4,348 research outputs found
GIRK2 and GABABR1 Downregulate in Response to TTX as GIRK2, GABABR1, and GABABR2 Are Not Affected by BC Treatment
Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer\u27s, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).
Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will be fewer of them found in the cell to offset the inhibition caused by TTX. However, there was no change in expression for GABABR2. In order to function, GABABR2 and GABABR1 rely on one another. Perhaps the decrease in GABABR1 expression is enough to offset the inhibition by TTX. Prolonged activity excitation of 48 hour BC treatment resulted in no significant change for GABABR1, GABABR2, and GIRK2 expressions. Although their expressions may not have changed, it is possible that their activity could still be increased
Comparison of Maternal Feeding Practices and Child Weight Status in Children from Three Countries
The present study considered three samples of mothers from Brazil, South Korea, and the United States to determine whether mothers demonstrate a consistent pattern of feeding practices associated with child overweight. Participants included 1204 mothers of children 6-10 years old.
Mothers completed questionnaires to report their children's demographics and their feeding practices with the Parent Mealtime Action Scale (PMAS). The South Korean children showed significantly less obesity (10.4%) than children from Brazil (17.0%) or the United States (19.6%). Confirmatory factor analysis for mothers from all three samples revealed good fit for the same nine PMAS dimensions of feeding practice. Hierarchical multiple regression revealed that after taking into account child age and gender, heavier child weight was found associated with more Fat Reduction and less Insistence on Eating by mothers from all three samples. Results from past experimental research suggest that these two maternal feeding practices would be counter-productive for teaching children's self-regulation of diet and weight management. Alternative maternal feeding practices are suggested
Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor
Eya proteins are transcription factors that play pivotal roles in organ formation during development by mediating interactions between Sine Oculis (SO) and Dachshund (DAC). Remarkably, the transcriptional activity of Eya proteins is regulated by a dephosphorylating activity within its Eya domain (ED). However, the molecular basis for the link between catalytic and transcriptional activities remains unclear. Here we report the first description of the crystal structure of the ED of human Eya2 (ED-Eya2), determined at 2.4-angstrom resolution. In stark contrast to other members of the haloacid dehalogenase (HAD) family to which ED-Eya2 belongs, the helix-bundle motif (HBM) is elongated along the back of the catalytic site. This not only results in a structure that accommodates large protein substrates but also positions the catalytic and the SO-interacting sites on opposite faces, which suggests that SO binding is not directly affected by catalytic function. Based on the observation that the DAC-binding site is located between the catalytic core and SO binding sites within ED-Eya2, we propose that catalytic activity can be translated to SO binding through DAC, which acts as a transcriptional switch. We also captured at two stages of reaction cycles-acyl-phosphate intermediate and transition state of hydrolysis step, which provided a detailed view of reaction mechanism. The ED-Eya2 structure defined here serves as a model for other members of the Eya family and provides a framework for understanding the role of Eya phosphatase mutations in disease.-Jung, S.-K., Jeong, D. G., Chung, S. J., Kim, J. H., Park, B. C., Tonks, N. K., Ryu, S. E., Kim, S. J.. Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor. FASEB J. 24, 560-569 (2010). www.fasebj.or
Dietary Cholesterol Promotes Adipocyte Hypertrophy and Adipose Tissue Inflammation in Visceral, But Not Subcutaneous, Fat in Monkeys
Objective—Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates.
Approach and Results—Age-matched, male African Green monkeys (n=5 per group) were assigned to one of three diets containing 0.002 (Lo), 0.2 (Med) or 0.4 (Hi) mg cholesterol/Kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a step-wise manner in visceral, but not subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r2=0.298; n=15; p=0.035). In visceral fat, dietary cholesterol intake was associated with: 1) increased pro-inflammatory gene expression and macrophage recruitment, 2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and 3) increased expression of proteins involved in FC efflux.
Conclusions—Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates
Artificial confocal microscopy for deep label-free imaging
Widefield microscopy methods applied to optically thick specimens are faced
with reduced contrast due to spatial crosstalk, in which the signal at each
point is the result of a superposition from neighboring points that are
simultaneously illuminated. In 1955, Marvin Minsky proposed confocal microscopy
as a solution to this problem. Today, laser scanning confocal fluorescence
microscopy is broadly used due to its high depth resolution and sensitivity,
which come at the price of photobleaching, chemical, and photo-toxicity. Here,
we present artificial confocal microscopy (ACM) to achieve confocal-level depth
sectioning, sensitivity, and chemical specificity, on unlabeled specimens,
nondestructively. We augmented a laser scanning confocal instrument with a
quantitative phase imaging module, which provides optical pathlength maps of
the specimen on the same field of view as the fluorescence channel. Using pairs
of phase and fluorescence images, we trained a convolution neural network to
translate the former into the latter. The training to infer a new tag is very
practical as the input and ground truth data are intrinsically registered and
the data acquisition is automated. Remarkably, the ACM images present
significantly stronger depth sectioning than the input images, enabling us to
recover confocal-like tomographic volumes of microspheres, hippocampal neurons
in culture, and 3D liver cancer spheroids. By training on nucleus-specific
tags, ACM allows for segmenting individual nuclei within dense spheroids for
both cell counting and volume measurements. Furthermore, taking the estimated
fluorescence volumes, as annotation for the phase data, we extracted dry mass
information for individual nuclei. Finally, our results indicate that the
network learning can be transferred between spheroids suspended in different
media.Comment: 35 pages, 6 figure
NLO QCD corrections to tW' and tZ' production in forward-backward asymmetry models
We consider Z' and W' models recently proposed to explain the top
forward-backward asymmetry at the Tevatron. We present the next-to-leading
order QCD corrections to associated production of such vector bosons together
with top quarks at the Large Hadron Collider, for centre-of-mass energies of 7
and 8 TeV. The corrections are significant, modifying the total production
cross-section by 30-50%. We consider the effects of the corrections on the top
and vector-boson kinematics. The results are directly applicable to current
experimental searches, for both the ATLAS and CMS collaborations.Comment: 62 pages, 13 figures, 36 tables. v3 Updated to correspond to Journal
version and incorporate supplementary materia
Neurotoxic syndrome developed after taking sertraline and risperidone
Neuroleptic malignant syndrome and serotonin syndrome share many common clinical features, and the term "Neurotoxic syndrome" can be used when a clear distinction cannot be made between the two. Here we present a case of 19-year-old man who experienced serotonin syndrome caused by sertraline intake, and consecutive neuroleptic malignant syndrome by risperidone. This case suggests that these two syndromes can be concomitantly induced in some patients who are susceptible to these drugs. Clinicians may have to pay close attention to this problem when prescribing drugs to patients who previously showed sensitivity to CNS-acting drugs
Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors
Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants
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