bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurology of rhizomelic chondrodysplasia punctata
Authors: Bams-Mengerink Annemieke M , Koelman Johannes HTM , Waterham Hans , Barth Peter G , Poll-The Bwee Tien
Published: October 2013

Background

To describe the neurologic profiles of Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature.

Methods

Observational study including review of clinical and biochemical abnormalities, genotype, presence of seizures and neurophysiological studies of a cohort of 16 patients with RCDP.

Results

Patients with the severe phenotype nearly failed to achieve any motor or cognitive skills, whereas patients with the milder phenotype had profound intellectual disability but were able to walk and had verbal communication skills. Eighty-eight percent of patients developed epileptic seizures. The age of onset paralleled the severity of the clinical and biochemical phenotype. Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. Visual evoked (VEP) and brain auditory potential (BAEP) studies showed initial normal latency times in 93% of patients. Deterioration of VEP occurred in a minority in both the severe and the milder phenotype. BAEP and somatosensory evoked potentials (SSEP) were more likely to become abnormal in the severe phenotype. Plasmalogens were deficient in all patients. In the milder phenotype levels of plasmalogens were significantly higher in erythrocytes than in the severe phenotype. Phytanic acid levels ranged from normal to severely increased, but had no relation with the neurological phenotype.

Conclusion

Neurodevelopmental deficits and age-related occurrence of seizures are characteristic of RCDP and are related to the rest-activity in plasmalogen biosynthesis. Evoked potential studies are more likely to become abnormal in the severe phenotype, but are of no predictive value in single cases of RCDP.
Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis
Authors: Crnkic Kapetanovic Meliha , Saxne Tore , Jönsson Göran , Truedsson Lennart , Geborek Pierre
Published: October 2013

Introduction

The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA).

Methods

Patients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post- and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥2.

Results

In total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%.

Conclusion

In this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment.

Trial registration

NCT00828997 and EudraCT EU2007-006539-29.
Top Notch cancer stem cells by paracrine NF-κB signaling in breast cancer
Authors: Zhang Weizhou , Grivennikov Sergei I
Published: October 2013

Cancer stem cells are likely to play critical roles in metastasis, therapy resistance, and recurrence of hematological and solid malignancies. It is well known that the stem cell niche plays a key role for asymmetric division and homeostasis of normal stem cells, whereas cancer stem cells seem to use these niches. Among many pathways involved in self-renewal of cancer stem cells, nuclear factor-kappa B (NF-κB) signaling has been documented to promote their expansion in a cell-autonomous fashion. A recent study, however, suggests that paracrine NF-κB activation promotes the expansion of cancer stem cells through the activation of Notch in basal-type breast cancer cells.
Microdomains in the membrane landscape shape antigen-presenting cell function
Authors: Zuidscherwoude Malou , de Winde Charlotte M , Cambi Alessandra , van Spriel Annemiek B
Published: October 2013

The plasma membrane of immune cells is a highly organized cell structure that is key to the initiation and regulation of innate and adaptive immune responses. It is well-established that immunoreceptors embedded in the plasma membrane have a nonrandom spatial distribution that is important for coupling to components of intracellular signaling cascades. In the last two decades, specialized membrane microdomains, including lipid rafts and TEMs, have been identified. These domains are preformed structures (“physical entities”) that compartmentalize proteins, lipids, and signaling molecules into multimolecular assemblies. In APCs, different microdomains containing immunoreceptors (MHC proteins, PRRs, integrins, among others) have been reported that are imperative for efficient pathogen recognition, the formation of the immunological synapse, and subsequent T cell activation. In addition, recent work has demonstrated that tetraspanin microdomains and lipid rafts are involved in BCR signaling and B cell activation. Research into the molecular mechanisms underlying membrane domain formation is fundamental to a comprehensive understanding of membrane-proximal signaling and APC function. This review will also discuss the advances in the microscopy field for the visualization of the plasma membrane, as well as the recent progress in targeting microdomains as novel, therapeutic approach for infectious and malignant diseases.
Reduced Expression of 11β-Hydroxysteroid Dehydrogenase Type 2 in Preeclamptic Placentas Is Associated With Decreased PPARγ but Increased PPARα Expression
Authors: He Ping , Chen Zhaoguang , Sun Qianqian , Li Yuan , Gu Hang , Ni Xin
Published: October 2013

Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is reduced in pregnancies complicated with preeclampsia (PE). Peroxisome proliferator-activated receptors β/δ (PPARβ/δ) have been shown to suppress 11β-HSD2 expression in human placental cells. Our objectives were to investigate whether the reduced 11β-HSD2 expression is associated with the changes in PPARs in PE placentas, and whether PPARα and PPARγ affect 11β-HSD2 expression in placental cells. PPARα and PPARβ/δ mRNA and protein expression was increased, whereas PPARγ mRNA and protein expression was decreased in PE placentas. 11β-HSD2 protein expression was inversely correlated with PPARβ/δ in normal placentas but correlated positively with PPARγ and inversely to PPARα in PE placentas. In cultured placental cells, PPARα agonist inhibited, whereas PPARγ agonist stimulated, 11β-HSD2 mRNA and protein expression and activity in a dose-dependent manner. Knockdown of retinoid X nuclear receptor α (RXRα) resulted in a loss of PPARγ effect but not PPARα effect on11β-HSD2. The PPARα effect remained, but the PPARγ effect was lost in the presence of the translational inhibitor cycloheximide. PPARγ agonist dose-dependently stimulated specificity protein 1 (Sp-1) protein expression. Inhibition or knockdown of Sp-1 resulted in a loss of the effects of PPARα and PPARγ. The Sp-1 protein level was not correlated with 11β-HSD2 and PPARs in normal placentas, whereas Sp-1 expression was correlated with 11β-HSD2, PPARγ, and PPARβ/δ in PE placentas. Our data indicate that 11β-HSD2 expression can be modulated by PPARα and PPARγ in placental trophoblasts through Sp-1. Decreased 11β-HSD2 expression in PE placenta might be associated with decreased PPARγ but increased PPARα expression.
Insulin-like 3-Induced Rat Preantral Follicular Growth Is Mediated by Growth Differentiation Factor 9
Authors: Xue Kai , Kim Ji Young , Liu Jia-yin , Tsang Benjamin K.
Published: October 2013

The communication of somatic cells and oocytes by intrafollicular paracrine factors is essential for follicular growth in the ovary. Insulin-like 3 (INSL3) is a theca cell-secreted paracrine factor. Androgens and growth differentiation factor 9 (GDF9), an oocyte-derived growth factor, are essential for follicular development. Using a rat preantral follicle culture model, we examined in the present study the influence of INSL3 on preantral follicular growth and the molecular mechanisms involved. We have observed that the receptor for INSL3, relaxin/insulin-like family peptide receptor 2 (RXFP2), was exclusively expressed in oocytes. Recombinant INSL3 stimulated Gdf9 expression, preantral follicular growth, and testosterone synthesis in vitro. Inhibition of the cAMP/protein kinase A signaling pathway (with cAMP antagonist, 8-bromoadenosine 3′,5′-cyclic monophosphorothioate, Rp-isomer) attenuated INSL3-induced Gdf9 expression and preantral follicular growth. Moreover, knocking down Gdf9 expression (with small interfering RNA) or inhibiting GDF9 signaling (with SB431542, an activin receptor-like kinase receptor 5 inhibitor, or specific inhibitor of mothers against decapentaplegic homolog 3) or androgen action (with flutamide, an androgen receptor antagonist) suppressed INSL3-induced preantral follicular growth. In addition, LH and DHT regulated the expression of Insl3 mRNA in preantral follicles. These observations suggest that INSL3 is a key theca cell-derived growth factor for preantral follicle and that its action is mediated by GDF9.
Bone Marrow Leptin Signaling Mediates Obesity-Associated Adipose Tissue Inflammation in Male Mice
Authors: Dib Lea H. , Ortega M. Teresa , Fleming Sherry D. , Chapes Stephen K. , Melgarejo Tonatiuh
Published: October 2013

Obesity is characterized by an increased recruitment of proinflammatory macrophages to the adipose tissue (AT), leading to systemic inflammation and metabolic disease. The pathogenesis of this AT inflammation, however, remains to be elucidated. The circulating adipokine leptin is increased in obesity and is involved in immune cell function and activation. In the present study, we investigated the role of leptin in the induction of obesity-associated inflammation. We generated radiation chimeric C57BL/6J mice reconstituted with either leptin receptor-deficient (db/db) or wild-type (WT) bone marrow and challenged them with a high-fat diet (HFD) for 16 weeks. Mice reconstituted with db/db bone marrow (WT/db), had significantly lower body weight and adiposity compared with mice with WT bone marrow (WT/WT). Gonadal AT in WT/db mice displayed a 2-fold lower expression of the inflammatory genes Tnfa, Il6, and Ccl2. In addition, gonadal fat of WT/db mice contained significantly fewer crown-like structures compared with WT/WT mice, and most of their AT macrophages expressed macrophage galactose-type C type lectin 1 (MGL1) and were C-C chemokine receptor type 2 (CCR2)-negative, indicative of an anti-inflammatory phenotype. Moreover, WT/db mice exhibited greater insulin sensitivity compared with WT/WT mice. These data show that disrupted leptin signaling in bone marrow-derived cells attenuates the proinflammatory conditions that mediate many of the metabolic complications that characterize obesity. Our findings establish a novel mechanism involved in the regulation of obesity-associated systemic inflammation and support the hypothesis that leptin is a proinflammatory cytokine.
β-Arrestin 1 and 2 and G Protein-Coupled Receptor Kinase 2 Expression in Pituitary Adenomas: Role in the Regulation of Response to Somatostatin Analogue Treatment in Patients With Acromegaly
Authors: Gatto Federico , Feelders Richard , van der Pas Rob , Kros Johan M. , Dogan Fadime , van Koetsveld Peter M. , van der Lelij Aart-Jan , Neggers Sebastian J. C. M. M. , Minuto Francesco , de Herder Wouter , Lamberts Steven W. J. , Ferone Diego , Hofland Leo J.
Published: October 2013

Recent in vitro studies highlighted G protein-coupled receptor kinase (GRK)2 and β-arrestins as important players in driving somatostatin receptor (SSTR) desensitization and trafficking. Our aim was to characterize GRK2 and β-arrestins expression in different pituitary adenomas and to investigate their potential role in the response to somatostatin analog (SSA) treatment in GH-secreting adenomas (GHomas). We evaluated mRNA expression of multiple SSTRs, GRK2, β-arrestin 1, and β-arrestin 2 in 41 pituitary adenomas (31 GHomas, 6 nonfunctioning [NFPAs], and 4 prolactinomas [PRLomas]). Within the GHomas group, mRNA data were correlated with the in vivo response to an acute octreotide test and with the GH-lowering effect of SSA in cultured primary cells. β-Arrestin 1 expression was low in all 3 adenoma histotypes. However, its expression was significantly lower in GHomas and PRLomas, compared with NFPAs (P < .01). GRK2 expression was higher in PRLomas and NFPAs compared with GHomas (P < .05). In the GHoma group, GRK2 expression was inversely correlated to β-arrestin 1 (P < .05) and positively correlated to β-arrestin 2 (P < .0001). SSA treatment did not affect GRK2 and β-arrestin expression in GHomas or in cultured rat pituitary tumor GH3 cells. Noteworthy, β-arrestin 1 was significantly lower (P < .05) in tumors responsive to octreotide treatment in vitro, whereas GRK2 and SSTR subtype 2 were significantly higher (P < .05). Likewise, β-arrestin 1 levels were inversely correlated with the in vivo response to acute octreotide test (P = .001), whereas GRK2 and SSTR subtype 2 expression were positively correlated (P < .05). In conclusion, for the first time, we characterized GRK2, β-arrestin 1, and β-arrestin 2 expression in a representative number of pituitary adenomas. β-Arrestin 1 and GRK2 seem to have a role in modulating GH secretion during SSA treatment.
Expression of Melanin-Concentrating Hormone Receptor 2 Protects Against Diet-Induced Obesity in Male Mice
Authors: Chee Melissa J. S. , Pissios Pavlos , Prasad Deepthi , Maratos-Flier Eleftheria
Published: October 2013

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide that is a ligand for two subtypes of MCH receptors, MCHR1 and MCHR2. MCHR1 is universally expressed in mammals ranging from rodents to humans, but the expression of MCHR2 is substantially restricted. In mammals, MCHR2 has been defined in primates as well as other species such as cats and dogs but is not seen in rodents. Although the role of MCHR1 in mediating the actions of MCH on energy balance is clearly defined using mouse models, the role of MCHR2 is harder to characterize because of its limited expression. To determine any potential role of MCHR2 in energy balance, we generated a transgenic MCHR1R2 mouse model, where human MCHR2 is coexpressed in MCHR1-expressing neurons. As shown previously, control wild-type mice expressing only native MCHR1 developed diet-induced obesity when fed a high-fat diet. In contrast, MCHR1R2 mice had lower food intake, leading to their resistance to diet-induced obesity. Furthermore, we showed that MCH action is altered in MCHR1R2 mice. MCH treatment in wild-type mice inhibited the activation of the immediate-early gene c-fos, and coexpression of MCHR2 reduced the inhibitory actions of MCHR1 on this pathway. In conclusion, we developed an experimental animal model that can provide insight into the action of MCHR2 in the central nervous system and suggest that some actions of MCHR2 oppose the endogenous actions of MCHR1.
Effects of Neurokinin B Administration on Reproductive Hormone Secretion in Healthy Men and Women
Authors: Jayasena Channa N. , Comninos Alexander N. , De Silva Akila , Abbara Ali , Veldhuis Johannes D. , Nijher Gurjinder M. K. , Ganiyu-Dada Zainab , Vaal Meriel , Stamp Gordon , Ghatei Mohammad A. , Bloom Stephen R. , Dhillo Waljit S.
Published: October 2013

Background:

Neurokinin B (NKB) is a member of the tachykinin family of peptides. Inactivating mutations in the tachykinin 3 or tachykinin 3 receptor gene are associated with pubertal failure and congenital hypogonadotrophic hypogonadism in humans. This suggests that NKB may have a critical role in human reproduction. The effects of NKB administration have not been investigated previously in humans.

Aim:

The aim of this study was to determine the effects of iv administration of NKB on gonadotrophin secretion in healthy male and female volunteers.

Methods:

A total of 23 healthy men and 11 healthy women participated in the study. After an initial dose-finding study (study 1), men received a 4-hour infusion of vehicle (gelofusin) followed by a 4-hour infusion of NKB (2.56 or 5.12 nmol/kg/h) (study 2), and an 8-hour infusion of vehicle or NKB during different visits (study 3). Healthy women underwent a dose-finding study consisting of a 3-hour NKB administration during the follicular phase of the menstrual cycle, and the maximum dose of NKB was also tested during the preovulatory and midluteal phases of menstrual cycle (study 4).

Results:

Mean LH, FSH, and T secretion were not significantly altered during a 90-minute infusion of NKB (0.4–5.12 nmol/kg/h), or a 4-hour infusion of NKB (5.12 nmol/kg/h). No alterations in gonadotrophin secretion or LH pulsatility were observed during an 8-hour infusion of NKB when compared with vehicle. Doses of 0.64–5.12 nmol/kg/h NKB did not significantly alter LH, FSH, or estradiol secretion in healthy women during the follicular phase of the menstrual cycle. Finally, 5.12 nmol/kg/h did not significantly alter reproductive hormone secretion during the preovulatory or midluteal phases of the menstrual cycle.

Conclusions:

This is the first clinical study of NKB administration. None of the doses of NKB tested were associated with significant alterations in reproductive hormone secretion in healthy male or female volunteers. These novel data add to our understanding of the physiological actions of NKB in human reproduction.
Absolute Color, Fluctuating Mischfarben, and Structurally Functional “Gypsy” Orchestration
Authors: DeThorne Jeffrey
Published: October 2013

Correlating particular instrumental colors with pitch chromaticism, three early twentieth-century scholars demonstrate how a methodical use of colorful winds, less colorful strings, and wind-string mixtures informed actual orchestrational practices. After demonstrating how Wagner’s use of instrumental “residue” creates an “articulate unity” in a passage from Lohengrin, Theodor Adorno describes how Alban Berg’s orchestration of the Frühen Lieder combines particular instrumental colors and generalized orchestral sonorities into articulate Mischfarben that distinguish whole-tone scales from functional harmony. After defining “absolute color” in the context of Gluck’s orchestration, Ernst Kurth demonstrates how “absolute” wind instrument colors delineate “absolute” “destructive” harmonic colors in Wagner’s Tristan instrumentation. Finally, Arnold Schoenberg’s functional orchestration of the “Rondo alla Zingarese” from Brahms’s G-minor Piano Quartet matches “indirectly related” harmonies with vivid wind and percussion colors and “closely related” harmonies with string-centered sonorities.
Stabilization and Modification of Gold Nanocube Surfaces with Layered Silicate
Authors: Eguchi Miharu , Ito Masae , Ishibashi Taka-aki
Published: October 2013

The surface stability of metal nanoparticles was enhanced by adsorption of layered silicate (so-called “clay”) on metal nanocubes whose surface was protected by a surfactant. The strong adsorption of the layered silicate to the metal nanocubes via the surfactant eliminated the need for using excess surfactant for metal nanoparticle dispersion. Furthermore, the surface of the negatively charged hybrids was demonstrated to be modifiable with cationic molecules.
Pricing and Revenue Management: The Value of Coordination
Authors: Kocabıyıkoğlu Ayşe , Popescu Ioana , Stefanescu Catalina
Published: October 2013

The integration of systems for pricing and revenue management must trade off potential revenue gains against significant practical and technical challenges. This dilemma motivates us to investigate the value of coordinating decisions on prices and capacity allocation in a stylized setting. We propose two pairs of sequential policies for making static decisions—on pricing and revenue management—that differ in their degree of integration (hierarchical versus coordinated) and their pricing inputs (deterministic versus stochastic). For a large class of stochastic, price-dependent demand models, we prove that these four heuristics admit tractable solutions satisfying intuitive sensitivity properties. We further evaluate numerically the performance of these policies relative to a fully coordinated model, which is generally intractable. We find it interesting that near-optimal performance is usually achieved by a simple hierarchical policy that sets prices first, based on a nonnested stochastic model, and then uses these prices to optimize nested capacity allocation. This tractable policy largely outperforms its counterpart based on a deterministic pricing model. Jointly optimizing price and allocation decisions for the high-end segment improves performance, but the largest revenue benefits stem from adjusting prices to account for demand risk.

This paper was accepted by Yossi Aviv, operations management.
Money, Status, and the Ovulatory Cycle
Authors: Durante Kristina M. , Griskevicius Vladas , Cantú Stephanie M. , Simpson Jeffry A.
Published: October 2013

Each month, millions of women experience an ovulatory cycle that regulates fertility. Previous consumer research has found that this cycle influences women's clothing and food preferences. The authors propose that the ovulatory cycle actually has a much broader effect on women's economic behavior. Drawing on theory in evolutionary psychology, the authors hypothesize that the week-long period near ovulation should boost women's desire for relative status, which should alter their economic decisions. Findings from three studies show that women near ovulation seek positional goods to improve their social standing. Additional findings reveal that ovulation leads women to pursue positional goods when doing so improves relative standing compared with other women but not compared with men. When playing the dictator game, for example, ovulating women gave smaller offers to a female partner but not to a male partner. Overall, women's monthly hormonal fluctuations seem to have a substantial effect on consumer behavior by systematically altering their positional concerns, a finding that has important implications for marketers, consumers, and researchers.
Single-Neuron Mechanisms Underlying Cost-Benefit Analysis in Frontal Cortex
Authors: Hosokawa Takayuki , Kennerley Steven W. , Sloan Jennifer , Wallis Jonathan D.
Published: October 2013

Effective decision-making requires consideration of costs and benefits. Previous studies have implicated orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) in cost-benefit decision-making. Yet controversy remains about whether different decision costs are encoded by different brain areas, and whether single neurons integrate costs and benefits to derive a subjective value estimate for each choice alternative. To address these issues, we trained four subjects to perform delay- and effort-based cost-benefit decisions and recorded neuronal activity in OFC, ACC, DLPFC, and the cingulate motor area (CMA). Although some neurons, mainly in ACC, did exhibit integrated value signals as if performing cost-benefit computations, they were relatively few in number. Instead, the majority of neurons in all areas encoded the decision type; that is whether the subject was required to perform a delay- or effort-based decision. OFC and DLPFC neurons tended to show the largest changes in firing rate for delay- but not effort-based decisions; whereas, the reverse was true for CMA neurons. Only ACC contained neurons modulated by both effort- and delay-based decisions. These findings challenge the idea that OFC calculates an abstract value signal to guide decision-making. Instead, our results suggest that an important function of single PFC neurons is to categorize sensory stimuli based on the consequences predicted by those stimuli.
Distinct Balance of Excitation and Inhibition in an Interareal Feedforward and Feedback Circuit of Mouse Visual Cortex
Authors: Yang Weiguo , Carrasquillo Yarimar , Hooks Bryan M. , Nerbonne Jeanne M. , Burkhalter Andreas
Published: October 2013

Mouse visual cortex is subdivided into multiple distinct, hierarchically organized areas that are interconnected through feedforward (FF) and feedback (FB) pathways. The principal synaptic targets of FF and FB axons that reciprocally interconnect primary visual cortex (V1) with the higher lateromedial extrastriate area (LM) are pyramidal cells (Pyr) and parvalbumin (PV)-expressing GABAergic interneurons. Recordings in slices of mouse visual cortex have shown that layer 2/3 Pyr cells receive excitatory monosynaptic FF and FB inputs, which are opposed by disynaptic inhibition. Most notably, inhibition is stronger in the FF than FB pathway, suggesting pathway-specific organization of feedforward inhibition (FFI). To explore the hypothesis that this difference is due to diverse pathway-specific strengths of the inputs to PV neurons we have performed subcellular Channelrhodopsin-2-assisted circuit mapping in slices of mouse visual cortex. Whole-cell patch-clamp recordings were obtained from retrobead-labeled FFV1→LM- and FBLM→V1-projecting Pyr cells, as well as from tdTomato-expressing PV neurons. The results show that the FFV1→LMpathway provides on average 3.7-fold stronger depolarizing input to layer 2/3 inhibitory PV neurons than to neighboring excitatory Pyr cells. In the FBLM→V1pathway, depolarizing inputs to layer 2/3 PV neurons and Pyr cells were balanced. Balanced inputs were also found in the FFV1→LMpathway to layer 5 PV neurons and Pyr cells, whereas FBLM→V1inputs to layer 5 were biased toward Pyr cells. The findings indicate that FFI in FFV1→LMand FBLM→V1circuits are organized in a pathway- and lamina-specific fashion.
Treatment with Thyroxine Restores Myelination and Clinical Recovery after Intraventricular Hemorrhage
Authors: Vose Linnea R. , Vinukonda Govindaiah , Jo Sungro , Miry Omid , Diamond Daniel , Korumilli Ritesh , Arshad Arslan , Zia Muhammad T. K. , Hu Furong , Kayton Robert J. , La Gamma Edmund F. , Bansal Rashmi , Bianco Antonio C. , Ballabh Praveen
Published: October 2013

Intraventricular hemorrhage (IVH) remains a major cause of white matter injury in preterm infants with no viable therapeutic strategy to restore myelination. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling, which is mediated by TH receptor α (TRα) and TRβ. In the brain, cellular levels of TH are regulated by deiodinases, with deiodinase-2 mediating TH activation and deiodinase-3 TH inactivation. Therefore, we hypothesized that IVH would decrease TH signaling via changes in the expression of deiodinases and/or TRs, and normalization of TH signaling would enhance maturation of oligodendrocytes and myelination in preterm infants with IVH. These hypotheses were tested using both autopsy materials from human preterm infants and a rabbit model of IVH. We found that deiodinase-2 levels were reduced, whereas deiodinase-3 levels were increased in brain samples of both humans and rabbits with IVH compared with controls without IVH. TRα expression was also increased in human infants with IVH. Importantly, treatment with TH accelerated the proliferation and maturation of oligodendrocytes, increased transcription of Olig2 and Sox10 genes, augmented myelination, and restored neurological function in pups with IVH. Consistent with these findings, the density of myelinating oligodendrocytes was almost doubled in TH-treated human preterm infants compared with controls. Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TRα. Given that TH promotes neurological recovery in IVH, TH treatment might improve the neurodevelopmental outcome of preterm infants with IVH.
Foxo3a Transcriptionally Upregulates AQP4 and Induces Cerebral Edema Following Traumatic Brain Injury
Authors: Kapoor Suraj , Kim Seon-Myung , Farook Justin M. , Mir Sajad , Saha Rahul , Sen Nilkantha
Published: October 2013

Increased cranial pressure due to development of edema contributes significantly to the pathology of traumatic brain injury (TBI). Induction of an astrocytic water channel protein, Aquaporin 4 (AQP4), is known to predominantly contribute to cytotoxic edema following TBI. However, the mechanism for the increase in AQP4 following 24 h of TBI is poorly understood. Here we show that transcriptional activation of a ubiquitously expressed mammalian forkhead transcription factor, Foxo3a, induces cerebral edema by increasing the AQP4 level in the controlled cortical impact model of TBI in mice. TBI stimulates nuclear translocation of Foxo3a in astrocytes and subsequently augments its binding to AQP4 promoter in pericontusional cortex. Nuclear accumulation of Foxo3a is augmented by a decrease in phosphorylation at its Ser256 residue due to inactivation of Akt after TBI. Depletion of Foxo3a in mice rescues cytotoxic edema by preventing induction of AQP4 as well as attenuates memory impairment after TBI in mice.
Estudo comparativo entre o trauma em idosos e não idosos atendidos em um Hospital Universitário de Curitiba
Authors: Broska Júnior César Augusto , Folchini Augusto Bernardo De , Ruediger Ricardo Rydygier de
Published: October 2013

OBJETIVO: comparar e identificar diferenças no perfil de pacientes idosos e não idosos atendidos por trauma. MÉTODOS: estudo transversal comparativo quantitativo retrospectivo realizado com 3112 pacientes entre 25/11/2010 e 25/02/2011 que foram classificados em GI idosos (60 anos ou mais) e GA não idosos (13 a 59 anos). Foram coletadas informações sobre mecanismo, lesões e fatores associados ao acidente que foram comparados entre os grupos através da utilização dos testes χ2, t de Student e proporções. RESULTADOS: as quedas foram mais frequentes em GI em destaque as de própria altura enquanto que violência, quedas e acidentes de trânsito (em especial os com moto) foram os mais importantes em GA. Ambos os grupos possuíram traumas leves (contusões, entorses) como os mais frequentes, seguido por traumatismo crânio-encefálico (TCE) e fraturas. Nos membros inferiores as fraturas de fêmur foram mais comuns em idosos enquanto que fraturas de mão e punho nos não idosos. Os idosos ficaram menos dias internados e não houve diferença quanto a presença de complicações, necessidade de UTI ou mortalidade entre os grupos. CONCLUSÃO: Quedas de mesmo nível são mais frequentes em idosos e acidentes de moto, violência interpessoal em não idosos. Ambos os grupos apresentaram traumas superficiais, TCE e fraturas como principais lesões decorrentes do trauma. Os idosos ficaram menos dias internados. Não houve diferença quanto a necessidade de UTI, presença de complicações e mortalidade.
Anemia mielotísica por osteopetrose em um cão: relato de caso
Authors: Mendes Neto E.C. , Gruchouskei L. , Viott A.M. , Nunes A.C.B. , Fukushima F.B. , Oyafuso M.K.
Published: October 2013

A osteopetrose é uma doença rara, caracterizada pelo aumento generalizado da densidade óssea. Tem como característica principal, a reabsorção osteoclástica defeituosa, resultando no acúmulo de massa óssea. Além disso, pode ocorrer retardo do crescimento, desnutrição progressiva, anemia e caquexia. O presente relato descreve o caso de uma cadela, com aproximadamente nove meses de idade, sem raça definida, com histórico de apatia e disorexia. Hemogramas seriados demonstraram pancitopenia persistente. Vários exames laboratoriais foram realizados para excluir doenças como erliquiose, leishmaniose e cinomose, porém todos foram negativos. O mielograma constatou hipocelularidade relativa por provável aplasia/hipoplasia medular. Exames radiográficos evidenciaram o aumento da radiopacidade óssea e hipertrofia da região cortical, e a necropsia confirmou a redução do canal medular. O exame histopatológico confirmou a osteopetrose. Conclui-se que a osteopetrose pode causar comprometimento na produção de células sanguíneas, sendo uma causa rara de anemia mielotísica, além de alterações neurológicas secundárias à má-formação dos ossos do crânio.
Anestesia local por tumescência com lidocaína em cadelas submetidas a mastectomia
Authors: Abimussi C.J.X. , Ferreira J.Z. , Floriano B.P. , Paes F. , Perri S.H.V. , Oliva V.N.L.S.
Published: October 2013

O presente estudo investigou os benefícios da anestesia por tumescência com lidocaína em cadelas submetidas à mastectomia, visando ao conforto do paciente e à sua recuperação pós-operatória. Foram utilizados sete animais, de peso e raças variadas, que apresentavam neoplasia em região de cadeia mamária e que foram submetidos à cirurgia de mastectomia. Todos os animais receberam o mesmo protocolo anestésico, sendo utilizado como MPA a associação entre acepromazina e morfina, nas doses de 0,04mg/kg e 0,4mg/kg (IM), respectivamente. Após 15 minutos, foi alocado um cateter em veia cefálica e realizou-se a indução com propofol 4mg/kg e midazolam 0,2mg/kg, seguida de manutenção anestésica com isofluorano. Posteriormente à instrumentação, procedeu-se à técnica de anestesia por tumescência com solução gelada composta por ringer lactato, lidocaína 2% sem vasoconstritor e adrenalina, em um volume total de 15mL/kg. Em média, o tempo de duração do procedimento foi de 74±18 minutos. O pico plasmático de lidocaína deu-se entre 30 e 60 minutos após a infiltração da solução. O resgate analgésico foi realizado após sete horas, aproximadamente, da infiltração. Pode-se concluir que a anestesia por tumescência com lidocaína deve ser considerada como constituinte do protocolo anestésico e analgésico de cadelas a serem submetidas à cirurgia de mastectomia, proporcionando estabilidade de parâmetros, segurança e recuperação pós-operatória de boa qualidade.
Desempenho e parâmetros sanguíneos de bezerros leiteiros que receberam sucedâneo lácteo ou silagem de colostro
Authors: Ferreira L.S. , Bittar C.M.M. , Silva J.T. , Soares M.C. , Oltramari C.E. , Nápoles G.G.O. , Paula M.R.
Published: October 2013

O objetivo deste estudo foi avaliar o desempenho e os parâmetros sanguíneos de bezerros que consumiram colostro bovino fermentado sob condições anaeróbias. Após o nascimento, 18 bezerros da raça Holandês foram alojados em abrigos individuais e passaram a receber 4L da dieta líquida, sucedâneo lácteo ou silagem de colostro, divididos em duas refeições. O consumo de concentrado inicial e o escore fecal foram registrados diariamente, enquanto a pesagem e as colheitas de amostras de sangue para a determinação das concentrações plasmáticas de glicose, nitrogênio ureico, ácidos graxos livres, β-hidroxibutirato e proteínas totais séricas foram realizadas semanalmente. Os animais alimentados com silagem de colostro apresentaram menores consumo de concentrado, ganho de peso diário e peso vivo. Todos os parâmetros sanguíneos avaliados foram afetados pelos tratamentos, exceto a concentração plasmática de proteínas totais. O escore fecal foi afetado pelos tratamentos durante a segunda semana de vida, com animais alimentados com silagem de colostro apresentando fezes anormais e secas. O fornecimento de silagem de colostro como dieta líquida exclusiva não resultou em desempenho animal adequado, não sendo uma boa alternativa de substituto de leite.
Desempenho de vacas Girolando mantidas em pastejo de Tifton 85 irrigado ou sequeiro
Authors: Teixeira A.M. , Jayme D.G. , Sene G.A. , Fernandes L.O. , Barreto A.C. , Rodrigues Júnior D.J. , Coutinho A.C. , Glória J.R.
Published: October 2013

Objetivou-se com este trabalho avaliar a taxa de lotação e a produção de leite de vacas mestiças Holandês x Zebu em pastagens de Tifton 85 irrigadas e em sequeiro, em Uberaba-MG. Os dados foram analisados em um delineamento de blocos inteiramente ao acaso, com três repetições por tratamento, num esquema fatorial 2x10 (dois tratamentos e 10 épocas). Foi utilizado um lote de 11 vacas em lactação por tratamento para avaliação do desempenho animal. As médias foram comparadas por meio do teste de Scott-Knott ao nível de 5% de probabilidade (P<0,05). A pastagem foi manejada em sistema de pastejo rotacionado com três e cinco dias de ocupação e 21 e 35 dias de descanso no período das águas e da seca, respectivamente. A taxa de lotação média do sistema irrigado, no período avaliado, foi de 4,6 UA.ha-1, valor superior (P<0,05) à taxa média de 2,2 UA.ha-1 observada para o sistema de sequeiro. Não houve diferenças nas produções diárias de leite das vacas (P<0,05). A produção de leite média obtida no sistema irrigado foi de 51,7 litros. ha-1.dia-1. A irrigação possibilitou uma considerável intensificação do sistema, na medida em que proporcionou uma taxa de lotação bastante superior ao sistema de sequeiro.
Effects of sex and genotype on performance and yield characteristics of free range broiler chickens
Authors: Del Castilho C.C. , Santos T.T , Rodrigues C.A.F. , Torres Filho R.A.
Published: October 2013

The purpose of this work was to evaluate the effect of genotype and sex on the performance characteristics (weight gain, feed conversion and livability) and yields (carcass, breast and legs) of six free-range genotypes: Pesadão Vermelho (GEN1), Carijó (GEN2), Pescoço Pelado 1 (GEN3), Pescoço Pelado 2 (GEN4), Pescoço Pelado 3 (GEN5) and Pescoço Pelado 4 (GEN6). A total of 1584 sexed one day old chicks (792 males and 792 females) were housed in 48 pens, 33 birds per pen. The experimental design was a completely randomized factorial 2 x 6 (six genotypes and two sexes) design, with four replicates each. Diets were based on corn and soybean meal (no animal protein) provided in a feeding program in four phases: pre-starter (1 to 21 days), starter (22 to 42 days), growth (43 to 77 days) and finisher (78 to 91 days). Feed intake, feed conversion and livability were measured at 21, 42, 77 and 91 days of age. There was no genotype x sex interaction. The effect of sex was observed in all ages regarding weight gain, feed conversion (except at 21 days) and yields. For all these characteristics, males performed better than females, except in breast yield, which was higher in females. For the livability and feed conversion at 21 days no effect of sex was found. The effect of genotype was observed only in carcass and breast yields. The fast (GEN1) and intermediate (GEN2, GEN5 and GEN6) growing genotypes showed higher weight gain than the slow growing genotypes (GEN4 and GEN3). Carcass and breast yields of naked neck genotypes (GEN3, GEN4, GEN5 and GEN6) did not differ among themselves, and were higher than the Carijó genotype (GEN2) and are therefore recommended for production systems that sell industrialized birds.
Efeito dos níveis de energia para poedeiras comerciais no período final de produção sobre o desempenho, a conversão alimentar e energética e a qualidade de ovos
Authors: Ribeiro P.A.P. , Matos Júnior J.B. , Queiroz A.C.A. , Lara L.J.C. , Baião N.C.
Published: October 2013

Foram utilizadas 1200 poedeiras comerciais da linhagem Lohmann LSL, com 64 semanas, em gaiolas convencionais. Estas foram divididas em cinco grupos, de acordo com o nível de energia metabolizável aparente corrigida pelo nitrogênio (EMAn) presente em sua dieta: 2700kcal/kg; 2775kcal/kg; 2850kcal/kg; 2925kcal/kg; e 3000kcal/kg, com seis repetições. As aves receberam as rações, á base de milho e farelo de soja, por 16 semanas. O delineamento experimental foi inteiramente ao acaso, e as médias foram submetidas à regressão polinomial e ao teste de Kruskal-Wallis. O aumento de EMAn não exerceu efeito sobre a produção, a massa e o peso de ovos, bem como sobre o peso das aves e a viabilidade. O consumo de ração diminuiu de acordo com o aumento na energia da dieta, porém a conversão energética foi pior com esse aumento. Em contrapartida, a conversão alimentar melhorou o aumento dos níveis de EMAn. O consumo de EMAn é constante independentemente do seu nível dietético. Não há diferença nas unidades Haugh, nos sólidos da gema e na porcentagem dos componentes do ovo. O peso específico melhora com o aumento dos níveis de EMAn. Os níveis nutricionais para poedeiras velhas podem estar sendo superestimados.
Os limites do conceito de empoderamento na prevenção ao HIV/Aids entre jovens gays e bissexuais no Brasil
Authors: Zago Luiz Felipe , Santos Luís Henrique Sacchi dos
Published: October 2013

O artigo objetiva realizar uma análise teórica dos limites do conceito de empowerment inserido em uma política de prevenção ao HIV/Aids entre jovens gays e bissexuais no Brasil. Parte de proposições de um documento oficial do Ministério da Saúde do Brasil, cuja forma é de um manual metodológico, que coloca o empowerment como conceito central na execução da prevenção para essa população. A análise utiliza-se do arcabouço teórico pós-estruturalista para examinar os modos como o conceito é descrito e operacionalizado nas atividades sugeridas pelo manual. Indica-se que o empowerment é uma estratégia de governamento dos corpos e das autonomias dos indivíduos que funciona dentro de uma racionalidade ampla de controle, constituindo-se em uma tecnologia de regulação das práticas sexuais e medição calculável das subjetividades. Exploram-se as noções de risco e responsabilização que circunscrevem a comunidade de jovens gays e bissexuais à qual a prevenção se dirige. Como conclusão, sublinham-se os impasses que a introdução desse conceito pode gerar no campo da resposta brasileira à epidemia de HIV/Aids, sem que seja feita uma revisão crítica dos modos como ele é concebido e implementado.
"Alô, Doutor!": estudo-piloto de intervenção radiofônica de Educação em Saúde desenvolvida em uma área rural de Minas Gerais
Authors: Gazzinelli Maria Flávia , Colares Laura Gazzinelli , Bernardino Letícia Moreira , Araújo Lucas Henrique Lobato , Soares Amanda Nathale
Published: October 2013

O objetivo do estudo foi analisar os efeitos de um Programa de Educação em Saúde desenvolvido por graduandos de medicina, com o emprego do rádio sobre a construção de conhecimentos por parte dos ouvintes residentes em um município do interior de Minas Gerais. Trata-se de estudo intervencional, com delineamento longitudinal e abordagem quantitativa, realizado na cidade de Gouveia, situada na região centro-sul do Vale do Jequitinhonha, Minas Gerais, Brasil. Verificou-se que os participantes do estudo conhecem vários aspectos sobre dengue, parasitoses, DST/HIV/Aids, bem como sobre os efeitos do uso do álcool e do tabaco. Denotou-se, igualmente, que o programa de rádio desempenhou papel importante nas aprendizagens relacionadas aos agravos abordados, expandindo significativamente o percentual de acertos das questões expostas. As considerações elucidadas apontam que a utilização de estratégias educativas legitimadas no cenário vivencial da população e pautadas em uma relação dialógica é essencial para a reconstrução de saberes fundamentada nos conhecimentos prévios dos educandos.
Rendimento de carcaça de codornas de corte em cruzamentos dialélicos
Authors: Drumond Eduardo Silva Cordeiro , Pires Aldrin Vieira , Bonafé Cristina Moreira , Moreira Joerley , Veloso Rogério de Carvalho , Rocha Graziela Maria de Freitas , Ballotin Lucília Maria Valadares , Alcântara Diego Coimbra
Published: October 2013

Objetivou-se com este trabalho avaliar o peso e rendimento de carcaça e cortes de codornas por meio da metodologia de cruzamentos dialélicos. Foram utilizadas quatro linhagens de codornas de corte, denominadas L1, L2, L3 e L4. O sistema de cruzamento proporcionou 16 grupos de progênies, sendo quatro parentais (puros), seis mestiços F1 e seis mestiços F1 recíprocos, alojadas em bateria experimental em três repetições. Aos 42 dias de idade, cinco machos de cada unidade experimental foram escolhidos ao acaso e destinados ao abate, para avaliação do peso aos 42 dias de idade, peso e rendimento de carcaça, do peito, das pernas e das asas. A análise dialélica foi desenvolvida de forma univariada, considerando-se a metodologia de dialelos completos, incluindo as p² combinações das linhagens, a partir das médias das combinações genotípicas. As análises de capacidade combinatória mostraram significância para capacidade geral de combinação (CGC) para peso corporal, da carcaça, peito, pernas e asas, enquanto a capacidade específica de combinação (CEC) foi significativa apenas para o peso e rendimento de pernas. Os quadrados médios da CGG apresentaram, de forma geral, valores maiores que da CEC, revelando a predominância de efeitos aditivos na expressão dessas características, o que indica que melhorias nestas características podem ser conseguidas por meio de processos de seleção intrapopulacional. As linhas L1, L2 e L4 apresentaram valores positivos para CGC em praticamente todas as características avaliadas, e podem ser consideradas superiores à média das linhagens envolvidas no dialelo, sendo, portanto, favoráveis para proporcionarem aumento nas características avaliadas. Foi observado maior efeito dos genes aditivos, indicando que a seleção das linhas puras pode trazer ganhos satisfatórios, sendo a linha L2 a mais promissora, com base em sua capacidade geral de combinação. Para peso de pernas, o cruzamento L2xL4 seria o mais indicado e, para o rendimento de pernas, o cruzamento L1xL4, com base na capacidade específica de combinação.
In vivo fertilization of banana
Authors: Soares Taliane Leila , Souza Everton Hilo de , Costa Maria Angélica Pereira de Carvalho , Silva Sebastião de Oliveira e , Serejo Janay Almeida dos Santos
Published: October 2013

The aim of this research was to study the in vivo fertilization process of banana cultivars. The diploid hybrid (AA) 091087-01 was the male progenitor. Flower samples were checked for fertilization from the first to the twentieth day after pollination. The size of the diploid ovules increased gradually at the beginning of the seed formation process. On the other hand, in the AAA triploids (Cavendish subgroup), the not fertilized ovules were aborted. In the AAB triploids (Prata subgroup) some ovules were fertilized. The flowers of Grand Naine, Nanicão and 'Pacovan' cultivars presented necrosis in the distal part of the ovary on the first day after pollination. Necrosis can hinder pollen tube growth towards the ovule, which might be related to the low seed yield in 'Pacovan' cultivars and to the absence of seeds in the Cavendish subgroup cultivars.