bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence-Free Medicine: Forgoing Evidence in Clinical Decision Making
Authors: Tonelli Mark R.
Published: April 2009

Despite being the central concept to evidence-based medicine (EBM), evidence remains an elusive and controversial notion. Ongoing debates regarding evidence primarily serve to confuse and obfuscate. Examination of the nature of medical decision making without any appeal to evidence reveals a more complete understanding of the optimal practice of clinical medicine. An “evidence-free medicine” allows for the incorporation of a variety of facts and warrants, reasons and reasoning, into clinical decisions. The relative weighting of potentially conflicting warrants for a medical decision comprises the critical process of clinical judgment. Forgoing evidence allows clinical medicine to once again be a personal and prudential undertaking, arising from and focused on the individual patient.
Theory-Based Medicine and the Role of Evidence: Why the Emperor Needs New Clothes, Again
Authors: Giacomini Mita
Published: April 2009

The evidence-based medicine (EBM) movement was established to combat capricious reasoning in clinical care, particularly arguments from authority. Critique of authority and appraisal of evidence remain EBM’s core values and should be revisited in this era of EBM’s maturity and influence. We are now faced with a new form of under-questioned authority: evidence from well-designed and methodologically appraised randomized controlled trials (RCTs). RCT evidence is now prized even when it is incapable of providing meaningful information—in particular, when underlying causal theory is inscrutable. Experimental trial evidence of the effectiveness of remote intercessory prayer provides an illustrative case that highlights systematic scientific blind spots in the institutions of EBM. Medicine—even evidence-based medicine—is theory-based at its core. EBM must cultivate greater capacity to address the crucial role of theory in both the generation and use of experimental evidence.
Evolution in the Post-Genome Era
Authors: Hughes Austin L.
Published: April 2009

The advent of nucleotide sequence data has created a new era in evolutionary biology. With theoretical underpinnings derived from the work of the late Motoo Kimura, evolutionary concepts have played a key role in the development of the field of bioinformatics. However, the maturation of modern evolutionary biology has been hindered by a conception of natural selection as an all-powerful force shaping every aspect of phenotypic evolution. In new books, Joram Piatigorsky and Michael Lynch provide a corrective to some outdated views and thus provide a glimpse of what the evolutionary biology of the 21st century may look like.
Are You Getting the Message?: The Effects of SimCom on the Message Received by Deaf, Hard of Hearing, and Hearing Students
Authors: Tevenal Stephanie , Villanueva Miako
Published: April 2009

When hearing speakers address a mixed audience of hearing and deaf participants, 1 they have a choice of three methods by which to convey the information in their presentation. They may choose to use English and provide an English-to-ASL interpreter, use ASL and provide an ASL-to-English interpreter, or use simultaneous communication (SimCom). The choice to use SimCom (i.e., to speak and sign at the same time) is based in part on the idea that equivalent information will be communicated directly and simultaneously to both hearing and deaf audience members. This study examines the effects of SimCom on the degree of correct information received by deaf, hard of hearing, and hearing students. Our objective is to ascertain whether a qualitative difference exists in the comprehensible input in order to determine whether all of the students are receiving equivalent information in the classroom. Previous research on SimCom shows that the auditory and visual messages produced are not equivalent; the current research seeks to determine whether the received messages are equivalent. Direct feedback from deaf, hard of hearing, and hearing students is the indicator of message equivalence. Our methodology consisted of showing several short video clips from various presentations given using SimCom. Participants viewed the clips and then responded to one or two questions about the information presented in them. The number of correct responses was tallied and compared across groups. Results show that the messages received by the different cohorts are not equivalent; therefore, the use of SimCom in the classroom needs to be reconsidered.
Meemul Tziij: An Indigenous Sign Language Complex of Mesoamerica
Authors: Fox Tree Erich
Published: April 2009

This article examines sign languages that belong to a complex of indigenous sign languages in Mesoamerica that K'iche'an Maya people of Guatemala refer to collectively as Meemul Tziij. It explains the relationship between the Meemul Tziij variety of the Yukatek Maya village of Chican (state of Yucatán, Mexico) and the hitherto undescribed Meemul Tziij variety used six hundred kilometers away in the K'ichee' Maya township of Nahualá (department of Sololá, Guatemala). Consistent with indigenous beliefs, these languages are distinct and unrelated to the European and Euramerican sign languages. The sign language varieties in question likely belong to a single ancient language family derived from an ancient signed lingua franca, given the fact that indigenous communities scattered across Mesoamerica still use the languages. The conclusion summarizes findings, discusses implications for Mesoamerican history, and suggests directions for future research.
"A Grave and Gracious Woman": Deaf People and Signed Language in Colonial New England
Authors: Carty Breda , Macready Susannah , Sayers Edna Edith
Published: April 2009

This article discusses a new source about the lives of deaf people in the first century of the American colonies—Increase Mather's An Essay for the Recording of Illustrious Providences (1684). One of the chapters in his Essay describes a signing deaf couple, Sarah and Matthew Pratt. Born in 1628 and 1640, they lived several decades before the first record of a signing deaf person on Martha's Vineyard. This source gives new insights into the use of signed language in colonial New England, and the way laypeople went about educating deaf children before deaf education became the job of "experts". Sarah and Matthew Pratt seem to have had a high level of participation in the Puritan community at Weymouth, Massachusetts, throughout their lives. Mather also discusses a wide range of international sources on deaf people's education, communication and spirituality, giving us a unique picture of what people knew about deafness in the seventeenth century, and showing that even mainstream writers were starting to become interested in deaf people. This is a valuable new source which contributes to the history of deaf education, sign language linguistics, and broader cultural history.
The Real "Toll" of A. G. Bell: Lessons about Eugenics
Authors: Greenwald Brian H.
Published: April 2009

Historian Brian Greenwald offers a revisionist interpretation of Bell. He reviews Bell's role and influence within the American eugenics movement and shows that Bell had the respect of the most prominent American eugenicists. His intimate knowledge of deafness, from personal experience with his mother and wife and from his studies of deaf people on Martha's Vineyard, caused American eugenicists to defer to him on matters related to the deaf population. Greenwald argues, therefore, that Bell could have been extremely destructive to deaf people's right to marry and reproduce as they wished. The opportunity was available for Bell to advocate invasive government eugenic measures against the American deaf population, but he did not do so. Greenwald believes that several factors explain Bell's behavior, but he concludes that Bell's personal contact with deaf people throughout his life "humanized and personalized" his approach.
Immunohistochemical Analysis of Laryngeal Muscles in Normal Horses and Horses With Subclinical Recurrent Laryngeal Neuropathy
Authors: Rhee Hannah S. , Steel Catherine M. , Derksen Frederik J. , Robinson N. Edward , Hoh Joseph F.Y.
Published: April 2009

We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber-type profiles of the right and left cricoarytenoideus dorsalis (CAD) and arytenoideus transversus (TrA) muscles of six horses without laryngoscopic evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal muscles of small mammals. Muscles from three horses showed fiber-type grouping bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping suggests that denervation and reinnervation of fibers had occurred, and that these horses had subclinical RLN. There was a virtual elimination of 2x fibers in these muscles, accompanied by a significant increase in the percentage of 2a and slow fibers, and hypertrophy of these fiber types. The results suggest that multiple pathophysiological mechanisms are at work in early RLN, including selective denervation and reinnervation of 2x muscle fibers, corruption of neural impulse traffic that regulates 2x and slow muscle fiber types, and compensatory hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN are able to remain subclinical by compensatory hypertrophy of surviving muscle fibers.
Sensory Weighting of Force and Position Feedback in Human Motor Control Tasks
Authors: Mugge Winfred , Schuurmans Jasper , Schouten Alfred C. , van der Helm Frans C. T.
Published: April 2009

In daily life humans integrate force and position feedback from mechanoreceptors, proprioception, and vision. With handling relatively soft, elastic objects, force and position are related and can be integrated to improve the accuracy of an estimate of either one. Sensory weighting between different sensory systems (e.g., vision and proprioception) has been extensively studied. This study investigated whether similar weighting can be found within the proprioceptive sensory system, more specifically between the modalities force and position. We hypothesized that sensory weighting is governed by object stiffness: position feedback is weighted heavier on soft objects (large deflections), while force feedback is weighted heavier on stiff objects (small deflections). Subjects were instructed to blindly reproduce either position or force while holding a one degree of freedom haptic manipulator that simulated a linear spring with one of four predetermined stiffnesses. In catch trials the spring was covertly replaced by a nonlinear spring. The difference in force (ΔF) and position (ΔX) between the regular and the catch trials revealed the sensory weighting between force and position feedback. A maximum likelihood estimation model predicted that: (1) task instruction did not affect the outcome measures, and (2) force feedback is weighted heavier with increasing object stiffness as was hypothesized. Both effects were found experimentally, and the subjects' sensory weighting closely resembled the optimal model predictions. To conclude, this study successfully demonstrated sensory weighting within the proprioceptive system.
Homeostatic and Nonhomeostatic Modulation of Learning in Human Motor Cortex
Authors: Jung Patrick , Ziemann Ulf
Published: April 2009

Motor learning is important throughout life for acquisition and adjustment of motor skill. The extent of motor learning may be modulated by the history of motor cortex activity, but little is known which metaplasticity rule (homeostatic vs nonhomeostatic) governs this interaction. Here, we explored in nine healthy adults the effects of three different paired associative stimulation (PAS) protocols on subsequent learning of rapid thumb flexion movements. PAS resulted in either a long-term potentiation (LTP)-like increase in excitability of the stimulated motor cortex (PASLTP), or a long-term depression (LTD)-like decrease (PASLTD), or no change (control condition, PASCON). Learning was indexed by the increase in peak acceleration of the trained movement. Delays of 0 and 90 min between PAS and motor practice were tested. At the 0 min delay, PASLTDstrongly facilitated motor learning (homeostatic interaction), and PASLTPalso facilitated learning, although to a lesser extent (nonhomeostatic interaction). At the 90 min delay, PASLTDfacilitated learning, whereas PASLTPdepressed learning (interactions both homeostatic). Therefore, facilitation of learning by previous brain stimulation occurs primarily and most effectively through homeostatic interactions, but at the 0 min delay, nonhomeostatic mechanisms such as LTP-induced blockade of LTD and nonsaturated LTP-induced facilitation of learning might also play a role. The present findings demonstrate that motor learning in humans can be modulated by noninvasive brain stimulation and suggest the possibility of enhancing motor relearning in defined neurological patients.
Short-Latency Visual Input to the Subthalamic Nucleus Is Provided by the Midbrain Superior Colliculus
Authors: Coizet Véronique , Graham John H. , Moss Jonathan , Bolam J. Paul , Savasta Marc , McHaffie John G. , Redgrave Peter , Overton Paul G.
Published: April 2009

The subthalamic nucleus (STN) is one of the principal input nuclei of the basal ganglia. Using electrophysiological techniques in anesthetized rats, we show that the STN becomes responsive to visual stimuli at short latencies when local disinhibitory injections are made into the midbrain superior colliculus (SC), an important subcortical visual structure. Significantly, only injections into the lateral, but not medial, deep layers of the SC were effective. Corresponding disinhibition of primary visual cortex also was ineffective. Complementary anatomical analyses revealed a strong, regionally specific projection from the deep layers of the lateral SC to neurons in rostral and dorsal sectors of the STN. Given the retinocentric organization of the SC, these results suggest that lower-field stimuli represented in the lateral colliculus have a direct means of communicating with the basal ganglia via the STN that is not afforded to visual events occurring in the upper visual field.
Differential Regulation of Gonadotropin-Releasing Hormone Neuron Activity and Membrane Properties by Acutely Applied Estradiol: Dependence on Dose and Estrogen Receptor Subtype
Authors: Chu Zhiguo , Andrade Josefa , Shupnik Margaret A. , Moenter Suzanne M.
Published: April 2009

Gonadotropin-releasing hormone (GnRH) neurons are critical to controlling fertility.In vivo, estradiol can inhibit or stimulate GnRH release depending on concentration and physiological state. We examined rapid, nongenomic effects of estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from ovariectomized mice with ionotropic GABA and glutamate receptors blocked. Estradiol was bath applied and measurements completed within 15 min. Estradiol from high physiological (preovulatory) concentrations (100 pm) to 100 nmenhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization amplitudes (ADP), and reducedIAHPand enhancedIADP. The reduction ofIAHPwas occluded by previous blockade of calcium-activated potassium channels. These effects were mimicked by an estrogen receptor (ER) β-specific agonist and were blocked by the classical receptor antagonist ICI182780. ERα or GPR30 agonists had no effect. The acute stimulatory effect of high physiological estradiol on firing rate was dependent on signaling via protein kinase A. In contrast, low physiological levels of estradiol (10 pm) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10 pmestradiol reduced firing of GnRH neurons; this was mimicked by an ERα agonist. ERα agonists reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to these cells. In contrast, ERβ agonists increased GABA transmission and postsynaptic response. These data suggest rapid intrinsic and network modulation of GnRH neurons by estradiol is dependent on both dose and receptor subtype. In cooperation with genomic actions, nongenomic effects may play a role in feedback regulation of GnRH secretion.
Acid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior
Authors: Coryell Matthew W. , Wunsch Amanda M. , Haenfler Jill M. , Allen Jason E. , Schnizler Mikael , Ziemann Adam E. , Cook Melloni N. , Dunning Jonathan P. , Price Margaret P. , Rainier Jon D. , Liu Zhuqing , Light Alan R. , Langbehn Douglas R. , Wemmie John A.
Published: April 2009

No animal models replicate the complexity of human depression. However, a number of behavioral tests in rodents are sensitive to antidepressants and may thus tap important underlying biological factors. Such models may also offer the best opportunity to discover novel treatments. Here, we used several of these models to test the hypothesis that the acid-sensing ion channel-1a (ASIC1a) might be targeted to reduce depression. Genetically disrupting ASIC1a in mice produced antidepressant-like effects in the forced swim test, the tail suspension test, and following unpredictable mild stress. Pharmacologically inhibiting ASIC1a also had antidepressant-like effects in the forced swim test. The effects of ASIC1a disruption in the forced swim test were independent of and additive to those of several commonly used antidepressants. Furthermore, ASIC1a disruption interfered with an important biochemical marker of depression, the ability of stress to reduce BDNF in the hippocampus. Restoring ASIC1a to the amygdala of ASIC1a−/−mice with a viral vector reversed the forced swim test effects, suggesting that the amygdala is a key site of ASIC1a action in depression-related behavior. These data are consistent with clinical studies emphasizing the importance of the amygdala in mood regulation, and suggest that ASIC1a antagonists may effectively combat depression.
The Translational Repressors Nanos and Pumilio Have Divergent Effects on Presynaptic Terminal Growth and Postsynaptic Glutamate Receptor Subunit Composition
Authors: Menon Kaushiki P. , Andrews Shane , Murthy Mala , Gavis Elizabeth R. , Zinn Kai
Published: April 2009

Pumilio (Pum) is a translational repressor that binds selectively to target mRNAs and recruits Nanos (Nos) as a corepressor. In the larval neuromuscular system, Pum represses expression of the translation factor eIF-4E and the glutamate receptor subunit GluRIIA. Here, we show that Nos, like Pum, is expressed at the neuromuscular junction (NMJ) and in neuronal cell bodies. Surprisingly, however, Nos and Pum have divergent functions on both the presynaptic and postsynaptic sides of the NMJ. Innosmutant andnosRNA interference larvae, the number of NMJ boutons is increased, whereas loss of Pum reduces the bouton number. On the postsynaptic side, Nos acts in opposition to Pum in regulating the subunit composition of the glutamate receptor. NMJ active zones are associated with GluRIIA- and GluRIIB-containing receptor clusters. Loss of Nos causes downregulation of GluRIIA and increases the levels of GluRIIB. Consistent with this finding, the electrophysiological properties of NMJs lacking postsynaptic Nos suggest that they use primarily GluRIIB-containing receptors. Nos can regulate GluRIIB in the absence of GluRIIA, suggesting that the effects of Nos on GluRIIB levels are at least partially independent of synaptic competition between GluRIIA and GluRIIB. Nos is a target for Pum repression, and Pum binds selectively to the 3′ untranslated regions of thenosandGluRIIAmRNAs. Our results suggest a model in which regulatory interplay among Pum, Nos, GluRIIA, and GluRIIB could cause a small change in Pum activity to be amplified into a large shift in the balance between GluRIIA and GluRIIB synapses.
Importin 13 Regulates Neurotransmitter Release at theDrosophilaNeuromuscular Junction
Authors: Giagtzoglou Nikolaos , Lin Yong Qi , Haueter Claire , Bellen Hugo J.
Published: April 2009

In an unbiased genetic screen designed to isolate mutations that affect synaptic transmission, we have isolated homozygous lethal mutations inDrosophila importin 13(imp13). Imp13 is expressed in and around nuclei of both neurons and muscles. At the larval neuromuscular junction (NMJ),imp13affects muscle growth and formation of the subsynaptic reticulum without influencing any presynaptic structural features. In the absence ofimp13, the probability of release of neurotransmitter and quantal content is increased, yet the abundance of the postsynaptic receptors and the amplitude of miniature excitatory junctional potentials are not affected. Interestingly,imp13is required in the muscles to control presynaptic release. Thus,imp13is a novel factor that affects neurotransmitter release at the fly NMJ. Its role in the context of synaptic homeostasis is discussed.
Distinct Encoding of Spatial and Nonspatial Visual Information in Parietal Cortex
Authors: Freedman David J. , Assad John A.
Published: April 2009

It is well established that the primate parietal cortex plays an important role in visuospatial processing. Parietal cortex damage in both humans and monkeys can lead to behavioral deficits in spatial processing, and many parietal neurons, such as in the macaque lateral intraparietal area (LIP), are strongly influenced by visual–spatial factors. Several recent studies have shown that LIP neurons can also convey robust signals related to nonspatial factors, such as color, shape, and the behavioral context or rule that is relevant for solving the task at hand. But what is the relationship between the encoding of spatial factors and more abstract, nonspatial, influences in LIP? To examine this, we trained monkeys to group visual motion patterns into two arbitrary categories, and recorded the activity of LIP neurons while monkeys performed a categorization task in which stimuli were presented either inside each neuron's receptive field (RF) or at a location in the opposite visual field. While the activity of nearly all LIP neurons showed strong spatial dependence (i.e., greater responses when stimuli were presented within neurons' RFs), we also found that many LIP neurons also showed reliable encoding of the category membership of stimuli even when the stimuli were presented away from neurons' RFs. This suggests that both spatial and nonspatial information can be encoded by individual LIP neurons, and that parietal cortex may be a nexus for the integration of visuospatial signals and more abstract task-dependent information during complex visually based behaviors.
p75 and TrkA Signaling Regulates Sympathetic Neuronal Firing Patterns via Differential Modulation of Voltage-Gated Currents
Authors: Luther Jason A. , Birren Susan J.
Published: April 2009

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) act through the tropomyosin-related receptor tyrosine kinases (Trk) and the pan-neurotrophin receptor (p75) to regulate complex developmental and functional properties of neurons. While NGF activates both receptor types in sympathetic neurons, differential signaling through TrkA and p75 can result in widely divergent functional outputs for neuronal survival, growth, and synaptic function. Here we show that TrkA and p75 signaling pathways have opposing effects on the firing properties of sympathetic neurons, and define a mechanism whereby the relative level of signaling through these two receptors sets firing patterns via coordinate regulation of a set of ionic currents. We show that signaling through the p75 pathway causes sympathetic neurons to fire in a phasic pattern showing marked accommodation. Signaling through the NGF-specific TrkA, on the other hand, causes cells to fire tonically. Neurons switch rapidly between firing patterns, on the order of minutes to hours. We show that changes in firing patterns are caused by neurotrophin-dependent regulation of at least four voltage-gated currents: the sodium current and the M-type, delayed rectifier, and calcium-dependent potassium currents. Neurotrophin release, and thus receptor activation, varies among somatic tissues and physiological state. Thus, these data suggest that target-derived neurotrophins may be an important determinant of the characteristic electrical properties of sympathetic neurons and therefore regulate the functional output of the sympathetic nervous system.
TrkB Signaling Is Required for Both the Induction and Maintenance of Tissue and Nerve Injury-Induced Persistent Pain
Authors: Wang Xidao , Ratnam Joseline , Zou Bende , England Pamela M. , Basbaum Allan I.
Published: April 2009

Activation of primary afferent nociceptors produces acute, short-lived pain, and tissue or nerve injury induces long-term enhancement of nociceptive processing, manifested as hypersensitivity to thermal and mechanical stimulation. Here we used a chemical–genetic and pharmacological approach to study the contribution of the receptor tyrosine kinase, type 2 (TrkB) to the generation and maintenance of injury-induced persistent pain. We performed the studies in wild-type mice and transgenic (TrkBF616A) mice that express mutant but fully functional TrkB receptors. By injecting a small molecule derivative of the protein kinase inhibitor protein phosphatase 1 (1NM-PP1), it is possible to produce highly selective inhibition of TrkB autophosphorylation in adult mice, without interfering with the activity of other protein kinases. We report that oral administration of 1NM-PP1, at doses that blocked phosphorylation of TrkB in the spinal cord, had no effect in behavioral tests of acute heat, mechanical, or chemical pain sensitivity. However, the same pretreatment with 1NM-PP1 prevented the development of tissue- or nerve injury-induced heat and mechanical hypersensitivity. Established hypersensitivity was transiently reversed by intraperitoneal injection of 1NM-PP1. Although interfering with TrkB signaling altered neither acute capsaicin nor formalin-induced pain behavior, the prolonged mechanical hypersensitivity produced by these chemical injuries was prevented by 1NM-PP1 inhibition of TrkB signaling. We conclude that TrkB signaling is not only an important contributor to the induction of heat and mechanical hypersensitivity produced by tissue or nerve injury but also to the persistence of the pain.
ABCG2 Is Upregulated in Alzheimer's Brain with Cerebral Amyloid Angiopathy and May Act as a Gatekeeper at the Blood–Brain Barrier for Aβ1–40Peptides
Authors: Xiong Huaqi , Callaghan Debbie , Jones Aimee , Bai Jianying , Rasquinha Ingrid , Smith Catherine , Pei Ke , Walker Douglas , Lue Lih-Fen , Stanimirovic Danica , Zhang Wandong
Published: April 2009

Alzheimer's disease (AD) is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition in cerebrovessels occurs in many AD patients and results in cerebral amyloid angiopathy (AD/CAA). Since Aβ can be transported across blood–brain barrier (BBB), aberrant Aβ trafficking across BBB may contribute to Aβ accumulation in the brain and CAA development. Expression analyses of 273 BBB-related genes performed in this study showed that the drug transporter, ABCG2, was significantly upregulated in the brains of AD/CAA compared with age-matched controls. Increased ABCG2 expression was confirmed by Q-PCR, Western blot, and immunohistochemistry. Abcg2 was also increased in mouse AD models, Tg-SwDI and 3XTg. Aβ alone or in combination with hypoxia/ischemia failed to stimulate ABCG2 expression in BBB endothelial cells; however, conditioned media from Aβ-activated microglia strongly induced ABCG2 expression. ABCG2 protein in AD/CAA brains interacted and coimmunoprecipitated with Aβ. Overexpression of hABCG2 reduced drug uptake in cells; however, interaction of Aβ1–40with ABCG2 impaired ABCG2-mediated drug efflux. The role of Abcg2 in Aβ transport at the BBB was investigated in Abcg2-null and wild-type mice after intravenous injection of Cy5.5-labeled Aβ1–40or scrambled Aβ40–1. Optical imaging analyses of live animals and their brains showed that Abcg2-null mice accumulated significantly more Aβ in their brains than wild-type mice. The finding was confirmed by immunohistochemistry. These results suggest that ABCG2 may act as a gatekeeper at the BBB to prevent blood Aβ from entering into brain. ABCG2 upregulation may serve as a biomarker of CAA vascular pathology in AD patients.
Protracted Withdrawal from Alcohol and Drugs of Abuse Impairs Long-Term Potentiation of Intrinsic Excitability in the Juxtacapsular Bed Nucleus of the Stria Terminalis
Authors: Francesconi Walter , Berton Fulvia , Repunte-Canonigo Vez , Hagihara Kazuki , Thurbon David , Lekic Dusan , Specio Sheila E. , Greenwell Thomas N. , Chen Scott A. , Rice Kenner C. , Richardson Heather N. , O'Dell Laura E. , Zorrilla Eric P. , Morales Marisela , Koob George F. , Sanna Pietro Paolo
Published: April 2009

The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala. Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the corticotropin-releasing factor (CRF) system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF1) antagonist R121919 [2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine)], but not of the CRF2antagonist astressin2-B, normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the intrinsic properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal.
Monkey Prefrontal Cortical Pyramidal and Putative Interneurons Exhibit Differential Patterns of Activity Between Prosaccade and Antisaccade Tasks
Authors: Johnston Kevin , DeSouza Joseph F. X. , Everling Stefan
Published: April 2009

Previous studies have shown that prefrontal cortex (PFC) neurons carry task-related activity; however, it is largely unknown how this selectivity is implemented in PFC microcircuitry. Here, we exploited known differences in extracellular action potential waveforms, and antidromic identification, to classify PFC neurons as putative pyramidal or interneurons, and investigate their relative contributions to task-selectivity. We recorded the activity of prefrontal neurons while monkeys performed a blocked pro/antisaccade task in which they were required to look either toward or away from a peripheral visual stimulus. We found systematic differences in activity between neuron classes. Putative pyramidal neurons had higher stimulus-related activity on antisaccade trials, whereas putative interneurons exhibited greater activity for prosaccades. These findings suggest that task-selectivity in the PFC may be shaped by interactions between these neuronal classes. They are also consistent with the robust deficits in antisaccade performance frequently observed in disease states associated with PFC dysfunction.
Synthesis, crystal structure, spectroscopic and thermal characterization of (Hampy)2[Ni(pydc)2(H2O)2] · 2 H2O
Authors: Çolak Alper Tolga , Akduman Demet , Yesilel Okan Zafer , Büyükgüngör Orhan
Published: April 2009

A supramolecular complex, bis(2-amino-3-methylpyridinium) diaquabis(pyridinedicarboxylato)nicke-late(II) dihydrate, (Hampy)2[Ni(pydc)2(H2O)2] · 2 H2O (ampy = 2-amino-3-methylpyridine, H2pydc = 2,5-pyridinedicarboxylic acid or isocinchomeronic acid) (1) has been prepared and characterized by elemental, spectral (IR and UV-vis.), thermal analysis, magnetic measurement and single crystal X-ray diffraction techniques. Ni(II) ion exhibits a distorted octahedral geometry coordinated by nitrogen and oxygen atoms of two pyridinedicarboxylate ligands, oxygen atoms from the two aqua ligands. The supramolecular network is constructed by N–H · · · O strong hydrogen bonds, π-π and C–H · · · π interactions.
2-Hydroxyacetophenone arylhydrazones. Supramolecular arrangements based on C–H · · · O(H), CH · · · O(NO), N–H · · · O(H), N–H · · · O(NO), C–H · · · π or π · · · π interactions
Authors: Baddeley Thomas C. , de Souza França Luciana , Howie R. Alan , de Lima Geraldo M. , Skakle Janet M.S. , de Souza Jose Dias , Wardell James L. , Wardell Solange M.S.V
Published: April 2009

Crystal structures, NMR and IR spectra and EI-MS+ of 2-hydroxyacetophenone arylhydrazones, 2-HOC6H4C(Me) = NNHC6H4Y (1: Y = 2-O2N, 3-O2N, 4-O2N, 4-Me, 4-MeO, H and 4-I) are reported. Two polymorphs of (1: Y = 2-O2N), triclinic and orthorhombic forms, have been identified. While strong intramolecular O–H · · · N(H) hydrogen bonds and layers of molecules are found for all solid 1, supramolecular arrangements of individual members are various and are derived from different combinations of intermolecular interactions, which include C–H · · · O(H), C–H · · · O(NO), N–H · · · O(H), N–H · · · O(NO) and C–H · · · π hydrogen bonds, as well as π · · · π stacking interactions. Intermolecular N–H · · · O hydrogen-bonds involving the phenolic OH group are present in (1: Y = H, 4-O2N, 4-Me, 4-MeO and 4-I), but are absent in ortho-and tri-(1: Y = 2-O2N) and (1: Y = 3-O2N). Instead, ortho-(1: Y = 2-O2N) exhibits intermolecular C–H · · · O(H) hydrogen bonds, while no intermolecular hydrogen bonds involving the OH group occur in either triclinic-(1: Y = 2-O2N) or (1: Y = 3-O2N). EI+-MS revealed the presence of oligomeric species, such as (nM + M′)+, where n is up to 4, and M′ = H, Na or K.
Mutation in Bovine β-Carotene Oxygenase 2 Affects Milk Color
Authors: Berry S D , Davis S R , Beattie E M , Thomas N L , Burrett A K , Ward H E , Stanfield A M , Biswas M , Ankersmit-Udy A E , Oxley P E , Barnett J L , Pearson J F , van der Does Y , MacGibbon A H K , Spelman R J , Lehnert K , Snell R G
Published: April 2009

β-Carotene biochemistry is a fundamental process in mammalian biology. Aberrations either through malnutrition or potentially through genetic variation may lead to vitamin A deficiency, which is a substantial public health burden. In addition, understanding the genetic regulation of this process may enable bovine improvement. While many bovine QTL have been reported, few of the causative genes and mutations have been identified. We discovered a QTL for milk β-carotene and subsequently identified a premature stop codon in bovine β-carotene oxygenase 2 (BCO2), which also affects serum β-carotene content. The BCO2 enzyme is thereby identified as a key regulator of β-carotene metabolism.
Evidence That Msh1p Plays Multiple Roles in Mitochondrial Base Excision Repair
Authors: Pogorzala Leah , Mookerjee Shona , Sia Elaine A
Published: April 2009

Mitochondrial DNA is thought to be especially prone to oxidative damage by reactive oxygen species generated through electron transport during cellular respiration. This damage is mitigated primarily by the base excision repair (BER) pathway, one of the few DNA repair pathways with confirmed activity on mitochondrial DNA. Through genetic epistasis analysis of the yeast Saccharomyces cerevisiae, we examined the genetic interaction between each of the BER proteins previously shown to localize to the mitochondria. In addition, we describe a series of genetic interactions between BER components and the MutS homolog MSH1, a respiration-essential gene. We show that, in addition to their variable effects on mitochondrial function, mutant msh1 alleles conferring partial function interact genetically at different points in mitochondrial BER. In addition to this separation of function, we also found that the role of Msh1p in BER is unlikely to be involved in the avoidance of large-scale deletions and rearrangements.
Effect of mobile cation on zeolite-polyamide thin film nanocomposite membranes
Authors: Lind Mary Laura , Jeong Byeong-Heon , Subramani Arun , Huang Xiaofei , Hoek Eric M.V.
Published: April 2009

Hybrid zeolite-polyamide thin film nanocomposite (TFN) reverse osmosis membranes were synthesized by incorporating Linde type A (LTA)-type zeolite molecular sieve nanocrystals in the interfacial polymerization reaction used to form polyamide thin films. Nanocrystals were prepared with two different mobile cations (Na+ and Ag+) exchanged within the LTA crystal matrix. Incorporation of molecular sieve nanocrystals into polyamide thin films during interfacial polymerization was verified by infrared spectroscopy. Both TFN membranes exhibited higher water permeability, while maintaining similar salt rejection to pure polyamide thin film composite membranes. Nanocomposite thin films containing LTA nanocrystals in the silver form (AgA) produced a greater increase in water permeability than those in the sodium form (NaA). Furthermore, AgA-TFN membranes exhibited more hydrophilic and smooth interfaces, which appeared to inhibit adhesion of bacteria cells onto the membranes. The AgA nanocrystals exhibited significant bactericidal activity; however, when encapsulated within polyamide thin films the antimicrobial activity was significantly reduced.
Micro/nanostructure observation of microwave-heated Fe3O4
Authors: Yoshikawa Noboru , Cao Ziping , Louzguin Dmitri , Xie Guoqiang , Taniguchi Shoji
Published: April 2009

To investigate the microwave (MW) processing of Fe3O4, for which occurrence of decrystallization has been reported, the micro/nanostructures of MW-heated Fe3O4 powder were observed in this study. The specimens were irradiated by 2.45 GHz MW at the position of magnetic (H)-field maximum in a TE10 single mode applicator. The specimen was heated well above the Curie temperature in H-field. The heated specimen above 1000 °C revealed the glass-like surface with the diminished x-ray diffraction (XRD) peak intensities. They resemble the reported features of decrystallization in an earlier work performed at Penn State University. According to the XRD profiles of the MW-heated specimens, formation of FeO and shift of Fe3O4 peaks to the lower angle with the broadened width were observed. To account for the findings, a model is presented that phase separation occurred into FeO and Fe3O4 resulting in an increased lattice parameter due to the increased oxygen content. This activity is caused by local transport of oxygen in nanoscale. Considering the shape of the main XRD Fe3O4 peak with a shoulder and the existence of halo in nanobeam diffraction (NBD), amorphous phase areas exist. As a result of transmission electron microscopy observation, it was shown that they were in nanoscaled localized regions, and it was not confirmed that the glass-like morphologies (or decrystallized morphologies) are totally amorphous. The observed micro/nanostructures and mechanism of the amorphous phase formation were discussed considering the Fe-O phase diagram.
Examination of an analytical phase-transformation model
Authors: Liu F. , Ma Y.Z. , Hu X. , Yang G.C.
Published: April 2009

A comparison between results of a recently published quasi-exact solution of the temperature integral used for the Avrami model of isochronal phase transformations and an analytical phase-transformation model in relation to exact solutions from numerical integration has been performed. The results for the transformed fraction from the quasi-exact solution are more precise than the corresponding results of the analytical model, whereas the results for the transformation rate from both models are sufficiently precise for the nucleation mode of site saturation or continuous nucleation. It has been further shown that an analytical solution of the transformation rate cannot be obtained using a quasi-exact solution of the temperature integral in case of mixed nucleation, and that the results of the corresponding solution with the analytical model substantially alleviate the influence of the approximated temperature integral. By this method, an analytical approach of modeling, which can substantially alleviate the deviation (of model prediction) arising from approximations to the temperature integral, has been developed. The proposed approach has been successfully applied to experimental data of the crystallization of bulk amorphous Pd-Ni-P-Cu alloys.
Positron lifetime and Doppler broadening study of defects in hydrogen charged Al–Mg alloys
Authors: Wang Xiaowei , Zhong Yurong , Wang Baoyi , Zhang Hongyan
Published: April 2009

The results of positron lifetime and Doppler broadening spectrum of defects in the hydrogen charged non-heat treatable 5xxx Al alloys are presented in this work. The yield stress of the sample was reduced for about 20 MPa after hydrogen was charged. A similar trend was observed in positron lifetime measurement, as the average lifetime τav descended remarkably to almost the level of Al matrix. The change in coincidence Doppler broadening (CDB) spectroscopy was also significant, exhibited by the characteristic change in CDB radio curves of a sample before and after hydrogen was charged. After hydrogen charging, there is an obvious enhancement in the high momentum region compensating dehancement in the low momentum region. This indicates the existence of hydrogen filling effect. The vacancies around the Mg atoms should be preferential filling sites for hydrogen because Mg has a strong affinity for hydrogen. The formation of an Mg–H bond parallel to a grain boundary is an important factor in weakening the grain boundary cohesion.
Improved ductility of aged Mg-9Al-1Zn alloy strip by electropulsing treatment
Authors: Jiang Yanbin , Tang Guoyi , Shek Chanhung , Zhu Yaohua , Guan Lei , Wang Shaonan , Xu Zhuohui
Published: April 2009

The effect of electropulsing treatment (EPT) on the microstructure and mechanical properties of aged Mg-9Al-1Zn alloy strip was studied. EPT was found to accelerate tremendously the β phase spheroidization in the aged Mg-9Al-1Zn alloy. This improved microstructure exhibits excellent mechanical properties, that is, increasing elongation to failure significantly without loss of tensile strength. The spheroidization of the β phase during EPT was attributed to the reduction of the nucleation thermodynamic barrier and enhancement of atomic diffusion.
Glass-forming region of the Ni–Nb–Ta ternary metal system determined directly from n-body potential through molecular dynamics simulations
Authors: Dai Y. , Li J.H. , Che X.L. , Liu B.X.
Published: April 2009

An n-body Ni–Nb–Ta potential is constructed to conduct molecular dynamics simulations using 129 solid solution models with various compositions. Comparing the relative stability of solid solutions versus their disordered counterparts, simulations determine two critical solid-solubility lines, which define a region in the composition triangle. If an alloy is located inside the defined region, a disordered state is energetically favored; if it is located outside, a crystalline solid solution is preserved. The region is therefore named as the metallic glass-forming region.
Structural, optical, and electronic properties of room temperature ferromagnetic GaCuN film grown by hybrid physical-chemical vapor deposition
Authors: Choi Chul Hwan , Kim Seon Hyo , Lee Hyo Jin , Jeong Yoon Hee , Jung Myung Hwa
Published: April 2009

Ferromagnetic Cu-doped GaN film was grown on a GaN-buffered sapphire (0001) substrate by a hybrid physical-chemical-vapor-deposition method (HPCVD). The GaCuN film (Cu: 3.6 at.%) has a highly c-axis-oriented hexagonal wurtzite crystal structure, which is similar to GaN buffer but without any secondary phases such as metallic Cu, CuxNy, and CuxGay compounds. Two weak near-band edge (NBE) emissions at 3.38 eV and donor-acceptor-pair (DAP) transition at 3.2 eV with a typical strong broad yellow emission were observed in photoluminescence spectra for GaN buffer. In contrast, the yellow emission was completely quenched in GaCuN film because Ga vacancies causing the observed yellow emission in undoped GaN were substituted by Cu atoms. In addition, GaCuN film exhibits a blue shift of NBE emission, which could be explained with the +2 oxidation state of Cu ions, replacing +3 Ga ions resulting in band gap increment. The valance sate of Cu in GaCuN film was also confirmed by x-ray photoelectron spectroscopy (XPS) analysis. The GaCuN film shows ferromagnetic ordering and possesses a residual magnetization of 0.12 emu/cm3 and a coercive field of 264 Oe at room temperature. The unpaired spins in Cu2+ ions (d9) are most likely to be responsible for the observed ferromagnetism in GaCuN.
Nanostructure of the nanopores in anodic aluminum oxide films used as template to fabricate Ag nanowires
Authors: Zhang Junping , Kielbasa Jerrold E. , Carroll David L.
Published: April 2009

Well-ordered nanoporous anodic aluminum oxide (AAO) templates have been prepared on aluminum substrates by a two-step anodization process. A voltage-controlled branching method was successfully used to thin the barrier layer of the AAO template. The nanostructures of the pores, the branched subpores, and the barrier layer in the AAO template were studied in association with the anodization process and barrier layer thinning methods. Results demonstrate the voltage-controlled branching method is a facile and effective way to thin the barrier layer. Uniform silver nanowires can be easily fabricated using alternating current (ac) electrodeposition into the pores of AAO after redressing the barrier layer.
Structure, electrical, and thermal expansion properties of (La0.8Ca0.2)(Cr0.9–xCo0.1Nix)O3–δinterconnect materials for intermediate temperature solid oxide fuel cells
Authors: Fu Yen-Pei , Wang Hsin-Chao
Published: April 2009

The microstructure, lattice parameters, electrical conductivity, thermal expansion, and mechanical properties of (La0.8Ca0.2)(Cr0.9–xCo0.1Nix)O3–δ(x= 0.03, 0.06, 0.09, 0.12) were systematically investigated in this work. Nickel doping of (La0.8Ca0.2)(Cr0.9Co0.1)O3–δis an effective way of increasing the thermal expansion coefficient (TEC) and stabilizing the high-temperature phase transformation from rhombohedral to tetragonal. As the nickel-doped content increases, the TEC increases parabolically by TEC (x) (ppm/°C) = 10.575 + 63.3x−240x2(x= 0.03−0.12). The electrical conductivity of (La0.8Ca0.2)(Cr0.9–xCo0.1Nix)O3–δspecimens increases systematically with increasing nickel substitution in the range of 0.03 ≤x≤ 0.09 and reaches a maximum for the composition of (La0.8Ca0.2)(Cr0.81Co0.1Ni0.09)O3–δ(σ850 °C∼60.36 S/cm). There is a slight increase in the fracture toughness with increasing nickel doping content, and the fracture toughness is strongly affected by the grain size. It seems that there is an increase in the fracture toughness with decreasing grain size. However, the microhardness does not significantly depend on the grain size in this study. The (La0.8Ca0.2)(Cr0.81Co0.1Ni0.09)O3–δspecimen shows high electrical conductivity, a moderate thermal expansion coefficient, and nearly linear thermal expansion behavior from room temperature to 800 °C. It will be suitable for interconnect materials for intermediate temperature solid oxide fuel cells (IT-SOFCs).