bluuebunny/crossref_metadata_2025 huggingface dataset:
DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells
Authors: Mulrooney Tiernan J , Posch Phillip E , Hurley Carolyn Katovich
Published: May 2013

KIR aid in the regulation of NK cell activity. In this study, the effect of the interaction between the KIR2DS and their adapter, DAP12, was investigated beyond the previously defined signaling function. Flow cytometry analysis showed enhanced KIR2DS surface expression on NKL cells when cotransfected with DAP12. Conversely, KIR2DS4 surface expression on primary cells was decreased when the cells were treated with DAP12-specific siRNA. Treatment of the KIR2DS and DAP12-transfected cells with CHX or BFA repressed KIR2DS surface expression, revealing a role for DAP12 in trafficking newly synthesized KIR to the cell surface. Immunoprecipitation of DAP12 revealed an interaction of DAP12 with an immature isoform of KIR2DS, indicating that the interaction likely initiates within the ER. An internalization assay demonstrated a significant impact of DAP12 on KIR2DS surface stability. Confocal microscopy showed that internalized KIR2DS molecules are recruited to lysosomal compartments independent of DAP12 expression. Our results suggest that in vivo conditions that adversely affect DAP12 expression will indirectly reduce surface expression and stability of KIR2DS. These effects could significantly impact ligand recognition and strength of signaling through KIR2DS molecules.
Predictive Gene Signature in MAGE-A3 Antigen-Specific Cancer Immunotherapy
Authors: Ulloa-Montoya Fernando , Louahed Jamila , Dizier Benjamin , Gruselle Olivier , Spiessens Bart , Lehmann Frédéric F. , Suciu Stefan , Kruit Wim H.J. , Eggermont Alexander M.M. , Vansteenkiste Johan , Brichard Vincent G.
Published: May 2013

Purpose

To detect a pretreatment gene expression signature (GS) predictive of response to MAGE-A3 immunotherapeutic in patients with metastatic melanoma and to investigate its applicability in a different cancer setting (adjuvant therapy of resected early-stage non–small-cell lung cancer [NSCLC]).

Patients and Methods

Patients were participants in two phase II studies of the recombinant MAGE-A3 antigen combined with an immunostimulant (AS15 or AS02B). mRNA from melanoma biopsies was analyzed by microarray analysis and quantitative polymerase chain reaction. These results were used to identify and cross-validate the GS, which was then applied to the NSCLC data.

Results

In the patients with melanoma, 84 genes were identified whose expression was potentially associated with clinical benefit. This effect was strongest when the immunostimulant AS15 was included in the immunotherapy (hazard ratio [HR] for overall survival, 0.37; 95% CI, 0.13 to 1.05; P = .06) and was less strong with the other immunostimulant AS02B (HR, 0.84; 95% CI, 0.36 to 1.97; P = .70). The same GS was then used to predict the outcome for patients with resected NSCLC treated with MAGE-A3 plus AS02B; actively treated GS-positive patients showed a favorable disease-free interval compared with placebo-treated GS-positive patients (HR, 0.42; 95% CI, 0.17 to 1.03; P = .06), whereas among GS-negative patients, no such difference was found (HR, 1.17; 95% CI, 0.59 to 2.31; P = .65). The genes identified were mainly immune related, involving interferon gamma pathways and specific chemokines, suggesting that their pretreatment expression influences the tumor's immune microenvironment and the patient's clinical response.

Conclusion

An 84-gene GS associated with clinical response for MAGE-A3 immunotherapeutic was identified in metastatic melanoma and confirmed in resected NSCLC.
Resolution ofClostridium difficile–Associated Diarrhea in Patients With Cancer Treated With Fidaxomicin or Vancomycin
Authors: Cornely Oliver A. , Miller Mark A. , Fantin Bruno , Mullane Kathleen , Kean Yin , Gorbach Sherwood
Published: May 2013

Purpose

Patients with cancer are at increased risk for Clostridium difficile–associated diarrhea (CDAD). Little is known about treatment response.

Patients and Methods

Two double-blind trials randomly allocated 1,105 patients with CDAD to fidaxomicin or vancomycin treatment (modified intent-to-treat [mITT]), and 183 of these had cancer. Univariate and multivariate post hoc analyses compared effects of treatment and patient characteristics on cure, recurrence, and sustained response after 4 weeks. Time to resolution of diarrhea (TTROD) was also evaluated.

Results

Patients with cancer had a lower cure rate and longer TTROD than patients without cancer. Recurrence rates were similar. Cure was more likely with fidaxomicin than vancomycin (odds ratio [OR] 2.0; P = .065), recurrence was less likely (OR = 0.37; P = .018), and sustained response more frequent (OR = 2.56; P = .003). Under vancomycin, median TTROD was longer in patients with cancer than in those without (123 v 58 hours; log-rank P < .001). With fidaxomicin, median TTROD was not significantly affected by presence of cancer (74 v 54 hours; log-rank P = .145). In the full mITT population, age, hypoalbuminemia, and cancer were inversely associated with clinical cure by multivariate analysis. Study treatment with vancomycin was a significant predictor of recurrence (P < .001). Within the cancer population, low albumin was negatively and fidaxomicin was positively associated with improved cure.

Conclusion

For patients with cancer, fidaxomicin treatment was superior to vancomycin, resulting in higher cure and sustained response rates, shorter TTROD, and fewer recurrences.
Prospective Investigation of Body Mass Index, Colorectal Adenoma, and Colorectal Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Kitahara Cari M. , Berndt Sonja I. , de González Amy Berrington , Coleman Helen G. , Schoen Robert E. , Hayes Richard B. , Huang Wen-Yi
Published: May 2013

Purpose

Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection.

Methods

We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models.

Results

Compared with normal-weight men (18.5 to 24.9 kg/m2), obese men (≥ 30 kg/m2) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women.

Conclusion

Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings.
Lgr proteins in epithelial stem cell biology
Authors: Barker Nick , Tan Shawna , Clevers Hans
Published: May 2013

The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various self-renewing tissues and in accelerating progress towards the development of effective stem cell therapies.
Fibronectin mediates mesendodermal cell fate decisions
Authors: Cheng Paul , Andersen Peter , Hassel David , Kaynak Bogac L. , Limphong Pattraranee , Juergensen Lonny , Kwon Chulan , Srivastava Deepak
Published: May 2013

Non-cell-autonomous signals often play crucial roles in cell fate decisions during animal development. Reciprocal signaling between endoderm and mesoderm is vital for embryonic development, yet the key signals and mechanisms remain unclear. Here, we show that endodermal cells efficiently promote the emergence of mesodermal cells in the neighboring population through signals containing an essential short-range component. The endoderm-mesoderm interaction promoted precardiac mesoderm formation in mouse embryonic stem cells and involved endodermal production of fibronectin. In vivo, fibronectin deficiency resulted in a dramatic reduction of mesoderm accompanied by endodermal expansion in zebrafish embryos. This event was mediated by regulation of Wnt signaling in mesodermal cells through activation of integrin-β1. Our findings highlight the importance of the extracellular matrix in mediating short-range signals and reveal a novel function of endoderm, involving fibronectin and its downstream signaling cascades, in promoting the emergence of mesoderm.
Polycomb complexes in stem cells and embryonic development
Authors: Aloia Luigi , Di Stefano Bruno , Di Croce Luciano
Published: May 2013

Polycomb group (PcG) proteins are epigenetic modifiers involved in controlling gene repression. Organized within multiprotein complexes, they regulate developmental genes in multiple cell types and tissue contexts, including embryonic and adult stem cells, and are essential for cell fate transitions and proper development. Here, we summarize recent breakthroughs that have revealed the diversity of PcG complexes acting in different cell types and genomic contexts. Intriguingly, it appears that particular PcG proteins have specific functions in embryonic development, in pluripotent stem cells and in reprogramming somatic cells into a pluripotent-like state. Finally, we highlight recent results from analyzing PcG protein functions in multipotent stem cells, such as neural, hematopoietic and epidermal stem cells.
Ageing stem and progenitor cells: implications for rejuvenation of the central nervous system
Authors: van Wijngaarden Peter , Franklin Robin J. M.
Published: May 2013

The growing burden of the rapidly ageing global population has reinvigorated interest in the science of ageing and rejuvenation. Among organ systems, rejuvenation of the central nervous system (CNS) is arguably the most complex and challenging of tasks owing, among other things, to its startling structural and functional complexity and its restricted capacity for repair. Thus, the prospect of meaningful rejuvenation of the CNS has seemed an impossible goal; however, advances in stem cell science are beginning to challenge this assumption. This Review outlines these advances with a focus on ageing and rejuvenation of key endogenous stem and progenitor cell compartments in the CNS. Insights gleaned from studies of model organisms, chiefly rodents, will be considered in parallel with human studies.
Induced pluripotent stem cells in medicine and biology
Authors: Takahashi Kazutoshi , Yamanaka Shinya
Published: May 2013

Differentiated cells can be reprogrammed to pluripotency and other cell fates by treatment with defined factors. The discovery of induced pluripotent stem cells (iPSCs) has opened up unprecedented opportunities in the pharmaceutical industry, in the clinic and in laboratories. In particular, the medical applications of human iPSCs in disease modeling and stem cell therapy have been progressing rapidly. The ability to induce cell fate conversion is attractive not only for these applications, but also for basic research fields, such as development, cancer, epigenetics and aging.
Forty years of olfactory navigation in birds
Authors: Gagliardo Anna
Published: May 2013

Forty years ago, Papi and colleagues discovered that anosmic pigeons cannot find their way home when released at unfamiliar locations. They explained this phenomenon by developing the olfactory navigation hypothesis: pigeons at the home loft learn the odours carried by the winds in association with wind direction; once at the release site, they determine the direction of displacement on the basis of the odours perceived locally and orient homeward. In addition to the old classical experiments, new GPS tracking data and observations on the activation of the olfactory system in displaced pigeons have provided further evidence for the specific role of olfactory cues in pigeon navigation. Although it is not known which odours the birds might rely on for navigation, it has been shown that volatile organic compounds in the atmosphere are distributed as fairly stable gradients to allow environmental odour-based navigation. The investigation of the potential role of olfactory cues for navigation in wild birds is still at an early stage; however, the evidence collected so far suggests that olfactory navigation might be a widespread mechanism in avian species.
Limits to sustained energy intake. XVII. Lactation performance in MF1 mice is not programmed by fetal number during pregnancy
Authors: Duah Osei A. , Monney Kweku A. , Hambly Catherine , Król Elzbieta , Speakman John R.
Published: May 2013

Several studies have suggested that lactation performance may be programmed by the number of fetuses during pregnancy, whereas other studies indicate that processes during lactation are more important. As gestation litter size and litter size in lactation are usually strongly correlated, separating the roles of pregnancy and lactation in lactation performance is difficult. To break this link, we experimentally manipulated litter size of MF1 mice to five or 16 pups per litter by cross-fostering. Litter size and mass at birth were recorded on day 1 of lactation prior to litter size manipulation. Maternal body mass and food intake, litter size and litter mass were measured daily throughout. After weaning, the potential differential utilisation of body tissues of the mothers was investigated. Relationships between maternal mass and food intake, including asymptotic daily food intake at peak lactation, offspring traits and other maternal parameters suggested that the number of fetuses the females had carried during pregnancy had no effect on lactation performance. Litter mass increases depended only on maternal food intake, which was highly variable between individuals, but was independent of fetal litter size. The sizes of key organs and tissues like the liver and alimentary tract were not related to maximal food intake at peak lactation or to fetal litter size, but the masses of the pelage, mammary glands and retroperitoneal fat pad were. These data suggest that while growth of the mammary glands and associated structures may be initiated in gestation, and vary in relation to the number of placentas, the ultimate sizes and activities of the tissues depends primarily on factors during lactation.
Iron(III)-catalyzed Highly Efficient, One-pot Synthesis of Triazolo[1,2-a]indazoletriones and Spirotriazolo[1,2-a]indazoletetraones
Authors: Reddy B V Subba , Umadevi N , Narasimhulu G , Yadav J S
Published: May 2013

Three-component coupling (3CC) of aldehyde, 1,3-dione, and 4-phenylurazole has been achieved in the presence of 10 mol % anhydrous FeCl3 in acetonitrile under reflux conditions to afford the corresponding triazolo[1,2-a]indazoletriones in excellent yields while the coupling of isatins with 4-phenylurazole and 1,3-diones gave the spirotriazolo[1,2-a]indazoletetraones under similar conditions.
Mussel-inspired Engineering of an Anodized Aluminum Oxide Membrane
Authors: Kim So Yeon , Lee Mi Yeon , Lee Jung Yup , Park Young Ho , Kim Hyun Gu , Jeong Chan Jin , Mosaiab Tamim , Park Byoungnam , Park Sung Young , In Insik
Published: May 2013

A thermosensitive membrane was prepared through mussel-inspired engineering of anodized aluminum oxide (AAO) membrane. Incorporation of catechol-functionalized copolymer having both 2-(dimethylamino)ethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAM) on AAO membrane provided stimuli-response to both temperature and pH. From the decrease of both water droplet contact angle and buffer solution transport rate above lower critical solution temperature (LCST) of copolymer, a “wettability”-controlled regulation mechanism of mass-transfer rate through engineered AAO membrane was proposed.
Preparation of Mesoporous Silica Monoliths Doped with Titanium Clusters
Authors: Nogawa Takashi , Matsushita Sachiko , Isobe Toshihiro , Nakajima Akira
Published: May 2013

Hierarchical nanoporous structures were fabricated from mesoporous silica and organic monolith with the aim of fabricating a high-efficiency catalyst carrier. The hierarchical structures were modified with photocatalytic titanium clusters. The hierarchical structures showed higher photodecomposition rate of isopropyl alcohol than mesoporous silica structures or monolith structure did, even though the surface area of the hierarchical structure was the smallest. In addition, the CH4 generation from CO2 photoreduction on the hierarchical mesoporous structure was also confirmed. These results suggest the possibilities of highly efficient mass-transport property and the ease of chemical modification of our hierarchical structure.
Conjugate Addition of α-Sulfur-substituted Alkylstannanes to α,β-Unsaturated Ketones Mediated by a Copper(II) Triflate and Chlorotrimethylsilane Combination
Authors: Kagoshima Hirotaka , Yahagi Takeshi
Published: May 2013

The copper(II) triflate and chlorotrimethylsilane combination was found to be effective for the conjugate addition of α-sulfur-substituted alkylstannanes to α,β-unsaturated ketones. Thus, the corresponding γ-sulfur-substituted ketones were obtained in good yields.
A domain sequence approach to pangenomics: applications to Escherichia coli
Authors: Snipen Lars-Gustav , Ussery David W
Published: May 2013

The study of microbial pangenomes relies on the computation of gene families, i.e. the clustering of coding sequences into groups of essentially similar genes. There is no standard approach to obtain such gene families. Ideally, the gene family computations should be robust against errors in the annotation of genes in various genomes. In an attempt to achieve this robustness, we propose to cluster sequences by their domain sequence, i.e. the ordered sequence of domains in their protein sequence. In a study of 347 genomes from Escherichia coli we find on average around 4500 proteins having hits in Pfam-A in every genome, clustering into around 2500 distinct domain sequence families in each genome. Across all genomes we find a total of 5724 such families. A binomial mixture model approach indicates this is around 95% of all domain sequences we would expect to see in E. coli in the future. A Heaps law analysis indicates the population of domain sequences is larger, but this analysis is also very sensitive to smaller changes in the computation procedure. The resolution between strains is good despite the coarse grouping obtained by domain sequence families. Clustering sequences by their ordered domain content give us domain sequence families, who are robust to errors in the gene prediction step. The computational load of the procedure scales linearly with the number of genomes, which is needed for the future explosion in the number of re-sequenced strains. The use of domain sequence families for a functional classification of strains clearly has some potential to be explored.
Prostitution use has non sexual functions - case report of a depressed psychiatric out-patient
Authors: Gysin Fátima , Gysin François
Published: May 2013

Case: A shy, depressed 30 year old male discussed his frequent ego-syntonic indoor prostitution consumption in small peer groups. Several distinctive non-sexual functions of this paid sex habit were identified.

Design and method: The patient had 40 hourly psychiatric sessions in the private practice setting over 14 months. The Arizona Sexual Experience Scale was applied to compare the subjective appraisal of both paid sex and sex in a relationship. The informal Social Atom elucidates social preferences and the Operationalized Psychodynamic Diagnostic-procedure was applied to describe a dominant relationship pattern.

Results: The paid sex consumption functioned as a proud male life style choice to reinforce the patients fragile identity. The effect on self esteem was a release similar to his favorite past-time of kick-boxing. With paid sex asserted as a group ritual, it was practiced even with frequent erectile dysfunction and when sex with a stable romantic partner was more enjoyable and satisfying. The therapeutic attitude of the female psychiatrist, with her own ethical values, is put in to context with two opposing theories about prostitution: the ‘Sex-Work-model’ and the ‘Oppression-model’. The therapist’s reaction to the patients’ information was seen as a starting point to understanding the intrapsychic function of paid sex as a coping mechanism against depressive feelings.

Conclusions: Exploring and understanding prostitution consumption patterns in young men can benefit the treatment of psychiatric disorders in the private practice setting. It is the psychiatrists task to investigate the patients hidden motives behind paid sex use to help patients achieve a greater inner and relational freedom.
The la-form: Russian verbs in Nanai speech
Authors: Oskolskaya Sofia , Stoynova Natasha
Published: May 2013

Nanai speakers who are fluent both in Nanai and Russian use verb forms with a Russian root and the suffix -la (called further “la-forms”) in their speech. The status of -la is under question: on the one hand, it resembles the Russian past tense form (-l), on the other hand, it can be interpreted as the Nanai derivational suffix -la/-lə, which is used in Standard Nanai for the verbalization of nouns. We argue that in modern Nanai this case turns out to be a complicated one, and that la-forms are maintained due to their links with both of these sources.
Tremors and Agitation Following Low-Dose Intravenous Hydromorphone Administration in a Patient with Kidney Dysfunction
Authors: Gagnon David J , Jwo Kevin
Published: May 2013

OBJECTIVE

To report a case of tremors and agitation associated with the administration of low doses of intravenous hydromorphone in a patient with acute kidney injury in the setting of chronic kidney disease.

CASE SUMMARY

A 91-year-old man was admitted for a left intertrochanteric hip fracture. On hospital days 1 and 2, the patient received hydromorphone 1 mg intravenously for pain. By hospital day 3, the patient had received a total of 3.5 mg of hydromorphone. He then became tremulous and agitated, which worsened as the dose was increased. During hospital day 4, the hydromorphone dosage was increased to 0.5 mg intravenously every 4 hours for what was perceived to be inadequate pain control, manifesting as tremors and agitation. On hospital day 5, hydromorphone, now considered a potential cause of the tremors and agitation, was discontinued. The total amount of hydromorphone administered was 8 mg over 5 days. By hospital day 6, the tremors and agitation had decreased in severity and had resolved by hospital day 7.

DISCUSSION

Previous reports suggest that hydromorphone-induced neurotoxicity is more likely to occur following high doses over extended periods, especially in patients with kidney dysfunction. There is a paucity of evidence suggesting that neurotoxicity can occur following low doses for short periods of time. Morphine-3-glucuronide has neuroexcitatory properties including myoclonus, allodynia, agitation, or tremors. Structural similarities between morphine-3-glucuronide and hydromorphone-3-glucuronide suggest that neuroexcitatory effects with hydromorphone are feasible. The Naranjo probability scale indicated that hydromorphone-induced tremors were possible. Our case is distinct because the patient received low doses of hydromorphone over a short period.

CONCLUSIONS

Neurotoxicity can occur in patients with kidney dysfunction while they receive low doses of intravenous hydromorphone over short periods. Diligent monitoring and reporting of such effects are necessary to better understand risk factors and a mechanism.
A Study of Total Focusing Method for Ultrasonic Nondestructive Testing
Authors: Tseng Po-Yen , Chang Young-Fo , Lin Chao-Ming , Nien Wei-Jen , Chang Chih-Hsiung , Huang Chih-Chung
Published: May 2013

Commercial ultrasonic phased array (PA) systems can perform multiple inspections in real-time using array transducers. This approach involves firing array elements in a particular sequence to produce high-resolution images at a high frame rate with excellent signal-to-noise ratio (SNR). Unfortunately, PA systems are complex and expensive. This study proposes a simpler, cheaper, non-real-time ultrasonic array system incorporating the total focusing method (TFM), and the performance of the proposed system is compared with that of a commercial PA system. Studying results shows that both systems have similar apparent axial resolution, but the apparent lateral resolution of the proposed system is far better than the L-scan but falls short in S-scan of a commercial PA system under a quiet testing environment. Moreover, the array performance indicator (API) values of TFM are lower than those of S-scan and L-scan, and the TFM has the highest SNR than the other methods. These results show that the performance of TFM array system is better than the commercial PA system, except for time consumption when switching the channels. Automatically switching the source and receiver channels could further the development of inexpensive, high-performance TFM arrays for ultrasonic nondestructive testing (NDT). It is anticipated that rapid advancements in electronic components, computer science, and digital signal processing will lead to improvements in near-real-time TFM array systems.
Two-Stage Group Acceptance Sampling Plan for Burr Type X Percentiles
Authors: Aslam Muhammad , Azam Muhammad , Lio Y. L. , Jun Chi-Hyuck
Published: May 2013

A two-stage group acceptance sampling plan for the percentile of lifetimes which have the Burr type X distribution is discussed under the time truncated life test. The sampling plan parameters for the two-stage sampling plan are determined such that the producer's risk and consumer's risk are satisfied simultaneously for the given tester size and experiment time. The advantage of the proposed two-stage sampling plan over the single-stage sampling plan is also discussed. Useful tables are given for practical purpose.
Application of the Stress-Energy Method for Generating Corrugated Board Cushion Curves
Authors: Daum Matthew , Darby Duncan , Batt Gregory , Campbell Lisi
Published: May 2013

Cushion curves are an important tool used for designing foam cushions, but no commercially available curves exist for corrugated board, despite its growing popularity as a cushioning material. This paper summarizes the theory and recent work applying the stress-energy method and different curve fit models to corrugated board for generating cushion curves. This paper also compares stress-energy predicted deceleration values to actual ASTM D1596 deceleration values as a method of determining whether the stress-energy method is a viable alternative for generating cushion curves for corrugated board. The results of this study suggest that the stress-energy method should not yet be recommended for generating cushion curves for corrugated board.
Electrical Stimulation of Semicircular Canal Afferents Affects the Perception of Head Orientation
Authors: Lewis Richard F. , Haburcakova Csilla , Gong Wangsong , Lee Daniel , Merfeld Daniel
Published: May 2013

Patients with vestibular dysfunction have visual, perceptual, and postural deficits. While there is considerable evidence that a semicircular canal prosthesis that senses angular head velocity and stimulates canal ampullary nerves can improve vision by augmenting the vestibulo-ocular reflex, no information is available regarding the potential utility of a canal prosthesis to improve perceptual deficits. In this study, we investigated the possibility that electrical stimulation of canal afferents could be used to modify percepts of head orientation. Two rhesus monkeys were trained to align a light bar parallel to gravity, and were tested in the presence and absence of electrical stimulation provided by an electrode implanted in the right posterior canal. While the monkeys aligned the light bar close to the true earth-vertical without stimulation, when the right posterior canal was stimulated their responses deviated toward their left ear, consistent with a misperception of head tilt toward the right. The deviation of the light bar from the earth-vertical exceeded the torsional deviation of the eyes, indicating that the perceptual changes were not simply visual in origin. Eye movements recorded during electrical stimulation in the dark were consistent with isolated activation of right posterior canal afferents, with no evidence of otolith stimulation. These results demonstrate that electrical stimulation of canal afferents affects the perception of head orientation, and therefore suggest that motion-modulated stimulation of canal afferents by a vestibular prosthesis could potentially improve vestibular percepts in patients lacking normal vestibular function.
Conflicts between Local and Global Spatial Frameworks Dissociate Neural Representations of the Lateral and Medial Entorhinal Cortex
Authors: Neunuebel Joshua P. , Yoganarasimha D. , Rao Geeta , Knierim James J.
Published: May 2013

Manipulation of spatial reference frames is a common experimental tool to investigate the nature of hippocampal information coding and to investigate high-order processes, such as cognitive coordination. However, it is unknown how the hippocampus afferents represent the local and global reference frames of an environment. To address these issues, single units were recorded in freely moving rats with multi-tetrode arrays targeting the superficial layers of the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two primary cortical inputs to the hippocampus. Rats ran clockwise laps around a circular track partitioned into quadrants covered by different textures (the local reference frame). The track was centered in a circular environment with distinct landmarks on the walls (the global reference frame). Here we demonstrate a novel dissociation between MEC and LEC in that the global frame controlled the MEC representation and the local frame controlled the LEC representation when the reference frames were rotated in equal, but opposite, directions. Consideration of the functional anatomy of the hippocampal circuit and popular models of attractor dynamics in CA3 suggests a mechanistic explanation of previous data showing a dissociation between the CA3 and CA1 regions in their responses to this local–global conflict. Furthermore, these results are consistent with a model of the LEC providing the hippocampus with the external sensory content of an experience and the MEC providing the spatial context, which combine to form conjunctive codes in the hippocampus that form the basis of episodic memory.
Extrasynaptic Targeting of NMDA Receptors Following D1 Dopamine Receptor Activation and Cocaine Self-Administration
Authors: Ortinski Pavel I. , Turner Jill R. , Pierce R. Christopher
Published: May 2013

We previously showed that after repeated exposure to cocaine, D1-like dopamine receptor (D1DR) stimulation reverses plastic changes of AMPA receptor-mediated signaling in the nucleus accumbens shell. However, there is little information on the impact of cocaine self-administration on D1–NMDA receptor interactions in this brain region. Here, using whole-cell patch-clamp recordings, we assessed whether cocaine self-administration alters the effects of D1DR stimulation on synaptic and extrasynaptic NMDA receptors (NMDARs). In slices from cocaine-naive rats, pretreatment with a D1DR agonist decreased synaptic NMDAR-mediated currents and increased the contribution of extrasynaptic NMDARs. In contrast, neither cocaine self-administration alone nor cocaine experience followed by D1DR stimulation had an effect on synaptic or extrasynaptic NMDAR signaling. Activation of extrasynaptic NMDARs relies on the availability of extracellular glutamate, which is regulated primarily by glutamate transporters. In cocaine-experienced animals, relative to cocaine-naive rats, administration of a glutamate reuptake blocker,dl-threo-β-benzyloxyaspartic acid, revealed increased extrasynaptic NMDAR activity and stronger baseline activity of glutamate uptake transporters. In cocaine-naive rats, the D1DR-mediated increase in extrasynaptic NMDAR signaling was independent of the activity of glutamate reuptake transporters. Together, these results indicate that cocaine experience blunts the influence of D1DRs on synaptic and extrasynaptic NMDAR signaling. Additionally, prior cocaine self-administration limits activation of the extrasynaptic NMDAR pool by increasing glutamate reuptake. These findings outline a pattern of adaptive interactions between D1DRs and NMDARs in the nucleus accumbens shell and demonstrate upregulation of extrasynaptic NMDAR signaling as a novel consequence of cocaine self-administration.
Regelung von doppeltspeisenden Drehstromgeneratoren für den energieeffizienten Betrieb
Authors: Hofmann Wilfried , Rabelo Baldino
Published: May 2013

Der Beitrag behandelt die Regelung von Windenergieanlagen, die mit doppeltspeisenden Asynchrongenerator ausgestattet sind. Die eingesetzte Regelstruktur ist so gestaltet, dass sie in der Lage ist moderne Anforderungen des Netzbetriebs zu erfüllen und diese mit einem energieeffizienten Betrieb des Energiewandlers zu verbinden. Diskutiert werden ausgehend von einer vereinfachten Regelstrecke die kaskadierten Regelkreise, die Reglerauslegung und die erreichten experimentellen Ergebnisse.
A Genetic Screen for High Copy Number Suppressors of the Synthetic Lethality Betweenelg1Δandsrs2Δin Yeast
Authors: Gazy Inbal , Liefshitz Batia , Bronstein Alex , Parnas Oren , Atias Nir , Sharan Roded , Kupiec Martin
Published: May 2013

Elg1 and Srs2 are two proteins involved in maintaining genome stability in yeast. After DNA damage, the homotrimeric clamp PCNA, which provides stability and processivity to DNA polymerases and serves as a docking platform for DNA repair enzymes, undergoes modification by the ubiquitin-like molecule SUMO. PCNA SUMOylation helps recruit Srs2 and Elg1 to the replication fork. In the absence of Elg1, both SUMOylated PCNA and Srs2 accumulate at the chromatin fraction, indicating that Elg1 is required for removing SUMOylated PCNA and Srs2 from DNA. Despite this interaction, which suggests that the two proteins work together, double mutants elg1Δ srs2Δ have severely impaired growth as haploids and exhibit synergistic sensitivity to DNA damage and a synergistic increase in gene conversion. In addition, diploid elg1Δ srs2Δ double mutants are dead, which implies that an essential function in the cell requires at least one of the two gene products for survival. To gain information about this essential function, we have carried out a high copy number suppressor screen to search for genes that, when overexpressed, suppress the synthetic lethality between elg1Δ and srs2Δ. We report the identification of 36 such genes, which are enriched for functions related to DNA- and chromatin-binding, chromatin packaging and modification, and mRNA export from the nucleus.
Genetic Variants That Confer Resistance to Malaria Are Associated with Red Blood Cell Traits in African-Americans: An Electronic Medical Record-based Genome-Wide Association Study
Authors: Ding Keyue , de Andrade Mariza , Manolio Teri A , Crawford Dana C , Rasmussen-Torvik Laura J , Ritchie Marylyn D , Denny Joshua C , Masys Daniel R , Jouni Hayan , Pachecho Jennifer A , Kho Abel N , Roden Dan M , Chisholm Rex , Kullo Iftikhar J
Published: May 2013

To identify novel genetic loci influencing interindividual variation in red blood cell (RBC) traits in African-Americans, we conducted a genome-wide association study (GWAS) in 2315 individuals, divided into discovery (n = 1904) and replication (n = 411) cohorts. The traits included hemoglobin concentration (HGB), hematocrit (HCT), RBC count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Patients were participants in the electronic MEdical Records and GEnomics (eMERGE) network and underwent genotyping of ~1.2 million single-nucleotide polymorphisms on the Illumina Human1M-Duo array. Association analyses were performed adjusting for age, sex, site, and population stratification. Three loci previously associated with resistance to malaria—HBB (11p15.4), HBA1/HBA2 (16p13.3), and G6PD (Xq28)—were associated (P ≤ 1 × 10−6) with RBC traits in the discovery cohort. The loci replicated in the replication cohort (P ≤ 0.02), and were significant at a genome-wide significance level (P < 5 × 10−8) in the combined cohort. The proportions of variance in RBC traits explained by significant variants at these loci were as follows: rs7120391 (near HBB) 1.3% of MCHC, rs9924561 (near HBA1/A2) 5.5% of MCV, 6.9% of MCH and 2.9% of MCHC, and rs1050828 (in G6PD) 2.4% of RBC count, 2.9% of MCV, and 1.4% of MCH, respectively. We were not able to replicate loci identified by a previous GWAS of RBC traits in a European ancestry cohort of similar sample size, suggesting that the genetic architecture of RBC traits differs by race. In conclusion, genetic variants that confer resistance to malaria are associated with RBC traits in African-Americans.
Infrequency of asymptomatic malaria in an endemic area in Amazonas, Brazil
Authors: Prata Aluizio , Urdaneta Margarita , McGreevy Patrick B. , Tada Mauro Shugiro
Published: May 2013

A malaria survey was conducted in an area of high transmission (Costa Marques, Rondonia, Brazil) to determine the prevalence of asymptomatic parasitemia and its clinical significance. Most of the people surveyed were immigrants who had lived in the endemic area < 5 years. The people had easy access to free diagnostic and treatment services at the Malaria Clinic in the town of Costa Marques. The prevalence of plasmodial parasitemia in 344 people was 22%. There were 36 individuals with asymptomatic infections among the 77 parasitemic patients. During the two days following the initial examination, 19 ofthe 36 individuals: with asymptomatic infections developed malaria. Among the 17 patients who remained asymptomatic for > 2 days, 4 had only gametocytes, 1 had taken inadequate anti-malarial treatment, 3 were under treatment and 2 moved. Six asymptomatic patients denied the use of anti-malarial drugs and they developed malaria 3-6 days after the initial parasitological diagnosis. The final patient remained asymptomatic during the 7 day observation period. He had a history of > 40 malaria attacks and denied the use of antimalarial treatment. With the exception of the latter all of the other asymptomatic patients, were either in the incubation period or had been treated It is concluded that asymptomatic malaria is rare in the Costa Marques area and that it is necessary to treat all individuals with plasmodial parasitemia.
Inquérito sobre fungos anemófilos na fronteira Brasil - Colômbia
Authors: Pecher Simão Arão , Castro Geny Brelaz de , Borrás Maria Rosa Lozano
Published: May 2013

Foi realizado um inquérito, sobre fungos anemófllos, em três vilarejos situados na fronteira Brasil-Colômbia, zona muito quente e úmida, durante o mês de julho de 1978. Em apenas uma coleta feita, em diferentes pontos, foram cultivadas colônias pertencentes a dezoito gêneros diferentes de fungos anemófllos, com predominância de Mucor (64,3%), Cândida (54,8%), Rhodotorula (38,1%) e Penicillium (38,1%).
Doença de Chagas aguda pós-transfusional sem miocardite
Authors: Campos Evanil Pires de , Maestá Izilda , Schmidt Fernando C. de L. , Sogayar Roberto , Campos Cláudia E. O. Pires de
Published: May 2013

Trata-se de paciente do sexo feminino, com 59 anos de idade, procedente de Itaporanga (SP), diabética e nefropata crônica, internada em virtude de surtos de pielonefnte e insuficiência renal aguda. Dentre outras medidas terapêuticas, recebeu transfusão de sangue. Cerca de dois dias após a última transfusão (sangue oriundo de doador, posteriormente identificado como chagásico) encontraram-se formas tripomastigotas de Trypanosoma cruzi em lâmina preparada para execução de hemograma. Iniciou-se tratamento com Benzonidazol. A paciente cursou para, pleuropneumonia e de secreção purulenta cirúrgica isolou-se Klebsiella spp. A septicemia conduziu a paciente ao êxito letal. Nenhuma lesão tecidual foi observada no miocárdio, no sistema nervoso central, adrenal ou nos demais órgãos examinados.
Family occurrence of schistosomal hepatosplenomegaly and maternal effect
Authors: Tavares-Neto José , Prata Aluizio
Published: May 2013

In this paper we present a study of members of 265 nuclear families, aged six or more. This study is based of family heredograms, and takes into account the clinical form ofschistosomiasis observed before treatment with oxamniquine. The probability of occurrence of two or more cases ofhepatosplenomegaly is low, notwithstanding the fact that it was observed in 38 families. Even less frequent is the occurrence of three or more cases observed in 17 families (P=0.002). The concentration of the hepatosplenic form was higher among siblings than it was among mothers and children, or fathers and children. It was found to be not significant between husband (father) and wife (mother). These observations reinforce the evidence for the presence of a genetic component in susceptibility to the hepatosplenic form of the disease. In cases in which the mother was hepatosplenic there was a higher incidence of hepatosplenic children; the relative risk was a least five times higher than in those in which the father was the affected member (the maternal effect). In cases where both members were affected by the hepatointestinal form, the risk to the filial generation was similar to that of the population in general. Thus, in the process towards severe forms of Schistosomiasis mansoni, pre and post natal factors might be involved.
Mecanismos pouco comuns de morte súbita no chagásico crônico: relato de três casos
Authors: Tostes Júnior Sebastião , Meneses Antonio Carlos Oliveira , Corrêa-Araujo Rosaly , Lopes Edison Reis
Published: May 2013

Relatam-se três casos de morte súbita, de chagásicos crônicos, por mecanismos de óbito pouco freqüentes. Em dois casos, foi inesperada, sendo o primeiro, por infarto encefálico e o segundo, por broncopneumonia consecutiva a infarto intestinal sem oclusões vasculares ( enfarte não oclusivo"). No terceiro caso, o paciente era cardiopata e teve morte súbita esperada por tamponamento cardíaco consecutivo à ruptura espontânea do ventrículo direito.
Usefulness of serology for the evaluation of Trypanosoma cruzi transmission in endemic areas of Chagas' disease
Authors: Chuit Roberto , Subias Elisabet , Pérez Analia C. , Paulone Irene , Wisnivesky-Colli Cristina , Segura Elsa L.
Published: May 2013

Thirteen communities from 7 Argentinian provinces were selected for the evaluation of serology as an indicator of transmission of Chagas disease. Of the communities appraised, 6 did not have a history of previous treatment with insecticides and 7 had received sporadic or continuous insecticide treatment. The inhabitants of 20% of the houses of each locality were studied by serology. The samples were obtained byfinger pricking and 50 fil of blood were mixed with 150μl of 50% glycerine solution in tissue culture media to be assayed by Indirect Hemagglutination and Indirect Immunofluorescence tests. In untreated areas, the prevalence of infection in infants 0-4 years old was 17.5%, reaching to over 22% for the 5-9 year old group, and to 33.3% in 10-14 year old individuals. The prevalence in treated and surveyed areas was 2.6% in 0-4 year old children, 5.4% in 5-9 year old and 6,2% in 10-14 year old youngsters. The differences between both areas were statistically significant (p < 0.005). This study favors serology as a valid indicator for the evaluation of transmission of Chagas disease in rural areas.
Leishmaniose cutânea experimental: I - sobre a susceptibilidade do primata Cebus apella (Cebidae) a infecção pela Leishmania (Viannia) lainsoni Silveira, Shaw, Braga e Ishikawa, 1987
Authors: Silveira Fernando T. , Lainson Ralph , Shaw Jeffrey J. , Garcez Lourdes M. , Souza Adelson A. , Braga Roseli R. , Ishikawa Edna A.
Published: May 2013

Foi investigada a susceptibilidade do primata Cebus apella (Cebidae) à infecção experimental pela Leishmaiua (Viannia) lainsoni, com o objetivo de estudara patogenia desse parasita, ainda pouco conhecido para o homem. Dessa forma, cinco espécimens jovens daquele primata, 2 machos e 3 fêmeas, foram inoculados, intraderme, em oito sítios diferentes da região dorsal da cauda com 3 x 10(6) de promastigotas do parasita (MHOMZBR/81/M6426, Benevides, Pará), obtidas de cultura da fase estacionária. Em seguida às inoculações, a infecção experimental nos animais foi comprovada, não só pela presença de amastigotas do parasita na pele dos animais inoculados, mas, também, pela concomitância desse achado associado ao desenvolvimento de lesão cutânea nos pontos da pele onde o parasita foi inoculado. Diante desses resultados, ficou demonstrada a susceptibilidade do primata Cebus apella à infecção experimental pela Leishmama lainsoni cujo período de infecção durou quase quatro meses, suficiente para testar drogas antileishmanióticas e estudar a patogênese da doença causada por este parasita.
Prevalência de megas em necrópsias realizadas no triângulo mineiro no período de 1954 a 1988
Authors: Lopes Edison Reis , Rocha Ademir , Meneses António Carlos O. , Lopes Marco Antonio B. , Fatureto Márcio Cunha , Lopes Gesner Pereira , Chapadeiro Edmundo
Published: May 2013

Dentre 1708 necrópsias de chagásicos crônicos, de um total de 4690, diagnosticamos 273 megas. Destes o mais freqüente foi o megacólon, seguido pelo megaesôfago, ocupando a associação megacólon e megaesôfago o terceiro lugar. Discutem-se e comparam-se os achados com outros de ordem clinico-epidemiológica e anatomopatológica. Confirmando dados da literatura, nossos achados atuais mostram, que a exemplo do que sucede na cardiopatia chagásica, o megacólon e o megaesôfago predominam no sexo masculino, discutindo-se os fatores que poderiam explicar a razão desse fato.
Freqüência das infecções oculares por clamídia nos portadores de conjuntivite, em clínica particular de Uberaba, MG
Authors: Couto-Junior Abelardo , Corrêa Sérgio Murilo , Campos Filho Walther , Bottari Cleide Ozimo , Sawan Fahim Miguel , Tavares-Neto José , Angotti Hélia Soares
Published: May 2013

Setecentos e oitenta pacientes com recidivas clínicas de infecções conjuntivais ou queixas persistentes de prurido, ardor, dor, lacrimejamento e hiperemia, foram submetidos ao raspado conjuntival com citologia e pesquisa de inclusões. Destes 247(31,7%) apresentaram inclusões citoplasmáticas; 235 pacientes foram, também, submetidos a coloração com anticorpo monoclonal fluorescente (imunofluorescência direta - DFA) com 90 (38,3%) casos positivos. Discute-se também, a importância do quadro clinico e dos métodos laboratoriais (coloração com anticorpo monoclonal fluorescente e pesquisa de inclusões citoplasmáticas) no diagnóstico. Os pacientes fazem parte de clientela de clínica particular e tem nível sócio-econômico de médio a alto.