bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study
Authors: Schmidt J Michael , Claassen Jan , Ko Sang-Bae , Lantigua Hector , Presciutti Mary , Lee Kiwon , Connolly E Sander , Mayer Stephan A , Seres David S , Badjatia Neeraj
Published: January 2012

Introduction

We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH).

Methods

We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE).

Results

Daily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels.

Conclusions

In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.
Descending aortic calcification increases renal dysfunction and in-hospital mortality in cardiac surgery patients with intraaortic balloon pump counterpulsation placed perioperatively: a case control study
Authors: Nowak-Machen Martina , Rawn James D , Shekar Prem S , Mitani Aya , Tuli Sagun , Bingold Tobias M , Lawlor Garrett , Eltzschig Holger K , Shernan Stanton K , Rosenberger Peter
Published: January 2012

Introduction

Acute kidney injury (AKI) after cardiac surgery increases length of hospital stay and in-hospital mortality. A significant number of patients undergoing cardiac surgical procedures require perioperative intra-aortic balloon pump (IABP) support. Use of an IABP has been linked to an increased incidence of perioperative renal dysfunction and death. This might be due to dislodgement of atherosclerotic material in the descending thoracic aorta (DTA). Therefore, we retrospectively studied the correlation between DTA atheroma, AKI and in-hospital mortality.

Methods

A total of 454 patients were retrospectively matched to one of four groups: -IABP/-DTA atheroma, +IABP/-DTA atheroma, -IABP/+DTA atheroma, +IABP/+DTA atheroma. Patients were then matched according to presence/absence of DTA atheroma, presence/absence of IABP, performed surgical procedure, age, gender and left ventricular ejection fraction (LVEF). DTA atheroma was assessed through standard transesophageal echocardiography (TEE) imaging studies of the descending thoracic aorta.

Results

Basic patient characteristics, except for age and gender, did not differ between groups. Perioperative AKI in patients with -DTA atheroma/+IABP was 5.1% versus 1.7% in patients with -DTA atheroma/-IABP. In patients with +DTA atheroma/+IABP the incidence of AKI was 12.6% versus 5.1% in patients with +DTA atheroma/-IABP. In-hospital mortality in patients with +DTA atheroma/-IABP was 3.4% versus 8.4% with +DTA atheroma/+IABP. In patients with +DTA atheroma/+IABP in hospital mortality was 20.2% versus 6.4% with +DTA atheroma/-IABP. Multivariate logistic regression identified DTA atheroma > 1 mm (P = *0.002, odds ratio (OR) = 4.13, confidence interval (CI) = 1.66 to 10.30), as well as IABP support (P = *0.015, OR = 3.04, CI = 1.24 to 7.45) as independent predictors of perioperative AKI and increased in-hospital mortality. DTA atheroma in conjunction with IABP significantly increased the risk of developing acute kidney injury (P = 0.0016) and in-hospital mortality (P = 0.0001) when compared to control subjects without IABP and without DTA atheroma.

Conclusions

Perioperative IABP and DTA atheroma are independent predictors of perioperative AKI and in-hospital mortality. Whether adding an IABP in patients with severe DTA calcification increases their risk of developing AKI and mortality postoperatively cannot be clearly answered in this study. Nevertheless, when IABP and DTA are combined, patients are more likely to develop AKI and to die postoperatively in comparison to patients without IABP and DTA atheroma.
Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
Authors: Guha Saurav , Rosenfeld Jeffrey A , Malhotra Anil K , Lee Annette T , Gregersen Peter K , Kane John M , Pe'er Itsik , Darvasi Ariel , Lencz Todd
Published: January 2012

Background

Relatively small, reproductively isolated populations with reduced genetic diversity may have advantages for genomewide association mapping in disease genetics. The Ashkenazi Jewish population represents a unique population for study based on its recent (< 1,000 year) history of a limited number of founders, population bottlenecks and tradition of marriage within the community. We genotyped more than 1,300 Ashkenazi Jewish healthy volunteers from the Hebrew University Genetic Resource with the Illumina HumanOmni1-Quad platform. Comparison of the genotyping data with that of neighboring European and Asian populations enabled the Ashkenazi Jewish-specific component of the variance to be characterized with respect to disease-relevant alleles and pathways.

Results

Using clustering, principal components, and pairwise genetic distance as converging approaches, we identified an Ashkenazi Jewish-specific genetic signature that differentiated these subjects from both European and Middle Eastern samples. Most notably, gene ontology analysis of the Ashkenazi Jewish genetic signature revealed an enrichment of genes functioning in transepithelial chloride transport, such as CFTR, and in equilibrioception, potentially shedding light on cystic fibrosis, Usher syndrome and other diseases over-represented in the Ashkenazi Jewish population. Results also impact risk profiles for autoimmune and metabolic disorders in this population. Finally, residual intra-Ashkenazi population structure was minimal, primarily determined by class 1 MHC alleles, and not related to host country of origin.

Conclusions

The Ashkenazi Jewish population is of potential utility in disease-mapping studies due to its relative homogeneity and distinct genomic signature. Results suggest that Ashkenazi-associated disease genes may be components of population-specific genomic differences in key functional pathways.
Stimulatory Effect of RFRP-3 on the Gonadotrophic Axis in the Male Syrian Hamster: The Exception Proves the Rule
Authors: Ancel Caroline , Bentsen Agnete H. , Sébert Marie-Emilie , Tena-Sempere Manuel , Mikkelsen Jens D. , Simonneaux Valérie
Published: January 2012

In seasonal mammals, a distinct photoneuroendocrine circuit that involves the pineal hormone melatonin tightly synchronizes reproduction with seasons. In the Syrian hamster, a seasonal model in which sexual activity is inhibited by short days, we have previously shown that the potent GnRH stimulator, kisspeptin, is crucial to convey melatonin's message; however, the precise mechanisms through which melatonin affects kisspeptin remain unclear. Interestingly, rfrp gene expression in the neurons of the dorsomedial hypothalamic nucleus, a brain region in which melatonin receptors are present in the Syrian hamster, is strongly down-regulated by melatonin in short days. Because a large body of evidence now indicates that RFamide-related peptide (RFRP)-3, the product of the rfrp gene, is an inhibitor of gonadotropin secretion in various mammalian species, we sought to investigate its effect on the gonadotrophic axis in the Syrian hamster. We show that acute central injection of RFRP-3 induces c-Fos expression in GnRH neurons and increases LH, FSH, and testosterone secretion. Moreover, chronic central administration of RFRP-3 restores testicular activity and Kiss1 levels in the arcuate nucleus of hamsters despite persisting photoinhibitory conditions. By contrast RFRP-3 does not have a hypophysiotrophic effect. Overall, these findings demonstrate that, in the male Syrian hamster, RFRP-3 exerts a stimulatory effect on the reproductive axis, most likely via hypothalamic targets. This places RFRP-3 in a decisive position between the melatonergic message and Kiss1 seasonal regulation. Additionally, our data suggest for the first time that the function of this peptide depends on the species and the physiological status of the animal model.
A function for Rac1 in the terminal differentiation and pigmentation of hair
Authors: Behrendt Kristina , Klatte Jennifer , Pofahl Ruth , Bloch Wilhelm , Smyth Neil , Tscharntke Michael , Krieg Thomas , Paus Ralf , Niessen Carien , Niemann Catherin , Brakebusch Cord , Haase Ingo
Published: January 2012

The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss. The resulting ‘rescue’ mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.
The role and mechanism of activin A in neurite outgrowth of embryonic dorsal root ganglia of chicken
Authors: Fang Lin , Wang Yi-Nan , Cui Xue-Ling , Fang Si-Yue , Ge Jing-Yan , Sun Yang , Liu Zhong-Hui
Published: January 2012

Activin A, a member of transforming growth factor β (TGF-β) superfamily, plays essential role in neuron survival as a neurotrophic and neuroprotective factor in central nervous system. However, the effects and mechanisms of activin A on the neurite outgrowth of dorsal root ganglia (DRG) remain unclear. In the present study, we found that activin A is expressed in DRG collected from chicken embryos on day 8 (E8). Moreover, activin A induced neurite outgrowth of the primary cultured DRG and maintained long-time survival of monolayer-cultured DRG neurons during the observation for 10 days. Follistatin (FS), an activin-binding protein, significantly inhibited activin A-induced neurite outgrowth of DRG, but fails to influence the effect of nerve growth factor (NGF) on DRG neurite outgrowth. Furthermore, the results showed that activin A significantly up-regulated mRNA expressions of activin receptor type IIA (ActRIIA) and calcitonin gene-related peptide (CGRP) in DRG, and stimulated serotonin (5-HT) production from DRG, indicating that activin A may induce DRG neurite outgrowth via promoting CGRP expression and stimulating 5-HT release. These data suggest that activin A plays an important role in the development of DRG by autocrine/paracrine manner.
Structure-function relationship of the Polo-like kinase in Trypanosoma brucei
Authors: Yu Zhonglian , Liu Yi , Li Ziyin
Published: January 2012

Polo-like kinases (Plks) play multiple roles in mitosis and cytokinesis in eukaryotes and are characterized by the C-terminal Polo-box domain (PBD) implicated in binding to Plk substrates, targeting Plk, and regulating Plk activity. The Plk homolog in Trypanosoma brucei possesses a similar architecture, but it lacks the crucial residues involved in substrate binding and regulates cytokinesis but not mitosis. Despite these, little is known about the regulation of TbPLK and the role of the PBD in TbPLK localization and function. Here, we addressed the requirement of the kinase activity and the PBD for TbPLK localization and function through coupling RNAi of endogenous TbPLK with ectopic expression of TbPLK mutants. We demonstrate that the kinase activity and phosphorylation of two threonine residues, Thr198 and Thr202, in the activation loop (T-loop) of the kinase domain are essential for TbPLK function but not for TbPLK localization. Deletion of the PBD abolishes TbPLK localization, but the PBD itself is not correctly targeted, indicating that TbPLK localization requires both the PBD and the kinase domain. Surprisingly, the kinase domain of TbPLK, but not the PBD, binds to its substrates, TbCentrin2 and p110, suggesting that TbPLK may interact with its substrate through different mechanisms. Finally, the PBD interacts with the kinase domain of TbPLK and inhibits its activity, and this inhibition is relieved when Thr198 is phosphorylated. Together, these results suggest an essential role of T-loop phosphorylation in TbPLK activation and crucial roles of the PBD in regulating TbPLK activity and localization.
A Meiotic Actin Ring (MeiAR) Essential for Proper Sporulation in Fission Yeast
Authors: Yan Hongyan , Balasubramanian Mohan K.
Published: January 2012

Sporulation is a unique form of cytokinesis that occurs following meiosis II in many yeasts, during which four daughter cells (spores) are generated within a single mother cell. Here we characterize the role of F-actin in the process of sporulation in the fission yeast Schizosaccharomyces pombe. As shown previously, we find that F-actin assembles into 4 ring structures per ascus, referred to as the MeiAR (meiotic actin ring). The actin nucleators Arp2/3 and formin-For3 assemble into ring structures that overlap with Meu14, a protein known to assemble into the so-called leading edge, a ring structure that is known to guide forespore membrane assembly. Interestingly, F-actin makes rings that occupy a larger region behind the leading edge ring. Time-lapse microscopy showed that the MeiAR assembles near the spindle pole bodies and undergoes an expansion in diameter during the early stages of meiosis II, followed by closure in later stages of meiosis II. MeiAR closure completes the process of forespore membrane assembly. Loss of MeiAR leads to excessive assembly of forespore membranes with a deformed appearance. The rate of closure of the MeiAR is dictated by the function of the Septation Initiation Network (SIN). We conclude that the MeiAR ensures proper targeting of the membrane biogenesis machinery to the leading edge, thereby ensuring the formation of spherically shaped spores.
Hydraulic leg extension is not necessarily the main drive in large spiders
Authors: Weihmann Tom , Günther Michael , Blickhan Reinhard
Published: January 2012

Unlike most other arthropods, spiders have no extensor muscles in major leg joints. Therefore, hydraulic pressure generated in the prosoma provides leg extension. For decades, this mechanism was held responsible for the generation of the majority of the ground reaction forces, particularly in the hind legs. During propulsion, the front leg pairs must shorten whereas the hind legs have to be extended. Assuming that hind legs are essentially driven by hydraulics, their force vectors must pass the leg joints ventrally. However, at least in accelerated escape manoeuvres, we show here for the large cursorial spider species Ancylometes concolor that these force vectors, when projected into the leg plane, pass all leg joints dorsally. This indicates a reduced impact of the hydraulic mechanism on the generation of ground reaction forces. Although hydraulic leg extension still modulates their direction, the observed steep force vectors at the hind legs indicate a strong activity of flexors in the proximal joint complex that push the legs against the substrate. Consequently, the muscular mechanisms are dominant at least in the hind legs of large spiders.
Polymorphic male color morphs visualized with steroids in monomorphic females: a tool for designing analysis of sex-limited trait inheritance
Authors: Olsson Mats , Healey Mo , Wilson Mark , Tobler Michael
Published: January 2012

In diploid animals, males and females share most of the genome (except sex-specific elements, such as sex chromosome genes), yet despite sharing the underlying genes that hard-wire traits, males and females may differ in their phenotypes when traits are controlled by proximate mechanisms, such as hormones. In color polymorphic species where coloration is only expressed in one sex, the design of studies of the inheritance of color and coevolved morph-specific traits (e.g. territorial vs sneaker strategies, skewed energetic investment in territorial defense vs sperm production, etc.) is compromised as the expression of morph-coding genes is only visualized in one sex. Here, we circumvented this problem by first characterizing oxidative stress traits in both sexes and then using testosterone implants in females to expose their otherwise ‘silent’ coloration. Males of our model species are highly territorial and exhibit morph-specific levels of aggression, whereas females are non-territorial and display very low levels of aggression. Interestingly, reactive oxygen species levels were found to be morph specific regardless of sex, despite considerable differences in lifestyle. Males and females did differ remarkably, however, in superoxide levels depending on whether they sported a colored throat bib or not, a trait also used in male sexual signaling. Females with throat bibs had significantly lower levels of superoxide than females without a bib, which was not the case for males.
Transient Ca2+ mobilization caused by osmotic shock initiates salmonid fish sperm motility
Authors: Takei Gen L. , Mukai Chinatsu , Okuno Makoto
Published: January 2012

Salmonid fish sperm motility is known to be suppressed in millimolar concentrations of extracellular K+, and dilution of K+ upon spawning triggers cAMP-dependent signaling for motility initiation. In a previous study, however, we demonstrated that suspending sperm in a 10% glycerol solution and subsequent dilution into a low-osmotic solution induced motility independently of extracellular K+ and cAMP. In the present study, we further investigated the glycerol-induced motility mechanism. We found that treatment with solutions consisting of organic or inorganic ions, as well as glycerol, induced sperm motility in an osmolarity-dependent manner. Elimination of intracellular Ca2+ by BAPTA-AM significantly inhibited glycerol-treated sperm motility, whereas removal of extracellular Ca2+ by EGTA did not. Monitoring intracellular Ca2+, using fluo-4, revealed that intracellular Ca2+ increased when sperm were suspended in hypertonic solutions, and a subsequent dilution into a hypotonic solution led to a decrease in intracellular Ca2+ concomitant with motility initiation. In addition, upon dilution of sperm into a hypertonic glycerol solution prior to demembranation, the motility of demembranated sperm was reactivated in the absence of cAMP. The motility recovery suggests that completion of axonemal maturation occurred during exposure to a hypertonic environment. As a result, it is likely that glycerol treatment of sperm undergoing hypertonic shock causes mobilization of intracellular Ca2+ from the intracellular Ca2+ store and also causes maturation of axonemal proteins for motility initiation. The subsequent dilution into a hypotonic solution induces a decrease in intracellular Ca2+ and flagellar movement. This novel mechanism of sperm motility initiation seems to act in a salvaging manner for the well-known K+-dependent pathway.
Growth and innate immunity are not limited by selection for high egg testosterone content in Japanese quail
Authors: Kankova Zuzana , Zeman Michal , Okuliarova Monika
Published: January 2012

The effects of maternal androgens on fitness-related traits of offspring are generally assumed to be epigenetic adaptations to the environment that may be encountered by the next generation. Possible constraints of high yolk androgen transfer are still not understood, although a suppressed immune response in offspring is frequently considered. The aim of our study was to examine the innate immune defence in high (HET) and low egg testosterone (LET) lines of Japanese quail, which differ in the hormonal milieu of their eggs, thus providing a good physiological model for the study of androgen-mediated maternal effects. Acute phase response was induced by a lipopolysaccharide injection in 12-day-old quail and plasma corticosterone and the heterophil:lymphocyte ratio were measured at 1 and 3 h post-treatment. Basal levels of non-specific antibodies (IgY) were determined in the circulation. We found that HET quail were heavier than LET quail from the second week of age, indicating enhanced post-hatching growth. At 1 h post-lipopolysaccharide challenge, plasma corticosterone concentrations increased in the HET but not in the LET line. The heterophil:lymphocyte ratio rose in both lines at 3 h post-immune challenge, with a more pronounced response in HET quail. Moreover, HET chicks displayed higher IgY levels than LET chicks, suggesting either enhanced passive immunoprotection or stimulated endogenous antibody production. In conclusion, our data demonstrate that the genetic selection for high egg testosterone content positively influences growth and, simultaneously, does not limit the acute phase response in young quail.
Smelling your way to food: can bed bugs use our odour?
Authors: Harraca V. , Ryne C. , Birgersson G. , Ignell R.
Published: January 2012

The resurgence in developed countries of the common bed bug, Cimex lectularius, has led to a search for new sustainable methods to monitor and control this human ectoparasite. Because of increased resistance to insecticides, traps baited with attractive cues are considered a promising method to be developed into efficient monitoring tools for bed bugs. Despite their potential as attractants, only a few studies have investigated the odorant cues implicated in the attraction of bed bugs to human hosts. In this study, we used aeration extracts from human volunteers to assess the role of olfaction in host searching by bed bugs. By coupled gas chromatography and single sensillum recordings on all the antennal sensilla, we measured the electrophysiological response elicited by the compounds present in our human odour extracts. Only five compounds were clearly detected by the olfactory receptor neurons housed in the smooth-peg sensilla of the bed bugs. We tested the behavioural effect of these extracts in a still-air arena and showed a gradient of repellence linked to the dose, as well as a higher propensity of local search behaviour associated with human odours containing a lower ratio of 6-methyl-5-hepten-2-one to C7–C10 aldehydes. We conclude that human odour alone has a weak influence on the behaviour of C. lectularius and we propose that human kairomones may have a significant impact on bed bug behaviour in combination with heat and carbon dioxide, the only two currently known attractive vertebrate cues used by bed bugs for host seeking.
A novel function for a carotenoid: astaxanthin used as a polarizer for visual signalling in a mantis shrimp
Authors: Chiou Tsyr-Huei , Place Allen R. , Caldwell Roy L. , Marshall N. Justin , Cronin Thomas W.
Published: January 2012

Biological signals based on color patterns are well known, but some animals communicate by producing patterns of polarized light. Known biological polarizers are all based on physical interactions with light such as birefringence, differential reflection or scattering. We describe a novel biological polarizer in a marine crustacean based on linear dichroism of a carotenoid molecule. The red-colored, dichroic ketocarotenoid pigment astaxanthin is deposited in the antennal scale of a stomatopod crustacean, Odontodactylus scyllarus. Positive correlation between partial polarization and the presence of astaxanthin indicates that the antennal scale polarizes light with astaxanthin. Both the optical properties and the fine structure of the polarizationally active cuticle suggest that the dipole axes of the astaxanthin molecules are oriented nearly normal to the surface of the antennal scale. While dichroic retinoids are used as visual pigment chromophores to absorb and detect polarized light, this is the first demonstration of the use of a carotenoid to produce a polarizing signal. By using the intrinsic dichroism of the carotenoid molecule and orienting the molecule in tissue, nature has engineered a previously undescribed form of biological polarizer.
Is ultrasound elastography of the liver ready to replace biopsy? A critical review of the current techniques
Authors: Jaffer Ounali S , Lung Phillip F C , Bosanac Diana , Shah Aarti , Sidhu Paul S
Published: January 2012

Accurate assessment of liver fibrosis in patients with chronic liver disease is necessary to determine prognosis, monitor disease progression and formulate treatment decisions. Currently, histological staging of liver biopsy is the most widely used reference standard for this purpose. Liver biopsy, however, has recognized risks, as well as sampling and observer error. These limitations have stimulated the search for new non-invasive approaches. Numerous methodologies, including serum markers, magnetic resonance elastography and ultrasound elastography, have evolved in the last decade to predict fibrosis in those with chronic liver disease. Ultrasound elastography methods assess liver fibrosis by determining liver stiffness and translate this into a quantifiable measurement for analysis. As these tests are non-invasive, without side-effect or discomfort, it is possible to conduct repeat examinations at much closer intervals than biopsy. The three most investigated ultrasound elastography methods are transient elastography, realtime elastography and acoustic radiation force impulse. Although significant strides have been made in the development of the technology, an unequivocal advocacy of elastography as a surrogate for biopsy is still not established. The aim of this review is to evaluate the advantages, limitations and clinical relevance of the three ultrasound-based modalities. Also, the review shall assess the current and possible future clinical application the modalities may serve both separate and in conjunction with liver biopsy.
Computational prediction of efficient splice sites for trans-splicing ribozymes
Authors: Meluzzi Dario , Olson Karen E. , Dolan Gregory F. , Arya Gaurav , Müller Ulrich F.
Published: January 2012

Group I introns have been engineered into trans-splicing ribozymes capable of replacing the 3′-terminal portion of an external mRNA with their own 3′-exon. Although this design makes trans-splicing ribozymes potentially useful for therapeutic application, their trans-splicing efficiency is usually too low for medical use. One factor that strongly influences trans-splicing efficiency is the position of the target splice site on the mRNA substrate. Viable splice sites are currently determined using a biochemical trans-tagging assay. Here, we propose a rapid and inexpensive alternative approach to identify efficient splice sites. This approach involves the computation of the binding free energies between ribozyme and mRNA substrate. We found that the computed binding free energies correlate well with the trans-splicing efficiency experimentally determined at 18 different splice sites on the mRNA of chloramphenicol acetyl transferase. In contrast, our results from the trans-tagging assay correlate less well with measured trans-splicing efficiency. The computed free energy components suggest that splice site efficiency depends on the following secondary structure rearrangements: hybridization of the ribozyme's internal guide sequence (IGS) with mRNA substrate (most important), unfolding of substrate proximal to the splice site, and release of the IGS from the 3′-exon (least important). The proposed computational approach can also be extended to fulfill additional design requirements of efficient trans-splicing ribozymes, such as the optimization of 3′-exon and extended guide sequences.
The archaeal COG1901/DUF358 SPOUT-methyltransferase members, together with pseudouridine synthase Pus10, catalyze the formation of 1-methylpseudouridine at position 54 of tRNA
Authors: Chatterjee Kunal , Blaby Ian K. , Thiaville Patrick C. , Majumder Mrinmoyee , Grosjean Henri , Yuan Y. Adam , Gupta Ramesh , de Crécy-Lagard Valérie
Published: January 2012

The methylation of pseudouridine (Ψ) at position 54 of tRNA, producing m1Ψ, is a hallmark of many archaeal species, but the specific methylase involved in the formation of this modification had yet to be characterized. A comparative genomics analysis had previously identified COG1901 (DUF358), part of the SPOUT superfamily, as a candidate for this missing methylase family. To test this prediction, the COG1901 encoding gene,HVO_1989,was deleted from theHaloferax volcaniigenome. Analyses of modified base contents indicated that while m1Ψ was present in tRNA extracted from the wild-type strain, it was absent from tRNA extracted from the mutant strain. Expression of the gene encoding COG1901 fromHalobacteriumsp. NRC-1, VNG1980C, complemented the m1Ψ minus phenotype of the ΔHVO_1989strain. This in vivo validation was extended with in vitro tests. Using the COG1901 recombinant enzyme fromMethanocaldococcus jannaschii(Mj1640), purified enzyme Pus10 fromM. jannaschiiand full-size tRNA transcripts or TΨ-arm (17-mer) fragments as substrates, the sequential pathway of m1Ψ54 formation in Archaea was reconstituted. The methylation reaction is AdoMet dependent. The efficiency of the methylase reaction depended on the identity of the residue at position 55 of the TΨ-loop. The presence of Ψ55 allowed the efficient conversion of Ψ54 to m1Ψ54, whereas in the presence of C55, the reaction was rather inefficient and no methylation reaction occurred if a purine was present at this position. These results led to renaming the Archaeal COG1901 members as TrmY proteins.
Berührungslose Mehrlagen-Schichtdickenmessung industrieller Beschichtungen mittels THz-Messtechnik
Authors: Feige Volker K. S. , Berta Milan , Nix Stephan , Ellrich Frank , Jonuscheit Joachim , Beigang René
Published: January 2012

In vielen Industriebereichen ist der Schutz von nicht-metallischen Substraten, wie z. B. Kunststoff, Holz und Beton, durch die aufgebrachten Beschichtungssysteme entscheidend. Nur wenn die richtigen Schichtdicken aufgetragen sind, existiert ein optimaler Schutz der Substrate. Zur Sicherstellung der exakten Schichtdicken und zur Defekterkennung werden zerstörungsfreie Messtechniken eingesetzt, wobei berührungslose Terahertz-basierende Messprinzipien ein hohes Anwendungspotenzial versprechen [1]. Elektromagnetische Wellen mit Wellenlängen von 50 bis 3000 μm durchdringen elektrisch nicht leitfähige Beschichtungen und ermöglichen vielfältige Analysemethoden aufgrund der charakteristischen komplexen Brechungsindizes im Terahertz-Frequenzspektrum. Schichtdickenmessungen wurden für faserverstärkte Kunststoffe mit elektromagnetischen Pikosekunden-Impulsen erforscht. Die spektralen Materialeigenschaften berücksichtigend stellen wir Algorithmen zur Schichtdickenbestimmung in Mehrlagen-Systemen vor.
Mutant mice derived by ICSI of evaporatively dried spermatozoa exhibit expected phenotype
Authors: Li Ming-Wen , Baridon Brian , Trainor Amanda , Djan Esi , Koehne Amanda , Griffey Stephen M , Biggers John D , Toner Mehmet , Lloyd K C Kent
Published: January 2012

Apolipoprotein E (Apoe)-deficient knockout mice were used to test the hypothesis that mutant mice preserved as evaporatively dried (ED) spermatozoa, stored at −80 °C for 6 months, and then recovered by ICSI will exhibit the same phenotype as before preservation. The birth rate of mice recovered by ICSI of evaporatively dried spermatozoa was lower than that of fresh spermatozoa (17.5 vs 38.0%). Progeny of mice preserved using evaporatively dried spermatozoa were reproductively sound. From these, the second generation of mice produced by natural mating showed lesions typical of APOE deficiency, including severe hypercholesterolemia, hypertriglyceridemia, markedly increased plasma low-density lipoprotein level, and extensive and severe atherosclerotic lesions in the aorta. We conclude that the expected phenotype caused by an induced genetic mutation can be faithfully recapitulated and sustained in subsequent generations of mice preserved and stored as ED spermatozoa and recovered using ICSI. Because it is simpler, faster, and cheaper than conventional (cryopreservation) and nonconventional (freeze–drying) preservation procedures, evaporative drying is a viable, cost-effective, and efficient method for preserving and storing valuable mutant mouse strains.
Importance of thiopurine s-methyltransferase gene test
Authors: Sipeky Csilla , Maász Anita , Tarlós Gréta , Komlósi Katalin , Pollák Éva , Melegh Béla
Published: January 2012

Thiopurine s-methyltransferase enzyme is responsible for the metabolism of immunosuppressant thiopurines, which are used in inflammatory bowel diseases, acute lymphoblastic leukemia and autoimmune diseases. Because of the relative narrow therapeutic index of thiopurines serious or life threatening side effects can occur. A total of 28 variant alleles of the gene coding for the thiopurine s-methyltransferase enzyme are responsible for altered catalytic activity of the enzyme. Patients with one non-functional (heterozygous) allele have intermediate, while those with two non-functional (homozygous) alleles have low enzyme activity. Using polymerase chain reaction/restriction fragment length polymorphism and direct DNA sequencing the authors determined the G238C, G460A and A719G polymorphisms of the thiopurine s-methyltransferase gene in a child with Crohn’s disease who developed thiopurine-induced severe agranulocytosis. The presence of the G460A and A719G polymorphic alleles in homozygous forms were detected which corresponded to the *3A variant allele. This variant has been shown to be associated with lower enzyme activity and low amount of the enzyme resulting in thiopurine toxicity and agranulocytosis. These findings underline the need for genotyping of the thiopurine s-methyltransferase variants prior to thiopurine treatment. Orv. Hetil., 2012, 153, 191–194.
Epidemiology, predictors and clinical aspects of loss of response to biological therapy
Authors: Lőrinczy Katalin , Miheller Pál , Kiss Sándor Lajos , Lakatos Péter László
Published: January 2012

In the last two decades, the treatment paradigms for Crohn’s disease and ulcerative colitis have significantly changed inclusive of a continuously increasing role of biological therapy (anti TNFs). Some patients, however, experience lack or loss of response to biological treatment, and in such cases the management of patients is often empirical. In this review, the authors aim to summarize the available data regarding epidemiology and predictors of loss of response to biological therapy considering the clinical factors and the relationship between serum concentrations, antibodies against biological agents, respectively. Monitoring drug levels and antibodies is expected to play an important role in the management of loss of response (i.e. to confirm adherence, allow dose adjustment, or provide rationale for switching to another biological agent or to a different class of biological agent) in the coming years. The optimal method of detection and cut-off values are, however, not clear. In clinical practice, meticulous complex assessment of clinical symptoms, confirmation of active disease by endoscopic or radiological imaging, and excluding complications remain necessary. Orv. Hetil., 2012, 153, 163–173.
Resource notes
Authors: Hickman Brian
Published: January 2012

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Custo da adequação quantitativa de profissionais de enfermagem em Unidade Neonatal
Authors: Fugulin Fernanda Maria Togeiro , Lima Antonio Fernandes Costa , Castilho Valéria , Bochembuzio Luciana , Costa Janaína Anchieta , Castro Liliana , Silva Natália Célia Lima , Gaidzinski Raquel Rapone
Published: January 2012

Este estudo descritivo, de natureza quantitativa, visou: identificar o tempo médio de assistência de enfermagem despendido e requerido pelos Recém-Nascidos (RN) internados na Unidade Neonatal do Hospital Universitário da Universidade de São Paulo; calcular o custo do tempo médio de assistência de enfermagem despendido e requerido por RN; verificar o montante financeiro da adequação do quadro de profissionais de enfermagem requerido para assistir os RN. O tempo médio de assistência despendido pela equipe de enfermagem e requerido pelos RN foi calculado por meio de equações disponíveis na literatura e aplicação do Nursing Activities Score. O custo do tempo médio de assistência e do montante financeiro da adequação do quadro de profissionais foi calculado com base no custo/hora dos enfermeiros e dos técnicos de enfermagem. O impacto financeiro da adequação quantitativa de profissionais de enfermagem correspondeu a um acréscimo de 30% no custo do quadro existente.
Fluência digital e uso de ambientes virtuais: caracterização de alunos de enfermagem
Authors: Costa Priscila Berenice , Prado Cláudia , Oliveira Luciana de Fátima Teixeira de , Peres Heloísa Helena Ciqueto , Massarollo Maria Cristina Komatsu Braga , Fernandes Maria de Fátima Prado , Leite Maria Madalena Januário , Freitas Genival Fernandes de
Published: January 2012

O objetivo do estudo foi caracterizar o perfil de licenciandos de enfermagem, identificar a fluência digital, o conhecimento, a habilidade e o interesse no uso de ambientes virtuais de aprendizagem. Trata-se de uma pesquisa quantitativa, exploratório-descritiva realizada com 51 licenciandos de enfermagem por meio de questionário. Dos participantes do estudo 51 (100%) afirmam ter conhecimento em informática, sendo que 26 (49%) indicam um nível intermediário; 47 (92%) fazem uso diário da Internet; 51 (100%) navegam em redes sociais e possuem e-mail; 51(100%) utilizam MSN e 32 (62,7%) Skype; 41 (82%) acessam Chats, 33 (64,7%) Fóruns de discussão e 22 (43%) Blogs; 33 (64,7%) utilizam frequentemente o Moodle e 26 (51%) o COL; e a grande maioria (45- 88,2%) relatou interesse no uso de ambientes virtuais de aprendizagem. Os alunos foram considerados fluentes digitais e apresentaram conhecimento, habilidade e expressivo interesse no uso de ambientes virtuais de aprendizagem em sua formação acadêmica.
Dimensionamento informatizado de profissionais de enfermagem: avaliação de um software
Authors: Pereira Irene Mari , Gaidzinski Raquel Rapone , Fugulin Fernanda Maria Togeiro , Peres Heloísa Helena Ciqueto , Lima Antônio Fernandes Costa , Castilho Valéria , Mira Vera Lúcia , Massarollo Maria Cristina Komatsu Braga
Published: January 2012

A complexidade para operacionalizar o método de dimensionamento de profissionais de enfermagem, diante das inúmeras variáveis relativas à identificação da carga de trabalho, do tempo efetivo de trabalho dos profissionais e do Índice de Segurança Técnica (IST), evidenciou a necessidade de desenvolver um software, denominado: Dimensionamento Informatizado de Profissionais de Enfermagem (DIPE). Este estudo exploratório descritivo teve como objetivo avaliar a qualidade técnica e o desempenho funcional do DIPE. Participaram como sujeitos da pesquisa dezoito avaliadores, sendo dez enfermeiros docentes ou enfermeiros gerentes de unidades de saúde hospitalar e oito especialistas em informática em saúde. A avaliação do software baseou-se na norma NBR ISO/IEC 9126-1, considerando as características funcionalidade, confiabilidade, usabilidade, eficiência e manutenibilidade. A avaliação do software obteve resultados positivos, sobre os quais os avaliadores concordaram em todas as características avaliadas. As sugestões relatadas serão importantes para a proposição de melhorias e aprimoramento do DIPE.
A inovação tecnológica como ferramenta para monitoramento da saúde dos trabalhadores de enfermagem
Authors: Baptista Patrícia Campos Pavan , Felli Vanda Elisa Andres , Mininel Vivian Aline , Karino Márcia Eiko , Silva Silmar Maria , Tito Renata Santos , Peduzzi Marina , Sarquis Leila Maria Mansano
Published: January 2012

O objetivo do estudo é descrever o processo de construção do software Sistema de Monitoramento da Saúde dos Trabalhadores de Enfermagem, uma inovação tecnológica desenvolvida para captar os agravos à saúde dos trabalhadores de enfermagem e os determinantes potenciais de desgaste e/ou fortalecimento, monitorando a saúde por meio de indicadores. O desenvolvimento do software englobou as fases de definição do objetivo, escolha do referencial teórico, estruturação do conteúdo e desenvolvimento da arquitetura do sistema. Considera-se importante a socialização deste processo aos pequisadores, gerentes e trabalhadores interessados na temática, uma vez que o monitoramento da situação de saúde dos trabalhadores de enfermagem é uma ação indispensável para o planejamento de estratégias que possam minimizar a ocorrência dos acidentes e das doenças ocupacionais, promovendo melhoria das condições de trabalho e qualidade de vida.
Estruturas secretoras de mucilagem em Hibiscus pernambucensis Arruda (Malvaceae): distribuição, caracterização morfoanatômica e histoquímica
Authors: Rocha Joecildo Francisco , Pimentel Rafael Ribeiro , Machado Silvia Rodrigues
Published: January 2012

No presente trabalho foram estudadas as estruturas secretoras de mucilagem de Hibiscus pernambucensis aos microscópios de luz e de varredura. Conhecida como guaxima-do-mangue e algodão-do-brejo, é espécie nativa encontrada no litoral brasileiro, vegetando áreas de manguezal e restinga, tendo grande importância ecológica nestes ecossistemas. É importante produtora de fibras têxteis e celulose, fornece abundante mucilagem suscetível das mesmas aplicações medicinais de outras malváceas, além da presença de tanino. Coléteres, glândulas peroladas, tricomas secretores longo-pedunculados, canais, cavidades e idioblastos foram observados. Os coléteres ocorrem no ápice caulinar, estípulas, primórdios foliares, folhas, sépalas e pétalas jovens. As glândulas peroladas são encontradas nas superfícies adaxial e abaxial dos primórdios foliares. Os canais e as cavidades encontram-se distribuídos nos eixos vegetativo aéreo e reprodutivo. Os idioblastos ocorrem nas raízes, em estágios primários e secundários de desenvolvimento e no mesofilo foliar. A secreção presente nas diferentes estruturas secretoras é constituída predominantemente por polissacarídeos ácidos e neutros, podendo ocorrer proteínas, lipídeos e substâncias fenólicas. A presença de mucilagem, tanto na superfície como no interior dos órgãos, em diferentes fases do ciclo vegetativo e reprodutivo, representa um importante mecanismo adaptativo e de sobrevivência da espécie aos ambientes de restinga e mangue.
Phosphate-solubilizing fungi isolated from a semiarid area cultivated with melon (Cucumis melo L. cv. gold mine)
Authors: Coutinho Flavia Paiva , Cavalcanti Maria Auxiliadora de Queiroz , Yano-Melo Adriana Mayumi
Published: January 2012

Considering that little is known about the occurrence of phosphate-solubilizing fungi from areas cultivated with melon, the phosphate solubilization ability of filamentous fungi isolated in these areas was evaluated. Three hundred and eighteen filamentous fungal isolates belonging to 23 genera were evaluated, besides Aphyllophorales and Mycelia sterilia. From those, 52 were able to solubilize P: Aphyllophorales (2), Aspergillus (34), Penicillium (10) and Rhizopus (6). These results will contribute to subsidizing further research regarding the capacity of these fungi to solubilize other sources of phosphate applied to the melon crop, as well as indicate the need for a screening program to select those with higher capacity and potential for solubilization.
Allelic diversity in populations of Solanum lycocarpum A. St.-Hil (Solanaceae) in a protected area and a disturbed environment
Authors: Moura Tânia Maria de , Sebbenn Alexandre Magno , Martins Karina , Moreno Maria Andreia , Oliveira Giancarlo Conde Xavier , Chaves Lázaro José , Kageyama Paulo Yoshio
Published: January 2012

This study aimed to compare the genetic diversity of populations of Solanum lycocarpum A.St.-Hil between natural and human disturbed environments, with the assumption that protected areas have greater genetic diversity than disturbed areas. For this study, two populations were sampled in Goiás State, Brazil. One was located in a conservation unit, Serra de Caldas Novas State Park, in the Caldas Novas municipality. The other was located in a pasture area in the municipality of Morrinhos. The two populations are 41 km apart. We sampled 60 individuals from each population, which were genotyped with five microsatellite loci (SSR). The highest number of alleles was recorded in the population of the conservation unit, where we found 11 exclusive and five rare alleles. In the disturbed area, we recorded only three exclusive alleles and one rare allele. Although we did not observe significant inbreeding in these populations, genetic divergence between them was high (G ST (Hedrick)=0.147 =0.147) for a species with long distance seed dispersal. The results corroborate the hypothesis that the population in the less disturbed area harbors greater allelic diversity. They also confirm the effectiveness of using protected areas to preserve the genetic diversity of the species.