cssi/SciSciGPT-SciSciNet huggingface dataset:
Follicular steroidogenesis: effect of reproductive condition.

Follicular steroidogenesis has been investigated extensively in nonpregnant animals. To determine if follicular steroidogenesis is altered during pseudopregnancy or pregnancy, large Graafian follicles (1.5-2.0 mm) were isolated from nonpregnant (NP), pseudopregnant (PSP) Days 7 (7PSP) and 15 (I5PSP)l and pregnant (P) IDays 7 (7P), 15 (15P) and 28 (28P)l rabbits and placed in perifusion chambers. After the establishment of a basal steroid output, follicles were stimulated with LH (100 ng, NIH-S20):FSH (50 ng, 50.4 X NIH-FSH-S1; Papkoff). Samples were collected continuously at 20 mm intervals and assayed for progesterone (P4), testosterone (T) and estradiol17a (E). Steroid concentrations are expressed as pg/follicle/20 mm. The secretion of P4 by unstimulated follicles was similar for all groups; however, differences were observed after LH:FSH stimulation. With increasing length of PSP or P, follicles secreted significantly less P4. The values for NP, 7PSP and 7P were different (P<0.01) from those of 15PSP and 15P, and 15P was different from 28P (P<0.025), whereas E secretion by NP was greater (P<0.001) than for PSP and P groups. After treatment with LH:FSU, T and E secretion by NP was elevated (P<0.025) over PSP and P. There were no differences among PSP and P groups, except that stimulated follicles of 28P group secreted significantly less T than did those of 7P or 15P groups (P<0.005). Serum P4 for NP was 0.21 ng/ml, whereas PSP and P rabbits had concentrations ranging from 6.83 to 17.86 nglml. Luteal P4 content was not significantly different for any groups, varying from 77.4 to 161.3 ng/mg protein. To ascertain if the presence of elevated serum P4 during PSP and P alters follicular steroidogenesis, follicles of NP rabbits were incubated with various concentrations of P4 (101 ng/ml-104 ng/mI) or its vehicle, then placed in a perfusion system and basal and LH-stimulated P4 and E secretion determined. Incubation of follicles in 101 or 102 ng/ml P4 did not alter subsequent follicular secretion of P4 from that of controls; 10#{176} and i0� ng/ml P4 significantly suppressed P4 secretion by perifused follicles. In contrast, LU-stimulated E secretion was suppressed by all
Collaboration and Simulation: Striving for Obstetric Excellence With the Emergency Department

Professional Issues Poster Presentation Purpose for the Program To coordinate the obstetric (OB) rapid response team with the emergency department trauma team of a busy community hospital. Attendance by OB and emergency staff at an Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) webinar, Perinatal Code Management, sparked a lively dialogue from which evolved a plan for simulation. A policy on management of the OB patient for the emergency department worked well in most situations. The focus was to fine‐tune the actual response times and process. How do we work together? Is it possible to deliver a newborn via emergency cesarean within the recommended 5 minutes after cardiac arrest? Because it could be applied to the emergency department, simulation often was used on the OB unit for staff training of critical situations. Proposed Change When the OB team responds to the emergency department in critical situations, coordination of both interdisciplinary teams is important for best patient outcomes and coordinated emergency response. Training most often occurs at department levels; this silo training can lead to challenges between the teams. Implementation, Outcomes, and Evaluation Coordinators first met to identify current process, team members, best practice, and purpose of the simulation. The multidisciplinary team participants identified included members from the emergency department, labor and delivery, neonatal intensive care unit, and other ancillary departments. The following education items were identified for presimulation review: communication, team purposes, roles, and equipment. A scenario was developed for the simulation that incorporated a pregnant female who had been in a motor vehicle accident and was experiencing cardiac arrest after admission to the emergency room. The debriefing after the simulations was used to identify elements that went well and opportunities for improvement. Initial notification of the teams worked well, as did management of patient care. Some opportunities identified were access and use of equipment, wayfinding, critical times, and communication. As a result of these findings, projects were assigned to specific team members to eliminate gaps. Subsequent simulations were planned to test these changes. Implications for Nursing Practice Two separate critical response teams working together bring differences in communication and processes that must be identified and understood by all participants to promote true interdisciplinary/interspecialty coordination. Teams who normally function well in rapid response situations may react differently when taken out of familiar environments. The OB department staff was familiar with the process of unit simulations; however, the emergency department primarily used simulation for large, emergency management drills. Crew resource management processes were used for communication and identification of roles. Additional simulations are planned using additional patient situations that require support by the OB rapid response team (e.g., stroke).
Toward a cure for chronic myeloid leukemia.

A diagnosis of chronic myeloid leukemia (CML) remains unwelcome news. Thanks to imatinib, however, the majority of newly diagnosed patients with chronic phase CML achieve a complete cytogenetic response (CCyR) and can expect long-term survival, often without major side effects ([1][1]).
Arsenic-rich GaAs(0 0 1) surface structure

Abstract This article discusses the past 40 years of research covering the equilibrium thermodynamic properties of the arsenic-rich GaAs(0 0 1) surface, which is the starting surface for producing the majority of optoelectronic devices worldwide. A coherent picture of the observed surface structures, theoretical calculations, and experimental results will be presented. The interplay in surface-free-energy-reduction between reconstruction transformation and roughening is now well understood for the GaAs(0 0 1) surface and will be discussed. The recent confirmations of the structural models for the ( 2 × 4 ) and c( 4 × 4 ) reconstructions as well as the discovery of preroughening aid in this understanding.
Tentacled snakes turn C-starts to their advantage and predict future prey behavior

Fish are elusive prey with a short-latency escape behavior--the C-start--initiated to either the left or right by a "race" between 2 giant Mauthner neurons in the fish brainstem. Water disturbances usually excite the ipsilateral neuron, which massively excites contralateral motor neurons, resulting in a rapid turn away from striking predators. Here, it is reported that tentacled snakes (Erpeton tentaculatus) exploit this normally adaptive circuitry by feinting with their body, triggering the Mauthner cell that is furthest from their head milliseconds before a ballistic strike is initiated. As a result, fish that were oriented parallel to the long axis of the snake's head most often turned toward the approaching jaws, sometimes swimming directly into the snake's mouth. When strikes were instead directed at fish oriented at a right angle to the snake's head, snakes anticipated future fish behavior by striking to where fish would later be if they escaped from the snake's body feint, which fish usually did. The results provide an example of a rare predator taking advantage of a prey's normally adaptive escape circuitry and suggest that the snake's sensory-motor system is adapted to predict future behavior.
Kinetic crystallography by Raman microscopy.

Abstract Raman spectra, obtained using a Raman microscope, offer a unique and incisive approach to follow interactions and reactions inside a single crystal under soak-in or soak-out conditions. The utility of this approach derives from the finding that the Raman spectra from single macromolecular crystals, under normal (non-resonance) conditions, are extremely stable, with a low “light background,” and provide ideal platforms for Raman difference spectroscopy. In turn, this allows the interrogation of sub-molecular changes in very large and complex macromolecular environments. There is often great synergy with X-ray crystallography, with the Raman spectroscopist providing crystallography colleagues with the best soak-in conditions to generate a targeted intermediate for flash freezing and X-ray analysis. On the other hand, X-ray structures at points along a reaction pathway provide invaluable benchmarks for interpreting the Raman data from populations seen by Raman to be changing in real-time. These principles will be illustrated by two reactions: the first involves a complex, branching reaction pathway underlying the inhibition of β-lactamases by clinically important pharmaceutical compounds, where different combinations of drug and enzyme function in different regions of the pathway. The second shows how temporal data can be derived for several events in the initiation step of RNA synthesis—more specifically, when one GTP molecule is joined to one ATP molecule to form a G∙A dimer in the active site of a 115,000 Dalton crystalline RNA polymerase. Finally, we will summarize the extension of Raman microscopy to nucleic acid crystals and the information that has been obtained for RNA-based enzymes. This article is part of a Special Issue entitled: Protein Structure and Function in the Crystalline State.
Changing Patterns of Tobacco and Alcohol Co-Use by Gender in the United States, 1976-2010

Background Smoking is a serious health concern both globally and in the U.S. Because drinking amplifies the negative health effects of smoking, the high association of these behaviors is an additional source of population morbidity. However, very little is known about trends in the co-use of smoking and drinking over time. Objective To describe trends in tobacco use, alcohol use, and their co-use among U.S. youth, and to separate out trends in the association of smoking and drinking from trends in their marginal distributions. Methods We use data on the smoking and drinking behaviors of 12th graders from 1976 to 2010 in the Monitoring the Future study to examine trends in smoking, drinking, and co-use separately by gender. In each year we estimate the degree of co-use attributable to tobacco and alcohol use probabilities as well as the association between tobacco and alcohol use. Results Although the prevalence of tobacco and alcohol co-use has declined over time, the association of the two has increased. This association accounts for an increasing proportion of the co-use of tobacco and alcohol. Conclusion We conclude that co-users of tobacco and alcohol are an increasingly select subpopulation. This suggests that continued decreases in the contribution of substance use to population health and mortality may not continue apace.
Role Thoery and Social Life

Systematic observation of organisms in their natural environments has always been important in science. Observed regularities in patterns of behavior in animals, including the human ones, are frequently the outcomes which scientists. want to describe precisely, classify, understand, explain, and predict. While explanation and prediction are the ultimate goals of science, the penultimate goals of description, classification, and understanding are necessary precursors which prove to be quite challenging in themselves. The ethnographic tradition in anthropology and sociology has produced documentation of similarities and differences in behavior between and within groups which gave rise to the concepts of culture, role, status, and norms. Such constructs do not explain observed patterns of human behavior, but they do provide essential and useful tools for describing the social contexts in which human beings interact. In emphasizing the social context of behavior, this chapter complements the other chapters in this Unit which focus primarily on intraindividual aspects of behavior.
Advances in the molecular dynamics flexible fitting method for cryo-EM modeling.

Abstract Molecular Dynamics Flexible Fitting (MDFF) is an established technique for fitting all-atom structures of molecules into corresponding cryo-electron microscopy (cryo-EM) densities. The practical application of MDFF is simple but requires a user to be aware of and take measures against a variety of possible challenges presented by each individual case. Some of these challenges arise from the complexity of a molecular structure or the limited quality of available structural models and densities to be interpreted, while others stem from the intricacies of MDFF itself. The current article serves as an overview of the strategies that have been developed since MDFF’s inception to overcome common challenges and successfully perform MDFF simulations.
Nucleic Acid Modifications in Regulation of Gene Expression

Nucleic acids carry a wide range of different chemical modifications. In contrast to previous views that these modifications are static and only play fine-tuning functions, recent research advances paint a much more dynamic picture. Nucleic acids carry diverse modifications and employ these chemical marks to exert essential or critical influences in a variety of cellular processes in eukaryotic organisms. This review covers several nucleic acid modifications that play important regulatory roles in biological systems, especially in regulation of gene expression: 5-methylcytosine (5mC) and its oxidative derivatives, and N(6)-methyladenine (6mA) in DNA; N(6)-methyladenosine (m(6)A), pseudouridine (Ψ), and 5-methylcytidine (m(5)C) in mRNA and long non-coding RNA. Modifications in other non-coding RNAs, such as tRNA, miRNA, and snRNA, are also briefly summarized. We provide brief historical perspective of the field, and highlight recent progress in identifying diverse nucleic acid modifications and exploring their functions in different organisms. Overall, we believe that work in this field will yield additional layers of both chemical and biological complexity as we continue to uncover functional consequences of known nucleic acid modifications and discover new ones.
Genic heterozygosity and rate of speciation

The hypothesis is proposed that mean level of heterozygosity is functionally re- lated to rate of speciation in evolutionary phylads. Under this hypothesis, phylads which speciate more rapidly do so because of increased level of within-species genetic variability which is then available to conversion to species differences under appropriate ecological or environmental conditions. An important corollary is that rate of speciation could be limited in phylads with low genetic variability, irrespective of environmental considerations. This hypothesis has been tested with respect to electrophoretically detectable variation in products of structural genes in two families of North American fishes characterized by grossly different rates of speciation. Totals of 69 species of the highly speciose Cyprinidae, and 19 species of the relatively depauperate Centrarchidae, were assayed for mean level of hetero- zygosity at 11-24 genetic loci. Since Cyprinidae and Centrarchidae exhibit on the average nearly identical levels of genic variation (H = 0.052 ? 0.004, and H = 0.049 + 0.009, respectively), the hypothesis that level of heterozygosity affects rate of speciation in these fishes is not supported. Nonetheless, the amount of genic variability in both Cyprinidae and Centrarchidae is large, comparable to mean levels in previously studied vertebrates. The great wealth of genome variability, reflected in the electrophoretic variation present in virtually all outcrossing organisms, apparently can accommodate considerable flexibility in rate and pattern of evo- lutionary response to the various environmental regimes challenging organisms.
Characteristics of L-alanine uptake in freshly isolated hepatocytes of elasmobranch Raja erinacea

The specific transport mechanisms that mediate the hepatic uptake of L-[3H]alanine and of an unnatural homologue, alpha-[14C]methylaminoisobutyric acid (MeAIB), were analyzed in hepatocyte suspensions from Raja erinacea. Aminooxyacetate, an inhibitor of aminotransferase activity was used to prevent alanine metabolism. After 3 h of incubation with either 0.5 mM alanine or MeAIB, hepatic concentrations of these amino acids were significantly higher in the presence than absence of Na+ (8 vs. 1 and 1 vs. 0.1 mM, respectively). Kinetic studies indicated that both alanine and MeAIB transport occurred via sodium-dependent saturable mechanisms. [14C]MeAIB uptake was completely inhibited by excess L-alanine. Uptake of [3H]alanine was inhibited by a 40-fold excess of serine and cysteine (53-54%), by MeAIB and methylalanine (26-31%), and by leucine (14%), whereas D-alanine, beta-alanine, taurine, and glutamate had no effect. Insulin and glucagon were unable to stimulate [3H]alanine uptake. Glucose release from hepatocytes was unaffected by 10 mM alanine or 2 mM aminooxyacetate, indicating that alanine is not a major gluconeogenic precursor in this marine elasmobranch. These results suggest that uptake of L-alanine by skate hepatocytes occurs predominantly via a sodium-dependent system, with properties similar to those exhibited by the ASC neutral amino acid transport system previously characterized in Ehrlich ascites tumor cells and rat hepatocytes.
Headache with Benign Alternating Hemiplegia

An 8-year-old boy with benign familial nocturnal alternating hemiplegia of childhood (BNAHC) and severe headache and vomiting during episodes is reported from the University of Rochester, NY.
Differential Effects of Aspergillus flavus and A. parasiticus on Survival of Heliothis zea (Boddie) and Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) Reared on Inoculated Diet

Larvae of the corn earworm, Heliothis zea (Boddie), and the fall armyworm, Spodoptera frugiperda (J. E. Smith), were reared under laboratory conditions on a diettreated with Aspergillus flavus Link or A. parasiticus Speare. Results indicate A. parasiticus is more toxic to the corn earworm than A. flavus when larvae are not transferred daily. The larval stage of the corn earworm sustains more toxic effects than either the pupal or adult stages. When larvae were transferred to fresh diet daily after initial exposure to treated diet, neither the corn earworm nor the fall armyworm showed any significant pathogenic effects ( P = 0.01). Overall, toxicity was more evident than pathogenicity.
Analysis of the Clinical Significance and Influencing Factors of Coronary Collateral Circulation in Patients with Chronic Total Occluded Coronary Artery Disease

OBJECTIVE To study the clinical significance of coronary collateral circulation in patients with chronic total occluded(CTO) coronary artery disease and factors influencing the development of collateral channel.METHODS 356 patients with total occluded coronary artery from Oct.2013 to Dec.2014 in our hospital were selected.157 patients were diagnosed as the CTO.According to the results of coronary angiography,patients were divided into two groups by Rentrop method,namely unsatisfactory collateral circulation group and satisfactory collateral circulation group.The clinical data and pathological features of the patients were compared.RESULTS Compared with patients in unsatisfactory collateral circulation group:patients in satisfactory collateral circulation group were younger(P0.05),the proportion of patients with previous myocardial infarction patients was lower(P0.05),the proportion of patients with moderate and severe smoking history was lower(P0.01),uric acid levels and fasting plasma glucose levels of patients were lower(both P0.05),the proportion of patients with ostial occlusion and excessive tortuosity were lower(both P0.05).Logistic regression analysis revealed that history of moderate to severe smoking and high level of blood glucose were independent predictors of poor condition of coronary collateral circulation(both P0.05).CONCLUSIONS History of moderate to severe smoking and high level of blood glucose were independent predictors of poor coronary collateral circulation.
Thinking About Thinking About the Army's Future: Paradigms and the Wicked Problem of 'Landpower'

The ongoing effort among the U.S. ground force concept development communities to describe the strategic value and role of land-based military power in the future is an opportunity to think about how these institutions go about thinking of wicked problems — and why. Wicked problems have no definable problem statement, no objectively correct answer, and layers of uncertainty and unpredictability that make efforts to “solve” them, especially through bureaucratic consensus, naive. Developing successful approaches to these wicked problems is impossible if we believe existing paradigms already provide the conventional frames, references, and processes for mechanically answering these concerns. This essay suggests that the landpower stakeholders should view this period of uncertainty in pre-paradigm terms. That new frame has three immediate implications: a reconsideration of whom the stakeholders ought to include in the broader community of interest; a resetting of expectations about what is achievable by the existing concept development process; and a realignment of the efforts used to study these wicked problems.
A qualitative study investigating the ethical decision making process: A proposed model

Abstract We describe the results of a qualitative research study involving senior military and civilian leaders of the Department of Defense. We followed a grounded theory approach in proposing an inductive model which integrates the theories of ethics, decision making, and leadership with the experiences and formal training of our respondents. Our model accomplishes two purposes. First, it illustrates the complex nature of the intervening steps between moral awareness and ethical/unethical decision outcomes. Second, it depicts a process for developing ethical decision making expertise. The proposed model is intended to stimulate educators, training and development professionals, and practicing leaders to design and implement programs to develop ethical leader decision making.
A data-driven approach to precise linearization of nonlinear dynamical systems in augmented latent space

A new approach to linearize a complex nonlinear dynamical system using latent variables is presented in this paper. It is shown that a class of nonlinear dynamical systems behaves linearly when it is recast in a high-dimensional latent variable space. Independent state variables are augmented by adding auxiliary variables that are needed for describing constitutive laws of individual system components, which may be nonlinear. The augmented space is then reduced to a minimum dimensional space through latent variable analysis of the data created with simulation of the original nonlinear dynamic equations. Based on Bond-Graph model of a dynamical system, the minimum-order of the augmented latent space that can completely recover all the original data points is obtained. A method for further truncating the latent variables for real-time computation is also obtained. Numerical simulations demonstrate that the proposed method can produce the precise linearization of a nonlinear system, strikingly different from the standard linear approximation using Taylor expansion.
Literature-filing system for vulvar conditions

Objective To develop a classification system for the retrieval of stored material on various vulvar conditions. Study design The major subject areas of vulvar conditions and management were identified. They were further classified into categories and subcategories. A numbering system was chosen for coding. The information was formatted to allow retrieval from the Internet in a framework ready for label printing. Results The classification system developed provides guidelines that are useful in making retrieval of stored material on various vulvar conditions more efficient. It can be expanded and personalized to fit the practitioner's needs and can be obtained from the Internet in the following manner by opening Netscape and entering the location: http:/(/)www.med.umich.edu/obgyn/vulva/ vulvalit.html. The filing system was formatted to allow standard, 5266, file-folder-sized label sheets to be inserted into the printer, allowing access to pretyped labels. A total of 464 labels will be printed. Conclusion This system for retrieving vulvar information will be useful to many people, including clinicians, educators and researchers. The information is easily obtained from the Internet and printed in label form. It aids in the development of a system for life-long learning.
Dance floor clustering: food-anticipatory behavior in persistent and reticent honey bee foragers

The honey bee time memory enables foragers to return to a profitable food source in anticipation of the time of day at which they previously collected food from that source. The time memory thus allows foragers to quickly resume exploiting a source after interruption, at the appropriate time of day, without the costs associated with having to rediscover it. A portion of a foraging group (the persistent foragers) will reconnoiter a previously profitable source and may do so for several days. The remaining bees (the reticent foragers) await confirmation of availability before revisiting the source. Recent work has shown that both persistent and reticent bees make extracurricular flights to alternative sources when one food source ceases being productive. Little else, however, is known about reticent foragers. In the present study, we determined that reticent bees congregate near the hive entrance in anticipation of the learned foraging time as do persistent foragers. We then confirmed that the food-anticipatory clustering takes place on the waggle dance floor, as suspected, but also found differences in the number of days that persistent and reticent foragers continue clustering. Finally, we found that persistent foragers had significantly more rewards per day at the source than did reticent foragers, supporting the hypothesis that experience at a food source influences a forager’s decision to become either persistent or reticent. Our findings demonstrate that persistence and reticence are not immutable characteristics of foragers themselves but rather strategies they employ toward different food sources. Much has been learned in recent years about the honey bee time memory and foraging behavior. Receiving scant attention, however, is the phenomenon of forager bees gathering near the hive entrance, anticipating the time of day when previously productive food sources become available. We show that both persistent and reticent bees (foragers that do and do not investigate the source, respectively) congregate on the waggle dance floor at the appropriate time of day, but, in the absence of food at the source, persistent bees continue to show this behavior a day or two longer than reticent bees do. We also show that experience with the source influences the decision to become persistent or reticent. Our results reveal how foraging experience influences the individual bee’s decision making, thereby providing insights into how foragers are reallocated efficiently among different resources in the environment.
Management of a Concealable Stigmatized Identity: A Qualitative Study of Concealment, Disclosure, and Role Flexing Among Young, Resilient Sexual and Gender Minority Individuals

Disclosure of a sexual or gender minority status has been associated with both positive and negative effects on wellbeing. Few studies have explored the disclosure and concealment process in young ...
The Efficacy and Safety Profile of Ocriplasmin in Vitreomacular Interface Disorders

Vitreomacular adhesion (VMA) describes the adhesion of the posterior hyaloid face to the inner retina in any part of the macula. This can arise after incomplete separation of the posterior vitreous cortex from the macula during vitreous liquefaction. While the VMA may resolve spontaneously, a strong and persistent adhesion can lead to a variety of anatomical changes, including vitreomacular traction (VMT) and macular hole (MH). Both conditions can present with metamorphopsia and decreased vision. In cases of symptomatic VMT and full-thickness macular hole, pars plana vitrectomy has long been the standard of care. However, due to the possible surgical complications and need for postoperative care, many have searched for non-surgical options via pharmacologic vitreolysis. Ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) is a recombinant protease approved in October 2012 for the treatment of symptomatic vitreomacular adhesion (VMA). There have been conflicting views on the safety of Ocriplasmin with changes in the ellipsoid zone seen on OCT and changes seen on ERG indicating photoreceptor damage. This publication reviews the efficacy and safety of ocriplasmin injection for VMA based on previously published data.
Validation of a Single-Time-Point Measurement of Total Abdominal Counts to Simplify Small Bowel and Colon Transit Analyses

The SNMMI EANM Procedure Guide on Gastrointestinal Transit currently indicates that the mean of total abdominal counts of seven time points (0-360 min) are used to define the total abdominal counts for bowel transit studies. The purpose of this study was to investigate the variability of total abdominal counts during the initial six hours of bowel transit and to determine if a simplified, single time point measurement can be used. METHODS: Thirty consecutive bowel transit studies were retrospectively analyzed. Patients received an oral dose of 4.6 MBq(125 µCi) 111In-DTPA in 300 cc of water together with a standard egg white solid-phase, gastric emptying meal to measure small bowel and colon transit. 111In-DTPA geometric mean and decay corrected total abdominal counts obtained at 0, 30, 60, 120, 180, 240, 300, and 360 minutes post meal ingestion were analyzed. The coefficient of variation (CV) was used to determine the variability of the mean total abdominal counts. Slope of the regression line, Student’s t-test and a Pearson Product-Moment Correlation Coefficient (PCC) were also calculated to determine the correlation of total abdominal counts at each time point compared to the mean of all time points. RESULTS: The mean CV of total abdominal counts of each patient was 3.3% with a range of 1.1% to 6.3%. The mean of the slope of the regression line of the total abdominal counts of the patients was -0.001±0.003. There was no significant difference between the measured slope of the regression line compared to a line with a slope of 0 (p>0.05). Comparing the counts at each time to the mean counts, there was no significant difference (p>0.05). The PCC of each of the counts showed a significant and strong correlation between each interval and the mean total abdominal counts (p
Cannabinoid Receptor Interacting Protein 1a Competition with β-Arrestin for CB1 Receptor Binding Sites

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminal-associated protein that alters CB1R interactions with G-proteins. We tested the hypothesis that CRIP1a is capable of also altering CB1R interactions with β-arrestin proteins that interact with the CB1R at the C-terminus. Coimmunoprecipitation studies indicated that CB1R associates in complexes with either CRIP1a or β-arrestin, but CRIP1a and β-arrestin fail to coimmunoprecipitate with each other. This suggests a competition for CRIP1a and β-arrestin binding to the CB1R, which we hypothesized could attenuate the action of β-arrestin to mediate CB1R internalization. We determined that agonist-mediated reduction of the density of cell surface endogenously expressed CB1Rs was clathrin and dynamin dependent and could be modeled as agonist-induced aggregation of transiently expressed GFP-CB1R. CRIP1a overexpression attenuated CP55940-mediated GFP-CB1R as well as endogenous β-arrestin redistribution to punctae, and conversely, CRIP1a knockdown augmented β-arrestin redistribution to punctae. Peptides mimicking the CB1R C-terminus could bind to both CRIP1a in cell extracts as well as purified recombinant CRIP1a. Affinity pull-down studies revealed that phosphorylation at threonine-468 of a CB1R distal C-terminus 14-mer peptide reduced CB1R-CRIP1a association. Coimmunoprecipitation of CB1R protein complexes demonstrated that central or distal C-terminal peptides competed for the CB1R association with CRIP1a, but that a phosphorylated central C-terminal peptide competed for association with β-arrestin 1, and phosphorylated central or distal C-terminal peptides competed for association with β-arrestin 2. Thus, CRIP1a can compete with β-arrestins for interaction with C-terminal CB1R domains that could affect agonist-driven, β-arrestin-mediated internalization of the CB1R.
Executive functions predict weight loss in a medically supervised weight loss programme

SummaryBackground Deficits in executive functions are related to poorer weight loss after bariatric surgery; however, less is known about the role that these deficits may play during participation in nonsurgical weight loss programmes. This study examined associations between objectively measured executive functions and weight loss during participation in a medically supervised weight loss programme. Methods Twenty-three adult patients (age 50.4 ± 15.1, BMI 44.2 ± 8.8, 68% female, 92% White) enrolled in a medically supervised weight loss programme, involving prescription of a very low calorie diet and strategies to change eating and activity behaviours, underwent comprehensive computerized testing of executive functions at baseline. Weight was obtained at baseline and 8 weeks. Demographic and clinical information were obtained through medical chart review. Results Participants lost an average of 9.8 ± 3.4% of their initial body weight at 8 weeks. Fewer correct responses on a set-shifting task and faster reaction time on a response inhibition task were associated with lower weight loss percentage at 8 weeks after adjusting for age, education and depressive symptoms. There were no associations between performance on tests of working memory or planning and weight loss. Conclusions This study shows that worse performance on a set-shifting task (indicative of poorer cognitive flexibility) and faster reaction times on a response inhibition test (indicative of higher impulsivity) are associated with lower weight loss among participants in a medically supervised weight loss programme. Pre-treatment assessment of executive functions may be useful in identifying individuals who may be at risk for suboptimal treatment outcomes. Future research is needed to replicate these findings in larger samples and identify underlying mechanisms.
Costimulatory Blockade Enhances Engraftment and Prevents Anti-Donor Antibody Generation in Nonmyeloablative Conditioned Prediabetic NOD Mice

Abstract Chimerism induces tolerance to organ and tissue grafts. Although the toxicity of conditioning has been significantly reduced with nonmyeloablative approaches, it would be beneficial to further reduce the intensity of conditioning in organ transplant recipients. Studies in normal mice and autoimmune NOD mice have revealed that the primary role for conditioning is to control host-versus-graft alloreactivity, allowing for immune-based conditioning to establish chimerism. Recent insights into the mechanism of interaction and crossregulation between innate and adaptive immune responses have led to the development of new approaches for immune-based conditioning. We previously demonstrated that preconditioning of diabetes-prone NOD mice with anti-CD8 monoclonal antibody (mAb) combined with anti-CD154 mAb allowed chimerism to be established with 550 cGy total body irradiation (TBI). Here we investigated whether combined costimulatory blockade can improve the nonmyeloablative regimen and enhance bone marrow chimerism in autoimmune recipients. Prediabetic NOD (H-2d) mice were treated with anti-CD8 antibody (day -3). After 500 cGy TBI (day 0), recipient NOD mice were transplanted with 30 × 106 B10.BR (H-2k) bone marrow cells (day 0) and received anti-CD154, anti-OX40L, and anti- inducible co-stimulatory molecule (ICOS) mAbs intraperitoneally (IP) (day 0, 1, 2, 3). Chimerism and multilineage analysis were quantitated by flow cytometry. Chimeric animals produced multilineage donor chimerism. While 18 prediabetic NOD mice demonstrated an average PB chimerism of ~37% at 1 month and 61% engraftment, 15 of 18 mice lost PB chimerism by 6 months. NOD mice were then transplanted with B10.BR donor skin grafts 1 month post BM transplant. Flow cytometry cross-match assays were performed to detect anti-donor antibody (Ab) in the sera collected 1 month post skin grafting. 44% of chimeric NOD mice (n=9) accepted their skin grafts for over 90 days, while 100% of non-chimeric animals (n=4) rejected their grafts within 60 days. NOD mice transplanted with B10.BR skin grafts alone rejected their grafts within 2 weeks and generated significantly higher levels of donor-specific Abs (mean fluorescence intensity: 251.2 ± 61.5, P
Assessing Abnormal Uterine Bleeding: Are Physicians Taking a Meaningful Clinical History?

Abstract Introduction: Women with abnormal uterine bleeding (AUB) report significant reductions in quality of life (QOL), which can be attributed in many cases to the fear of embarrassing episodes of bleeding. We performed this study to determine whether or not during clinical encounters physicians addressed the impact of AUB on patient-reported QOL. Materials and Methods: Between October 2008 and May 2009, we conducted a cross-sectional study of members of the American College of Obstetricians and Gynecologists. Surveys were distributed using a mixed method (web- and mail-based) and included questions about physician characteristics and types of questions used when obtaining a clinical history from a patient with AUB. We calculated the proportion of physicians who endorsed asking each type of clinical question with 95% confidence intervals (CIs). Results: Four hundred seventeen questionnaires were returned (52%). Ninety-nine percent (95% CI 98.4%–99.9%) reported always asking a bleeding heaviness questio...
Cortical Representation of Pain and Touch: Evidence from Combined Functional Neuroimaging and Electrophysiology in Non-human Primates

Human functional MRI studies in acute and various chronic pain conditions have revolutionized how we view pain, and have led to a new theory that complex multi-dimensional pain experience (sensory-discriminative, affective/motivational, and cognitive) is represented by concurrent activity in widely-distributed brain regions (termed a network or pain matrix). Despite these breakthrough discoveries, the specific functions proposed for these regions remain elusive, because detailed electrophysiological characterizations of these regions in the primate brain are lacking. To fill in this knowledge gap, we have studied the cortical areas around the central and lateral sulci of the non-human primate brain with combined submillimeter resolution functional imaging (optical imaging and fMRI) and intracranial electrophysiological recording. In this mini-review, I summarize and present data showing that the cortical circuitry engaged in nociceptive processing is much more complex than previously recognized. Electrophysiological evidence supports the engagement of a distinct nociceptive-processing network within SI (i.e., areas 3a, 3b, 1 and 2), SII, and other areas along the lateral sulcus. Deafferentation caused by spinal cord injury profoundly alters the relationships between fMRI and electrophysiological signals. This finding has significant implications for using fMRI to study chronic pain conditions involving deafferentation in humans.
“Never known as anything but an absence, I dare not name him as god:” queer theology and the via negativa

ABSTRACTFarley draws a parallel between the philosophical anti-essentialism of queer theory and the theological anti-essentialism of apophatic theology. She argues that absolutizing interpretations of authority conspire with dogmatic theology to strip reality of its mystery and human beings of their dignity. Greater attention to anti-essentialist theology provides one strategy toward appreciation of plurality, not least queer embodiments of the human adventure.
Effects of a phosphonate anchoring group on the excited state electron transfer rates from a terthiophene chromophore to a ZnO nanocrystal

Terthiophene dyes were synthesized having a carboxylate or a phosphonate moiety at the 2-position which serves as an anchoring group to zinc oxide nanocrystals (ZnO NCs). Electronic absorption and fluorescence measurements, combined with reduction potentials, provided estimates of -1.81 and -1.86 V vs. NHE for the excited state reduction potential of the carboxylate and phosphonate, respectively. Static quenching was observed when the dyes were bound to the surface of acetate-capped ZnO NCs having a diameter of 2.8 nm. Stern-Volmer studies conducted at several dye concentrations established that a minor fraction of the adsorbed dye remained unquenched even at 1 : 1 dye to NC ratios. Adsorption isotherm measurements established that the phosphonate binds more strongly than the carboxylate and that saturation coverage was ∼1.2 dyes per nm2 for both dyes. Ultrafast transient absorption spectroscopic experiments were used to probe excited state dynamics. In the presence of ZnO NCs, disappearance of the singlet excited state of the dye corresponded to appearance of the spectroscopic signature of the oxidized dye with a time constant of 1.5 ± 0.1 and 6.1 ± 0.2 ps, respectively, for the carboxylate and phosphonate dye. The difference in the electron transfer rates was attributed to a larger electronic coupling for the dye having the carboxylate anchoring group.
Draft Genome Sequence of Bacillus velezensis GF610, a Producer of Potent Anti-Listeria Agents.

ABSTRACT Bacillus velezensis GF610 was isolated from soil in Illinois, USA, and found to produce amyloliquecidin GF610, a potent two-component antimicrobial peptide. We report here the GF610 strain draft genome sequence, which contains 4.29 Mb and an overall GC content of 45.91%.
Dietary Folate, B Vitamins and the Brain: The Homocysteine Connection

It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer’s and Parkinson’s diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Deficiencies of vitamins B6 (pyridoxine) and B12 (cobalamin) may also have adverse consequences for the developing and adult nervous systems, by increasing homocysteine levels. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5, 10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair; in mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with B vitamins as a primary means of normalizing homocysteine levels and increasing the healthspan of the nervous system.
Internet Use and Preventive Health Behaviors Among Couples in Later Life: Evidence from the Health and Retirement Study.

Background and objectives The aim of this study was to examine the link between internet use and preventive health behaviors. We focused on couples to examine whether there were cross-partner associations between internet use and preventive health behaviors. Research design and methods The data for this study came from the 2010 and 2012 waves of the Health and Retirement Study and the sample consisted of 5,143 pairs of coupled-individuals. Preventive health behaviors included cancer screenings (mammogram and prostate tests), cholesterol tests, and flu shots. Logistic multilevel actor-partner interdependence models were employed to test the study hypotheses. Results Internet use was associated with a higher likelihood of receiving prostate exams and cholesterol tests for husbands, net of demographic and health characteristics, and insurance status. We found that wives' internet use was associated with a higher likelihood of receiving flu shots and prostate exams for husbands, but husbands' internet use was not associated with wives' preventive health behaviors. Discussion and implications Research linking internet use and preventive health behaviors is important because such behaviors are associated not only with health of the older population but also with substantial reductions in health care expenditures. Our findings suggested that internet use of older adults is associated with their own preventive health behaviors, as well as their spouses' preventive health behaviors. Interventions and programs to facilitate older adults' preventive health behaviors should consider couple-based approaches.
Hobbes: Language and the IS-Ought

Hobbes considers speech — names and their connections — as invention: ‘The most noble and profitable invention’ (EW Will, 18.)1 Speech separates man from the beast, without it there would be no commonwealth and, consequently, no peace. Also, there would be no science and little art. In Leviathan, Hobbes says, ‘The general use of speech, is to transfer our mental discourse, into verbal’ (ibid.). This makes for two benefits which provide a neat distinction between ‘mark’ and ‘sign’. Marks serve the memory of the user; they need not be words nor need they be known to other than him who uses them to remember. Marks suggest the benefit of language including signs, as a mnemotechnical device. Signs have the function of communication. The greater complexity of using signs is suggested by its function. Communication involves the connection and ordering of words one to another with attention to systematic exactness and agreed upon meaning. From the use of language proceed both specific political benefits and entertainments; and, with each of these a corresponding possibility for abuse.
Animal Models and the Implications of Their Use

The introductory chapter to any book concerning animal models of human diseases should not ignore the arguments that have been made against the use of animals in biomedical research. These arguments appear to have two principal components. The first component is an ethnical/moral concern for the rights of animals, which may be viewed as the more fundamental of the two. The second component seeks to dismiss the benefit to humans that has been derived from biomedical research using animals. Generally, a concern for animals underlies both arguments.
Muscle Contraction; Overview

This article is designed to give an overview of the basic molecular components of muscle, outlining its structure and function. Details of the sarcomere and the electrical and mechanical coupling of its elements will provide the basis for understanding the ability of muscle to generate force. The structural portions through which this force is transduced will also be covered. Abnormalities in any of these components can lead to well-defined neuromuscular diseases and wherever possible these pathophysiological correlates are described.