bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression
Authors: de Mattos Ana Barbosa Marcondes , Pinto Mônica Jordão S , Oliveira Cristiane , Biz Carolina , Ribeiro Eliane Beraldi , do Nascimento Claudia Maria Oller , Andersen Monica Levy , Tufik Sergio , Oyama Lila Missae
Published: November 2008

Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-α of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-α. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-α gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression.
The synchronous occurrence of squamous cell carcinoma and gastrointestinal stromal tumor (GIST) at esophageal site
Authors: Spinelli Gian Paolo , Miele Evelina , Tomao Federica , Rossi Luigi , Pasciuti Giulia , Zullo Angelo , Zoratto Federica , Nunnari Jose , Pisanelli Giovanni Codacci , Tomao Silverio
Published: November 2008

Background

Esophageal squamous cell carcinoma is a relative common malignancy with a very poor prognosis, even adopting an integrated and multidisciplinary approach. According to the literature, gastrointestinal stromal tumors (GISTs) rarely originate from the esophagus. Moreover there are not reports of synchronous occurrence of squamous cell carcinoma and GIST at esophageal site.

Case presentation

We describe a case of a 74 year old patient who underwent surgery for squamous cell carcinoma of the lower third of the esophagus with an incidental pathologic diagnosis of a concomitant GIST in the thoracic tract.

Conclusion

In literature there is no evidence of concomitant squamous carcinoma and GIST of the thoracic esophagus, even if esophageal GISTs are sometimes described. The occasional finding of this neoplastic lesion underlines the importance of a carefully pathological diagnosis for its identification. Surgery, followed by a multidisciplinary approach remains the first-line treatment in both squamous and stromal neoplasm.
Implantation of neural stem cells embedded in hyaluronic acid and collagen composite conduit promotes regeneration in a rabbit facial nerve injury model
Authors: Zhang Han , Wei Yue Teng , Tsang Kam Sze , Sun Chong Ran , Li Jin , Huang Hua , Cui Fu Zhai , An Yi Hua
Published: November 2008

The implantation of neural stem cells (NSCs) in artificial scaffolds for peripheral nerve injuries draws much attention. NSCs were ex-vivo expanded in hyaluronic acid (HA)-collagen composite with neurotrophin-3, and BrdU-labeled NSCs conduit was implanted onto the ends of the transected facial nerve of rabbits. Electromyography demonstrated a progressive decrease of current threshold and increase of voltage amplitude in de-innervated rabbits after implantation for one, four, eight and 12 weeks compared to readouts derived from animals prior to nerve transection. The most remarkable improvement, observed using Electrophysiology, was of de-innervated rabbits implanted with NSCs conduit as opposed to de-innervated counterparts with and without the implantation of HA-collagen, NSCs and HA-collagen, and HA-collagen and neurotrophin-3. Histological examination displayed no nerve fiber in tissue sections of de-innervated rabbits. The arrangement and S-100 immunoreactivity of nerve fibers in the tissue sections of normal rabbits and injured rabbits after implantation of NSCs scaffold for 12 weeks were similar, whereas disorderly arranged minifascicles of various sizes were noted in the other three arms. BrdU+ cells were detected at 12 weeks post-implantation. Data suggested that NSCs embedded in HA-collagen biomaterial could facilitate re-innervations of damaged facial nerve and the artificial conduit of NSCs might offer a potential treatment modality to peripheral nerve injuries.
Kinin B2receptor regulates chemokines CCL2 and CCL5 expression and modulates leukocyte recruitment and pathology in experimental autoimmune encephalomyelitis (EAE) in mice
Authors: Dos Santos Adriana C , Roffê Ester , Arantes Rosa ME , Juliano Luiz , Pesquero Jorge L , Pesquero João B , Bader Michael , Teixeira Mauro M , Carvalho-Tavares Juliana
Published: November 2008

Background

Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously shown that the chemokines CCL2 and CCL5 play an important role in the adhesion of leukocytes to the brain microcirculation in EAE. The aim of the present study was to evaluate the relevance of B2receptors to leukocyte-endothelium interactions in the cerebral microcirculation, and its participation in CNS inflammation in the experimental model of myelin-oligodendrocyte-glycoprotein (MOG)35–55-induced EAE in mice.

Methods

In order to evaluate the role of B2 receptor in the cerebral microvasculature we used wild-type (WT) and kinin B2 receptor knockout (B2-/-) mice subjected to MOG35–55-induced EAE. Intravital microscopy was used to investigate leukocyte recruitment on pial matter vessels in B2-/-and WT EAE mice. Histological documentation of inflammatory infiltrates in brain and spinal cords was correlated with intravital findings. The expression of CCL5 and CCL2 in cerebral tissue was assessed by ELISA.

Results

Clinical parameters of disease were reduced in B2-/-mice in comparison to wild type EAE mice. At day 14 after EAE induction, there was a significant decrease in the number of adherent leukocytes, a reduction of cerebral CCL5 and CCL2 expressions, and smaller inflammatory and degenerative changes in B2-/-mice when compared to WT.

Conclusion

Our results suggest that B2receptors have two major effects in the control of EAE severity: (i) B2regulates the expression of chemokines, including CCL2 and CCL5, and (ii) B2modulates leukocyte recruitment and inflammatory lesions in the CNS.
Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein
Authors: Yang Ting , Arslanova Dilyara , Gu Yongli , Augelli-Szafran Corinne , Xia Weiming
Published: November 2008

Background

Deposition of amyloid-β protein (Aβ) is a major pathological hallmark of Alzheimer's disease (AD). Aβ is generated from γ-secretase cleavage of amyloid precursor protein (APP). In addition to APP, γ-secretase also cleaves other type I integral membrane proteins, including the Notch receptor, a key molecule involved in embryonic development.

Results

To explore selective γ-secretase inhibitors, a combination of five methods was used to systematically determine these inhibitors' profiles on the γ-secretase cleavage of APP and Notch. When two potent γ-secretase inhibitors, compound E (cpd E) and DAPT, were used in a conventional in vitro γ-secretase activity assay, cpd E completely blocked Aβ generation from the cleavage of substrate APP C100, but only had a minor effect on Notch cleavage and NICD generation. Next, cpd E and DAPT were applied to HEK293 cells expressing a truncated Notch substrate NotchΔE. Both cpd E and DAPT were more potent in blocking Aβ generation than NICD generation. Third, a reporter construct was created that carried the NICD targeting promoter with three Su(H) binding sequences followed by the luciferase gene. We found that the inhibition of NICD generation by cpd E and DAPT was consistent with the reduced expression of luciferase gene driven by this Notch targeting promoter. Fourth, levels of "Notch-Aβ-like" (Nβ*) peptide derived from two previously reported chimeric APP with its transmembrane domain or the juxtamembrane portion replaced by the Notch sequence were quantified. Measurement of Nβ* peptides by ELISA confirmed that EC50's of cpd E were much higher for Nβ* than Aβ. Finally, the expression levels of Notch target gene her6 in cpd E or DAPT-treated zebrafish were correlated with the degree of tail curvature due to defective somitogenesis, a well characterized Notch phenotype in zebrafish.

Conclusion

Our ELISA-based quantification of Aβ and Nβ* in combination with the test in zebrafish provides a novel approach for efficient cell-based screening and in vivo validation of APP selective γ-secretase inhibitors.
Absence of Somatic SQSTM1 Mutations in Paget’s Disease of Bone
Authors: Matthews Brya G. , Naot Dorit , Bava Usha , Callon Karen E. , Pitto Rocco P. , McCowan Stuart A. , Wattie Diana , Cundy Tim , Cornish Jill , Reid Ian R.
Published: November 2008

Background: Paget’s disease is a common focal bone disorder that appears to be caused by a combination of genetic and environmental factors. Mutations in the SQSTM1 gene are found in about one third of families with Paget’s disease and 8% of sporadic cases. Other potential loci linked to the disease have also been identified, and a number of environmental factors have been suggested to be involved in the disease. However, the focal nature of Paget’s is still unexplained. Therefore, we examined the possibility that somatic mutations in the SQSTM1 gene are present in the local lesions, using RNA collected from primary osteoblast and bone marrow cell cultures of patients with this condition.

Methods: SQSTM1 was sequenced, and allelic discrimination for the common P392L mutation was performed in cDNA samples from 14 osteoblast cultures and from 14 cultures of bone marrow cells.

Results: In these 28 samples drawn from 23 patients, the wild-type sequence of SQSTM1 was found in all but one marrow sample, which was heterozygous for the P392L mutation. DNA from peripheral blood in this subject had an identical sequence of SQSTM1, indicating that this was a germline mutation.

Conclusion: We conclude that somatic mutations for SQSTM1 are not commonly present in Paget’s disease.
Common Type 2 Diabetes Risk Gene Variants Associate with Gestational Diabetes
Authors: Lauenborg Jeannet , Grarup Niels , Damm Peter , Borch-Johnsen Knut , Jørgensen Torben , Pedersen Oluf , Hansen Torben
Published: November 2008

Objective: We aimed to examine the association between gestational diabetes mellitus (GDM) and 11 recently identified type 2 diabetes susceptibility loci.

Research Design and Methods: Type 2 diabetes risk variants in TCF7L2, CDKAL1, SLC30A8, HHEX/IDE, CDKN2A/2B, IGF2BP2, FTO, TCF2, PPARG, KCNJ11, and WFS1 loci were genotyped in a cohort of women with a history of GDM (n = 283) and glucose-tolerant women of the population-based Inter99 cohort (n = 2446).

Results: All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio (OR) greater than 1 for the GDM group compared with the control group ranging from 1.13 [95% confidence interval (CI) 0.88–1.46] to 1.44 (95% CI 1.19–1.74) except for the WFS1 rs10010131 variant with OR 0.87 (95% CI 0.73–1.05). Combined analysis of all 11 variants showed a highly significant additive effect of multiple risk alleles on risk of GDM [OR 1.18 (95% CI 1.10–1.27)] per risk allele, P = 3.2 × 10−6). Applying receiver-operating characteristic showed an area under the receiver-operating characteristic curve of 0.62 for the genetic test alone and 0.73 when combining information on age, body mass index, and genotypes of the 11 gene variants.

Conclusions: The prevalence in a prior GDM group of several previously proven type 2 diabetes risk alleles equals the findings from association studies on type 2 diabetes. This supports the hypothesis that GDM and type 2 diabetes are two of the same entity.
Hematologic Effects of Levothyroxine in Iron-Deficient Subclinical Hypothyroid Patients: A Randomized, Double-Blind, Controlled Study
Authors: Cinemre Hakan , Bilir Cemil , Gokosmanoglu Feyzi , Bahcebasi Talat
Published: November 2008

Context: In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, anemia does not adequately respond to oral iron therapy.

Objective: We studied whether iron-deficiency anemia might indicate treatment of subclinical hypothyroidism.

Design: Patients were assigned to a control or experimental group: 240 mg/d oral iron alone (iron group) or 240 mg/d oral iron plus 75 μg/d levothyroxine (iron/levothyroxine group). Levels of hemoglobin, hematocrit, red blood cell count, serum iron levels, ferritin, total iron-binding capacity, TSH, and free T4 were measured before and after treatment.

Setting: The study was conducted at a university hospital outpatient clinic.

Patients: Fifty-one patients with coexisting iron-deficiency anemia and subclinical hypothyroidism participated in the study.

Intervention: Patients were treated as described above in either the iron group or the iron/levothyroxine group.

Main Outcome Measure: A clinically satisfactory increase in hemoglobin was regarded as successful.

Results: Mean hemoglobin levels increased by 0.4 g/dl in the iron group [95% confidence interval (CI) 0.2–0.7, P = 0.001], whereas it increased by a mean of 1.9 g/dl in the iron/levothyroxine group (95% CI 1.5–2.3, P < 0.0001). The increase in serum iron was greater in the iron/levothyroxine group by a mean of 47.6 μg/dl (95% CI 34.5–60.6, P < 0.0001). Increases in hemoglobin, red blood cells, hematocrit, and serum ferritin levels after treatment were statistically significantly greater in the iron/levothyroxine group (P < 0.0001). Starting hemoglobin and increase in hemoglobin were negatively correlated in the iron/levothyroxine group (r = −0.531, P = 0.006).

Conclusions: Subclinical hypothyroidism should be treated in iron-deficiency anemia patients when both conditions coexist. This would provide a desired therapeutic response to oral iron replacement and prevent ineffective iron therapy.
Bariatric Surgery: Risks and Rewards
Authors: Pories Walter J.
Published: November 2008

Context

Over 23 million Americans are afflicted with severe obesity, i.e. their body mass index (in kilograms per square meter) values exceed 35. Of even greater concern is the association of the adiposity with comorbidities such as diabetes, hypertension, cardiopulmonary failure, asthma, pseudotumor cerebri, infertility, and crippling arthritis.

Objective: Diets, exercise, behavioral modification, and drugs are not effective in these individuals. This article examines the effect of surgery on the control of the weight and the comorbidities, as well as the safety of these operations.

Interventions: Although the article focuses on the outcomes of the three most commonly performed operations, i.e. adjustable gastric banding, the gastric bypass, and the biliopancreatic bypass with duodenal switch, it aims for perspective with the inclusion of abandoned and current investigational procedures, a review of the complications, and an emphasis on the appropriate selection of patients.

Positions: Ample evidence, including controlled randomized studies, now document that bariatric surgery produces durable weight loss exceeding 100 lb (46 kg), full and long-term remission of type 2 diabetes in over 80% with salutary effects on the other comorbidities as well with significant reductions in all-cause mortality. Although the severely obese present with serious surgical risks, bariatric surgery is performed safely with a 0.35% 90-d mortality in Centers of Excellence throughout the United States—similar to the complication rates after cholecystectomy.

Conclusions

Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity.
Inhibition of the ATP-gated P2X7 receptor promotes axonal growth and branching in cultured hippocampal neurons
Authors: Díaz-Hernandez Miguel , del Puerto Ana , Díaz-Hernandez Juan Ignacio , Diez-Zaera María , Lucas José Javier , Garrido Juan José , Miras-Portugal María Teresa
Published: November 2008

During the establishment of neural circuits, the axons of neurons grow towards their target regions in response to both positive and negative stimuli. Because recent reports show that Ca2+ transients in growth cones negatively regulate axonal growth, we studied how ionotropic ATP receptors (P2X) might participate in this process. Our results show that exposing cultured hippocampal neurons to ATP induces Ca2+ transients in the distal domain of the axon and the concomitant inhibition of axonal growth. This effect is mediated by the P2X7 receptor, which is present in the growth cone of the axon. Pharmacological inhibition of P2X7 or its silencing by shRNA interference induces longer and more-branched axons, coupled with morphological changes to the growth cone. Our data suggest that these morphological changes are induced by a signalling cascade in which CaMKII and FAK activity activates PI3-kinase and modifies the activity of its downstream targets. Thus, in the absence or inactivation of P2X7 receptor, axons grow more rapidly and form more branches in cultured hippocampal neurons, indicative that ATP exerts a negative influence on axonal growth. These data suggest that P2X7 antagonists have therapeutic potential to promote axonal regeneration.
Effect of High Magnetic Field on the Fabrication of One-dimensional Tellurium Microstructures via a Solvothermal Treatment
Authors: Xu Yongbin , Ren Zhongming , Cao Guanghui , Ren Weili , Deng Kang , Zhong Yunbo
Published: November 2008

The magnetic-field-assisted solvothermal approach has been used in the shape-controlled growth of Te microcrystals. By applying a high magnetic field to the reaction system, the shape of obtained Te microcrystals could be changed greatly. Various techniques such as X-ray diffraction and scanning electron microscopy have been used to characterize the obtained products. The results show that the magnetic field plays a key role in the growth behavior of Te microcrystals. The possible cause of magnetic field effects is discussed.
Luminescent Ionic Liquid Crystals Based on Tripodal Pyridinium Salts
Authors: Tanabe Kana , Yasuda Takuma , Kato Takashi
Published: November 2008

Three-fold symmetrical pyridinium salts tethering tridodecyloxyphenyl substituents form liquid-crystalline columnar and micellar cubic phases and exhibit photoluminescent properties in liquid-crystalline states.
Metal–Metal Bond Formed in Tetrakis(2-pyridonato)Copper(II)–Platinum(II)/Palladium(II) Complexes
Authors: Ichieda Naoko , Kamimura Tetsuya , Wasada-Tsutsui Yuko , Funahashi Yasuhiro , Ozawa Tomohiro , Jitsukawa Koichiro , Masuda Hideki
Published: November 2008

New tetrakis(2-pyridonato)copper(II)–palladium(II)/platinum(II) complexes, [CuPd(2-pyrd)4(py)] (1), [CuPt(2-pyrd)4(py)] (2), [CuPd(2-pyrd)4(H2O)] (3), and [CuPt(2-pyrd)4(H2O)] (4) (2-pyrd = 2-pyridone, py = pyridine), were prepared, and the metal–metal bonds between PtII/PdII and CuII atoms were evidenced on the basis of X-ray structural and ESR spectroscopic methods, which were also supported from the DFT calculations.
Hydrogen Selective Catalytic Reduction of NOx Assisted by In Situ Ammonia Formation over Pt Catalyst Supported on Fe-doped Tin Phosphate
Authors: Saito Makoto , Itoh Masahiro , Iwamoto Jun , Machida Ken-ichi
Published: November 2008

In situ formation of ammonia and NOx reduction with high N2 selectivity based on it were observed in the hydrogen selective catalytic reduction (H2-SCR) of NOx over a platinum catalyst supported on a Fe-doped SnP2O7 powder with strong solid acidity even under conditions of high oxygen contents of about 10 vol %.
Meeting provides update on Faculty's year
Authors: Garrett Matthew
Published: November 2008

The annual meeting of the regional advisors, specialty advisors and faculty tutors of the Faculty of Dental Surgery (FDS) was held on Friday 28 March 2008. The aim of this day is to provide an update of the Faculty's work and an opportunity for colleagues to exchange views. This year was attended by over 40 delegates who were treated to a most informative range of presentations that led to plenty of lively discussion.
Healthcare Quality Improvement Partnership
Authors: Percival Alison
Published: November 2008

The white paper, Trust, Assurance and Safety, called for clinical audit to be revitalised. In response, in April 2008 the Department of Health appointed the Healthcare Quality Improvement Partnership (HQIP) to manage the National Clinical Audit and Patient Outcomes Programme (NCAPOP) and to support local clinical audit activity. HQIP is led by a consortium of the Academy of Medical Royal Colleges, the Royal College of Nursing and the Long-term Conditions Alliance. Its purpose is to promote better health care by providing support and advice to those responsible for managing quality improvement work.
Teaching ENT to GPs
Authors: Hackett Jon
Published: November 2008

From polyclinics to federations (see page 334) to supervising GPs with a special interest (see page 332), closer working between surgeons and GPs is increasingly on the health care agenda. The College's education department is embracing this through its first course aimed specifically at GPs instead of surgeons or the surgical team. Otolaryngology for GPs allows general practitioners to benefit from the knowledge and experience of ear, nose and throat (ENT) surgeons. It is the brainchild of College otorhinolarnyngology tutor, Gus Alusi, who is consultant otorhinolaryngologist at Barts and the London NHS Trust.
Medical secretaries – heading for extinction?
Authors: Perkins Kathy
Published: November 2008

Medical secretaries have long represented a vital link between the patient and the hospital, providing a human touch that is increasingly lacking in the NHS. These people are expert guides for patients, helping them to navigate through the complex and unfamiliar world of the hospital at a time in their lives that is often stressful and unsettling.
Nanocrystalline silicon carbide films for solar photovoltaics: The role of dangling-bond defects
Authors: Lim Koeng Su , Shevaleevskiy Oleg
Published: November 2008

Thin films of microcrystalline hydrogenated silicon (µc-Si:H) and nanocrystalline silicon carbide (nc-SiC:H) provide a new class of advanced nanostructured materials for solar photovoltaic (PV) devices. We have worked on the fabrication, characterization, and application of these materials for thin film PV solar cells based on amorphous silicon. Here we present an overview of the preparation and characterization methods for heterogeneous SiC:H-based layers. Hydrogenated nc-SiC:H thin film materials with high crystalline volume fraction were deposited using photo-assisted chemical vapor deposition (photo-CVD) technique. The behavior of spin-containing dangling-bond (DB) defects was performed using electron spin resonance (ESR) and transport measurements as a function of sample crystallinity, doping level, and temperature. The electronic and structural properties of intrinsic and doped µc-Si:H and nc-SiC:H thin films are reviewed with the emphasis of the essential role of DB defects on the photoelectronic transport parameters.
Identification of a Motif in the Acetylcholine Receptor β Subunit Whose Phosphorylation Regulates Rapsyn Association and Postsynaptic Receptor Localization
Authors: Borges Lucia S. , Yechikhov Sergey , Lee Young I. , Rudell John B. , Friese Matthew B. , Burden Steven J. , Ferns Michael J.
Published: November 2008

At the neuromuscular junction, the acetylcholine receptor (AChR) is specifically clustered in the postsynaptic membrane via interactions with rapsyn and other scaffolding proteins. However, it remains unclear where these proteins bind on the AChR and how the interactions are regulated. Here, we define a phosphorylation-dependent binding site on the receptor that mediates agrin-induced clustering. Using chimeric proteins in which CD4 is fused to the large intracellular loop of each of the AChR subunits we found that agrin induced clustering of only chimeras containing the β subunit loop. By making deletions in the β loop we defined a 20 amino-acid sequence that is sufficient for clustering. The sequence contains a conserved tyrosine (Y390) whose phosphorylation is induced by agrin and whose mutation abolished clustering of β loop chimeras and their ability to inhibit agrin-induced clustering of the endogenous AChR. Phosphorylation of the AChR β subunit is correlated with increased rapsyn/AChR binding, suggesting that the effect of βY390 phosphorylation on clustering is mediated by rapsyn. Indeed, we found that rapsyn associated with CD4-β loop chimeras in a phosphorylation-dependent manner, and that agrin increased the ratio of rapsyn binding to wild type AChR but not to AChR-β3F/3F, which lacks β loop tyrosine phosphorylation sites. Together, these findings suggest that agrin-induced phosphorylation of the β subunit motif increases the stoichiometry of rapsyn binding to the AChR, thereby helping to stably cluster the receptor and anchor it at high density in the postsynaptic membrane.
Increased Cognitive Functioning in Symptomatic Huntington's Disease As Revealed by Behavioral and Event-Related Potential Indices of Auditory Sensory Memory and Attention
Authors: Beste Christian , Saft Carsten , Güntürkün Onur , Falkenstein Michael
Published: November 2008

Cognitive functions are thought to deteriorate globally in late stages of various neurodegenerative disorders. Here we describe that this general assumption is not justified and fails in Huntington's disease (HD). Presymptomatic gene mutation carriers (pHDs) and healthy controls performed worse compared with symptomatic HDs in an auditory signal detection task. During task performance, behavioral data and event-related potentials (ERPs) [i.e., MMN (mismatch negativity), P3a, and RON (reorienting negativity)] were recorded. Not only behavioral performance but also neurophysiological correlates of auditory sensory memory and attentional reorientation indicate enhanced performance occurring primal in late stages of a neurodegenerative disorder. Increased activity of the NMDA-receptor system, an assumed pathogenic mechanism in HD, might facilitate signal propagation at striatal level that enables more efficient task execution through a winner-take-all process. The results challenge the view that late stage neurodegeneration is necessarily related to a global decline in cognitive abilities in HD. In contrast, selectively enhanced cognitive functioning can emerge together with otherwise impaired cognitive functioning.
Folate Deficiency InducesIn Vitroand Mouse Brain Region-Specific Downregulation of Leucine Carboxyl Methyltransferase-1 and Protein Phosphatase 2A Bα Subunit Expression That Correlate with Enhanced Tau Phosphorylation
Authors: Sontag Jean-Marie , Nunbhakdi-Craig Viyada , Montgomery Lisa , Arning Erland , Bottiglieri Teodoro , Sontag Estelle
Published: November 2008

Altered folate homeostasis is associated with many clinical and pathological manifestations in the CNS. Notably, folate-mediated one-carbon metabolism is essential for methyltransferase-dependent cellular methylation reactions. Biogenesis of protein phosphatase 2A (PP2A) holoenzyme containing the regulatory Bα subunit, a major brain tau phosphatase, is controlled by methylation. Here, we show that folate deprivation in neuroblastoma cells induces downregulation of PP2A leucine carboxyl methyltransferase-1 (LCMT-1) expression, resulting in progressive accumulation of newly synthesized demethylated PP2A pools, concomitant loss of Bα, and ultimately cell death. These effects are further accentuated by overexpression of PP2A methylesterase (PME-1) but cannot be rescued by PME-1 knockdown. Overexpression of either LCMT-1 or Bα is sufficient to protect cells against the accumulation of demethylated PP2A, increased tau phosphorylation, and cell death induced by folate starvation. Conversely, knockdown of either protein accelerates folate deficiency-evoked cell toxicity. Significantly, mice maintained for 2 months on low-folate or folate-deficient diets have brain-region-specific alterations in metabolites of the methylation pathway. Those are associated with downregulation of LCMT-1, methylated PP2A, and Bα expression and enhanced tau phosphorylation in susceptible brain regions. Our studies provide novel mechanistic insights into the regulation of PP2A methylation and tau. They establish LCMT-1- and Bα-containing PP2A holoenzymes as key mediators of the role of folate in the brain. Our results suggest that counteracting the neuronal loss of LCMT-1 and Bα could be beneficial for all tauopathies and folate-dependent disorders of the CNS.
Neural Correlates of High-Gamma Oscillations (60–200 Hz) in Macaque Local Field Potentials and Their Potential Implications in Electrocorticography
Authors: Ray Supratim , Crone Nathan E. , Niebur Ernst , Franaszczuk Piotr J. , Hsiao Steven S.
Published: November 2008

Recent studies using electrocorticographic (ECoG) recordings in humans have shown that functional activation of cortex is associated with an increase in power in the high-gamma frequency range (∼60–200 Hz). Here we investigate the neural correlates of this high-gamma activity in local field potential (LFP). Single units and LFP were recorded with microelectrodes from the hand region of macaque secondary somatosensory cortex while vibrotactile stimuli of varying intensities were presented to the hand. We found that high-gamma power in the LFP was strongly correlated with the average firing rate recorded by the microelectrodes, both temporally and on a trial-by-trial basis. In comparison, the correlation between firing rate and low-gamma power (40–80 Hz) was much smaller. To explore the potential effects of neuronal firing on ECoG, we developed a model to estimate ECoG power generated by different firing patterns of the underlying cortical population and studied how ECoG power varies with changes in firing rate versus the degree of synchronous firing between neurons in the population. Both an increase in firing rate and neuronal synchrony increased high-gamma power in the simulated ECoG data. However, ECoG high-gamma activity was much more sensitive to increases in neuronal synchrony than firing rate.
Chelation of Mitochondrial Iron Prevents Seizure-Induced Mitochondrial Dysfunction and Neuronal Injury
Authors: Liang Li-Ping , Jarrett Stuart G. , Patel Manisha
Published: November 2008

Chelatable iron is an important catalyst for the initiation and propagation of free radical reactions and implicated in the pathogenesis of diverse neuronal disorders. Studies in our laboratory have shown that mitochondria are the principal source of reactive oxygen species production after status epilepticus (SE). We asked whether SE modulates mitochondrial iron levels by two independent methods and whether consequent mitochondrial dysfunction and neuronal injury could be ameliorated with a cell-permeable iron chelator. Kainate-induced SE resulted in a time-dependent increase in chelatable iron in mitochondrial but not cytosolic fractions of the rat hippocampus. Systemically administeredN,N′-bis (2-hydroxybenzyl) ethylenediamine-N,N′-diacetic acid (HBED), a synthetic iron chelator, ameliorated SE-induced changes in chelatable iron, mitochondrial oxidative stress (8-hydroxy-2′ deoxyguanosine and glutathione depletion), mitochondrial DNA integrity and hippocampal cell loss. Measurement of brain HBED levels after systemic administration confirmed its penetration in hippocampal mitochondria. These results suggest a role for mitochondrial iron in the pathogenesis of SE-induced brain damage and subcellular iron chelation as a novel therapeutic approach for its management.
Corticofugal Modulation of Initial Sound Processing in the Brain
Authors: Luo Feng , Wang Qianzhou , Kashani Alireza , Yan Jun
Published: November 2008

The brain selectively extracts the most relevant information in top-down processing manner. Does the corticofugal system, a “back projection system,” constitute the neural basis of such top-down selection? Here, we show how focal activation of the auditory cortex with 500 nA electrical pulses influences the auditory information processing in the cochlear nucleus (CN) that receives almost unprocessed information directly from the ear. We found that cortical activation increased the response magnitudes and shortened response latencies of physiologically matched CN neurons, whereas decreased response magnitudes and lengthened response latencies of unmatched CN neurons. In addition, cortical activation shifted the frequency tunings of unmatched CN neurons toward those of the activated cortical neurons. Our data suggest that cortical activation selectively enhances the neural processing of particular auditory information and attenuates others at the first processing level in the brain based on sound frequencies encoded in the auditory cortex. The auditory cortex apparently implements a long-range feedback mechanism to select or filter incoming signals from the ear.
Unraveling Epistasis With Triple Testcross Progenies of Near-Isogenic Lines
Authors: Reif Jochen C , Kusterer Barbara , Piepho Hans-Peter , Meyer Rhonda C , Altmann Thomas , Schön Chris C , Melchinger Albrecht E
Published: November 2008

Libraries of near-isogenic lines (NILs) are a powerful plant genetic resource to map quantitative trait loci (QTL). Nevertheless, QTL mapping with NILs is mostly restricted to genetic main effects. Here we propose a two-step procedure to map additive-by-additive digenic epistasis with NILs. In the first step, a generation means analysis of parents, their F1 hybrid, and one-segment NILs and their triple testcross (TTC) progenies is used to identify in a one-dimensional scan loci exhibiting QTL-by-background interactions. In a second step, one-segment NILs with significant additive-by-additive background interactions are used to produce particular two-segment NILs to test for digenic epistatic interactions between these segments. We evaluated our approach by analyzing a random subset of a genomewide Arabidopsis thaliana NIL library for growth-related traits. The results of our experimental study illustrated the potential of the presented two-step procedure to map additive-by-additive digenic epistasis with NILs. Furthermore, our findings suggested that additive main effects as well as additive-by-additive digenic epistasis strongly influence the genetic architecture underlying growth-related traits of A. thaliana.
Exploring Biological Relationships Between Calving Traits in Primiparous Cattle with a Bayesian Recursive Model
Authors: de Maturana Evangelina López , Wu Xiao-Lin , Gianola Daniel , Weigel Kent A , Rosa Guilherme J M
Published: November 2008

Structural equation models (SEMs) of a recursive type with heterogeneous structural coefficients were used to explore biological relationships between gestation length (GL), calving difficulty (CD), and perinatal mortality, also known as stillbirth (SB), in cattle, with the last two traits having categorical expression. An acyclic model was assumed, where recursive effects existed from the GL phenotype to the liabilities (latent variables) to CD and SB and from the liability to CD to that of SB considering four periods regarding GL. The data contained GL, CD, and SB records from 90,393 primiparous cows, sired by 1122 bulls, distributed over 935 herd-calving year classes. Low genetic correlations between GL and the other calving traits were found, whereas the liabilities to CD and SB were high and positively correlated, genetically. The model indicated that gestations of ∼274 days of length (3 days shorter than the average) would lead to the lowest CD and SB and confirmed the existence of an intermediate optimum of GL with respect to these traits.
Long-Term Effects of Inducible Mutagenic DNA Repair on Relative Fitness and Phenotypic Diversification in Pseudomonas cichorii 302959
Authors: Weigand Michael R , Sundin George W
Published: November 2008

Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for ∼500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of “round” and “fuzzy” colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.
Simple Telomeres in a Simple Animal: Absence of Subtelomeric Repeat Regions in the PlacozoanTrichoplax adhaerens
Authors: Robertson Hugh M
Published: November 2008

Simple telomeres were identified in the genome assembly of the basal placozoan animal Trichoplax adhaerens. They have 1–2 kb of TTAGGG telomeric repeats, which are preceded by a subtelomeric region of 1.5–13 kb. Unlike subtelomeric regions in most animals examined, these subtelomeric regions are unique to each telomere.
Association Between Parapneumonic Effusion and Pericardial Effusion in a Pediatric Cohort
Authors: Roberts Jon E. , Bezack Brian J. , Winger David I. , Pollack Simcha , Shah Rakesh A. , Cataletto Mary , Katz Douglas S. , Montoya-Iraheta Carlos , Schroeder Scott A. , Quintos-Alagheband Maria Lyn
Published: November 2008

OBJECTIVE. Associations between pleural and pericardial effusions have been described in malignancy and autoimmune disorders. Bacterial pneumonia is the most frequent cause of parapneumonic effusion; however, knowledge of the relationship between parapneumonic effusion and the presence of pericardial fluid in children is limited. We examined this relationship.

METHODS. We performed a retrospective chart review of pediatric patients who were admitted to our institution during a 6-year period with a diagnosis of either parapneumonic effusion or empyema and who had undergone an echocardiogram, a computed tomography scan of the thorax, or both. All demographic, clinical, radiographic, and laboratory data of these patients were collected, and statistical analysis was done with Student's t tests and χ2 analyses.

RESULTS. We reviewed the charts of 59 children with parapneumonic effusions. Forty-eight underwent 2-dimensional echocardiography, chest computed tomography scan, or both. Of these 48 patients, 54.2% (n = 26) were found to have a concomitant pericardial effusion. The majority of patients with pericardial effusions had left-sided pleural disease. Patients with pericardial effusions had more symptomatic days before hospitalization, lower pleural fluid albumin levels, elevated serum white blood cell counts, elevated pleural fluid white blood cell and absolute neutrophil counts, and an increased incidence of surgical intervention. One patient had evidence of hemodynamic compromise that required pericardiocentesis.

CONCLUSIONS. We found a high incidence of pericardial effusions in pediatric patients with parapneumonic effusions. Leukocytosis, higher pleural fluid leukocyte and neutrophil counts, and a propensity for surgical intervention suggest a prognostic relationship between pericardial effusions and more severe parapneumonic disease. The majority of these pericardial collections resolve with treatment of the underlying pleural disease.
Potencial de multiplicação in vitro de cultivares de amoreira-preta
Authors: Oliveira Roberto Pedroso de , Nino Antonio Fernando Pacheco , Ferreira Letícia Vanni
Published: November 2008

Este trabalho foi realizado com o objetivo de avaliar o potencial de multiplicação in vitro de sete cultivares de amoreira-preta: Brazos, Cherokee, Comanche, Ébano, Guarani, Tupy e Xavante. Utilizou-se protocolo da Embrapa Clima Temperado empregado em laboratórios comerciais. A desinfestação dos explantes foi realizada em soluções à base de álcool e hipoclorito de sódio; a cultura dos meristemas em meio semi-sólido MS com 1 mg L-1 BAP, 0,01 mg L-1 ANA e 0,1 mg L-1 AG3; a multiplicação em MS com 0,8 mg L-1 BAP; e o enraizamento em ½MS com 0,5 mg L-1 ANA, sempre a 25±4ºC, 20 µE m-2 s-1, e fotoperíodo de 16 horas. Partiu-se de 60 meristemas de cada cultivar, avaliando-se a taxa de multiplicação e os níveis de contaminação, vitrificação e oxidação durante as fases de estabelecimento (60 dias), multiplicação (seis subcultivos de 40 dias) e enraizamento in vitro (30 dias). O número estimado de plantas obtidas por meristema foi de 16.335 para 'Brazos', 24.211 para 'Cherokee', 19.778 para 'Comanche', 106.550 para 'Ébano', 14.275 para 'Guarani', 34.022 para 'Tupy' e 24.651 para 'Xavante'. A quantificação dessa variabilidade de resposta in vitro é importante para o planejamento da produção de mudas de cada cultivar nos laboratórios de micropropagação.
Determination of thermal diffusivity in papaya pulp as a function of maturation stage
Authors: Corrêa Savio Figueira , Souza Maximiliano Silva de , Pereira Talita , Alves Gustavo Verçosa de Lima , Oliveira Jurandi Gonçalves de , Silva Marcelo Gomes da , Vargas Helion
Published: November 2008

In order to determine the penetration of the thermal wave in the papaya fruit pulp (Carica papaya L.), cv. Golden, thermal diffusivity of the pulp was obtained measuring temperature at four different depths. Measurements were carried out initially with the fruit on the first stage of maturity. The changes of the thermal diffusivity were expressed as a function of ripening. A temporal decrease of the thermal diffusivity was observed. Chemical (pH, soluble solids and total titratable acidity) and physical (pulp firmness) properties were measured as well and the results were compared to the thermal diffusivity change.
Níveis de produção em vinhedos de altitude da cv. Malbec e seus efeitos sobre os compostos fenólicos
Authors: Silva Leonardo Cury da , Kretzschmar Aike Anneliese , Rufato Leo , Brighenti Alberto Fontanella , Schlemper Caroline
Published: November 2008

O presente trabalho teve como objetivo obter informações sobre a evolução dos compostos fenólicos, de acordo com o nível de raleio de cachos, durante a maturação de uvas cv. Malbec, de modo a estabelecer critérios que contribuam para definir o manejo mais apropriado ao vinhedo. Os ensaios foram conduzidos durante as safras de 2005/06 e 2006/07, em um talhão do vinhedo Villa Francioni, no município de São Joaquim - Santa Catarina, com videiras da cultivar Malbec, enxertadas sobre 'Paulsen 1103' conduzidas em espaldeira, com espaçamento de 3,0m x 1,2m e cobertura antigranizo. Os níveis de raleio de cachos, ajustados na virada de cor "véraison", corresponderam a 13 t ha-1 (Testemunha), 11 t ha-1 (T1), 9 t ha-1 (T2) e 7 t ha-1 (T3), compondo um delineamento em blocos casualizados. Avaliou-se a evolução dos compostos fenólicos durante as oito semanas antecedentes à colheita, conforme os três níveis de raleio. Dos resultados obtidos, conclui-se que, para as condições de altitude, a prática de raleio de cachos influencia na composição fenólica das bagas da cultivar Malbec, aumentando o conteúdo de antocianinas facilmente extraíveis para um tratamento de raleio de cachos com uma produção esperada de aproximadamente 10 t ha-1, melhorando a composição fenólica das bagas, atributos favoráveis à produção de vinhos tintos finos amplos e estruturados.
Avaliação genética de indivíduos e progênies de cupuaçuzeiro no estado do Pará e estimativas de parâmetros genéticos
Authors: Alves Rafael Moysés , Resende Marcos Deon Vilela de
Published: November 2008

O presente trabalho relata a avaliação genotípica de progênies de cupuaçuzeiro, no Estado do Pará, para os caracteres número de frutos (NF) em quatro safras, intensidade de ocorrência de vassoura- de-bruxa na inflorescência (VBI) e nos frutos (VBF), e peso de vassoura-de-bruxa (PVB). Apresenta também estimativas de parâmetros genéticos que permitem inferir sobre o controle genético e nível de variabilidade genética presente no material avaliado. Todos os caracteres apresentaram considerável variabilidade genética, com coeficientes de variação genética variando de 27% a 88% no âmbito de progênie e de 38% a 123% no âmbito individual. Isto revela excelentes possibilidades para a seleção nessa população experimental híbrida. As estimativas de herdabilidade individual no sentido restrito, em uma safra, variaram de 25% a 54%, e as repetibilidades individuais para NF equivaleram a 35%. Com as quatro safras realizadas, a herdabilidade em nível individual aumentou para 48%, propiciando acurácia seletiva de 70%, para a seleção de indivíduos. O ganho em eficiência, quando se usa mais de cinco safras, é praticamente desprezível. Para NF, ganhos acima de 60% podem ser obtidos com a seleção dos cinco melhores indivíduos. Poderão ser selecionados indivíduos com produção anual de 17 frutos, valor muito superior à média geral de 10 frutos, encontrada nos plantios comerciais. Verificam-se ganhos genéticos bastante superiores quando se faz a propagação clonal dos melhores indivíduos em relação ao que se verifica quando se realiza a propagação sexuada. Para o melhor indivíduo, o ganho genético aumenta de 75.5% para 88.3%, ou seja, de 17 para quase 19 frutos por planta. Isto revela um grande potencial para a clonagem comercial de cupuaçuzeiro. Para os caracteres VBI e VBF, verificaram-se altas herdabilidades individuais no sentido restrito com valores variando entre 30% e 54%. Isto revela o excelente potencial da seleção recorrente para melhorar, gradativamente, o nível de resistência. Parece suficiente considerar na seleção apenas o número de vassouras, não sendo necessário considerar o peso. A correlação entre resistência no fruto e na inflorescência foi alta (0.84), indicando algum controle genético comum aos dois caracteres. Foram identificadas progênies superiores, simultaneamente, para produção de frutos e resistência à vassoura.