bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of apical membrane organization and V-ATPase regulation in blowfly salivary glands
Authors: Baumann Otto , Bauer Alexandra
Published: March 2013

Secretory cells in blowfly salivary gland are specialized via morphological and physiological attributes in order to serve their main function, i.e. the transport of solutes at a high rate in response to a hormonal stimulus, namely serotonin (5-HT). This study examines the way that 5-HT-insensitive precursor cells differentiate into morphologically complex 5-HT-responsive secretory cells. By means of immunofluorescence microscopy, immunoblotting and measurements of the transepithelial potential changes, we show the following. (1) The apical membrane of the secretory cells becomes organized into an elaborate system of canaliculi and is folded into pleats during the last pupal day and the first day of adulthood. (2) The structural reorganization of the apical membrane is accompanied by an enrichment of actin filaments and phosphorylated ERM protein (phospho-moesin) at this membrane domain and by the deployment of the membrane-integral part of vacuolar-type H+-ATPase (V-ATPase). These findings suggest a role for phospho-moesin, a linker between actin filaments and membrane components, in apical membrane morphogenesis. (3) The assembly and activation of V-ATPase can be induced immediately after eclosion by way of 8-CPT-cAMP, a membrane-permeant cAMP analogue. (4) 5-HT, however, produces the assembly and activation of V-ATPase only in flies aged for at least 2 h after eclosion, indicating that, at eclosion, the 5-HT receptor/adenylyl cyclase/cAMP signalling pathway is inoperative upstream of cAMP. (5) 5-HT activates both the Ca2+ signalling pathway and the cAMP signalling cascade in fully differentiated secretory cells. However, the functionality of these signalling cascades does not seem to be established in a tightly coordinated manner during cell differentation.
Technical Note—Optimal Inventory Policy in the Presence of a Long-Term Supplier and a Spot Market
Authors: Chen Youhua (Frank) , Xue Weili , Yang Jian
Published: March 2013

We consider a stochastic inventory control problem in which a buyer makes procurement decisions while facing periodic random demand and two supply sources, namely, a long-term contract supplier and a spot market. The contract between the buyer and the supplier partially shields the latter from the vicissitudes of the spot market, in that the price paid by the buyer to the supplier is only partially linked to the spot price at the moment. After fulfilling the minimum-order commitment with the supplier, the buyer has the full freedom to source from both the supplier and the market. Procurement from the spot market also incurs a fixed setup cost. We show that an optimal policy consists of three different policy forms, with the realization of each depending on the buyer's inventory level and the prevalent spot price. Certain conditions are identified under which monotone trends exist between policy parameters and the current spot price.
Dynamic Pay-Per-Action Mechanisms and Applications to Online Advertising
Authors: Nazerzadeh Hamid , Saberi Amin , Vohra Rakesh
Published: March 2013

We examine the problem of allocating an item repeatedly over time amongst a set of agents. The value that each agent derives from consumption of the item may vary over time. Furthermore, it is private information to the agent, and prior to consumption it may be unknown to that agent. We describe a mechanism based on a sampling-based learning algorithm that under suitable assumptions is asymptotically individually rational, asymptotically Bayesian incentive compatible, and asymptotically ex ante efficient. Our mechanism can be interpreted as a pay-per-action or pay-per-acquisition (PPA) charging scheme in online advertising. In this scheme, instead of paying per click, advertisers pay only when a user takes a specific action (e.g., purchases an item or fills out a form) on their websites.
Reduce Readmissions with Pharmacy Programs; USP Updates Heparin Label; Insulin Concentration Rarely Needed on Orders
Authors: Cohen Michael R. , Smetzer Judy L.
Published: March 2013

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Prazosin: Benign Prostatic Hyperplasia
Authors: Generali Joyce A. , Cada Dennis J.
Published: March 2013

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Comparison of the Efficacy and Safety of Two Different Insulin Infusion Protocols in the Medical Intensive Care Unit
Authors: Perez Mirza E. , Varga Lindsay I. , Rose Christina , Gaughan John P.
Published: March 2013

Background

New guidelines recommend using less intensive glycemic goals in critically ill patients receiving insulin infusions.

Objective

To compare the efficacy and safety of a modified insulin infusion protocol (MIIP) with less stringent blood glucose (BG) goals to an intensive insulin infusion protocol (IIIP) in patients in a medical intensive care unit (MICU)

Methods

Retrospective review of patients receiving an insulin infusion for at least 24 hours. Patients treated for hyperglycemic emergencies were excluded. The primary endpoint of the study was mean area under the BG curve (BG-AUC) at 24 and 48 hours. Other endpoints included mean BG, hours until BG at goal, rate of BG above goal, frequency of BG measurements, and rate of hypoglycemia.

Results

BG-AUC at 24 hours was similar between the groups (MIIP = 5177.7 ± 1221.3 mg/dL x h vs IIIP = 4850.3 ± 1301.7 mg/dL x h; P = .20). The mean BG level at 24 hours was 225.1 ± 91.1 mg/dL in the MIIP group and 205.7 ± 89.7 mg/dL in the IIIP group ( P = .06). In the MIIP group, 61.7% of the BG levels were above goal as compared to 87.5% in the IIIP group ( P < .0001). Patients were able to achieve BG goals faster with the MIIP (12.58 ± 10.5 hours vs 29.37 ± 16.8 hours; P < .001). The rate of severe hypoglycemia was lower at 24 hours in the patients following the MIIP (0% vs 0.3%; P = .01).

Conclusion

The study showed that by having less intensive glycemic goals, goal BG levels can achieved faster and the rate of severe hypoglycemia can decrease.
Case Report: Dabigatran-Associated Gynecologic Bleeding
Authors: Winans S. Alexander , Ademolu Adetola
Published: March 2013

Purpose

The case of a patient who experienced major gynecological bleeding after initiation of dabigatran therapy for atrial fibrillation is reported.

A 33-year-old Hispanic female with multiple medical problems presented to the emergency department (ED) with a 5-day history of menorrhagia and a 3-day history of dizziness, fatigue, and weakness. Prior to ED presentation, she had been initiated on dabigatran 150 mg twice daily for atrial fibrillation. Four days later, she began having profuse vaginal bleeding. She discontinued all of her home medications including dabigatran, and her bleeding subsided the next day. Upon presentation to the ED, her hemoglobin was 7.1 g/dL, for which she was transfused 2 units of packed red blood cells, increasing her hemoglobin to 9.6 g/dL. Because the patient was in atrial fibrillation, warfarin was initiated once she was clinically stable and she was never restarted on dabigatran. Her hemoglobin was stable throughout admission with no further bleeding. She was discharged on warfarin and closely followed without incident.

Conclusion

A 33-year-old Hispanic female with no pre-existing gynecologic abnormalities had a major gynecological bleed shortly after starting dabigatran that resolved after discontinuation.
Teriflunomide
Authors: Cada Dennis J. , Demaris Kendra , Levien Terri L. , Baker Danial E.
Published: March 2013

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. A drug class review is now published monthly with The Formulary Monograph Service.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The March 2013 monograph topics are apixaban, bedaquiline, raxibacumab, teduglutide, and loxapine inhalation. The DUE/MUE is on apixaban.
Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Authors: Baker Danial E.
Published: March 2013

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
Inhaled Corticosteroid Metered-Dose Inhalers: How Do Variations in Technique for Solutions Versus Suspensions Affect Drug Distribution?
Authors: Robinson Christie A , Tsourounis Candy
Published: March 2013

OBJECTIVE

To assess the literature that evaluates how variations in metereddose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions.

DATA SOURCES

PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION

All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified.

DATA SYNTHESIS

Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs.

CONCLUSIONS

Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.
Prevalence and Risk of Potential Cytochrome P450–Mediated Drug-Drug Interactions in Older Hospitalized Patients with Polypharmacy
Authors: Doan Julie , Zakrzewski-Jakubiak Hubert , Roy Julie , Turgeon Jacques , Tannenbaum Cara
Published: March 2013

BACKGROUND

As rates of polypharmacy rise and medication regimens become more complex, the risk of potential cytochrome P450 (CYP)–mediated drug-drug interactions (DDIs) is a growing clinical concern for older adults. objective: To determine the prevalence of potential CYP-mediated DDIs in older hospitalized adults with polypharmacy and analyze the relationship between the number of drugs dispensed and the probability of these interactions in this high-risk population.

METHODS

A prospective 16-week cohort study was conducted among consecutive new patients aged 65 years and older with polypharmacy (>5 drugs) admitted to a community hospital. The medication profiles of these patients were analyzed with a new multidrug cytochrome-specific software program. The prevalence of potential CYP-mediated DDIs was determined, with the probability calculated as a function of the number of medications dispensed using multivariate Poisson regression adjusted for age and sex. Comparative performance of the software program and a standard 2-drug alert program for detecting these DDIs was evaluated using the Wilcoxon-Mann-Whitney rank-sum test. Pharmacists' decisions to recommend medication adjustment based on the probability of CYP-mediated DDIs were recorded.

RESULTS

The prevalence of potential CYP-mediated DDIs detected among 275 older adults with polypharmacy was 80%. The probability of at least 1 CYP-mediated DDI was 50% for persons taking 5–9 drugs, 81% with 10–14 drugs, 92% with 15–19 drugs, and 100% with 20 or more drugs. Addition of each medication to a 5-drug regimen conferred a 12% increased risk of a potential CYP-mediated DDI after adjustment for age and sex (OR 1.12; 95% CI 1.09–1.14). The multidrug software identified a median increase of 3 (95% CI 2.5–3.5) potential CYP-mediated DDIs per patient, compared to use of the standard 2-drug alert software. Pharmacists targeted patients for medication adjustment or close clinical monitoring in 23% of cases.

CONCLUSIONS

The prevalence of potential CYP-mediated DDIs is high in geriatric patients with polypharmacy. The risk of DDIs increases as a function of the number of medications dispensed. Pharmacists' decision to intervene for potential CYP-mediated DDIs depends on clinical judgment in addition to the output from drug alert software programs, but may be facilitated by a single multicomponent, multidrug potential CYP-mediated DDI assessment.
Oxidative cyclization for the synthesis of complex tetrahydrofuran-containing natural products
Authors: Pullin Robert D. C. , Lipiński Radosław M. , Donohoe Timothy J.
Published: March 2013

The osmium-catalyzed oxidative cyclization of vicinal diols onto proximal olefins to generate 2,5-cis-substituted tetrahydrofurans (THFs) has been exploited as the key step for the construction of several complex THF-containing natural products, namely, the annonaceous acetogenins cis-sylvaticin, sylvaticin, and the excitatory amino acid neo-dysiherbaine A. Recently modified conditions that employ a Lewis acid enable the cyclization to proceed under milder conditions, providing greater tolerance to acid-sensitive functional groups, as demonstrated in two of the syntheses. Flexibility for the construction of 2,5-trans-THFs was demonstrated in the synthesis of sylvaticin by utilization of an intramolecular hydride-shift sequence.
Cardiac Troponin Assay Classification by Both Clinical and Analytical Performance Characteristics: A Study on Outcome Prediction
Authors: Venge Per , Lindahl Bertil
Published: March 2013

BACKGROUND

Cardiac troponin assays have been classified according to whether they measure the 99th percentile concentration of a healthy reference population with imprecision (expressed as CV) of ≤10%, between 10% and 20%, or >20%. Assays in these categories have been deemed “guideline acceptable,” “clinically usable,” or “not acceptable,” respectively. We compared four widely used “clinically usable” cardiac troponin I (cTnI) assays with an assay designated “not acceptable” for accuracy in predicting the clinical outcome of death.

METHODS

Blood was collected from 259 men and 249 women, mean (SD) age 68.8 (17.8) and 70.2 (17.8) years, respectively, admitted to the emergency department for suspected myocardial infarction. We measured cTnI by the Access, Architect, i-Stat, Stratus CS, and VIDAS assays. Deaths in this population were recorded over a 31-month period.

RESULTS

We found VIDAS cTnI assay measurement CVs of 10% and 20% at concentrations of 0.04 and 0.02 μg/L, respectively. Comparing at the 10% CV cutoff concentration, VIDAS cTnI was less sensitive than the Access and Architect assays (P < 0.001) but more sensitive than i-Stat (P < 0.001) and Stratus CS (P < 0.001) in identifying patients with poor outcomes. At the 20% CV cutoff, the VIDAS assay was equivalent to the other assays in identifying patients with poor outcomes.

CONCLUSIONS

For outcome prediction, the VIDAS cTnI assay was clinically equivalent or superior to other cTnI assays judged to be acceptable from a pure analytical standpoint. Thus, comparison of cardiac troponin assays should consider not only analytical performance, but also clinical performance characteristics.
Critical Role of the Astrocyte for Functional Remodeling in Contralateral Hemisphere of Somatosensory Cortex after Stroke
Authors: Takatsuru Yusuke , Eto Kei , Kaneko Ryosuke , Masuda Hiroko , Shimokawa Noriaki , Koibuchi Noriyuki , Nabekura Junichi
Published: March 2013

After ischemic stroke, the corresponding area contralateral to the lesion may partly compensate for the loss of function. We previously reported the remodeling of neuronal circuits in the contralateral somatosensory cortex (SSC) during the first week after infarction for processing bilateral information, resulting in functional compensation. However, the underlying processes in the contralateral hemisphere after stroke have not yet been fully elucidated. Recent studies have shown that astrocytes may play critical roles in synaptic reorganization and functional compensation after a stroke. Thus, we aim to clarify the contribution of astrocytes using a rodent stroke model.In vivocalcium imaging showed a significantly large number of astrocytes in the contralateral SSC responding to ipsilateral limb stimulation at the first week after infarction. Simultaneously, extracellular glutamine level increased, indicating the involvement of astrocytes in the conversion of glutamate to glutamine, which may be an important process for functional recovery. This hypothesis was supported further by the observation that application of (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy} aspartate, a glial glutamate transporter blocker, disturbed the functional recovery. These findings indicate the involvement of astrocytes in functional remodeling/recovery in the area contralateral to the lesion. Our study has provided new insights into the mechanisms underlying synaptic remodeling after cerebral infarction, which contributes to the development of effective therapeutic approaches for patients after a stroke.
Postsynaptic Density Scaffold SAP102 Regulates Cortical Synapse Development through EphB and PAK Signaling Pathway
Authors: Murata Yasunobu , Constantine-Paton Martha
Published: March 2013

Membrane-associated guanylate kinases (MAGUKs), including SAP102, PSD-95, PSD-93, and SAP97, are scaffolding proteins for ionotropic glutamate receptors at excitatory synapses. MAGUKs play critical roles in synaptic plasticity; however, details of signaling roles for each MAGUK remain largely unknown. Here we report that SAP102 regulates cortical synapse development through the EphB and PAK signaling pathways. Using lentivirus-delivered shRNAs, we found that SAP102 and PSD-95, but not PSD-93, are necessary for excitatory synapse formation and synaptic AMPA receptor (AMPAR) localization in developing mouse cortical neurons. SAP102 knockdown (KD) increased numbers of elongated dendritic filopodia, which is often observed in mouse models and human patients with mental retardation. Further analysis revealed that SAP102 coimmunoprecipitated the receptor tyrosine kinase EphB2 and RacGEF Kalirin-7 in neonatal cortex, and SAP102 KD reduced surface expression and dendritic localization of EphB. Moreover, SAP102 KD prevented reorganization of actin filaments, synapse formation, and synaptic AMPAR trafficking in response to EphB activation triggered by its ligand ephrinB. Last, p21-activated kinases (PAKs) were downregulated in SAP102 KD neurons. These results demonstrate that SAP102 has unique roles in cortical synapse development by mediating EphB and its downstream PAK signaling pathway. Both SAP102 and PAKs are associated with X-linked mental retardation in humans; thus, synapse formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may be crucial for cognitive development.
Spontaneous and Task-Evoked Brain Activity Negatively Interact
Authors: He Biyu J.
Published: March 2013

A widely held assumption is that spontaneous and task-evoked brain activity sum linearly, such that the recorded brain response in each single trial is the algebraic sum of the constantly changing ongoing activity and the stereotypical evoked activity. Using functional magnetic resonance imaging signals acquired from normal humans, we show that this assumption is invalid. Across widespread cortices, evoked activity interacts negatively with ongoing activity, such that higher prestimulus baseline results in less activation or more deactivation. As a consequence of this negative interaction, trial-to-trial variability of cortical activity decreases following stimulus onset. We further show that variability reduction follows overlapping but distinct spatial pattern from that of task-activation/deactivation and it contains behaviorally relevant information. These results favor an alternative perspective to the traditional dichotomous framework of ongoing and evoked activity. That is, to view the brain as a nonlinear dynamical system whose trajectory is tighter when performing a task. Further, incoming sensory stimuli modulate the brain's activity in a manner that depends on its initial state. We propose that across-trial variability may provide a new approach to brain mapping in the context of cognitive experiments.
Angiotensin Type 1a Receptors in the Paraventricular Nucleus of the Hypothalamus Protect against Diet-Induced Obesity
Authors: de Kloet Annette D. , Pati Dipanwita , Wang Lei , Hiller Helmut , Sumners Colin , Frazier Charles J. , Seeley Randy J. , Herman James P. , Woods Stephen C. , Krause Eric G.
Published: March 2013

Obesity is associated with increased levels of angiotensin-II (Ang-II), which activates angiotensin type 1a receptors (AT1a) to influence cardiovascular function and energy homeostasis. To test the hypothesis that specific AT1awithin the brain control these processes, we used the Cre/lox system to delete AT1afrom the paraventricular nucleus of the hypothalamus (PVN) of mice. PVN AT1adeletion did not affect body mass or adiposity when mice were maintained on standard chow. However, maintenance on a high-fat diet revealed a gene by environment interaction whereby mice lacking AT1ain the PVN had increased food intake and decreased energy expenditure that augmented body mass and adiposity relative to controls. Despite this increased adiposity, PVN AT1adeletion reduced systolic blood pressure, suggesting that this receptor population mediates the positive correlation between adiposity and blood pressure. Gene expression studies revealed that PVN AT1adeletion decreased hypothalamic expression of corticotrophin-releasing hormone and oxytocin, neuropeptides known to control food intake and sympathetic nervous system activity. Whole-cell patch-clamp recordings confirmed that PVN AT1adeletion eliminates responsiveness of PVN parvocellular neurons to Ang-II, and suggest that Ang-II responsiveness is increased in obese wild-type mice. Central inflammation is associated with metabolic and cardiovascular disorders and PVN AT1adeletion reduced indices of hypothalamic inflammation. Collectively, these studies demonstrate that PVN AT1aregulate energy balance during environmental challenges that promote metabolic and cardiovascular pathologies. The implication is that the elevated Ang-II that accompanies obesity serves as a negative feedback signal that activates PVN neurons to alleviate weight gain.
The Slow Afterhyperpolarization: A Target of β1-Adrenergic Signaling in Hippocampus-Dependent Memory Retrieval
Authors: Zhang Lei , Ouyang Ming , Ganellin C. Robin , Thomas Steven A.
Published: March 2013

In rodents, adrenergic signaling by norepinephrine (NE) in the hippocampus is required for the retrieval of intermediate-term memory. NE promotes retrieval via the stimulation of β1-adrenergic receptors, the production of cAMP, and the activation of both protein kinase A (PKA) and the exchange protein activated by cAMP. However, a final effector for this signaling pathway has not been identified. Among the many targets of adrenergic signaling in the hippocampus, the slow afterhyperpolarization (sAHP) is an appealing candidate because its reduction by β1signaling enhances excitatory neurotransmission. Here we report that reducing the sAHP is critical for the facilitation of retrieval by NE. Direct blockers of the sAHP, as well as blockers of the L-type voltage-dependent calcium influx that activates the sAHP, rescue retrieval in mutant mice lacking either NE or the β1receptor. Complementary to this, a facilitator of L-type calcium influx impairs retrieval in wild-type mice. In addition, we examined the role of NE in the learning-related reduction of the sAHP observedex vivoin hippocampal slices. We find that this reduction in the sAHP depends on the induction of persistent PKA activity specifically in conditioned slices. Interestingly, this persistent PKA activity is induced by NE/β1signaling during slice preparation rather than during learning. These observations suggest that the reduction in the sAHP may not be present autonomouslyin vivo, but is likely induced by neuromodulatory input, which is consistent with the idea that NE is requiredin vivofor reduction of the sAHP during memory retrieval.
Serotonin 1A Receptors Alter Expression of Movement Representations
Authors: Scullion Kathleen , Boychuk Jeffery A. , Yamakawa Glenn R. , Rodych Justin T.G. , Nakanishi Stan T. , Seto Angela , Smith Victoria M. , McCarthy Ryan W. , Whelan Patrick J. , Antle Michael C. , Pittman Quentin J. , Teskey G. Campbell
Published: March 2013

Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT1Areceptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT1A/7agonist 8-OH-DPAT lowered movement thresholdsin vivoand increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT1Aantagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT1Areceptor. Next we developed a novelin vitroICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT1Areceptors, plays an excitatory role in forelimb motor map expression.
The Organization of Prefrontal-Subthalamic Inputs in Primates Provides an Anatomical Substrate for Both Functional Specificity and Integration: Implications for Basal Ganglia Models and Deep Brain Stimulation
Authors: Haynes William I. A. , Haber Suzanne N.
Published: March 2013

The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. Our experiments were designed to demonstrate the existence and organization of prefrontal-STN projections, help delineate the “limbic” STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate, and dorsal prefrontal cortices ofMacaca nemestrinaandMacaca fascicularisto analyze the organization of terminals and passing fibers in the STN.

Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior.
Motor Learning Interference Is Proportional to Occlusion of LTP-Like Plasticity
Authors: Cantarero Gabriela , Tang Byron , O'Malley Rebecca , Salas Rachel , Celnik Pablo
Published: March 2013

Learning interference occurs when learning something new causes forgetting of an older memory (retrograde interference) or when learning a new task disrupts learning of a second subsequent task (anterograde interference). This phenomenon, described in cognitive, sensory, and motor domains, limits our ability to learn multiple tasks in close succession. It has been suggested that the source of interference is competition of neural resources, although the neuronal mechanisms are unknown. Learning induces long-term potentiation (LTP), which can ultimately limit the ability to induce further LTP, a phenomenon known as occlusion. In humans we quantified the magnitude of occlusion of anodal transcranial direct current stimulation-induced increased excitability after learning a skill task as an index of the amount of LTP-like plasticity used. We found that retention of a newly acquired skill, as reflected by performance in the second day of practice, is proportional to the magnitude of occlusion. Moreover, the degree of behavioral interference was correlated with the magnitude of occlusion. Individuals with larger occlusion after learning the first skill were (1) more resilient to retrograde interference and (2) experienced larger anterograde interference when training a second task, as expressed by decreased performance of the learned skill in the second day of practice. This effect was not observed if sufficient time elapsed between training the two skills and LTP-like occlusion was not present. These findings suggest competition of LTP-like plasticity is a factor that limits the ability to remember multiple tasks trained in close succession.
The “Ethics Rupture” Summit, Fredericton, New Brunswick, Canada, October 25–28, 2012
Authors: Van Den Hoonaard Will C.
Published: March 2013

This report explains the background of the “Ethics Rupture” Summit held in New Brunswick, Canada, October 2012, focusing on the disconnect between research-ethics policies and the nature and purpose of social-science research—an unintended “rupture” in ethics governance. Ethics is about human relationships, and the governance of ethics must reflect that fact rather than function as a bureaucratic, self-legitimating system of control. The themes that emerged from the Summit point to: Structural problems with the current system; an undermining of the original, historical mission of some social-science disciplines; a discomfort with new methodologies; ethics committees and the well-being and education of social-science students; the possibilities of reform and renewal; and the next steps. Finally, the report refers in broad outlines to a “New Brunswick Declaration,” which is currently being considered by participants of the Summit.
Perspectives of Egyptian Research Ethics Committees regarding Their Effective Functioning
Authors: Matar Amal , Silverman Henry
Published: March 2013

The recent increase in research in the Middle East has been associated with the establishment of research ethics committees (RECs). Our aim was to obtain perspectives of RECs regarding the challenges that impede their effective functioning. We conducted in-depth interviews using a semi-structured interview guide. We transcribed and analyzed the interviews to uncover major themes and subthemes. We identified the following themes: Membership composition; Revised training needs of members; Revised availability of human and capital resources; Revised role of the national government; Revised concerns with the informed consent process; Revised government scrutiny of research; Revised investigator-related issues; Revised and concerns with transfer of biological samples to other countries. Our interview study revealed several barriers that need to be considered by appropriate stakeholders to enhance adequate functioning of RECs.
Ethical Challenges and Opportunities for Nurses in HIV and AIDS Community-Based Participatory Research in Jamaica
Authors: Davison Colleen M. , Kahwa Eulalia , Edwards Nancy , Atkinson Uki , Roelofs Susan , Hepburn-Brown Cerese , Aiken Joyette , Dawkins Pauline , Rae Tania , MacFarlane Denise
Published: March 2013

As part of a multinational program of research, we undertook a community-based participatory research project in Jamaica to strengthen nurses' engagement in HIV and AIDS policy. Three leadership hubs were purposefully convened and included small groups of people (6–10) from diverse HIV and AIDS stakeholder groups in Jamaica: Frontline nurses and nurse managers in primary and secondary care settings; Revised researchers; Revised health care decision makers; Revised and other community members. People living with HIV or AIDS were among the hub members. Using a relational public health ethics framework, we outline some of the ethical challenges and opportunities experienced by the research team and the leadership hubs. Data included research assistant field notes and hub progress reports. Emerging ethical concerns were associated with relational person-hood, social justice, relational autonomy, relational solidarity, and sustainability of the hub activities.
A Community-Based Participatory Research Study of HIV and HPV Vulnerabilities and Prevention in Two Pacific Islander Communities: Ethical Challenges and Solutions
Authors: Distefano Anthony , Quitugua Lourdes , Hui Brian , Barrera-Ng Angelica , Peters Ruth , Vunileva 'Isileli , Dimaculangan Jeany , Tui'one Vanessa , Takahashi Lois , Tanjasiri Sora Park
Published: March 2013

We describe ethical issues that emerged during a one-year CBPR study of HIV and human papillomavirus (HPV) vulnerabilities and prevention in two Pacific Islander (PI) communities, and the collaborative solutions to these challenges reached by academic and community partners. In our project case study analysis, we found that ethical tensions were linked mainly to issues of mutual trust and credibility in PI communities; Revised cultural taboos associated with the nexus of religiosity and traditional PI culture; Revised fears of privacy breaches in small, interconnected PI communities; Revised and competing priorities of scientific rigor versus direct community services. Mutual capacity building and linking CBPR practice to PI social protocols are required for effective solutions and progress toward social justice outcomes.
Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas
Authors: Mazzucco M B , Higa R , Capobianco E , Kurtz M , Jawerbaum A , White V
Published: March 2013

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects.
Thermoelectric behaviour of p- and n- type Ti-Ni-Sn half Heusler alloy variants and their amorphous equivalents
Authors: Zhu Song , Vitta Satish , Tritt Terry M.
Published: March 2013

Ti-Ni-Sn type half-Heusler alloys which have the versatility to be either p- or n-type depending on the type of substitution, have been synthesized and investigated in the present work. The added advantage of doping them with multiple elements is that they will be amenable to bulk amorphous phase formation. The hole doped alloys were predominantly single phase with a cubic structure, while the electron doped alloys were found to have minor additional phases. All the alloys exhibit extremely weak metallic-like or degenerate semiconductor transport behaviour in the temperature range 20 K to 1000 K. The resistivity of p-type alloys exhibits semi-metallic-to-semiconducting transition at ∼ 500 K while the n-type alloys exhibit a weak metallic-like behaviour in the complete temperature range. The Seebeck coefficient has strong temperature dependence with a maximum of 45 μV K−1 in the temperature range 600-700 K in the p-type alloys. The n-type alloys however exhibit a linear variation of the Seebeck coefficient with temperature. The total thermal conductivity of the alloys increases with increasing temperature without any peak at low temperatures indicating significant disorder induced scattering. The p-type alloys have the lowest thermal conductivity compared to the n-type alloys. These alloys become amorphous after pulsed laser deposition except one alloy which exhibits compensated transport behaviour.
Grazing Incidence X-ray Topographic Studies of Threading Dislocations in Hydrothermal Grown ZnO Single Crystal Substrates
Authors: Zhou Tianyi , Raghothamachar Balaji , Wu Fangzhen , Dudley Michael
Published: March 2013

ZnO single crystal substrates grown by the hydrothermal method have been characterized by grazing incidence X-ray topography using both monochromaticand whitesynchrotron X ray beams.11$\bar 2$4 reflection wasrecorded from the (0001) wafers and the different contrast patterns produced by different threading defects were noted. To uniquely identify the Burgers vectors of these threading dislocation defects, we use raytracingsimulation to compare with observed defect contrast. Our studies showed that threading screw dislocations are not commonly observed.Most threading edge dislocationshavetheBurgers vector of1⁄3[2$\bar 1$$\bar 1$0] or1⁄3[12$\bar 2$10]and a density of 2.88×104/cm2.
Quantum mechanical description of Electronic transitions in Cylindrical nanostructures, including pores in semiconductors
Authors: Vorobiev Yuri V. , Horley Pavel , González-Hernández Jesus
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Effect of Single-Wall Carbon Nanotubes Layer on Photoelectric Response of Au/Si Photovoltaic Structures
Authors: Dmitruk Nicholas L. , Borkovskaya OlgaYu. , Havrylenko Tetyana.S. , Mamykin Sergey V. , Romanyuk VladimirR. , Basiuk ElenaV.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Iron Silicide Nanostructures Prepared by E-Gun Evaporation and Annealing on Si(001)
Authors: Molnár György , Dózsa László , Vértesy Zofia , Horváth Zsolt J.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Comparative study of Photoluminescence variation in InAs Quantum dots embedded in InAlGaAs Quantum wells
Authors: Casas Espinola J.L. , Torchynska T.V. , Diosdado L. D. Cruz. , Polupan G.
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Emission Variety in ZnO Nanocrystals Obtained At Different Growth Temperatures
Authors: Velázquez Lozada Erick , Castañeda Luis
Published: March 2013

Papers in the Appendix were published in electronic format as Volume 1534
Triggered Cell Release from Shellac-Cells Composite Microcapsules
Authors: Hamad Shwan A. , Stoyanov Simeon D. , Paunov Vesselin N.
Published: March 2013

We have fabricated novel shellac-cells composite microcapsules capable of pH-stimulus induced release of cells in a narrow pH range. The microcapsules were produced with yeast cells as a model for probiotics which were co-precipitated from an aqueous solution of ammonium shellac doped with pH-sensitive polyelectrolytes. The yeast cells in the composite shellac-cell microcapsules retained their viability even when treated with aqueous solutions of very low pH and subjected to shear stress. We studied the pH triggered release of cells from these microcapsules and measured their disintegration times. These microcapsules showed versatile responses ranging from slow release to explosive swelling at higher pH depending on the type and concentration of the polyelectrolyte integrated in the shellac microcapsules. We also observed growth-triggered release of cells from these microcapsules upon exposure to culture media. In both cases the cells retained their viability following their release from the microcapsules into the aqueous solution.
Microfluidics via Controlled Imbibition
Authors: Jokinen Ville , Franssila Sami
Published: March 2013

Strategies for controlled imbibition utilizing both topographical cues as well as patterned surface chemistries are presented. Triangle-like microstructures were used for directional wetting of liquids into a limited sector of the surface. Chemical patterns on top of a nanopillar geometry allowed the patterning of both water and oil droplets. Applications of controlled imbibition in dried droplet mass spectrometry as well as liquid-liquid extraction are also presented.
Spider silk morphology for responsive materials
Authors: Guan Juan , Porter David , Vollrath Fritz
Published: March 2013

This study reveals that an “old” mechanism for shape memory in oriented polymers is in fact just one separate contribution for “supercontraction” in Nephila spider major ampulate silks. When Nephila spider silks are in contact with liquid water, they “super”-contract up to 28% of the original stretched length. However, we discovered that under glass transition conditions these silks only relax with a maximum shrinkage of 13%, and this phenomenon is defined as Tg-contraction. Structural components permanent order (PO), permanent disorder (PD), meta order (MO) and meta disorder (MD) were proposed from the primary amino-acid sequence of the silk protein to explain morphological changes in the two contraction phenomena: MD contributes 13% of the full supercontraction and contributes to Tg-contraction; whereas MO (the proline-containing motifs) contributes the rest for the full super-contraction and does not contribute to Tg-contraction. The morphology in Nephila spider silk structure suggests two separate mechanisms to generate the shape memory effect in synthetic polymers.
Determination of the Critical Period for Weed Control in Corn
Authors: Gantoli Geoffroy , Ayala Victor Rueda , Gerhards Roland
Published: March 2013

Field experiments were conducted in western Atakora, Benin, to determine the critical time period of weed competition in hand-weeded corn. Weeds were removed until different crop growth stages and then allowed to reemerge. Other treatments began weed control at different growth stages (four-, eight-, and ten-leaf stages and flowering) and were maintained until harvest. One treatment was permanently kept weed-free and one treatment was uncontrolled until harvest. Yields without weed competition ranged from 2.8 to 3.4 t ha−1. As expected, yield loss increased with duration of weed infestation and ranged from 38 to 65% compared to permanent weed-free plots. In three out of four site-years, the critical period for weed control started at the four- to six-leaf stage and continued until ten-leaf stage or flowering of corn. Approximately four hand-weeding applications were required in this critical period of weed control.