culture, including against acyclovir-resistant mutants, and as a result have the potential to be developed as antiviral drugs targeting these viruses. We recently described a convenient final-step amidation strategy to their synthesis, and this was used to generate 57 amide-substituted alpha HTs that were tested against hepatitis B virus. The following manuscript describes the evaluation of this library against HSV-1, as well as a subset against HSV-2. The structure-function analysis obtained from these studies demonstrates the importance of lipophilicity and rigidity to alpha HT-based anti-HSV potency, consistent with our prior work on smaller libraries. We used this information to synthesize and test a targeted library of 4 additional amide-appended alpha HTs. The most potent of this new series had a 50% effective concentration (EC50) for viral inhibition of 72 nM, on par with the most potent alpha HT antivirals we have found to date. Given the ease of synthesis of amide-appended alpha HTs, this new class of antiviral compounds and the chemistry to make them should be highly valuable in future anti-HSV drug development.
The increase in the number of authors per article is a well-documented phenomenon across various academic disciplines. While prior studies have examined this trend in specific fields and countries, they in most cases ...
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The increase in the number of authors per article is a well-documented phenomenon across various academic disciplines. While prior studies have examined this trend in specific fields and countries, they in most cases did not compare the increase in the number of authors between countries. While it has previously shown that the number of authors in neuroscience publications has risen in the G10 countries, no study has yet addressed whether it reflects a global trend in the field. To address this gap, we quantified the global trend in the number of authors in neuroscience publications from 2001 to 2022. Our findings reveal a consistent increase in authorship across nearly all the countries examined. Italy ranks highest in terms of average authorship per article, while Ukraine ranks the lowest. On the other hand, China shows the largest increase in authorship over the years, followed by Norway and Egypt. South Korea is the only country showing a slight decreasing trend rather than growth. These results contribute to a better understanding of authorship patterns in neuroscience and can stimulate further investigations on the reasons behind such an increase in terms of socio-economic factors, the need for collaborative efforts in some fields, or, on the negative side, the effect of utilitarian reasons to meet career evaluation criteria.
作者：
Newton, HadleyCUNY
Grad Ctr PhD Program Art Hist New York NY 10016 USA
During its twelve-year existence from 1974 to 1986, the arts gallery Just Above Midtown (JAM) occupied spaces in three disparate buildings in three distinct districts of Manhattan: in Midtown on West 57th Street;then ...
During its twelve-year existence from 1974 to 1986, the arts gallery Just Above Midtown (JAM) occupied spaces in three disparate buildings in three distinct districts of Manhattan: in Midtown on West 57th Street;then in Tribeca;and, finally, also Downtown, in SoHo. This article considers the role of architecture in the production of the gallery as a Black artistic, commercial, and social space. Beyond the physical structures and neighborhoods that JAM occupied, changes made to the spaces by JAM and the reflections of gallery administrators and artists are also considered. The gallery's multiple built environments ultimately reveal a metaphorical transformation of JAM's ambitions. With each physical manifestation, JAM moved closer toward its aspiration of realizing a space that supported the complete self-determination of its artists.
Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'ti...
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Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether they display learning dynamics required for encoding different temporal contexts. To explore this, we developed a new behavioral paradigm requiring mice to distinguish temporal contexts. Combined with methods for cellular resolution calcium imaging, we found that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we found that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we found evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience. The authors examine the role of medial entorhinal cortex (MEC) in learning complex timing behavior. MEC inactivation disrupts task learning, and MEC time cells display context-dependent dynamics that evolve over learning and predict timing behavior.
A theoretical study of the formation of carbamic acids of pyrazole and indazole has been carried out using DFT computational methods. The effects of the substituents and the solvent (using explicit and implicit solven...
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A theoretical study of the formation of carbamic acids of pyrazole and indazole has been carried out using DFT computational methods. The effects of the substituents and the solvent (using explicit and implicit solvent models) have been considered. In addition, the deprotonation of the carbamic acid and its influence on the stability of the system has been calculated. In the neutral systems, only the formation of indazole-1-carbamic acid derivatives is favored vs. the non-covalent complexes between pyrazole or indazole with CO2. The deprotonation of the carbamic acid highly stabilizes the system preventing its dissociation.
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