bluuebunny/crossref_metadata_2025 huggingface dataset:
Rivaroxaban in Nonvalvular Atrial Fibrillation
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E.
Published: April 2012

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 April 2012 monograph topics are on ivacaftor, vismodegib, axitinib, glucarpidase, and loxapine inhalation. The DUE/MUE is on glucarpidase.
How Patient-Centric is your Practice?
Authors: Felkey Bill G. , Fox Brent I.
Published: April 2012

“Patient-centric” likely means many different things to different people. Some may argue that patient-centric is a philosophical approach to how care is provided. Others may argue that patient-centric is demonstrated by the resources provided to patients to enable them to be proactive participants in their own care. In this installment, we describe several different ways that a practice can be patient-centric.
Recent Publications on Medications and Pharmacy
Authors: Russett Flint
Published: April 2012

Hospital Pharmacy presents this feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest regarding a broad scope of topics are abstracted monthly.
Artemether-Lumefantrine: An Option for Malaria
Authors: Stover Kayla R , King S Travis , Robinson Jessica
Published: April 2012

Objective:

To review the pharmacology, pharmacokinetics, safety, and efficacy of artemether-lumefantrine for the treatment of Plasmodium falciparum malaria.

Data Sources:

English-language articles indexed in PubMed (1947-November 2011) were identified, using the search terms artemether-lumefantrine, artemether-lumefantrine AND malaria, Coartem, and Coartem AND malaria.

Study Selection and Data Extraction:

Available English-language articles were reviewed. In addition, the malaria treatment regimens recommended by region as provided by the World Health Organization and the treatment guidelines from the Centers for Disease Control and Prevention were reviewed.

Data Synthesis:

Artemether-lumefantrine is an artemisinin-derived combination antimalarial approved by the Food and Drug Administration in 2009 for the treatment of P. falciparum malaria. The dual mechanisms of action of artemether-lumefantrine provide rapid and sustained parasite clearance. In the reviewed studies, the polymerase chain reaction (PCR)-corrected 28-day cure rates of artemether-lumefantrine were noninferior to the most common comparators, including chloroquine, dapsone, and other artemisinin derivatives (86-100% vs 51-100%, respectively). PCR-corrected day-42 cure rates were 92-99.3% for artemether-lumefantrine versus 62-100% for the comparator groups. The major adverse effects (gastrointestinal and central nervous system) were mild to moderate in severity and did not require a change in therapy. Although adherence to artemether-lumefantrine has been described as a potential problem due to the complicated dosing schedule, studies have described clinical cure rates similar to those of other antimalarials.

Conclusions:

Artemether-lumefantrine is a safe and effective treatment for children and adults with P. falciparum malaria.
Health Care Reform 2011: Opportunities for Pharmacists
Authors: Matzke Gary R.
Published: April 2012

The health reforms of the last several years at the federal and state levels have created many opportunities for pharmacists to become actively involved in the direct patient care provision. Indeed, the statutory language in some sections of the Affordable Care Act of 2010 creates expectations of pharmacists that will require practice transformation if we are to arise to accept the responsibilities associated with these expectations. These new opportunities open the door for pharmacists to benefit community-dwelling patients with chronic medical conditions, those with acute/emergent care needs, those experiencing a transition between chronic and acute care and vice versa, as well as others in long-term care settings. Although the profession has demonstrated value in many practice environments, our contributions to improved medication-related patient outcomes through medication therapy management (MTM) and the other pharmaceutical care services remain to be rigorously quantified. Incorporation of pharmacists either by their physical presence within the practice or through the design of effective community linkages, such as electronic health records, must be developed to meet the needs of rural and urban patients seen in a variety of practice settings. New business models that build upon cognitive and direct patient care services in addition to the provision of drug products will surely need to emerge for the profession to become a viable and vital component of the US health care system.
Ontario Pharmacists Practicing in Family Health Teams and the Patient-Centered Medical Home
Authors: Dolovich Lisa
Published: April 2012

The patient-centered medical home (PCMH) approach continues to gather momentum in the United States and Canada as a broad approach to reform the delivery of the complete primary care system. The family health team (FHT) model implemented in Ontario, Canada, best mirrors the PCMH approach of the United States. The integration of pharmacists as key members of the health care team providing on-site, in-office coordinated care to FHT patients was included from the start of planning the FHT model and represents a substantial opportunity for pharmacists to realize their professional vision. Several research projects in Canada and elsewhere have contributed to providing evidence to support the integration of pharmacists into primary care practice sites. Two major research programs, the Seniors Medication Assessment Research Trial (SMART) cluster randomized controlled trial and the Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics (IMPACT) multipronged demonstration project made substantial contributions to evidence-informed policy decisions supporting the integration of pharmacists into FHTs. These projects can provide useful information to support the integration of pharmacists into the PCMH and to encourage further research to better measure the effect of the pharmacist from the holistic patient-centered perspective.
The Future of Health-System Pharmacy: Opportunities and Challenges in Practice Model Change
Authors: Zellmer William A.
Published: April 2012

Key factors outside of health-system pharmacy that will shape this sector of the profession in the coming years are (1) the national economy, (2) national politics, (3) the debt of the federal government, (4) global megatrends (including terrorism and economic globalization), (5) health care reform, and (6) trends in the development and use of medicines. These factors will translate into payment cutbacks to hospitals, expanded mandates to improve the quality of health care, increased focus on patient-centered care, more team-based care, and a higher degree of integration across the range of health care settings and providers. In this environment, pharmacists in hospitals and other health systems will have rich opportunities to help improve patient care and institutional sustainability by continuing to move from order-fulfillment and product-preparation functions toward team leadership of drug therapy management. The American Society of Health-System Pharmacists Pharmacy Practice Model Initiative (PPMI) was created to encourage hospital and health-system practice leaders to examine how they deploy their resources (ie, pharmacist time, technician time, and technology) to ensure that the efforts of the pharmacy department are aligned with the most urgent needs of patients and institutions. Key recommendations of the PPMI and evidence about gaps in the provision of drug therapy management services are presented. It is important for every pharmacist and pharmacy technician in health-system practice to understand the imperatives for changing the profession's practice model and to actively pursue appropriate changes in that model.
The Virginia Pharmacy Practice Transformation Conference: Outcomes and Next Steps
Authors: Silvester Janet A.
Published: April 2012

Thought leaders in Virginia came together to achieve consensus on the pharmacy practice innovations required to advance the medication-related health outcomes of patients in the Commonwealth, The participants identified key elements and strategies needed for practice transformation and these became the foundation for practice change. The primary key elements included legislation and regulation modifications, payment reform, and business model development. The Virginia Pharmacy Congress, which represents key pharmacy stakeholders in the Commonwealth, became the home for the transformation movement and the development and implementation of a unified action plan for achieving the envisioned practice transformation.
Alignment of Multimodal Sensory Input in the Superior Colliculus through a Gradient-Matching Mechanism
Authors: Triplett Jason W. , Phan An , Yamada Jena , Feldheim David A.
Published: April 2012

The superior colliculus (SC) is a midbrain structure that integrates visual, somatosensory, and auditory inputs to direct head and eye movements. Each of these modalities is topographically mapped and aligned with the others to ensure precise behavioral responses to multimodal stimuli. While it is clear that neural activity is instructive for topographic alignment of inputs from the visual cortex (V1) and auditory system with retinal axons in the SC, there is also evidence that activity-independent mechanisms are used to establish topographic alignment between modalities. Here, we show that the topography of the projection from primary somatosensory cortex (S1) to the SC is established during the first postnatal week. Unlike V1–SC projections, the S1–SC projection does not bifurcate when confronted with a duplicated retinocollicular map, showing that retinal input in the SC does not influence the topography of the S1–SC projection. However, S1–SC topography is disrupted in mice lacking ephrin-As, which we find are expressed in graded patterns along with their binding partners, the EphA4 and EphA7, in both S1 and the somatosensory recipient layer of the SC. Together, these data support a model in which somatosensory inputs into the SC map topographically and establish alignment with visual inputs in the SC using a gradient-matching mechanism.
GABA Site Agonist Gaboxadol Induces Addiction-Predicting Persistent Changes in Ventral Tegmental Area Dopamine Neurons But Is Not Rewarding in Mice or Baboons
Authors: Vashchinkina Elena , Panhelainen Anne , Vekovischeva Olga Yu. , Aitta-aho Teemu , Ebert Bjarke , Ator Nancy A. , Korpi Esa R.
Published: April 2012

Dopamine neurons of the ventral tegmental area (VTA) are involved at early phases of drug addiction. Even the firstin vivodose of various abused drugs induces glutamate receptor plasticity at the excitatory synapses of these neurons. Benzodiazepines that suppress the inhibitory GABAergic interneurons in the VTA via facilitation of synaptic GABAAreceptors have induced neuroplasticity in dopamine neurons due to this disinhibitory mechanism. Here, we have tested a non-benzodiazepine direct GABA site agonist 4,5,6,7-tetrahydroisoxazolol[4,5-c]pyridine-3-ol (THIP) (also known as gaboxadol) that acts preferentially via high-affinity extrasynaptic GABAAreceptors. A single sedative dose of THIP (6 mg/kg) to mice induced glutamate receptor plasticity for at least 6 d after administration. Increased AMPA/NMDA receptor current ratio and increased frequency, amplitude, and rectification of AMPA receptor responses suggested persistent targeting of GluA2-lacking AMPA receptors in excitatory synapses of VTA dopamine neuronsex vivoafter THIP administration. This effect was abolished in GABAAreceptor δ−/−mice, which have a loss of extrasynaptic GABAAreceptors. In behavioral experiments, we found neither acute reinforcement in intravenous self-administration sessions with THIP at relevant doses using a yoked control paradigm in mice nor in baboons using a standard paradigm for assessing drug abuse liability; nor was any place preference found after conditioning sessions with various doses of THIP but rather a persistent aversion in 6 mg/kg THIP-conditioned mice. In summary, we found that activation of extrasynaptic δ-subunit-containing GABAAreceptors leads to glutamate receptor plasticity of VTA dopamine neurons, but is not rewarding, and, instead, induces aversion.
Lysosomal Dysfunction in a Mouse Model of Sandhoff Disease Leads to Accumulation of Ganglioside-Bound Amyloid-β Peptide
Authors: Keilani Serene , Lun Yi , Stevens Anthony C. , Williams Hadis N. , Sjoberg Eric R. , Khanna Richie , Valenzano Kenneth J. , Checler Frederic , Buxbaum Joseph D. , Yanagisawa Katsuhiko , Lockhart David J. , Wustman Brandon A. , Gandy Sam
Published: April 2012

Alterations in the lipid composition of endosomal–lysosomal membranes may constitute an early event in Alzheimer's disease (AD) pathogenesis. In this study, we investigated the possibility that GM2 ganglioside accumulation in a mouse model of Sandhoff disease might be associated with the accumulation of intraneuronal and extracellular proteins commonly observed in AD. Our results show intraneuronal accumulation of amyloid-β peptide (Aβ)-like, α-synuclein-like, and phospho-tau-like immunoreactivity in the brains of β-hexosaminidase knock-out (HEXBKO) mice. Biochemical and immunohistochemical analyses confirmed that at least some of the intraneuronal Aβ-like immunoreactivity (iAβ-LIR) represents amyloid precursor protein C-terminal fragments (APP-CTFs) and/or Aβ. In addition, we observed increased levels of Aβ40 and Aβ42 peptides in the lipid-associated fraction ofHEXBKO mouse brains, and intraneuronal accumulation of ganglioside-bound Aβ (GAβ) immunoreactivity in a brain region-specific manner. Furthermore, α-synuclein and APP-CTFs and/or Aβ were found to accumulate in different regions of the substantia nigra, indicating different mechanisms of accumulation or turnover pathways. Based on the localization of the accumulated iAβ-LIR to endosomes, lysosomes, and autophagosomes, we conclude that a significant accumulation of iAβ-LIR may be associated with the lysosomal–autophagic turnover of Aβ and fragments of APP-containing Aβ epitopes. Importantly, intraneuronal GAβ immunoreactivity, a proposed prefibrillar aggregate found in AD, was found to accumulate throughout the frontal cortices of postmortem human GM1 gangliosidosis, Sandhoff disease, and Tay–Sachs disease brains. Together, these results establish an association between the accumulation of gangliosides, autophagic vacuoles, and the intraneuronal accumulation of proteins associated with AD.
Diabetes Impairs Cortical Plasticity and Functional Recovery Following Ischemic Stroke
Authors: Sweetnam Danielle , Holmes Andrew , Tennant Kelly A. , Zamani Akram , Walle Mark , Jones Paul , Wong Charles , Brown Craig E.
Published: April 2012

Diabetics are at greater risk of having a stroke and are less likely to recover from it. To understand this clinically relevant problem, we induced an ischemic stroke in the primary forelimb somatosensory (FLS1) cortex of diabetic mice and then examined sensory-evoked changes in cortical membrane potentials and behavioral recovery of forelimb sensory-motor function. Consistent with previous studies, focal stroke in non-diabetic mice was associated with acute deficits in forelimb sensorimotor function and a loss of forelimb evoked cortical depolarizations in peri-infarct cortex that gradually recovered over several weeks time. In addition, we discovered that damage to FLS1 cortex led to an enhancement of forelimb evoked depolarizations in secondary forelimb somatosensory (FLS2) cortex. Enhanced FLS2 cortical responses appeared to play a role in stroke recovery given that silencing this region was sufficient to reinstate forelimb impairments. By contrast, the functional reorganization of FLS1 and FLS2 cortex was largely absent in diabetic mice and could not be explained by more severe cortical infarctions. Diabetic mice also showed persistent behavioral deficits in sensorimotor function of the forepaw, which could not be rescued by chronic insulin therapy after stroke. Collectively these results indicate that diabetes has a profound effect on brain plasticity, especially when challenged, as is often the case, by an ischemic event. Further, our data suggest that secondary cortical regions play an important role in the restoration of sensorimotor function when primary cortical regions are damaged.
Glutamate Controls tPA Recycling by Astrocytes, Which in Turn Influences Glutamatergic Signals
Authors: Cassé Frédéric , Bardou Isabelle , Danglot Lydia , Briens Aurélien , Montagne Axel , Parcq Jérôme , Alahari Anuradha , Galli Thierry , Vivien Denis , Docagne Fabian
Published: April 2012

Tissue-type plasminogen activator (tPA) regulates physiological processes in the brain, such as learning and memory, and plays a critical role in neuronal survival and neuroinflammation in pathological conditions. Here we demonstrate, by combining mousein vitroandin vivodata, that tPA is an important element of the cross talk between neurons and astrocytes. The data show that tPA released by neurons is constitutively endocytosed by astrocytes via the low-density lipoprotein-related protein receptor, and is then exocytosed in a regulated manner. The exocytotic recycling of tPA by astrocytes is inhibited in the presence of extracellular glutamate. Kainate receptors of astrocytes act as sensors of extracellular glutamate and, via a signaling pathway involving protein kinase C, modulate the exocytosis of tPA. Further, by thus capturing extracellular tPA, astrocytes serve to reduce NMDA-mediated responses potentiated by tPA. Overall, this work provides the first demonstration that the neuromodulator, tPA, may also be considered as a gliotransmitter.
Adenosine Release during Seizures Attenuates GABAAReceptor-Mediated Depolarization
Authors: Ilie Andrei , Raimondo Joseph V. , Akerman Colin J.
Published: April 2012

Seizure-induced release of the neuromodulator adenosine is a potent endogenous anticonvulsant mechanism, which limits the extension of seizures and mediates seizure arrest. For this reason several adenosine-based therapies for epilepsy are currently under development. However, it is not known how adenosine modulates GABAergic transmission in the context of seizure activity. This may be particularly relevant as strong activation of GABAergic inputs during epileptiform activity can switch GABAAreceptor (GABAAR) signaling from inhibitory to excitatory, which is a process that plays a significant role in intractable epilepsies. We used gramicidin-perforated patch-clamp recordings to investigate the role of seizure-induced adenosine release in the modulation of postsynaptic GABAAR signaling in pyramidal neurons of rat hippocampus. Consistent with previous reports, GABAAR responses during seizure activity transiently switched from hyperpolarizing to depolarizing and excitatory. We found that adenosine released during the seizure significantly attenuated the depolarizing GABAAR responses and also reduced the extent of the after-discharge phase of the seizure. These effects were mimicked by exogenous adenosine administration and could not be explained by a change in chloride homeostasis mechanisms that set the reversal potential for GABAARs, or by a change in the conductance of GABAARs. Rather, A1R-dependent activation of potassium channels increased the cell's membrane conductance and thus had a shunting effect on GABAAR currents. As depolarizing GABAAR signaling has been implicated in seizure initiation and progression, the adenosine-induced attenuation of depolarizing GABAAR signaling may represent an important mechanism by which adenosine can limit seizure activity.
Genetic Evidence for a Contribution of EphA:EphrinA Reverse Signaling to Motor Axon Guidance
Authors: Dudanova Irina , Kao Tzu-Jen , Herrmann Julia E. , Zheng Binhai , Kania Artur , Klein Rüdiger
Published: April 2012

Repulsive Eph forward signaling from limb-derived ephrins guides the axons of lateral motor column (LMC) motor neurons. LMC axons also express ephrinAs, while their EphA receptors are expressed in the limb mesenchyme.In vitrostudies have suggested that reverse signaling from limb-derived EphA4 to axonal ephrinAs might result in attraction of LMC axons. However, genetic evidence for this function is lacking. Here we use the Dunn chamber turning assay to show that EphA proteins are chemoattractants and elicit fast turning responses in LMC neuronsin vitro. Moreover, ectopic expression of EphA4 in chick hindlimb changes the limb trajectory of LMC axons. Nervous system-specific deletion of EphA4 in mice resulted in fewer LMC axon projection errors than the ubiquitous deletion of EphA4. Additionally, a signaling-incompetent EphA4 mutant partially rescued guidance errors in the hindlimb, suggesting that limb-derived EphA4 contributes to the establishment of LMC projections. In summary, we provide evidence for a role of EphA:ephrinA attractive reverse signaling in motor axon guidance andin vivoevidence of in-parallel forward Eph and reverse ephrin signaling function in the same neuronal population.
Frontostriatal White Matter Integrity Mediates Adult Age Differences in Probabilistic Reward Learning: Figure 1.
Authors: Samanez-Larkin Gregory R. , Levens Sara M. , Perry Lee M. , Dougherty Robert F. , Knutson Brian
Published: April 2012

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.
Gating the Polarity of Endocannabinoid-Mediated Synaptic Plasticity by Nitric Oxide in the Spinal Locomotor Network
Authors: Song Jianren , Kyriakatos Alexandros , El Manira Abdeljabbar
Published: April 2012

The final motor output underlying behavior arises from an appropriate balance between excitation and inhibition within neural networks. Retrograde signaling by endocannabinoids adapts synaptic strengths and the global activity of neural networks. In the spinal cord, endocannabinoids are mobilized postsynaptically from network neurons and act retrogradely on presynaptic cannabinoid receptors to potentiate the locomotor frequency. However, it is still unclear whether mechanisms exist within the locomotor networks that determine the sign of the modulation by cannabinoid receptors to differentially regulate excitation and inhibition. In this study, using the lamprey spinal cordin vitro, we first report that 2-AG (2-arachidonyl glycerol) is mobilized by network neurons and underlies a form of modulation that is embedded within the locomotor networks. We then show that the polarity of the endocannabinoid modulation is gated by nitric oxide to enable simultaneously potentiation of excitation and depression of inhibition within the spinal locomotor networks. Our results suggest that endocannabinoid and nitric oxide systems interact to mediate inversion of the polarity of synaptic plasticity within the locomotor networks. Thus, endocannabinoid and nitric oxide shift in the excitation–inhibition balance to set the excitability of the spinal locomotor network.
Dopamine Modulation ofIhImproves Temporal Fidelity of Spike Propagation in an Unmyelinated Axon
Authors: Ballo Aleksander W. , Nadim Farzan , Bucher Dirk
Published: April 2012

We studied how conduction delays of action potentials in an unmyelinated axon depended on the history of activity and how this dependence was changed by the neuromodulator dopamine (DA). The pyloric dilator axons of the stomatogastric nervous system in the lobster,Homarus americanus, exhibited substantial activity-dependent hyperpolarization and changes in spike shape during repetitive activation. The conduction delays varied by several milliseconds per centimeter, and, during activation with realistic burst patterns or Poisson-like patterns, changes in delay occurred over multiple timescales. The mean delay increased, whereas the resting membrane potential hyperpolarized with a time constant of several minutes. Concomitantly with the mean delay, the variability of delay also increased. The variability of delay was not a linear or monotonic function of instantaneous spike frequency or spike shape parameters, and the relationship between these parameters changed with the increase in mean delay. Hyperpolarization was counteracted by a hyperpolarization-activated inward current (Ih), and the magnitude ofIhcritically determined the temporal fidelity of spike propagation. Pharmacological block ofIhincreased the change in delay and the variability of delay, and increasingIhby application of DA diminished both. Consequently, the temporal fidelity of pattern propagation was substantially improved in DA. Standard measurements of changes in excitability or delay with paired stimuli or tonic stimulation failed to capture the dynamics of spike conduction. These results indicate that spike conduction can be extremely sensitive to the history of axonal activity and to the presence of neuromodulators, with potentially important consequences for temporal coding.
Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment
Authors: Wang Jun , Ferruzzi Mario G. , Ho Lap , Blount Jack , Janle Elsa M. , Gong Bing , Pan Yong , Gowda G. A. Nagana , Raftery Daniel , Arrieta-Cruz Isabel , Sharma Vaishali , Cooper Bruce , Lobo Jessica , Simon James E. , Zhang Chungfen , Cheng Alice , Qian Xianjuan , Ono Kenjiro , Teplow David B. , Pavlides Constantine , Dixon Richard A. , Pasinetti Giulio M.
Published: April 2012

While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. In this study, we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of ∼400 nm. Most importantly, we report for the first time that a biosynthetic epicatechin metabolite, 3′-O-methyl-epicatechin-5-O-β-glucuronide (3′-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3′-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in AD and other forms of dementia.
A Role for the Calmodulin Kinase II-Related Anchoring Protein (αkap) in Maintaining the Stability of Nicotinic Acetylcholine Receptors
Authors: Mouslim Chakib , Aittaleb Mohamed , Hume Richard I. , Akaaboune Mohammed
Published: April 2012

αkap, a muscle specific anchoring protein encoded within theCamk2agene, is thought to play a role in targeting multiple calcium/calmodulin kinase II isoforms to specific subcellular locations. Here we demonstrate a novel function of αkap in stabilizing nicotinic acetylcholine receptors (AChRs). Knockdown of αkap expression with shRNA significantly enhanced the degradation of AChR α-subunits (AChRα), leading to fewer and smaller AChR clusters on the surface of differentiated C2C12 myotubes. Mutagenesis and biochemical studies in HEK293T cells revealed that αkap promoted AChRα stability by a ubiquitin-dependent mechanism. In the absence of αkap, AChRα was heavily ubiquitinated, and the number of AChRα was increased by proteasome inhibitors. However, in the presence of αkap, AChRα was less ubiquitinated and proteasome inhibitors had almost no effect on AChRα accumulation. The major sites of AChRα ubiquitination reside within the large intracellular loop and mutations of critical lysine residues in this loop to arginine increased AChRα stability in the absence of αkap. These results provide an unexpected mechanism by which αkap controls receptor trafficking onto the surface of muscle cells and thus the maintenance of postsynaptic receptor density and synaptic function.
Fire on the Mountain
Authors: Van Horn Gavin
Published: April 2012

Aldo Leopold’s essay ‘Thinking Like a Mountain’ was more than a parable about a redemptive personal moment; it was the fruition of a larger effort on Leopold’s part to effectively communicate the fundamentals of a ‘land ethic’. I explore striking narrative antecedents to Leopold’s ‘green ?re’ moment, including writings by Henry David Thoreau and Ernest Thompson Seton, and articulate why wolves provided the quintessential totem animal for communicating a larger ecological ‘drama’. Both these literary antecedents and the essay’s ongoing—sometimes surprising—impacts are worth exploring, not just because of the high regard in which the essay itself is held but because Leopold succeeded in navigating a problem that persists in our own time: the gap between scienti?cally informed understandings of the world and effectively communicating those understandings to the public.
‘Thinking like a Mystic’
Authors: Pryor Ashley
Published: April 2012

Most Aldo Leopold scholars acknowledge P.D. Ouspensky’s in?uence on both Leopold’s proto-Land Ethic of the early 1920s and insight that the earth is more than inert material and is itself a ‘living thing’. The possibility that Leopold’s later philosophical, ecological, and spiritual development were in?uenced by his reading of Ouspensky, however, has received little attention. A close reading of Leopold’s ‘Thinking Like a Mountain’, as well as key passages of A Sand County Almanac through the theoretical lens of Ouspensky’s analysis in Tertium Organum, suggests that Leopold’s frequent attribution of affective and psychical states, especially love, to nonhuman beings (and Leopold’s most curious and haunting suggestion that dead things too might listen) is consistent with Ouspensky’s theory if not a direct heir to it.
Building Receptivity
Authors: Norlock Kathryn J.
Published: April 2012

Aldo Leopold’s A Sand County Almanac emphasizes values of receptivity and perceptivity that appear to be mutually reinforcing, critical to an ecological conscience, and cultivatable through concrete and embodied experience. His priorities bear striking similarities to elements of the ethics of care elaborated by feminist philosophers, especially Nel Noddings, who notably recommended receptivity, direct and personal experience, and even shared Leopold’s attentiveness to joy and play as sources of moral motivation. These commonalities are so fundamental that ecofeminists can and should see Leopold as a philosophical ally. The three ecofeminist scholars who have devoted the most concerted attention to Leopold’s work argue that his Land Ethic is not, and does not provide a basis for, an ecofeminist ethic. I dispute the main criticisms of these scholars, and conclude that ecofeminists should attend more often to Leopold’s work, which extends possibilities for excellent praxis.
The Worldview Concept and Aldo Leopold’s Project of ‘World View’ Remediation
Authors: Callicott J. Baird
Published: April 2012

A Sand County Almanac has a single overarching theme and purpose—worldview remediation: to replace the biblical with an evolutionary-ecological worldview. The epistemological foundations of the worldview concept were established by Kant, who rendered ‘reality’ phenomenal and potentially plural. No worldview is true, but competing worldviews may be adjudicated by the application of three criteria of tenability: (1) self-consistency; (2) consistency with and comprehensive of all phenomenal experience; (3) aesthetical and spiritual satisfaction. A Sand County Almanac’s ‘Marshland Elegy’ and ‘On a Monument to the Pigeon’ explore the aesthetic and spiritual potentiality of the theory of evolution. ‘Odyssey’, ‘Thinking Like a Mountain’, and ‘Song of the Gavilan’ explore the aesthetic and spiritual potentiality of ecology. ‘The Land Ethic’ explores the axiological and normative implication of the evolutionary-ecological worldview. Subsequent changes in ecology problematize the summary moral maxim of ‘The Land Ethic’. Worldview remediation is now more challenging, but also more necessary than ever.
List of Reviewers
Authors: Witt Joseph D
Published: April 2012

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Microfossils in micrites from Serra da Bodoquena (MS), Brazil: taxonomy and paleoenvironmental implications
Authors: Utida Giselle , Petri Setembrino , Oliveira Emiliano C. , Boggiani Paulo C.
Published: April 2012

Microfossils present in Quaternary micrites from Serra da Bodoquena, Mato Grosso do Sul State, Brazil, are here described for the first time. The studied taxa are: a) ostracods: Candona sp., Candonopsis sp., Cyclocypris sp., Cypria sp., Cypridopsis sp., Notodromas sp., Ilyocypris sp., Cyprideis sp., Wolburgiopsis cf. chinamuertensis (Musacchio 1970), Darwinula sp. and 5 morphotypes; b) microgastropod Acrobis sp., and c) Characeae remains and gyrogonites Chara sp.. The presence of these microfossils suggests clear-water shallow lacustrine paleoenvironments and the presence of aquatic vegetation. Similarities between microfossils and the living taxa suggest possible Holocene ages for these deposits, which is in accordance with previous C14 dates.
Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient
Authors: Ibrahim Karim Yaqub , Carvalho Noemia Barbosa , Moura Maria Luisa do Nascimento , Piza Felipe Maia de Toledo , Mimicos Evanthia Vetos , Ho Yeh-Li , França Francisco Oscar de Siqueira
Published: April 2012

We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.
Diagnose foliar na cana-de-açúcar: VIII - nota sobre o efeito da quantidade de chuva nos teores foliares de N, P e K na cana - soca
Authors: Malavolta E. , Carvalho J. Guedes de
Published: April 2012

Usando-se os teores de N, P e K de folha +3 encontradas em amostragens sucessivas e a quantidade de chuvas que caiu nos 2 meses anteriores, foram calculadas as equações de regressão correspondentes. Em seguida, calculou-se o aumento esperado nos teores de N e P devido a queda de 200 mm de chuva 2 meses antes da amostragem.
Diagnose foliar na cana-de-açúcar: IX - efeito da quantidade de chuva nos teores foliares de Ca, Mg e S na cana-soca (nota)
Authors: Malavolta E. , Carvalho J. Guedes de
Published: April 2012

Os teores de Ca, Mg e S da folha +3 encontrados em amostragens sucessivas e a quantidade de chuvas que caiu nos 2 meses anteriores foram usados no cálculo de correlação entre as duas variáveis e no estabelecimento de equações de regressão. Em seguida foram calculadas os aumentos esperados nos níveis foliares de Mg e S em função de 200 mm de precipitação, sessenta dias antes da amostragem.
Suscetibilidade do pimentão (Capsicum annuum L.) a inundações temporárias do sistema radicular
Authors: Cruciani Décio Eugênio , Minami Keigo
Published: April 2012

O presente trabalho foi conduzido no Departamento de Agricultura e Horticultura da ESALQ, de outubro de 1981 a fevereiro de 1982. Teve como objetivos determinar a sensibilidade da cultura de pimentão a inundações temporárias do sistema radicular, a fim de quantificar os prejuízos de sua produção em fases distintas do seu ciclo vegetativo. O trabalho procura contribuir ao estabelecimento do coeficiente de drenagem, necessário em projetos que visem a utilização dessa solanácea, com base nos seus parâmetros de produção. Os resultados revelaram que o pimentão é sensível a condições de excesso de água no solo, com acentuados prejuízos na produção, em número e peso de frutos, quando as plantas foram submetidas a 2, 4 e 6 dias de inundação. Em vista dos resultados, recomenda-se que o tempo de drenagem da zona radicular dessa cultura deve ser inferior a 2 dias.
Efeitos de reguladores vegetais na produtividade do tomateiro
Authors: Castro Paulo R.C. , Pastore José C. , Demétrio Clarice G.B.
Published: April 2012

Estudaram-se em condições de casa de vegetação, os efeitos de reguladores vegetais no peso, número e peso médio dos frutos de tomateiro (Lycopersiaon esculentun Mill.). Cloreto (2-cloroetil) trimetilamônio (CCC) 1.000 ppm e ácido succínico-2,2-dimetilhidrazida (SADH) 2.000 ppm foram aplicados antes da abertura floral e duas semanas depois, ácido 3-clorofenoxipropiônico (Fruitone-CPA) 50 ppm pulverizado 4 semanas após a antese das primeiras flores e ácido N-acetil tiazolidin-4-carboxílico com ácido fólico (Ergostim) 0,75 ml/l aplicado durante a antese das primeiras flores dos 3 cachos. Observou-se que o SADH reduziu o peso, número e peso médio dos frutos de tomateiro, Ergostim diminuiu o peso total e o peso médio dos frutos produzidos. Aplicação de Fruitone-CPA mostrou uma tendência de aumentar o peso total e o número de frutos, colhidos.
Estudo sobre o controle de qualidade do palmito (Euterpe edulis Mart.) processado por apertização
Authors: Nogueira João N. , Fonseca Homero
Published: April 2012

Com o objetivo de melhorar as condições de seu controle de qualidade, foi estudada a influência de alguns parâmetros nos atributos de qualidade do palmito (Euterpe edulis Mart.) processado por apertização. Os resultados mostraram que, dependendo dos tratamentos empregados, alguns atributos de qualidade podem sofrer variações importantes durante o processamento e armazenamento do produto enlatado.
Nutrição mineral de hortaliças: XXXVIII. deficiências de macronutrientes em alface (Juactuoa sativa L.), cv. Brasil e Clause's Aurélia
Authors: Garcia Lina L.C. , Haag Henrique P. , Diehl Neto Walter
Published: April 2012

Com os objetivos de: a) obter o quadro síntomatológico das deficiências de macronutrientes; b) relacionar o quadro sintomatológico a composição química das plantas, foi conduzido um ensaio em casa de vegetação, cultivando o cv. Brasil 48 e Clause's Aurélia em solução nutritiva, tendo como substrato silica finamente moida. Os tratamentos foram: completo, omissão de nitrogênio, omissão de fósforo, omissão de potássio, omissão de cálcio, omissão de magnésio e omissão de enxofre. Os autores observaram e identificaram as deficiências de nutrientes que se traduziram por sintomas típicos e facilmente identificáveis, com exceção do enxofre. As concentrações de macronutrientes nas folhas para plantas sem sintomas e com sintomas para o cultivar Brasil 48 foram: N% 3,37 a 1,86; P% 0,44 a 0,16; K% 5,54 a 1,32; Ca% 0,97 a 0,20; Mg% 0,35 a 0,05. As concentrações de S% foram iguais a 0,16. Para o cv. Clause's Aurélia, as concentrações nas folhas correspondentes a plantas sem e com deficiências foram: N% 3,02 a 2,68; P% 0,71 a 0,19; K% 7,7 a 1,54; Ca% 1 ,47 a 0,31; Mg% 0,43 a 0,10 e S% 0,25 a 0,24.
Nutrição mineral de hortaliças. XLIX. concentração e acúmulo de macronutrientes em alface (Lactuca sativa L.) Cv. Brasil 48 e Clause's Aurélia
Authors: Garcia Lina L.C. , Haag Henrique Paulo , Minami Keigo , Dechen Antônio R.
Published: April 2012

Com os objetivos de: - obter e analisar o crescimento dos cultivares; - determinar a concentração e extração de macronutrientes nas plantas em função da idade. Foi realizado um ensaio de campo no qual os dois cultivares foram plantados colhendo-se plantas aos 20, 30, 40, 50, 60 e 70 dias de idade após o transplante. Determinou-se a produção de matéria seca e as concentrações de macronutrientes. Observou-se que o crescimento e a extração de nutrientes foi lenta no ensaio sofrendo aceleração a partir dos 30 dias, mantendo-se intensos e não alcançando o ponto de máxima acumulação até a colheita. O crescimento expresso de produção de matéria seca, foi semelhante para os dois cultivares, 12,7 g/planta para o cultivar Brasil 48 e 12,5 g/planta para o cultuvar Clause's Aurélia. Porcentagens acima de 59 da matéria seca e entre 43% a 69% dos nutrientes foram acumuladas pelos dois cultivares durante os 20 dias que antecederam a colheita. Uma planta do cultivar Brasil 48 acumulou por ocasião da colheita 469 mg N, 100 mg P, 1017 mg K, 161 mg Ca, 47 mg Mg e 21 mg S. Quantidades semlehantes foram acumuladas por uma planta do cultivar Clause's Aurélia - 410 mg N, 100 mg P, 759 mg K, 200 mg Ca, 52 mg Mg e 21 mg S.
Efeitos de estimulantes vegetais na frutificação do tomateiro 'Miguel Pereira'
Authors: Carlucci Marisa Vazquez , Castro Paulo R.C.
Published: April 2012

Na cultura do tomateiro tem-se utilizado técnicas avançadas de cultivo, sendo que a aplicação de estimulantes vegetais, usada como técnica complementar, poderá levar a um aumento significativo de produção. O presente estudo teve como finalidade determinar a ação de estimulantes vegetais na frutificação do tomateiro Lycopersicon esculentum cv. Miguel Pereira. Em condições de casa de vegetação realizou-se a aplicação na planta inteira de Cytozyme (bioestimulante composto por citocinina, ênzimos, micronutrientes: Zn, Fe, Cu, Mn, Bo, combinados com derivados de etoxilato-siloxano e aminoácidos) e Ergostim (ácido N-acetil tiazolidin-4-carboxílico com ácido fólico). Cytozyme 5 ml/l foi aplicado 70 dias após o plantio, aos 70 e 84 dias após plantio. Ergostim 1,5 ml/l foi pulverizado na florescência de cada cacho; e Ergostim 3,0 ml/l na florescência, fixação dos frutos do segundo cacho e quando os mesmos atingiram metade do desenvolvimento. Os frutos maduros dos três primeiros cachos foram colhidos semanalmente em dez coletas no período de 07 de novembro a 09 de janeiro. Observou-se o número, peso e comprimento dos frutos, assim como o número de flores e de flores abortadas. Determinou-se também a classificação dos frutos e a germinação das sementes. Foi verificado que Cytozyme 5 ml/l, 70 e 65 dias após plantio aumentou o número e o comprimento dos frutos e o número total de flores. Ergostim não afetou a frutificação e floração do tomateiro, nem a formação e germinação das sementes.
Efeitos do Trylone e Tomatotone na frutificação do tomateiro 'Miguel Pereira'
Authors: Carlucci Marisa Vazquez , Castro Paulo R.C.
Published: April 2012

Técnicas culturais avançadas utilizadas atualmente no cultivo do tomateiro têm levado à aplicação de reguladores vegetais com a finalidade de promover aumentos na produtividade de forma quantitativa e qualitativa. O presente ensaio teve como objetivo determinar a ação do ácido 2-hidroximetil-4-clorofenoxiacético (Trylone) e do ácido para-clorofenoxiacético (Tomatotone) na frutificação do tomateiro (Lycopersicon esculentum cv. Miguel Pereira). Em condições de casa de vegetação efetuou-se pulverização dirigida aos cachos com Trylone a 10 ml/l e 20 ml/l e Tomatotone a 10 ml/l e 20 ml/l, na antese das duas primeiras flores dos três primeiros cachos. Foram coletados os frutos maduros dos três primeiros cachos, em dez colheitas efetuadas no período de 7 de novembro a 9 de janeiro. Foi observado o número, peso e comprimento dos frutos, assim como o número de flores e de flores abortadas. Foi também determinada a classificação dos frutos e a germinação das sementes. Verificou-se que o Tomatotone 10 ml/l e 20 ml/l aumentou o número, comprimento e peso dos frutos de tomateiro; Tomatotone 20 ml/l induziu a formação de frutos de melhor classificação. Tomatotone e Trylone diminuíram o número de flores abortadas. Trylone 20 ml/l aumentou a percentagem de frutos paternocârpicos.
Nutrição mineral de hortaliças: LII-crescimento do pepino (Cucumis sativus L.) var. Aodai cultivado em condições de campo
Authors: Solís Francisco Augusto Mora , Haag Henrique Paulo , Minami Keigo
Published: April 2012

Plantas de pepino (Cucumis sativus L.) var. Aodai, foram cultivadas no município de Piracicaba, SP (LS: 22° 41'31' e LW: 47º31'01''), em solo Terra Roxa Estruturada, série Luiz de Queiroz, devidamente adubado. O delineamento estatístico foi o inteiramente casualizado com quatro repetições, com amostragens das plantas aos 12, 24, 36, 48, 60, 72 e 84 dias após a emergência, sendo subdivididas em caule, folhas do caule, folhas dos ramos, flores masculinas, flores femininas e frutos. As partes da planta foram lavadas e secadas, e atingido o peso constante do material, determinou-se o peso da matéria seca. As seguintes conclusões foram obtidas: a) o crescimento é contínuo, acelerando-se até a maturidade da planta com a incorporação da matéria seca produzida pelos ramos e suas folhas, e pela contribuição dos frutos; b) aos 84 dias da cultura no campo, a quantidade de matéria seca estimada, produzida pela parte aérea, por planta, atingiu: 63,4 g no caule e ramos (25,7%); 88,4 g nas folhas (41,4%); 61,5 g nas flores e frutos (28,8%); sendo o total produzido pela planta de.... 213,28 g.