bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-partum fever and cerebral palsy in Khartoum, Sudan
Authors: Abdullahi Hala , Satti Mohamed , Rayis Duria A , Imam Abdulmutalab M , Adam Ishag
Published: April 2013

Background

Cerebral palsy (CP) is a major cause of childhood disability. There are various maternal and neonatal predictors associated with the development of CP, and they are variable across different populations. This case–control study was designed to investigate maternal and neonatal predictors of CP at Khartoum pediatric neurology clinics. Data (maternal sociodemographic characteristics and neonatal expected predictors) were collected from mothers of children with CP and healthy controls using questionnaires.

Results

One hundred and eleven cases of CP and 222 controls were included. Spastic CP was the most common type (69.4%). In logistic regression, maternal age, parity, birth weight, and sex were not associated with CP. However, maternal fever (OR = 8.4, CI = 2.3–30.5; P = 0.001), previous neonatal death (OR = 5.4, CI = 1.8–16.2; P = 0.003), and poor sucking (OR = 30.5, CI = 10.0–93.1; P < 0.001) were predictors of CP.

Conclusions

Fever during labor is a significant risk factor for developing CP in children. Further efforts are required for labor management to prevent CP in this setting.
Lexical Change in Farming Terms
Authors: DeBary Sandra
Published: April 2013

During the 30-year period between the collection of the original LAGS (Linguistic Atlas of the Gulf States) data and the collection of this data in 2001, the field of agriculture has undergone sweeping changes, and the people of southwest Georgia, as a rule, are less focused on agriculture, having turned to other occupations. By replicating a small portion of the original LAGS study using modern speakers as subjects, the study shows that lexical change in farming words during this time stems from changing agricultural methods, technological advancements, and the increased availability of information. The various Linguistic Atlas Projects provide contemporary researchers with a wealth of data that can and should be mined in conjunction with new research to study the forces involved in language change.
OST4 is a subunit of the mammalian oligosaccharyltransferase required for efficient N-glycosylation
Authors: Dumax-Vorzet Audrey , Roboti Peristera , High Stephen
Published: April 2013

The eukaryotic oligosaccharyltransferase (OST) is a membrane-embedded protein complex that catalyses N-glycosylation of nascent polypeptides in the lumen of the endoplasmic reticulum (ER), a highly conserved biosynthetic process that enriches protein structure and function. All OSTs contain a homologue of the catalytic STT3 subunit, although in many cases this is assembled with several additional components that influence function. In S. cerevisiae, one such component is Ost4p, an extremely small membrane protein that appears to stabilise interactions between subunits of assembled OST complexes. OST4 has been identified as a putative human homologue, but to date neither its relationship to the OST complex, nor its role in protein N-glycosylation, have been directly addressed. Here, we establish that OST4 is assembled into native OST complexes containing either the catalytic STT3A or STT3B isoforms. Co-immunoprecipitation studies suggest that OST4 associates with both STT3 isoforms and ribophorin I, an accessory subunit of mammalian OSTs. These presumptive interactions are perturbed by a single amino acid change to the transmembrane region of OST4. Using siRNA knockdowns and native gel analysis, we show that OST4 plays an important role in maintaining native OST complexes stability. Hence, upon OST4 depletion well defined OST complexes are partially destabilised and a novel ribophorin I-containing subcomplex is detected. Strikingly, cells depleted of either OST4 or STT3A show a remarkably similar defect in the N-glycosylation of endogenous prosaposin, and we conclude that OST4 most likely promotes co-translational N-glycosylation by stabilising STT3A-containing OST isoforms.
Regulation of IRS1/Akt insulin signaling by microRNA-128a during myogenesis
Authors: Motohashi Norio , Alexander Matthew S. , Shimizu-Motohashi Yuko , Myers Jennifer A. , Kawahara Genri , Kunkel Louis M.
Published: April 2013

Skeletal muscle possesses a strong ability to regenerate following injury, a fact that has been largely attributed to satellite cells. Satellite cells are skeletal muscle stem cells located beneath the basal lamina of the myofiber and are the principal cellular source of growth and regeneration in skeletal muscle. MicroRNAs (miRNAs) play key roles in modulating several cellular processes by targeting multiple mRNAs that comprise of a single or multiple signaling pathway. Several miRNAs have been shown to regulate satellite cell activity, such as miRNA-489 which functions to maintain satellite cells in a quiescent state. While muscle-specific miRNAs have been identified, many of the molecular mechanisms that regulate myogenesis that are regulated by miRNAs still remain unknown. In this study, we have shown that miR-128a is highly expressed in brain and skeletal muscle, and increases during myoblast differentiation. MiR-128a was found to regulate the target genes involved in insulin signaling, which include: Insr, Irs1, and Pik3r1 at both the mRNA and protein level. Overexpression of miR-128a in myoblasts inhibited cell proliferation by targeting IRS1. Conversely, inhibition of miR-128a induced myotube maturation and myofiber hypertrophy in vitro and in vivo. Moreover, our results demonstrate that miR-128a expression levels are negatively controlled by tumor necrosis factor-alpha (TNF-α). TNF-α promoted myoblast proliferation and myotube hypertrophy by facilitating IRS1/Akt signaling via a direct decrease of miR-128a expression in both myoblasts and myotubes. In summary, we demonstrate that miR-128a regulates myoblast proliferation and myotube hypertrophy, and provides a novel mechanism through which IRS1-dependent insulin signaling is regulated in skeletal muscle.
Polymeric immunoglobulin receptor traffics through two distinct apically targeted pathways in primary lacrimal gland acinar cells
Authors: Xu Shi , Ma Linlin , Evans Eunbyul , Okamoto Curtis T. , Hamm-Alvarez Sarah F.
Published: April 2013

The polymeric immunoglobulin receptor (pIgR) mediates transcytosis of dimeric immunoglobulin A (dIgA) and its release into mucosal secretions. The present study reveals the complexity of the trafficking of pIgR to the apical plasma membrane in epithelial cells with exocrine secretory functions; in rabbit lacrimal gland acinar cells (LGACs), trafficking of pIgR involves both the transcytotic pathway and one arm of the regulated secretory pathway. By specifically tracking pIgR endocytosed from the basolateral membrane, we show here that the Rab11a-regulated transcytotic pathway mediates the basal-to-apical transport of pIgR, and that pIgR sorted into the transcytotic pathway does not access the regulated secretory pathway. However, previous work in LGACs expanded in the present study has shown that some pIgR is localized to Rab3D-enriched mature secretory vesicles (SVs). Myosin Vb and myosin Vc motors modulate release of proteins from the Rab11a-regulated transcytotic pathway and the Rab3D-enriched secretory pathway in LGACs, respectively. Confocal fluorescence microscopy and biochemical assays showed that inhibition of myosin Vb and myosin Vc activity by overexpression of their dominant-negative mutants each significantly but differentially impaired aspects of apically targeted pIgR trafficking and secretory component release, suggesting that these motors function to regulate pIgR trafficking in both the transcytotic and exocytotic pathways. Intriguingly, a second mature SV population enriched in Rab27b was devoid of pIgR cargo, suggesting the specialization of Rab3D-enriched mature SVs to carry a particular subset of cargo proteins from the trans-Golgi network to the apical plasma membrane.
microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn
Authors: Ninio-Many Lihi , Grossman Hadas , Shomron Noam , Chuderland Dana , Shalgi Ruth
Published: April 2013

Fyn, a member of the Src family kinases (SFKs) has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. microRNAs (miRNAs) play a major role in post-transcriptional repression of proteins expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor suppressing miRNA that is down-regulated in several cancer cell types and based on our bioinformatics studies, we chose to examine Fyn's post-transcription regulation by miR-125a-3p, in a model of HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p, after which the activity of Fyn-downstream-proteins such as FAK, paxillin and Akt, proteins known to be overexpressed in various tumors, is also reduced. On a broader level, we showed that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p as well as by numerous cancer cell lines showing a significant down-regulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, implying it has a therapeutic potential in overexpressed Fyn-related diseases.
Sox9 modulates cell survival and adipogenic differentiation of multipotent adult rat mesenchymal stem cells
Authors: Stöckl Sabine , Bauer Richard , Bosserhoff Anja , Göttl Claudia , Grifka Joachim , Grässel Susanne
Published: April 2013

Sox9 is a key transcription factor in early chondrogenesis with distinct roles in differentiation processes and during embryonic development. Here, we report that Sox9 modulates cell survival and contributes to the commitment of MSC to adipogenic or osteogenic differentiation lineage. Sox9 activity level affect the expression of the key transcription factor in adipogenic differentiation, C/EBPß, and moreover, cyclin D1 mediated, the expression of osteogenic marker osteocalcin in undifferentiated adult bone marrow derived rat mesenchymal stem cells (rMSC).

Introducing a stable Sox9 knockdown in undifferentiated rMSC resulted in a marked decrease in proliferation rate and an increase in apoptotic activity. This was linked to a profound upregulation of p21 and cyclin D1 gene and protein expression accompanied with an induction of caspase 3/7 activity and an inhibition of Bcl-2.

We observed that Sox9 silencing provoked a delayed S-phase progression and an increased nuclear localization of p21. The protein stability of cyclin D1 was induced in the absence of Sox9 presumably as a function of altered p38 signalling.

In addition, the major transcription factor for adipogenic differentiation, C/EBPß, was repressed after silencing Sox9. The nearly complete absence of C/EBPß protein due to increased destabilization of the C/EBPß mRNA and the impact on osteocalcin gene expression and protein synthesis, suggests that a delicate balance of Sox9 level is not only imperative for proper chondrogenic differentiation of progenitor cells, but also affects the adipogenic and most likely osteogenic differentiation pathways of MSC.

Our results identified Sox9 as an important link between differentiation, proliferation and apoptosis in undifferentiated adult rat mesenchymal stem cells, emphasizing the importance of the delicate balance of a precisely regulated Sox9 activity in MSC not only for proper skeletal development during embryogenesis but likely also for successful repair and regeneration of tissues and organs in adults.
Interphase nuclear matrix and metaphase scaffolding structures
Authors: Lewis Catherine D. , Lebkowski Jane S. , Daly Ann K. , Laemmli Ulrich K.
Published: April 2013

The protein compositions of purified metaphase chromosomes, nuclei and their residual scaffold and matrix structures, are reported. The protein pattern of nuclei on sodium dodecyl sulphate/ polyacrylamide gels is considerably more complex and rich in non-histone proteins than that of chromosomes. Nuclei contain about three to four times more non-histone proteins relative to their histones than chromosomes. Besides the protein components of the peripheral lamina, several protein bands are specific or at least highly enriched in nuclei. Conversely, two proteins X0 (33X 103Mr) and XI (37x103Mr) are highly enriched in the pattern of metaphase chromosomes.

We have compared morphologically the previously defined nuclear matrices type I and II. The type I nuclear matrix is composed of the known lamina proteins, which form the peripheral lamina structure, and a complex series of proteins that form the internal network of the matrix as observed by electron microscopy. This internal network is stabilized similarly to the metaphase scaffolding by metalloprotein interaction. Both the scaffolding and the internal network of the matrix dissociate if thiols or certain metal chelators are used in the extraction buffer. Under these conditions the resulting nuclear structure, called matrix type II, appears empty in the electron microscope, with the exception of some residual nucleolar material. This latter material can be extracted from the internal network by exhaustive treatment of the nuclei with RNase before extraction with high salt.

Immunoblotting and activity studies show RNA polymerase II to be tightly bound to the type I, but not to the type II matrix, or to the scaffolding structure. No polymerase II enzyme was detected in isolated metaphase chromosomes. Another nuclear enzyme, poly(ADP-ribose) polymerase is not bound to either of the residual nuclear matrices or to the scaffolding structures. The association of RNA polymerase with the internal network of the nuclear matrix is consistent with the idea that transcription occurs in close association with this structure.
The rRNA methyltransferase Bud23 shows functional interaction with components of the SSU processome and RNase MRP
Authors: Sardana Richa , White Joshua P. , Johnson Arlen W.
Published: April 2013

Bud23 is responsible for the conserved methylation of G1575 of 18S rRNA, in the P-site of the small subunit of the ribosome. bud23Δ mutants have severely reduced small subunit levels and show a general failure in cleavage at site A2 during rRNA processing. Site A2 is the primary cleavage site for separating the precursors of 18S and 25S rRNAs. Here, we have taken a genetic approach to identify the functional environment of BUD23. We found mutations in UTP2 and UTP14, encoding components of the SSU processome, as spontaneous suppressors of a bud23Δ mutant. The suppressors improved growth and subunit balance and restored cleavage at site A2. In a directed screen of 50 ribosomal trans-acting factors, we identified strong positive and negative genetic interactions with components of the SSU processome and strong negative interactions with components of RNase MRP. RNase MRP is responsible for cleavage at site A3 in pre-rRNA, an alternative cleavage site for separating the precursor rRNAs. The strong negative genetic interaction between RNase MRP mutants and bud23Δ is likely due to the combined defects in cleavage at A2 and A3. Our results suggest that Bud23 plays a role at the time of A2 cleavage, earlier than previously thought. The genetic interaction with the SSU processome suggests that Bud23 could be involved in triggering disassembly of the SSU processome, or of particular subcomplexes of the processome.
Anticoagulation; New Pharmacologic Methods to Prevent Venous Thromboembolism in Older Adults: A Meta-Analysis
Authors: Pebanco Glenn Dexter O , Kaiser Stephanie A , Haines Stuart T
Published: April 2013

OBJECTIVE

To conduct a meta-analysis of randomized controlled trials that used newly approved drugs to prevent venous thromboembolism (VTE) in older adults.

DATA SOURCES

PubMed, EMBASE, and International Pharmaceutical Abstracts (through July 2012).

STUDY SELECTION AND DATA EXTRACTION

Full-text clinical trial reports were included if they (1) had a randomized controlled design, (2) used a pharmacologic method approved or anticipated to be approved in the US, (3) enrolled at least 300 subjects, (4) enrolled subjects with a mean age of 65 years or older or performed a subgroup analysis in adults in that population, and (5) scored at least 7 of 8 on quality criteria for clinical trials. Twenty unique studies met the inclusion criteria.

DATA SYNTHESIS

The most common indications for pharmacologic VTE prophylaxis in the identified studies were orthopedic procedures involving the lower extremities and general surgery. Only 2 studies enrolled acutely ill patients admitted to hospital medical services. Fondaparinux (5 studies) was more effective than enoxaparin in preventing VTE (OR 0.5, 95% CI 0.37–0.67; p < 0.00001) but had more bleeding (OR 1.48, 95% CI 1.05–2.08; p = 0.03). Dabigatran 150 mg once daily (3 studies) was less effective than enoxaparin in preventing VTE (OR 1.30, 95% CI 1.09–1.56; p = 0.004) with a similar bleeding risk (OR 0.74, 95% CI 0.46–1.22; p = 0.24). Dabigatran 220 mg once daily (4 studies) was as effective as enoxaparin in preventing VTE (OR 1.02, 95% CI 0.83–1.26; p = 0.84) and had similar bleeding (OR 1.08, 95% CI 0.66–1.76; p = 0.76). Rivaroxaban (4 studies) was more effective than enoxaparin in preventing VTE (OR 0.38, 95% CI 0.23–0.61; p < 0.0001) with a trend toward a higher rate of bleeding (OR 1.8, 95% CI 0.90–3.60; p = 0.09). Apixaban (5 studies) was more effective than enoxaparin in preventing VTE (OR 0.64, 95% CI 0.43–0.96; p = 0.0002) and had a similar rate of bleeding (OR 0.71, 95% CI 0.42–1.21; p = 0.21).

CONCLUSIONS

When compared to enoxaparin, newer drugs exhibit slightly different safety and efficacy profiles when used for VTE prevention in older adults undergoing major orthopedic surgery. There are insufficient data for other indications. The benefits and risks of new pharmacologic methods of VTE prevention are unclear in the oldest old (age ≥85 years) and in those admitted to a hospital for an acute medical illness or to a skilled nursing facility.
Inappropriate Medication Administration Practices in Canadian Adult ICUs: A Multicenter, Cross-Sectional Observational Study
Authors: Kanji Salmaan , Lam Jason , Goddard Rob D , Johanson Christel , Singh Avinder , Petrin Lee , Coons Patricia , McIntyre Lauralyn A , Turgeon Alexis F
Published: April 2013

BACKGROUND

Critically ill patients often receive multiple medications via continuous intravenous infusion. Coadministration of multiple medications through the same port of a venous access device often is necessary but requires an assessment of compatibility.

OBJECTIVE

To describe the frequency of inappropriate coadministration of continuously infused medications via a Y-site and the use of intravenous catheters in patients in Canadian intensive care units (ICUs) in a multicenter, cross-sectional observational study.

METHODS

Data pertaining to medication compatibility via Y-site infusion (medication combinations known to be incompatible or not known to be compatible), frequency of specific medications administered via continuous infusion, and catheter use (median number, location, and types of venous catheters) were collected from medical records of 434 patients in the ICUs of 13 teaching hospitals in Canada.

RESULTS

Forty-six percent of patients were receiving 2 or more medication infusions simultaneously. Forty episodes of inappropriate coadministration of these infusions were identified in 37 patients. The prevalence of inappropriate coadministration of drugs via a Y-site port in all patients was 8.5% (95% CI 5.8–11.2). The prevalence of incompatible combinations via Y-site in patients with 2 or more medication infusions was 18.7%. Twenty-five of these 37 patients could have had their drug schedules rearranged into acceptable combinations, leaving 12 patients who would have required additional intravenous access to facilitate appropriate medication infusions. Median (range) number of central and peripheral venous access devices inserted per patient were 1 (0–4) and 1 (0–5), respectively. Seventeen of 95 patients with 2 or more central venous catheters could have had their medication infusions rearranged to render 1 catheter idle.

CONCLUSIONS

Inappropriate Y-site combinations of medications continuously infused in Canadian ICUs are common. Management of medication infusions could, however, have been optimized in most of these situations.
Adrenocorticotropic Hormone for the Treatment of West Syndrome in Children
Authors: Shumiloff Nicole A , Lam Weng Man , Manasco Kalen B
Published: April 2013

OBJECTIVE

To review the current literature on the efficacy and safety of low-versus high-dose adrenocorticotropic hormone (ACTH) regimens, low-dose ACTH regimens, and comparison of ACTH with oral corticosteroids or vigabatrin for the treatment of West syndrome.

DATA SOURCES

A literature search was performed using MEDLINE, PubMed, and International Pharmaceutical Abstracts (1975-November 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: infantile spasms, West syndrome, adrenocorticotropic hormone, corticotropin, symptomatic West syndrome, cryptogenic West syndrome, pediatric, children, infant, adolescent, and neonate.

STUDY SELECTION AND DATA EXTRACTION

Studies included in this article evaluated low-dose versus high-dose ACTH, low-dose ACTH, and ACTH compared with vigabatrin and oral corticosteroids. Data reporting the efficacy and adverse effects of ACTH, vigabatrin, and oral corticosteroids were extracted from each publication. Only English-language publications were included. We initially reviewed 20 studies, and 14 were included: 5 prospective randomized clinical trials and 9 chart reviews.

DATA SYNTHESIS

West syndrome is an age-specific epileptic disorder that occurs in infancy and early childhood. It is characterized by the triad of infantile spasms, neurodevelopmental regression or delay, and hypsarrhythmia on electroencephalogram (EEG). The efficacy and adverse events of ACTH with different dosage regimens were reviewed and analyzed. ACTH compared with vigabatrin and oral corticosteroids was also evaluated. Based on this review, low-dose ACTH is probably as effective as high-dose ACTH. Compared with other agents, ACTH is suggested to be more effective than oral corticosteroids, and compared with vigabatrin, it has improved outcomes in the cessation of spasms. However, studies evaluating the efficacy of ACTH are limited by small sample size, inconsistent dosage regimens, and the use of synthetic or natural ACTH products. Serious adverse events, includ ing intracranial hemorrhage, brain atrophy, Cushing syndrome, infection, weight gain, and hypertension, may deter the use of ACTH. Short-term therapy is recommended to reduce the risk of adverse effects.

CONCLUSIONS

The current literature suggests that short-term, low-dose ACTH should be considered first-line treatment of infantile spasms.
Gustatory Stimuli Representing Different Perceptual Qualities Elicit Distinct Patterns of Neuropeptide Secretion from Taste Buds
Authors: Geraedts Maartje C. P. , Munger Steven D.
Published: April 2013

Taste stimuli that evoke different perceptual qualities (e.g., sweet, umami, bitter, sour, salty) are detected by dedicated subpopulations of taste bud cells that use distinct combinations of sensory receptors and transduction molecules. Here, we report that taste stimuli also elicit unique patterns of neuropeptide secretion from taste buds that are correlated with those perceptual qualities. We measured tastant-dependent secretion of glucagon-like peptide-1 (GLP-1), glucagon, and neuropeptide Y (NPY) from circumvallate papillae ofTas1r3+/+,Tas1r3+/−andTas1r3−/−mice. Isolated tongue epithelia were mounted in modified Ussing chambers, permitting apical stimulation of taste buds; secreted peptides were collected from the basal side and measured by specific ELISAs. Appetitive stimuli (sweet: glucose, sucralose; umami: monosodium glutamate; polysaccharide: Polycose) elicited GLP-1 and NPY secretion and inhibited basal glucagon secretion. Sweet and umami stimuli were ineffective inTas1r3−/−mice, indicating an obligatory role for the T1R3 subunit common to the sweet and umami taste receptors. Polycose responses were unaffected by T1R3 deletion, consistent with the presence of a distinct polysaccharide taste receptor. The effects of sweet stimuli on peptide secretion also required the closing of ATP-sensitive K+(KATP) channels, as the KATPchannel activator diazoxide inhibited the effects of glucose and sucralose on both GLP-1 and glucagon release. Both sour citric acid and salty NaCl increased NPY secretion but had no effects on GLP-1 or glucagon. Bitter denatonium showed no effects on these peptides. Together, these results suggest that taste stimuli of different perceptual qualities elicit unique patterns of neuropeptide secretion from taste buds.
Mushroom Body Extrinsic Neurons in the Honeybee Brain Encode Cues and Contexts Differently
Authors: Hussaini Syed Abid , Menzel Randolf
Published: April 2013

Free-flying honeybees (Apis mellifera carnica) are known to learn the context to solve discrimination tasks. Here we apply classical conditioning of the proboscis extension response in restrained bees in combination with single-unit extracellular recordings from mushroom body (MB) extrinsic neurons elucidating the neural correlates of context-dependent olfactory discrimination. The contexts were light, colors, and temperatures, either alone or in combination. We found that bees learn context rules quickly and use them for better discrimination. They also solved a transwitching and a cue/context reversal task. Neurons extrinsic to the α lobe of the MB reduced the responses to the rewarded odor, whereas they increased their responses to the context. These results indicate that MB extrinsic neurons encode cues and contexts differently. Data are discussed with reference to MB function.
Cocaine Drives Aversive Conditioning via Delayed Activation of Dopamine-Responsive Habenular and Midbrain Pathways
Authors: Jhou Thomas C. , Good Cameron H. , Rowley Courtney S. , Xu Sheng-ping , Wang Huikun , Burnham Nathan W. , Hoffman Alexander F. , Lupica Carl R. , Ikemoto Satoshi
Published: April 2013

Many strong rewards, including abused drugs, also produce aversive effects that are poorly understood. For example, cocaine can produce aversive conditioning after its rewarding effects have dissipated, consistent with opponent process theory, but the neural mechanisms involved are not well known. Using electrophysiological recordings in awake rats, we found that some neurons in the lateral habenula (LHb), where activation produces aversive conditioning, exhibited biphasic responses to single doses of intravenous cocaine, with an initial inhibition followed by delayed excitation paralleling cocaine's shift from rewarding to aversive. Recordings in LHb slice preparations revealed similar cocaine-induced biphasic responses and further demonstrated that biphasic responses were mimicked by dopamine, that the inhibitory phase depended on dopamine D2-like receptors, and that the delayed excitation persisted after drug washout for prolonged durations consistent with findingsin vivo. c-Fos experiments further showed that cocaine-activated LHb neurons preferentially projected to and activated neurons in the rostromedial tegmental nucleus (RMTg), a recently identified target of LHb axons that is activated by negative motivational stimuli and inhibits dopamine neurons. Finally, pharmacological excitation of the RMTg produced conditioned place aversion, whereas cocaine-induced avoidance behaviors in a runway operant paradigm were abolished by lesions of LHb efferents, lesions of the RMTg, or by optogenetic inactivation of the RMTg selectively during the period when LHb neurons are activated by cocaine. Together, these results indicate that LHb/RMTg pathways contribute critically to cocaine-induced avoidance behaviors, while also participating in reciprocally inhibitory interactions with dopamine neurons.
Disruption of Intracellular Calcium Regulation Is Integral to Aminoglycoside-Induced Hair Cell Death
Authors: Esterberg Robert , Hailey Dale W. , Coffin Allison B. , Raible David W. , Rubel Edwin W.
Published: April 2013

Intracellular Ca2+is a key regulator of life or death decisions in cultured neurons and sensory cells. The role of Ca2+in these processes is less clearin vivo, as the location of these cells often impedes visualization of intracellular Ca2+dynamics. We generated transgenic zebrafish lines that express the genetically encoded Ca2+indicator GCaMP in mechanosensory hair cells of the lateral line. These lines allow us to monitor intracellular Ca2+dynamics in real time during aminoglycoside-induced hair cell death. After exposure of live larvae to aminoglycosides, dying hair cells undergo a transient increase in intracellular Ca2+that occurs shortly after mitochondrial membrane potential collapse. Inhibition of intracellular Ca2+elevation through either caged chelators or pharmacological inhibitors of Ca2+effectors mitigates toxic effects of aminoglycoside exposure. Conversely, artificial elevation of intracellular Ca2+by caged Ca2+release agents sensitizes hair cells to the toxic effects of aminoglycosides. These data suggest that alterations in intracellular Ca2+homeostasis play an essential role in aminoglycoside-induced hair cell death, and indicate several potential therapeutic targets to stem ototoxicity.
Subthalamic Nucleus Neurons Are Synchronized to Primary Motor Cortex Local Field Potentials in Parkinson's Disease
Authors: Shimamoto Shoichi A. , Ryapolova-Webb Elena S. , Ostrem Jill L. , Galifianakis Nicholas B. , Miller Kai J. , Starr Philip A.
Published: April 2013

In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia–cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4–30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50–200 Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower-frequency rhythm (phase-amplitude coupling), such that “waves” of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge.
Distinct and Separable Roles for Endogenous CRY1 and CRY2 within the Circadian Molecular Clockwork of the Suprachiasmatic Nucleus, as Revealed by the Fbxl3AfhMutation
Authors: Anand Sneha N. , Maywood Elizabeth S. , Chesham Johanna E. , Joynson Greg , Banks Gareth T. , Hastings Michael H. , Nolan Patrick M.
Published: April 2013

The circadian clock of the suprachiasmatic nucleus (SCN) drives daily rhythms of behavior. Cryptochromes (CRYs) are powerful transcriptional repressors within the molecular negative feedback loops at the heart of the SCN clockwork, where they periodically suppress their own expression and that of clock-controlled genes. To determine the differential contributions of CRY1 and CRY2 within circadian timingin vivo, we exploited theN-ethyl-N-nitrosourea-induced afterhours mutantFbxl3Afhto stabilize endogenous CRY. Importantly, this was conducted in CRY2- and CRY1-deficient mice to test each CRY in isolation. In both CRY-deficient backgrounds, circadian rhythms of wheel-running and SCN bioluminescence showed increased period length with increasedFbxl3Afhdosage. Although both CRY proteins slowed the clock, CRY1 was significantly more potent than CRY2, and in SCN slices, CRY1 but not CRY2 prolonged the interval of transcriptional suppression. Selective CRY-stabilization demonstrated that both CRYs are endogenous transcriptional repressors of clock-controlled genes, but again CRY1 was preeminent. Finally, althoughCry1−/−;Cry2−/−mice were behaviorally arrhythmic, their SCN expressed short period (∼18 h) rhythms with variable stability.Fbxl3Afh/Afhhad no effect on these CRY-independent rhythms, confirming its circadian action is mediated exclusively via CRYs. Thus, stabilization of both CRY1 and CRY2 are necessary and sufficient to explain circadian period lengthening byFbxl3Afh/Afh. Both CRY proteins dose-dependently lengthen the intrinsic, high-frequency SCN rhythm, and CRY2 also attenuates the more potent period-lengthening effects of CRY1. Incorporation of CRY-mediated transcriptional feedback thus confers stability to intrinsic SCN oscillations, establishing periods between 18 and 29 h, as determined by selective contributions of CRY1 and CRY2.
Focal Electrical Stimulation of Major Ganglion Cell Types in the Primate Retina for the Design of Visual Prostheses
Authors: Jepson Lauren H. , Hottowy Paweł , Mathieson Keith , Gunning Deborah E. , Dąbrowski Władysław , Litke Alan M. , Chichilnisky E. J.
Published: April 2013

Electrical stimulation of retinal neurons with an advanced retinal prosthesis may eventually provide high-resolution artificial vision to the blind. However, the success of future prostheses depends on the ability to activate the major parallel visual pathways of the human visual system. Electrical stimulation of the five numerically dominant retinal ganglion cell types was investigated by simultaneous stimulation and recording in isolated peripheral primate (Macaca sp.) retina using multi-electrode arrays. ON and OFF midget, ON and OFF parasol, and small bistratified ganglion cells could all be activated directly to fire a single spike with submillisecond latency using brief pulses of current within established safety limits. Thresholds for electrical stimulation were similar in all five cell types. In many cases, a single cell could be specifically activated without activating neighboring cells of the same type or other types. These findings support the feasibility of direct electrical stimulation of the major visual pathways at or near their native spatial and temporal resolution.
#VirtualTourist: Embracing Our Audience through Public History Web Experience
Authors: Lindsay Anne
Published: April 2013

Public historians at sites of cultural heritage tourism struggle to engage with an ever-changing audience. The solution proposed in this work is the cultivation of the virtual community as a valuable audience and future donor base. Through an analysis of the web presence and social media activities of three high profile heritage locations in Virginia, Mount Vernon, Monticello, and Colonial Williamsburg, it is possible to devise best practices for interaction with the virtual tourist. These principles can be implemented at any site, large or small, and seek to create an immersive educational experience to be enjoyed by guests of many ages and interests. The key consideration must be to court the virtual visitor as a new and valuable audience essential to the continuation of perceived relevance at heritage locations across the country.
Effective Dynamic Constitutive Relations for 3-D Periodic Elastic Composites
Authors: Srivastava Ankit , Nemat-Nasser Sia
Published: April 2013

Central to the idea of metamaterials is the concept of dynamic homogenization which seeks to define frequency dependent effective properties for Bloch wave propagation. Recent advances in the theory of dynamic homogenization have established the coupled form of the constitutive relation (Willis constitutive relation). This coupled form of the constitutive relation naturally emerges from ensemble averaging of the dynamic fields and automatically satisfies the dispersion relation in the case of periodic composites. Its importance is also notable due to its invariance under transformational acoustics. Here we discuss the explicit form of the effective dynamic constitutive equations. We elaborate upon the existence and emergence of coupling in the dynamic constitutive relation and further symmetries of the effective tensors.
Thermal Conductivity Measurement of Graphene Composite
Authors: Hu Jiuning , Park Wonjun , Ruan Xiulin , Chen Yong P.
Published: April 2013

Graphene composites (GCs) have attracted much attention recently. It is interesting to explore thermal properties of GCs in which graphene filler concentrations are tunable. Here, we use 3ω method to measure the thermal conductivity of GCs synthesized from reduced graphene oxide (RGO) dispersed in polystyrene. To avoid the detrimental effect of lithography processes to GCs, we have developed a novel method employing polyvinyl alcohol and poly(methyl methacrylate) (PMMA) as a holder film to transfer micrometer-sized metal heaters/sensors onto GC surface. Room temperature measurements of the thermal conductivity of GCs are performed. The thermal conductivity is enhanced by ∼ 35 % when adding 5 vol.% of RGO filler concentration. Our measurements will be helpful to probe and understand the thermal transport properties of graphene based composites.
Tratamento da distrofia muscular progressiva com lactato de sódio
Authors: Levy José Antonio , Andrade Almir Ferreira de
Published: April 2013

Com base em trabalhos anteriores, 13 casos de distrofia muscular progressiva foram tratados com lactato de sódio 1/6 molar associado a ATP e complexo B. O exame da força muscular, realizado antes e após o tratamento — salvo em dois casos nos quais ocorreram melhoras muito discretas — não mostrou qualquer efeito favorável da medicação. Os autores sugerem a verificação de possíveis alterações enzimáticas provocadas pelo lactato de sódio, o que serviria para melhor avaliação do efeito terapêutico.
Cisto dermóide na região do bregma: relato de dois casos
Authors: Pereira Walter C. , Andrade Almir F. , Lopes Pedro G.
Published: April 2013

São relatados dois casos de cisto dermóide extracranianos situados sobre a fontanela bregmática em meninos de 4 e 8 meses de idade. O diagnóstico pré-operatório em ambos havia sido de meningencefalocele. Os autores chamam a atenção para a normalidade do exame neurológico e da angiografia cerebral nos dois pacientes, dados que devem ser valorizados para o diagnóstico diferencial de casos futuros.
Hidroma subdural na fossa posterior
Authors: Vasques José Carlos , Coutinho Mário F.
Published: April 2013

Os autores relatam um caso de hidroma subdural na fossa craniana posterior conseqüente a traumatismo na região occipital. O paciente foi operado com pleno sucesso. A raridade da localização de hidroma na fossa posterior é salientada, sendo discutidos os possíveis mecanismos etio-patogênicos.
Estudo clínico do trabalho mental de 62 pacientes epilépticos adolescentes
Authors: Coelho Lúcia , Marques-Assis Luís
Published: April 2013

Foram estudados 62 pacientes epilépticos adolescentes, normais do ponto de vista neurológico. Foi feita investigação psicológica dos casos, tendo sido valorizados os dados relacionados ao aproveitamento escolar. Foram considerados os casos com rendimento escolar baixo e elevado, tendo o estudo sido feito em relação ao tipo de crise (presença ou não de convulsões), ao tempo de doença, à freqüência das crises e ao padrão eletrencefalográfico. Num segundo tempo, foram estudados também, em relação a essas mesmas variáveis, os casos com rendimento escolar baixo. Os resultados, submetidos a análise estatística, permitiram aos autores chegarem às seguintes conclusões: 1) em 31 casos (50%) o rendimento escolar foi baixo; 2) o tipo de crise, o tempo de doença é a freqüência dos ataques não interferiram significativamente no rendimento escolar; 3) melhor aproveitamento foi alcançado pelos pacientes com EEG normal; dentre os casos com rendimento mais baixo, predominaram aqueles com anormalidades eletrencefalográficas difusas; 4) considerados apenas os casos com baixo rendimento escolar, predominaram os pacientes com manifestações convulsivas, com menor tempo de doença e com crises mais freqüentes.
Cistos aracnóideos
Authors: Assis Nelson , Pereira Walter C.
Published: April 2013

São relatados 3 casos de cistos aracnóideos em crianças, situando-se um deles na fossa posterior e os outros dois acima do tentório. Nos 3 pacientes havia sinais de hipertensão intracraniana de evolução crônica, não sendo observado, contudo, abaulamento diretamente relacionado com a localização do cisto. Em dois casos a etiologia do processo era provavelmente inflamatória e, congênita, em um. O tratamento cirúrgico foi empregado nos 3 casos, havendo resultado satisfatório em dois; o paciente com cisto localizado na fossa posterior faleceu quinze dias após a operação.
Testes visuomotores em crianças com estrabismo
Authors: Caldeira Jorge Alberto F. , Whitaker Ferreira Beatriz H. , Lapa Maria Cecilia , Lauleta Maria Antonia
Published: April 2013

Em 43 crianças estrábicas nas quais foi determinado o quociente intelectual foram aplicados os testes visuomotores de Goldstein-Scheerer, Bender-Santucci, lateralidade e estereognosia. Os resultados foram comparados com os obtidos em 44 controles dos mesmos grupos etários e sócio-econômicamente semelhantes. Sugere-se o prosseguimento desta pesquisa com o estudo comparativo entre o teste de Goldstein-Scheerer e o "visual retention test" de Benton (1963) nos quais a análise do fator memória visual pode ser útil para averiguar dificuldades relacionadas com a prontidão para a alfabetização. Sugere-se, também, o estudo de um grupo de crianças em idade escolar com e sem perturbações da motilidade ocular extrínseca para avaliar a influência da escolaridade nos resultados dos testes.
Cintilografia dos espaços liquoricos com soroalbumina radioiodada (SARI)
Authors: Seixas Valter , Tenuto Rolando , Fischer-Thom Annelise , Gnecco Oswaldo , Kiefer Julio
Published: April 2013

Os espaços liquóricos foram estudados com SARI (soroalbumina radioiodada) em 25 pacientes. Para cada um foram realizados 3 mapeamentos num total de 75. Esses mapeamentos foram feitos 2, 6 e 24 horas após a injeção da SARI. Esta foi injetada no ventrículo lateral em 5 pacientes nos quais havia necessidade de estudar o sistema ventricular; na cisterna magna em 2, para estudo do espaço subaracnóideo intracraniano e intra-raqueano; nos outros 18 foi injetada por via lombar com a finalidade de estudar todo o canal raqueano. Os resultados obtidos pela cintilografia, comparados com aqueles fornecidos pelos exames neuroradiológicos, mostraram alto índice de positividade, tendo mesmo oferecido melhores informações em alguns deles. Isto se verifica principalmente nas aracnoidites. Nos processos expansivos do canal raqueano pode-se, com apenas uma injeção de SARI localizar o processo e determinar seus limites. Não se observou qualquer complicação grave. Em um caso verificou-se, no LCR, uma pleocitose sem sinais clínicos e em outro, um extravazamento da substância para o espaço peridural através do orifício de punção. Trata-se, pois, de método que oferece boa segurança para o diagnóstico neurológico, não provocando complicações temíveis.
Alterações eletrencefalográficas relacionadas a deficiências nutritivas
Authors: Ribeiro Valeriana Moura , Ribeiro Rubens Moura , Braga Montelli T. , Rolando Edgard
Published: April 2013

Foram estudadas as alterações eletrencefalográficas em 20 crianças desnutridas. Foi assinalada diferença significativa entre o EEG dos pacientes com desnutrição global e daqueles com desnutrição protêica. Essas alterações foram caracterizadas pela presença de anormalidades encefálicas difusas e/ou descargas focais de tipo epiléptico. A incidência relativamente alta de descargas focais pode ser explicada pelo limiar convulsiógeno muito baixo do cérebro de crianças com desnutrição.
Diagnóstico clínico diferencial entre oclusão da artéria carótida interna e da artéria cerebral média
Authors: Melaragno Roberto , Sanvito Wilson Luíz , Cinelli Junior Mario , Cordeiro Anoi Castro
Published: April 2013

Foi feito um estudo comparativo entre o quadro clínico inicial de 61 casos de oclusão da artéria carótida interna e o de 23 casos de oclusão da artéria cerebral média, diagnosticados pela angiografia cerebral e/ou pela necropsia em pacientes submetidos ou não à cirurgia vascular. Os autores comparam a idade dos pacientes, o sexo, o modo de início da afecção, a existência ou não de convulsões e/ou cefaléias, a ocorrência do acidente cerebral durante o sono ou em vigília, a existência de ictos prévios, os níveis de pressão arterial, o grau de consciência, a força muscular, os achados eletrencefalográficos, a palpação e ausculta das carótidas em nível cervical. Os resultados são demonstrados em índices percentuais, pelos quais os autores inferem que não há significância estatística nesses elementos com três exceções: a maior ocorrência de convulsões nas oclusões da artéria cerebral média em relação às da carótida, a oftalmodinamometria e a sintomatologia carotídea cervical. A oftalmodinamometria revela valores significantemente menores nas pressões da artéria central da retina, no mesmo lado da trombose da carótida em 70,0% dos casos, enquanto que medidas normais e simétricas verificaram-se em todos os casos de oclusão da artéria cerebral média em que o exame foi realizado. No que concerne a sinais arteriais no pescoço, havia anormalidades palpatórias e auscultatórias em 52,4% dos pacientes com trombose da carótida e em 8,6% dos casos com oclusão da cerebral média. Concluem os autores, portanto, que apenas a angiografia cerebral permite um diagnóstico seguro entre ambas as sedes da oclusão.
Reações inflamatórias leptomeníngeas em neurocirurgia
Authors: Rocha A. Gama da , Guenni-Bejar D. , Lins E. Farias , Tenuto R. A. , Spina-França A.
Published: April 2013

Revisão de 840 casos de pacientes submetidos a intervenções neurocirúrgicas na Unidade de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo durante 5 anos (1962-1967) para verificar a incidência de reações inflamatórias leptomeníngeas (RIL) no pós-operatório. Em 106 casos (12,6%) foi demonstrada a ocorrência de RIL. O diagnóstico de RIL foi comprovado pelo quadro liquórico; em apenas um caso êle resultou dos achados do exame necroscópico exclusivamente. Analisando os 105 casos em que o LCR foi estudado verificou-se ser a hipertermia, a cefaléia, os sinais meníngeos e as alterações da consciência os sintomas que com mais freqüência sugeriam o diagnóstico; este foi comprovado em média 10 dias após o ato cirúrgico, mediante o exame do LCR. Baseando -se nas alterações do LCR os casos foram divididos em três grupos: RIL provavelmente asséptica (72 casos), RIL provavelmente séptica (26 casos), RIL sépticas (7 casos). Em 59 casos associava-se à RIL hemorragia sub-aracnóidea, dado considerado indicativo de gravidade, pois dos 24 pacientes que vieram a falecer, 20 apresentavam hemorragia sub-aracnóidea e RIL.