bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide detection of copy number variations using high-density SNP genotyping platforms in Holsteins
Authors: Jiang Li , Jiang Jicai , Yang Jie , Liu Xuan , Wang Jiying , Wang Haifei , Ding Xiangdong , Liu Jianfeng , Zhang Qin
Published: February 2013

Background

Copy number variations (CNVs) are widespread in the human or animal genome and are a significant source of genetic variation, which has been demonstrated to play an important role in phenotypic diversity. Advances in technology have allowed for identification of a large number of CNVs in cattle. Comprehensive explore novel CNVs in the bovine genome would provide valuable information for functional analyses of genome structural variation and facilitating follow-up association studies between complex traits and genetic variants.

Results

In this study, we performed a genome-wide CNV detection based on high-density SNP genotyping data of 96 Chinese Holstein cattle. A total of 367 CNV regions (CNVRs) across the genome were identified, which cover 42.74Mb of the cattle genome and correspond to 1.61% of the genome sequence. The length of the CNVRs on autosomes range from 10.76 to 2,806.42 Kb with an average of 96.23 Kb. 218 out of these CNVRs contain 610 annotated genes, which possess a wide spectrum of molecular functions. To confirm these findings, quantitative PCR (qPCR) was performed for 17 CNVRs and 13(76.5%) of them were successfully validated.

Conclusions

Our study demonstrates the high density SNP array can significantly improve the accuracy and sensitivity of CNV calling. Integration of different platforms can enhance the detection of genomic structure variants. Our results provide a significant replenishment for the high resolution map of copy number variation in the bovine genome and valuable information for investigation of genomic structural variation underlying traits of interest in cattle.
Blomia tropicalis Blo t 5 and Blo t 21 recombinant allergens might confer higher specificity to serodiagnostic assays than whole mite extract
Authors: Carvalho Kellyanne dos Anjos , de Melo-Neto Osvaldo Pompílio , Magalhães Franklin Barbalho , Ponte João Carlos Marques , Felipe Filipe Adriano Borba , dos Santos Mariese Conceição Alves , dos Santos Lima Givaneide , Cruz Álvaro Augusto , Pinheiro Carina Silva , Pontes-de-Carvalho Lain Carlos , Alcantara-Neves Neuza Maria
Published: February 2013

Background

Blomia tropicalisis a dust mite and an important source of allergens in tropical regions. Up to now, the assays to diagnose atopy to this mite use whole body extract as antigens. However, anti-B. tropicalisIgE antibodies cross-react withAscaris lumbricoidesantigens, hindering the diagnosis of allergy to this mite. In this study,B. tropicalisrecombinant allergens were evaluated with the purpose of developing an immunodiagnostic assay for allergy to this mite with greater specificity than those commercially available.

Methods

TwoB. tropicalisallergens (Blo t 5 and Blo t 21) were cloned into a plasmidial expression vector, expressed inEscherichia coliand purified by affinity chromatography. Sixty-three sera containing anti-B. tropicalisextract (BtE) IgE antibodies were used to investigate IgE reactivity to the recombinant Blot 5 and 21 allergens. Inhibition assays with 20 sera pre-adsorbed withA. lumbricoidesextract were performed using rBlo t 5, rBlo t 21, and BtE as antigens. All the assays were carried using indirect ELISA.

Results

Eighty-two point nine percent and 80.0% of the sera with anti-BtE antibodies from 35 children reacted with rBlo t 5 and rBlo t 21, respectively, whereas 92.8% and 89.3% of the 28 sera with anti-BtE antibodies from adult asthma patients reacted with the same allergens, and 96.4% of these sera reacted with a mixture of rBlo t 5 and rBlo t 21. In an inhibition ELISA, the absorption of sera byA. lumbricoidesextract affected less the reaction with rBlo t 5 and rBlo t 21 than with BtE.

Conclusions

The rBlo t 5 and rBlo t 21 allergens contain important epitopes recognized by IgE antibodies of individuals allergic toB. tropicalisantigens. Moreover, the assays using the recombinant allergens had lower IgE cross-reactivity withA. lumbricoidesantigens, a fact which would confers higher specificity to serodiagnostic assays than the crude mite extract. However, additional recombinant allergens should be evaluated in order to reach the same sensitivity of the commercially available assays based on mite extract.
Inferring patient to patient transmission of Mycobacterium tuberculosisfrom whole genome sequencing data
Authors: Bryant Josephine M , Schürch Anita C , van Deutekom Henk , Harris Simon R , de Beer Jessica L , de Jager Victor , Kremer Kristin , van Hijum Sacha A F T , Siezen Roland J , Borgdorff Martien , Bentley Stephen D , Parkhill Julian , van Soolingen Dick
Published: February 2013

Background

Mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. However, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required.

Methods

We attempted to estimate a molecular clock by sequencing 199 isolates from epidemiologically linked tuberculosis cases, collected in the Netherlands spanning almost 16 years.

Results

Multiple analyses support an average mutation rate of ~0.3 SNPs per genome per year. However, all analyses revealed a very high degree of variation around this mean, making the confirmation of links proposed by epidemiology, and inference of novel links, difficult. Despite this, in some cases, the phylogenetic context of other strains provided evidence supporting the confident exclusion of previously inferred epidemiological links.

Conclusions

This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies. However, the superior resolution of whole genome sequencing can provide the phylogenetic context to allow the confident exclusion of possible transmission events previously inferred via traditional DNA fingerprinting techniques and epidemiological cluster investigation. Despite the slow generation of variation even at the whole genome level we conclude that the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.
Impact on quality of life in teachers after educational actions for prevention of voice disorders: a longitudinal study
Authors: Pizolato Raquel Aparecida , Rehder Maria Inês Beltrati Cornacchioni , de Castro Meneghim Marcelo , Ambrosano Glaucia Maria Bovi , Mialhe Fábio Luiz , Pereira Antonio Carlos
Published: February 2013

Background

Voice problems are more common in teachers due to intensive voice use during routine at work. There is evidence that occupational disphonia prevention programs are important in improving the quality voice and consequently the quality of subjects’ lives.

Aim

To investigate the impact of educational voice interventions for teachers on quality of life and voice.

Methods

A longitudinal interventional study involving 70 teachers randomly selected from 11 public schools, 30 to receive educational intervention with vocal training exercises and vocal hygiene habits (experimental group) and 40 to receive guidance on vocal hygiene habits (control group control). Before the process of educational activities, the Voice-Related Quality of Life instrument (V-RQOL) was applied, and 3 months after conclusion of the activities, the subjects were interviewed again, using the same instrument. For data analysis, Prox MIXED were applied, with a level of significance α < 0.05. Results: Teachers showed significantly higher domain and overall V-RQOL scores after preventive intervention, in both control and experimental groups. Nevertheless, there was no statistical difference in scores between the groups.

Conclusion

Educational actions for vocal health had a positive impact on the quality of life of the participants, and the incorporation of permanent educational actions at institutional level is suggested.
Structural, electrical, and optical properties of Ti-doped ZnO films fabricated by atomic layer deposition
Authors: Ye Zhi-Yuan , Lu Hong-Liang , Geng Yang , Gu Yu-Zhu , Xie Zhang-Yi , Zhang Yuan , Sun Qing-Qing , Ding Shi-Jin , Zhang David Wei
Published: February 2013

High-quality Ti-doped ZnO films were grown on Si, thermally grown SiO2, and quartz substrates by atomic layer deposition (ALD) at 200°C with various Ti doping concentrations. Titanium isopropoxide, diethyl zinc, and deionized water were sources for Ti, Zn, and O, respectively. The Ti doping was then achieved by growing ZnO and TiO2 alternately. A hampered growth mode of ZnO on TiO2 layer was confirmed by comparing the thicknesses measured by spectroscopic ellipsometry with the expected. It was also found that the locations of the (100) diffraction peaks shift towards lower diffraction angles as Ti concentration increased. For all samples, optical transmittance over 80% was obtained in the visible region. The sample with ALD cycle ratio of ZnO/TiO2 being 20 had the lowest resistivity of 8.874 × 10−4 Ω cm. In addition, carrier concentration of the prepared films underwent an evident increase and then decreased with the increase of Ti doping concentration.
Clinical significance of treatment delay in status epilepticus
Authors: Hillman Jonas , Lehtimäki Kai , Peltola Jukka , Liimatainen Suvi
Published: February 2013

Background

Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE.

Methods

This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition.

Results

The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome.

Conclusions

The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE.
Dexamethasone uptake in the murine organ of Corti with transtympanic versus systemic administration
Authors: Grewal Amandeep S , Nedzelski Julian M , Chen Joseph M , Lin Vincent YW
Published: February 2013

Objective

To investigate glucocorticoid uptake in auditory hair cells following transtympanic versus systemic administration of dexamethasone.

Study design

Controlled experimental study.

Setting

Translational science experimental laboratory.

Methods

Swiss-Webster mice were injected with dexamethasone via transtympanic or systemic administration. At 1, 6, or 12 hours post-injection the temporal bones were harvested. After cryosectioning, immunohistochemical staining was performed using an antibody for dexamethasone.

Results

Dexamethasone labelling was greatest at 1 hour. Inner hair cells demonstrated much higher steroid uptake than outer hair cells. Both transtympanic injection and high-dose systemic administration resulted in strong dexamethasone labelling of hair cells, and a decreasing basal-to-apical gradient of hair cell fluorescence intensity was observed. Systemically delivered dexamethasone was rapidly eliminated from the inner ear, demonstrating mild labelling after 6 hours and none after 12 hours. In contrast, the mice receiving transtympanic injection had persistent moderate intensity fluorescence at 6 and 12 hours post-injection.

Conclusion

There is similar uptake of dexamethasone by auditory hair cells after transtympanic and high-dose systemic delivery. Novel findings include the presence of a decreasing basal-apical gradient of steroid uptake, and demonstration of greater affinity of inner hair cells for dexamethasone compared to outer hair cells. In this animal model transtympanic injection resulted in prolonged steroid uptake. These findings help further our understanding of the pharmacokinetics of steroids in the cochlea, with a focus on auditory hair cells.
5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual Acetylcholinesterase/Butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety
Authors: Nadri Hamid , Pirali-Hamedani Morteza , Moradi Alireza , Sakhteman Amirhossein , Vahidi Alireza , Sheibani Vahid , Asadipour Ali , Hosseinzadeh Nouraddin , Abdollahi Mohammad , Shafiee Abbas , Foroumadi Alireza
Published: February 2013

Background

Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.

Methods

The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.

Results

The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.

Conclusions

In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.
Characterization of hepatic tumors using [11C]metomidate through positron emission tomography: comparison with [11C]acetate
Authors: Roivainen Anne , Naum Alexandru , Nuutinen Heikki , Leino Rauli , Nurmi Heimo , Någren Kjell , Parkkola Riitta , Virtanen Johanna , Kallajoki Markku , Kujari Harry , Ovaska Jari , Roberts Peter , Seppänen Marko
Published: February 2013

Background

Using positron emission tomography (PET), we compared two tracers, [11C]metomidate ([11C]MTO) and [11C]acetate ([11C]ACE), for the characterization of hepatic tumors.

Methods

Thirty-three patients underwent PET with [11C]MTO and [11C]ACE and magnetic resonance imaging (MRI). Based on the histology of the tumor biopsy, 14 patients had hepatocellular carcinoma (HCC), 9 patients had focal nodular hyperplasia (FNH), and 10 patients had other types of hepatic tumors. Tumor uptake was evaluated by calculating the maximum and mean standardized uptake value and tumor-to-liver ratio.

Results

Altogether, 120 hepatic lesions (59 HCC, 18 FNH, 30 metastases of different primaries, 9 adenomas, and 4 regenerating nodules of liver cirrhosis) were detected by MRI. The overall tumor detection rate was slightly higher for [11C]MTO (39%) than for [11C]ACE (33%). [11C]ACE was more sensitive for HCC detection (50% versus 43%, respectively), whereas [11C]MTO was more sensitive for FNH detection (78% versus 44%, respectively). In HCC patients, the tumor grade correlated with [11C]ACE, but not with [11C]MTO. All of the patients with liver metastases, from various primary tumors (n = 10), were negative for both tracers.

Conclusions

Due to low sensitivity, [11C]MTO and [11C]ACE PET have only limited value in diagnosing hepatic tumors.
A half doubling dose change in bronchial hyperresponsiveness in a population represents an important difference
Authors: Weatherall Mark , Fingleton James , Eyers Sally , Beasley Richard
Published: February 2013

Background

The prevalence of asthma has increased over recent decades and the reasons for this are poorly understood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness (BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference in BHR for an individual is accepted to be around one doubling dose, the minimum important change in a population is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and cholesterol, a change that is not clinically important in an individual may be extremely important in public health terms.

Findings

To assess the potential impact of a small absolute change in BHR across a population, we modelled the effect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population. We calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR by 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe asthma, this would be highly significant in public health terms.

Conclusions

We propose that a one half doubling dose worsening in BHR across a population may represent an important change.
Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?
Authors: Bjersing Jan L , Erlandsson Malin , Bokarewa Maria I , Mannerkorpi Kaisa
Published: February 2013

Introduction

Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients.

Methods

In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF).

Results

Baseline FIQ fatigue correlated negatively with serum leptin (r = -0.345; P = 0.016) and nerve growth factor (NGF; r = -0.412; P = 0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r = -0.694; P = 0.038). FIQ Fatigue associated negatively with CSF resistin (r = -0.365; P = 0.073). Similarly, FIQ fatigue (r = -0.444; P = 0.026) and MFIGF correlated negatively with CSF adiponectin (r = -0.508; P = 0.01). In lean patients, FIQ fatigue (P = 0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P = 0.017), overweight (MFIGF: P = 0.001), and obese patients (MFIGF: P = 0.016). After 15 weeks, total IGF-1 increased in lean (P = 0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P = 0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r = -0.329; P = 0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r = -0.463; P = 0.034) and positively with ∆neuropeptide Y (NPY) (r = 0.469; P = 0.032). Resistin increased after 30 weeks (P = 0.034). ∆MFIGF correlated negatively with ∆resistin (r = -0.346; P = 0.031), being strongest in obese patients (r = -0.815; P = 0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r = -0.711; P = 0.032).

Conclusions

Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects.

Trial registration

ClinicalTrials.gov: NCT00643006
Overexpression of SETβ, a protein localizing to centromeres, causes precocious separation of chromatids during the first meiosis of mouse oocyte
Authors: Qi Shu-Tao , Wang Zhen-Bo , Ouyang Ying-Chun , Zhang Qing-Hua , Hu Meng-Wen , Huang Xin , Ge Zhaojia , Guo Lei , Wang Ya-Peng , Hou Yi , Schatten Heide , Sun Qing-Yuan
Published: February 2013

Chromosome segregation in mammalian oocyte meiosis is an error-prone process, and any mistake in this process may result in aneuploidy, which is the main cause of infertility, abortion and many genetic diseases. It is now well known that shugoshin and protein phosphatase 2A (PP2A) play important roles in the protection of centromeric cohesion during the first meiosis. PP2A can antagonize the phosphorylation of rec8-cohesin at the centromeres and thus prevent rec8 from cleavage and maintain the cohesion of chromatids. SETβis a novel protein that physically interacts with shugoshin and inhibits PP2A activity. We thus hypothesized that SETβ may regulate cohesion protection and chromosome segregation during oocyte meiotic maturation. Here we report for the first time the expression, subcellular localization and functions of SETβ during mouse oocyte meiosis. Immunobloting analysis showed that the expression level of SETβ was stable from the GV stage to the MII stage of oocyte meiosis. Immunofluorescent analysis showed SETβ accumulation in the nucleus at the GV stage, while it was targeted mainly to the inner centromere area and faintly localized to the interchromatid axes from GVBD to MI stages. At the MII stage, SETβ still localized at the inner centromere area, but could relocalize to kinetochores in a process perhaps depending on the tension on the centromeres. SETβ partly co-localized with PP2A at the inner centromere area. Overexpression of SETβ in mouse oocytes caused precocious separation of sister chromatids, but depletion of SETβ by RNAi showed little effects on the meiotic maturation process. Taken together, our results suggest that SETβ, even though it localizes to centromeres, is not essential for chromosome separation during mouse oocyte meiotic maturation, although its forced overexpression causes premature chromatid separation.
Citron-kinase mediates transition from constriction to abscission through its coiled-coil domain
Authors: Watanabe Sadanori , De Zan Tihana , Ishizaki Toshimasa , Narumiya Shuh
Published: February 2013

Cytokinesis is initiated by constriction of the cleavage furrow, and completed with separation of the two daughter cells by abscission. Control of transition from constriction to abscission is therefore crucial for cytokinesis. However, the underlying mechanism is largely unknown. Here, we analyzed the role of Citron-Kinase (Citron-K) that localizes at the cleavage furrow and the midbody, and dissected its action mechanisms during this transition. Citron-K forms a stable ring-like structure at the midbody, and its depletion affected the maintenance of the intercellular bridge, resulting in fusion of two daughter cells after the cleavage furrow ingression. Citron-K RNAi reduced accumulation of RhoA, Anillin, and septins at the intercellular bridge in mid telophase, and impaired concentration and maintenance of KIF14 and PRC1 at the midbody in late telophase. RNAi rescue experiments revealed that these functions of Citron-K are mediated by its coiled-coil (CC) domain, and not by its kinase domain. The carboxyl terminal part of CC contains a Rho-binding domain and a cluster-forming region, and is important for concentrating Citron-K from the cleavage furrow to the midbody. The amino terminal part of CC directly binds to KIF14, and this interaction is required for timely transfer of Citron-K to the midbody after furrow ingression. We propose that the CC-domain-mediated translocation and actions of Citron-K ensure proper stabilization of the midbody structure during the transition from constriction to abscission.
Six1 regulates proliferation of Pax7+ muscle progenitors in zebrafish
Authors: Nord Hanna , Skalman Lars Nygård , von Hofsten Jonas
Published: February 2013

In the embryonic zebrafish, skeletal muscle fibres are formed from muscle progenitors in the paraxial mesoderm. The embryonic myotome is mostly constituted of fast twitch specific fibres, which are formed from a fast specific progenitor cell pool. The most lateral fraction of the fast domain in the myotome of zebrafish embryos derive from the Pax7 positive dermomyotome-like cells. In this study we show that two genes, belonging to the sine oculus class 1 (six1) genes (six1a and six1b) both are essential for the regulation of Pax7+ cell proliferation and consequently in their differentiation during the establishment of the zebrafish dermomyotome. Both in six1a and in six1b morphant embryos, Pax7+ cells are initially formed, but fail to proliferate as detected by the reduced proliferation marker phosphohistone3 and brdU incorporation. In congruence, overexpression of six1a or six1b leads to increased Pax7+ cell number and reduced or alternatively delayed fibre cell differentiation. BMP signalling has previously been suggested to inhibit differentiation of Pax7+ cells in the dermomyotome. Here we show that the remaining Pax7+ cells in six1a and six1b morphant embryos also have significantly reduced pSmad1/5/8 levels and propose that this leads to a reduced proliferative activity, which may result in a premature differentiation of Pax7+ cells in the zebrafish dermomyotome. In summary, we show a mechanism for Six1a and Six1b in establishing the Pax7+ cell derived part of the fast muscle and suggest new important roles for Six1 in the regulation of the Pax7+ muscle cell population through pSmad1/5/8 signalling.
Multi-functional norrin is a ligand for the LGR4 receptor
Authors: Deng Cheng , Reddy Pradeep , Cheng Yuan , Luo Ching-Wei , Hsiao Chih-Lun , Hsueh Aaron J. W.
Published: February 2013

Mammalian LGR4, 5, and 6 are seven transmembrane receptors important for diverse physiological processes. These receptors are orthologous to DLGR2, a Drosophila receptor activated by the burs/pburs heterodimer important for morphogenesis. Although recent studies indicated that four R-spondin proteins are cognate ligands for LGR4, 5, and 6 receptors, several BMP antagonists in vertebrates have been postulated to be orthologous to burs and pburs. Based on newly available genome sequences, we now showed norrin is a vertebrate ortholog for insect burs and pburs and stimulates Wnt signaling mediated by LGR4, but not LGR5 and 6, in mammalian cells. Although norrin could only activate LGR4, binding studies suggested interactions between norrin and LGR4, 5, and 6. Norrin, the Norrie disease gene product, is also capable of activating Wnt signaling mediated by the Frizzled4 receptor and serves as a BMP antagonist. Mutagenesis studies indicated that different norrin mutations found in patients with Norrie disease can be categorized into subgroups showing defects for signaling through the three distinct binding proteins. Thus, norrin is a rare ligand capable of binding three receptors/binding proteins important for BMP and Wnt signaling pathways.
Sensorimotor responsiveness and resolution in the giraffe
Authors: More Heather L. , O'Connor Shawn M. , Brøndum Emil , Wang Tobias , Bertelsen Mads F. , Grøndahl Carsten , Kastberg Karin , Hørlyck Arne , Funder Jonas , Donelan J. Maxwell
Published: February 2013

The ability of an animal to detect and respond to changes in the environment is crucial to its survival. However, two elements of sensorimotor control – the time required to respond to a stimulus (responsiveness) and the precision of stimulus detection and response production (resolution) – are inherently limited by a competition for space in peripheral nerves and muscles. These limitations only become more acute as animal size increases. In this paper, we investigated whether the physiology of giraffes has found unique solutions for maintaining sensorimotor performance in order to compensate for their extreme size. To examine responsiveness, we quantified three major sources of delay: nerve conduction delay, muscle electromechanical delay and force generation delay. To examine resolution, we quantified the number and size distribution of nerve fibers in the sciatic nerve. Rather than possessing a particularly unique sensorimotor system, we found that our measurements in giraffes were broadly comparable to size-dependent trends seen across other terrestrial mammals. Consequently, both giraffes and other large animals must contend with greater sensorimotor delays and lower innervation density in comparison to smaller animals. Because of their unconventional leg length, giraffes may experience even longer delays compared with other animals of the same mass when sensing distal stimuli. While there are certainly advantages to being tall, there appear to be challenges as well – our results suggest that giraffes are less able to precisely and accurately sense and respond to stimuli using feedback alone, particularly when moving quickly.
Spatial memory and stereotypy of flight paths by big brown bats in cluttered surroundings
Authors: Barchi Jonathan R. , Knowles Jeffrey M. , Simmons James A.
Published: February 2013

The big brown bat, Eptesicus fuscus, uses echolocation for foraging and orientation. The limited operating range of biosonar implies that bats must rely upon spatial memory in familiar spaces with dimensions larger than a few meters. Prior experiments with bats flying in obstacle arrays have revealed differences in flight and acoustic emission patterns depending on the density and spatial extent of the obstacles. Using the same method, combined with acoustic microphone array tracking, we flew big brown bats in an obstacle array that varied in density and distribution in different locations in the flight room. In the initial experiment, six bats learned individually stereotyped flight patterns as they became familiar with the space. After the first day, the repetition rate of sonar broadcasts dropped to a stable level, consistent with low-density clutter. In a second experiment, after acquiring their stable paths, each bat was released from each of two unfamiliar locations in the room. Each bat still followed the same flight path it learned originally. In a third experiment, performed 1 month after the first two experiments, three of the bats were re-flown in the same configuration of obstacles; these three resumed flying in their accustomed path. The other three bats were flown in a mirror-image reconfiguration of the obstacles; these bats quickly found stable flight paths that differed from their originally learned paths. Overall, the flight patterns indicate that the bats perceive the cluttered space as a single scene through which they develop globally organized flight paths.
Anemonefish oxygenate their anemone hosts at night
Authors: Szczebak Joseph T. , Henry Raymond P. , Al-Horani Fuad A. , Chadwick Nanette E.
Published: February 2013

Many stony coral-dwelling fishes exhibit adaptations to deal with hypoxia among the branches of their hosts; however, no information exists on the respiratory ecophysiology of obligate fish associates of non-coral organisms such as sea anemones and sponges. This study investigated metabolic and behavioral interactions between two-band anemonefish (Amphiprion bicinctus) and bulb-tentacle sea anemones (Entacmaea quadricolor) at night. We measured the net dark oxygen uptake (, μmol O2 h−1) of fish–anemone pairs when partners were separate from each other, together as a unit, and together as a unit but separated by a mesh screen that prevented physical contact. We also measured the effects of water current on sea anemone and quantified the nocturnal behaviors of fish in the absence and presence of host anemones in order to discern the impacts of anemone presence on fish behavior. Net of united pairs was significantly higher than that of both separated pairs and united pairs that were separated by a mesh screen. Anemone increased with flow rate from 0.5 to 2.0 cm s−1, after which remained constant up to a water flow rate of 8.0 cm s−1. Furthermore, the percentage time and bout frequency of flow-modulating behaviors by fish increased significantly when anemones were present. We conclude that physical contact between anemonefish and sea anemones elevates the of at least one of the partners at night, and anemonefish behavior at night appears to oxygenate sea anemone hosts and to augment the metabolism of both partners.
Bumblebee calligraphy: the design and control of flight motifs in the learning and return flights ofBombus terrestris
Authors: Philippides Andrew , de Ibarra Natalie Hempel , Riabinina Olena , Collett Thomas S.
Published: February 2013

Many wasps and bees learn the position of their nest relative to nearby visual features during elaborate ‘learning’ flights that they perform on leaving the nest. Return flights to the nest are thought to be patterned so that insects can reach their nest by matching their current view to views of their surroundings stored during learning flights. To understand how ground-nesting bumblebees might implement such a matching process, we have video-recorded the bees' learning and return flights and analysed the similarities and differences between the principal motifs of their flights. Loops that take bees away from and bring them back towards the nest are common during learning flights and less so in return flights. Zigzags are more prominent on return flights. Both motifs tend to be nest based. Bees often both fly towards and face the nest in the middle of loops and at the turns of zigzags. Before and after flight direction and body orientation are aligned, the two diverge from each other so that the nest is held within the bees' fronto-lateral visual field while flight direction relative to the nest can fluctuate more widely. These and other parallels between loops and zigzags suggest that they are stable variations of an underlying pattern, which enable bees to store and reacquire similar nest-focused views during learning and return flights.
Coordinating compass-based and nest-based flight directions during bumblebee learning and return flights
Authors: Collett Thomas S. , de Ibarra Natalie Hempel , Riabinina Olena , Philippides Andrew
Published: February 2013

Bumblebees tend to face their nest over a limited range of compass directions when learning the nest's location on departure and finding it on their approach after foraging. They thus obtain similar views of the nest and its surroundings on their learning and return flights. How do bees coordinate their flights relative to nest-based and compass-based reference frames to get such similar views? We show, first, that learning and return flights contain straight segments that are directed along particular compass bearings, which are independent of the orientation of a bee's body. Bees are thus free within limits to adjust their viewing direction relative to the nest, without disturbing flight direction. Second, we examine the coordination of nest-based and compass-based control during likely information gathering segments of these flights: loops during learning flights and zigzags on return flights. We find that bees tend to start a loop or zigzag when flying within a restricted range of compass directions and to fly towards the nest and face it after a fixed change in compass direction, without continuous interactions between their nest-based and compass-based directions of flight. A preferred trajectory of compass-based flight over the course of a motif, combined with the tendency of the bees to keep their body oriented towards the nest automatically narrows the range of compass directions over which bees view the nest. Additionally, the absence of interactions between the two reference frames allows loops and zigzags to have a stereotyped form that can generate informative visual feedback.
Molecular weight distributions of acetylated lignocellulosic biomasses recovered from an ionic liquid system
Authors: Qu Chen , Kishimoto Takao , Hamada Masahiro , Nakajima Noriyuki
Published: February 2013

Recently, a method was presented for the dissolution and nuclear magnetic resonance analysis of cell wall components in lignocellulosic biomass, which involves cell wall ball-milling, dissolution in ionic liquids (ILs), in situ acetylation, and the recovery of acetylated materials. However, the dissolution in ILs and the relatively long ball-milling times may partially degrade the plant cell wall components. In the present study, the molecular weight (MW) distributions of acetylated biomasses from fir (Abies sachalinensis), birch (Betula platyphylla), and bamboo (Phyllostachys nigra) recovered from IL systems were examined by size exclusion chromatography. The effects of IL types, cosolvents, dissolution temperatures and times, and ball-milling times were evaluated. The MW of acetylated fir woods recovered from 1-allyl-3-methylimidazolium chloride at 30–80°C or from 1-butyl-3-methylimidazolium chloride at 100°C for 2 h were similar to those materials that were recovered from the N-methylimidazole/dimethyl sulfoxide system. In contrast, a significant decrease in MW was observed with 1-ethyl-3-methylimidazolium acetate ([Emim]OAc) even at 30°C. The degradation of cell wall components in [Emim]OAc was reduced to some extent in the presence of N,N-dimethylacetamide or pyridine. The MW decreased gradually with increased ball-milling time.
Infrared thermography for detailed registration of thermoregulation in premature infants
Authors: Heimann Konrad , Jergus Katrin , Abbas Abbas Khudair , Heussen Nicole , Leonhardt Steffen , Orlikowsky Thorsten
Published: February 2013

Objective: To evaluate skin temperature by using different positions with non-contact infrared thermography (IRT) in multiple body areas of preterm infants for detailed information about temperature regulation and distribution.

Methods: The temperature of ten premature infants (median: 27 weeks; age 36 days; weight 1322 g) was determined via IRT (leg, back, arm, head, upper abdomen; diameter 1 cm, scale 0.00°C), and comparison was made with two conventional sensors. There were measurements of 10 min each: first incubator phase (I1), standardized skin-to-skin care (SSC) at the beginning (SSC1), after 90 min (SSC2), and then there was a second incubator phase (I2).

Results: From I1 to SSC1, patients cooled down (max. 0.62°C; both methods). From SSC1 to SSC2 temperature on central areas (abdomen, back) was maintained but rose distinctively on the head and leg (P<0.05). In the incubator (I2), temperature niveau in all IRT-areas was significantly lower than before SSC.

Conclusion: Via IRT, it is possible to detect fluctuations in temperature of premature infants. The cooling in I2 after SSC should be taken into account before routine daily care.
The SRY gene of the Y chromosome successfully identifies gender of endemic Mexican shrews (Mammalia: Soricomorpha)
Authors: Cervantes Fernando A. , Arcangeli Jésica , Morales Rogelio A. Alonso
Published: February 2013

In shrews, it is difficult to identify the gender of an individual if it is not reproductively active. An alternative that has already been successfully tested in other mammals is using a molecular marker such as the SRY gene of the Y chromosome of males. This study aims to identify the sex in shrews through polymerase chain reaction (PCR) amplification of the SRY gene of Mexican endemic shrews (Cryptotis, Sorex and Megasorex). PCR products were sequenced and compared through the basic local alignment search tool (BLAST). Male tissues produced a 202-bp DNA fragment for Cryptotis, a 155-bp fragment for Sorex and a 189-bp fragment for Megasorex; no female sample of any of the three species produced a positive amplification. Therefore, the sex of these shrew species was successfully identified. This is particularly useful for immature individuals or incomplete specimens found in pitfall traps. These results may be valuable to ecological studies and benefit conservation actions of threatened taxa.
Multimodal Convergence within the Intraparietal Sulcus of the Macaque Monkey
Authors: Guipponi Olivier , Wardak Claire , Ibarrola Danielle , Comte Jean-Christophe , Sappey-Marinier Dominique , Pinède Serge , Ben Hamed Suliann
Published: February 2013

The parietal cortex is highly multimodal and plays a key role in the processing of objects and actions in space, both in human and nonhuman primates. Despite the accumulated knowledge in both species, we lack the following: (1) a general description of the multisensory convergence in this cortical region to situate sparser lesion and electrophysiological recording studies; and (2) a way to compare and extrapolate monkey data to human results. Here, we use functional magnetic resonance imaging (fMRI) in the monkey to provide a bridge between human and monkey studies. We focus on the intraparietal sulcus (IPS) and specifically probe its involvement in the processing of visual, tactile, and auditory moving stimuli around and toward the face. We describe three major findings: (1) the visual and tactile modalities are strongly represented and activate mostly nonoverlapping sectors within the IPS. The visual domain occupies its posterior two-thirds and the tactile modality its anterior one-third. The auditory modality is much less represented, mostly on the medial IPS bank. (2) Processing of the movement component of sensory stimuli is specific to the fundus of the IPS and coincides with the anatomical definition of monkey ventral intraparietal area (VIP). (3) A cortical sector within VIP processes movement around and toward the face independently of the sensory modality. This amodal representation of movement may be a key component in the construction of peripersonal space. Overall, our observations highlight strong homologies between macaque and human VIP organization.
Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination
Authors: Pais-Vieira Miguel , Lebedev Mikhail A. , Wiest Michael C. , Nicolelis Miguel A. L.
Published: February 2013

The rat somatosensory system contains multiple thalamocortical loops (TCLs) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial, and the posterior medial thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations before the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal's discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal's performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system.
The Angelman Syndrome Protein Ube3a/E6AP Is Required for Golgi Acidification and Surface Protein Sialylation
Authors: Condon Kathryn H. , Ho Jianghai , Robinson Camenzind G. , Hanus Cyril , Ehlers Michael D.
Published: February 2013

Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3Am−/p+) mice. In Ube3a knockdown cell lines andUBE3Am−/p+cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Bothin vitroandin vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS.
Safety Encoding in the Basal Amygdala
Authors: Sangha Susan , Chadick James Z. , Janak Patricia H.
Published: February 2013

Learning to fear and avoid life-threatening stimuli are critical survival skills but are maladaptive when they persist in the absence of a direct threat. Thus, it is important to detect when a situation is safe and to increase behaviors leading to naturally rewarding actions, such as feeding and mating. It is unclear how the brain distinguishes between dangerous and safe situations. Here, we present a novel protocol designed to investigate the processing of cues that predict danger, safety, or reward (sucrose).In vivosingle unit recordings were obtained in the basal amygdala of freely behaving rats undergoing simultaneous reward, fear, and safety conditioning. We observed a population of neurons that did not respond to a Fear Cue but did change their firing rate during the combined presentation of a fear cue simultaneous with a second, safety, cue; this combination of Fear + Safety Cues signified “no shock.” This neural population consisted of two subpopulations: neurons that responded to the Fear + Safety Cue but not the Fear or Reward Cue (“safety” neurons), and neurons that responded to the Fear + Safety and Reward Cue but not the Fear Cue (“safety + reward” neurons). These data demonstrate the presence of neurons in the basal amygdala that are selectively responsive to Safety Cues. Furthermore, these data suggest that safety and reward learning use overlapping mechanisms in the basal amygdala.