bluuebunny/crossref_metadata_2025 huggingface dataset:
Drawing ecological inferences from coincident patterns of population‐ and community‐level biodiversity
Authors: Vellend Mark , Lajoie Geneviève , Bourret Audrey , Múrria Cesc , Kembel Steven W. , Garant Dany
Published: April 2014

Biodiversity is comprised of genetic and phenotypic variation among individual organisms, which might belong to the same species or to different species. Spatial patterns of biodiversity are of central interest in ecology and evolution for several reasons: to identify general patterns in nature (e.g. species–area relationships, latitudinal gradients), to inform conservation priorities (e.g. identifying hotspots, prioritizing management efforts) and to draw inferences about processes, historical or otherwise (e.g. adaptation, the centre of origin of particular clades). There are long traditions in ecology and evolutionary biology of examining spatial patterns of biodiversity among species (i.e. in multispecies communities) and within species, respectively, and there has been a recent surge of interest in studying these two types of pattern simultaneously. The idea is that examining both levels of diversity can materially advance the above‐stated goals and perhaps lead to entirely novel lines of inquiry. Here, we review two broad categories of approach to merging studies of inter‐ and intraspecific variation: (i) the study of phenotypic trait variation along environmental gradients and (ii) the study of relationships between patterns of molecular genetic variation within species and patterns of distribution and diversity across species. For the latter, we report a new meta‐analysis in which we find that correlations between species diversity and genetic diversity are generally positive and significantly stronger in studies with discrete sampling units (e.g. islands, lakes, forest fragments) than in studies with nondiscrete sampling units (e.g. equal‐area study plots). For each topic, we summarize the current state of knowledge and key future directions.
Life history influences how fire affects genetic diversity in two lizard species
Authors: Smith Annabel L. , Bull C. Michael , Gardner Michael G. , Driscoll Don A.
Published: April 2014

‘Fire mosaics’ are often maintained in landscapes to promote successional diversity in vegetation with little understanding of how this will affect ecological processes in animal populations such as dispersal, social organization and re‐establishment. To investigate these processes, we conducted a replicated, spatiotemporal landscape genetics study of two Australian woodland lizard species [Amphibolurus norrisi (Agamidae) and Ctenotus atlas (Scincidae)]. Agamids have a more complex social and territory structure than skinks, so fire might have a greater impact on their population structure and thus genetic diversity. Genetic diversity increased with time since fire in C. atlas and decreased with time since fire in A. norrisi. For C. atlas, this might reflect its increasing population size after fire, but we could not detect increased gene flow that would reduce the loss of genetic diversity through genetic drift. Using landscape resistance analyses, we found no evidence that postfire habitat succession or topography affected gene flow in either species and we were unable to distinguish between survival and immigration as modes of postfire re‐establishment. In A. norrisi, we detected female‐biased dispersal, likely reflecting its territorial social structure and polygynous mating system. The increased genetic diversity in A. norrisi in recently burnt habitat might reflect a temporary disruption of its territoriality and increased male dispersal, a hypothesis that was supported with a simulation experiment. Our results suggest that the effects of disturbance on genetic diversity will be stronger for species with territorial social organization.
Complex phylogeography and historical hybridization between sister taxa of freshwater sculpin (Cottus)
Authors: Baumsteiger Jason , Kinziger Andrew P. , Reid Stewart B. , Aguilar Andres
Published: April 2014

Species ranges that span different geographic landscapes frequently contain cryptic species‐ or population‐level structure. Identifying these possible diversification factors can often be accomplished under a comparative phylogeographic framework. However, comparisons suffer if previous studies are limited to a particular group or habitat type. In California, a complex landscape has led to several phylogeographic breaks, primarily in terrestrial species. However, two sister taxa of freshwater fish, riffle sculpin (Cottus gulosus) and Pit sculpin (Cottus pitensis), display ranges based on morphological identifications that do not coincide with these breaks. Using a comprehensive sampling and nuclear, mitochondrial and microsatellite markers, we hypothesized that proposed species ranges are erroneous based on potential hybridization/gene flow between species. Results identified a phylogeographic signature consistent with this hypothesis, with breaks at the Coast Range Mountains and Sacramento/San Joaquin River confluence. Coastal locations ofC. gulosusrepresent a unique lineage, and ‘true’C. gulosuswere limited to the San Joaquin basin, both regions under strong anthropogenic influence and potential conservation targets.C. pitensislimits extended historically throughout the Sacramento/Pit River basin but currently are restricted to the Pit River. Interestingly, locations in the Sacramento River contained low levels of ancestral hybridization and gene flow fromC. gulosusbut now appear to be a distinct population. The remaining population structure was strongly correlated with Sierra Nevada presence (high) or absence (low). This study stresses the importance of testing phylogeographic breaks across multiple taxa/habitats before conservation decisions are made, but also the potential impact of different geographic landscapes on evolutionary diversification.
Unexpected ancestry of Populus seedlings from a hybrid zone implies a large role for postzygotic selection in the maintenance of species
Authors: Lindtke Dorothea , Gompert Zachariah , Lexer Christian , Buerkle C. Alex
Published: April 2014

In the context of potential interspecific gene flow, the integrity of species will be maintained by reproductive barriers that reduce genetic exchange, including traits associated with prezygotic isolation or poor performance of hybrids. Hybrid zones can be used to study the importance of different reproductive barriers, particularly when both parental species and hybrids occur in close spatial proximity. We investigated the importance of barriers to gene flow that act early vs. late in the life cycle of European Populus by quantifying the prevalence of homospecific and hybrid matings within a mosaic hybrid zone. We obtained genotypic data for 11 976 loci from progeny and their maternal parents and constructed a Bayesian model to estimate individual admixture proportions and hybrid classes for sampled trees and for the unsampled pollen parent. Matings that included one or two hybrid parents were common, resulting in admixture proportions of progeny that spanned the whole range of potential ancestries between the two parental species. This result contrasts strongly with the distribution of admixture proportions in adult trees, where intermediate hybrids and each of the parental species are separated into three discrete ancestry clusters. The existence of the full range of hybrids in seedlings is consistent with weak reproductive isolation early in the life cycle of Populus. Instead, a considerable amount of selection must take place between the seedling stage and maturity to remove many hybrid seedlings. Our results highlight that high hybridization rates and appreciable hybrid fitness do not necessarily conflict with the maintenance of species integrity.
Dual DNA binding and coactivator functions of Aspergillus nidulans TamA, a Zn(II)2Cys6 transcription factor
Authors: Downes Damien J. , Davis Meryl A. , Wong Koon Ho , Kreutzberger Sara D. , Hynes Michael J. , Todd Richard B.
Published: April 2014

Transcription factors containing DNA binding domains generally regulate transcription by direct interaction with DNA. For most transcription factors, including the fungal Zn(II)2Cys6 zinc binuclear cluster transcription factors, the DNA binding motif is essential for function. However, Aspergillus nidulans TamA and the related Saccharomyces cerevisiae Dal81p protein contain Zn(II)2Cys6 motifs shown to be dispensable for function. TamA acts at several promoters as a coactivator of the global nitrogen GATA transcription factor AreA. We now show that TamA is the major transcriptional activator of gdhA, encoding the key nitrogen metabolism enzyme NADP‐glutamate dehydrogenase. Moreover, activation of gdhA by TamA occurs primarily by a mechanism requiring the TamA DNA binding motif. We show that the TamA DNA binding motif is required for DNA binding of FLAG‐epitope‐tagged TamA to the gdhA promoter. We identify a conserved promoter element required for TamA activation, and show that TamA and AreA are reciprocally required for full binding at the gdhA promoter under conditions where AreA is inactive at most promoters but active at gdhA. Therefore TamA has dual functions as a DNA‐binding transcription factor and a non‐DNA‐binding coactivator. Dual DNA‐binding and coactivator functions provide an additional level of combinatorial control to mediate gene‐specific expression.
Bovine pancreatic trypsin inhibitor is a new antifungal peptide that inhibits cellular magnesium uptake
Authors: Bleackley Mark R. , Hayes Brigitte M. , Parisi Kathy , Saiyed Tamana , Traven Ana , Potter Ian D. , van der Weerden Nicole L. , Anderson Marilyn A.
Published: April 2014

Antimicrobial peptides (AMPs) are promising agents for control of bacterial and fungal infections. Traditionally, AMPs were thought to act through membrane disruption but recent experiments have revealed a diversity of mechanisms. Here we describe a novel antifungal activity for bovine pancreatic trypsin inhibitor (BPTI). BPTI has several features in common with a subset of antimicrobial proteins in that it is small, cationic and stabilized by disulphide bonds. BPTI inhibits growth of Saccharomyces cerevisiae and the human pathogen Candida albicans. Screening of the yeast heterozygous essential deletion collection identified the magnesium transporter Alr1p as a potential BPTI target. BPTI treatment of wild type cells resulted in a lowering of cellular Mg2+ levels. Populations treated with BPTI had fewer cells in S‐phase of the cell cycle and a corresponding increase of cells in G0/G1 and G2 phases. The same patterns of cell cycle arrest obtained with BPTI were also obtained with the magnesium channel inhibitor hexamine(III)cobalt chloride. Analysis of the growth inhibition of C. albicans revealed that BPTI is inhibiting growth via the same mechanism in the two yeast species. Inhibition of magnesium uptake by BPTI represents a novel mechanism of action for AMPs.
Components of priming‐induced resistance to Fusarium head blight in wheat revealed by two distinct mutants of Fusarium graminearum
Authors: Ravensdale Michael , Rocheleau Hélène , Wang Li , Nasmith Charles , Ouellet Thérèse , Subramaniam Rajagopal
Published: April 2014

Two mutants (tri6Δ and noxABΔ) of the fungal pathogen Fusarium graminearum were assessed for their ability to prime immune responses in wheat (cv. Roblin) against challenge with pathogenic F. graminearum. Priming treatments generated Fusarium head blight (FHB)‐resistant wheat phenotypes and reduced the accumulation of fungal mycotoxins in infected tissues. Microarray analysis identified 260 transcripts that were differentially expressed during the priming period. Expression changes were observed in genes associated with immune surveillance systems, signalling cascades, antimicrobial compound production, oxidative burst, secondary metabolism, and detoxification and transport. Specifically, genes related to jasmonate, gibberellin and ethylene biosynthesis exhibited differential expression during priming. In addition, the induction of the phenylpropanoid pathways that lead to flavonoid, coumarin and hydroxycinnamic acid amide accumulation was also observed. This study highlights the utility of nonpathogenic mutants to both elicit and delineate stages of defence responses in wheat.
Patellins 3 and 6, two members of thePlantPatellin family, interact with the movement protein ofAlfalfa mosaic virusand interfere with viral movement
Authors: Peiro Ana , Izquierdo‐Garcia Ana Cristina , Sanchez‐Navarro Jesus Angel , Pallas Vicente , Mulet Jose Miguel , Aparicio Frederic
Published: April 2014

Movement proteins (MPs) encoded by plant viruses interact with host proteins to facilitate or interfere with intra‐ and/or intercellular viral movement. Using yeast two‐hybrid and bimolecular fluorescence complementation assays, we herein presentin vivoevidence for the interaction betweenAlfalfa mosaic virus(AMV)MPand ArabidopsisPatellin 3 (atPATL3) andPatellin 6 (atPATL6), two proteins containing aSec14 domain. Proteins withSec14 domains are implicated in membrane trafficking, cytoskeleton dynamics, lipid metabolism and lipid‐mediated regulatory functions. Interestingly, the overexpression ofatPATL3and/oratPATL6interfered with the plasmodesmata targeting ofAMV MPand correlated with reduced infection foci size. Consistently, the viralRNAlevels increased in the single and double Arabidopsis knockout mutants foratPATL3andatPATL6. Our results indicate that, in general,MP–PATLinteractions interfere with the correct subcellular targeting ofMP, thus rendering the intracellular transport of viralMP‐containing complexes less efficient and diminishing cell‐to‐cell movement.
Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin‐like growth factor‐1 signalling
Authors: Wadowska Magdalena , Woods Julie , Rogozinska Magdalena , Briones Teresita L.
Published: April 2014

Aims

Use of enriched environment (EE) housing has been shown to promote recovery from cerebral ischaemic injury but the underlying mechanisms of their beneficial effects remains unclear. Here we examined whether the beneficial effects of EE housing on ischaemia‐induced neurodegeneration and cognitive impairment are associated with increased insulin‐like growth factor‐1 (IGF‐1) signalling in the hippocampus.

Methods

Forty‐two adult male Wistar rats were included in the study and received either ischaemia or sham surgery. Rats in each group were further randomized to either: EE or standard laboratory cage housing (control). Rats were placed in their assigned housing condition immediately after recovery from anaesthesia. Behavioural testing in the cued learning and discrimination learning tasks were conducted 2 weeks after ischaemia. Rats were euthanized after behavioural testing and the hippocampus was analysed for IGF‐1 level, IGF‐1 receptor (IGF‐1R) activation, protein kinase B (Akt) pathway activation, neurone loss and caspase 3 expression.

Results

Our data showed that EE housing: (1) mitigated ischaemia‐induced neuronal loss; (2) attenuated ischaemia‐induced increase in caspase 3 immunoreactivity in the hippocampus; (3) ameliorated ischaemia‐induced cognitive impairments; and (4) increased IGF‐1R activation and signalling through the Akt pathway after ischaemic injury.

Conclusion

Ultimately, these findings suggest the possibility that IGF‐1 signalling may be one of the underlying mechanisms involved in the beneficial effects of EE in optimizing recovery following cerebral ischaemic injury.
Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia‐response and RNA processing functions
Authors: Raman Rohini , Allen Scott P , Goodall Emily F , Kramer Shelley , Ponger Lize‐Linde , Heath Paul R. , Milo Marta , Hollinger Hannah C. , Walsh Theresa , Highley J Robin , Olpin Simon , McDermott Christopher J. , Shaw Pamela J. , Kirby Janine
Published: April 2014

Aims

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are two syndromic variants within the motor neurone disease spectrum. As PLS and most ALS cases are sporadic (SALS), this limits the availability of cellular models for investigating pathogenic mechanisms and therapeutic targets. The aim of this study was to use gene expression profiling to evaluate fibroblasts as cellular models for SALS and PLS, to establish whether dysregulated biological processes recapitulate those seen in the central nervous system and to elucidate pathways that distinguish the clinically defined variants of SALS and PLS.

Methods

Microarray analysis was performed on fibroblast RNA and differentially expressed genes identified. Genes in enriched biological pathways were validated by quantitative PCR and functional assays performed to establish the effect of altered RNA levels on the cellular processes.

Results

Gene expression profiling demonstrated that whilst there were many differentially expressed genes in common between SALS and PLS fibroblasts, there were many more expressed specifically in the SALS fibroblasts, including those involved in RNA processing and the stress response. Functional analysis of the fibroblasts confirmed a significant decrease in miRNA production and a reduced response to hypoxia in SALS fibroblasts. Furthermore, metabolic gene changes seen in SALS, many of which were also evident in PLS fibroblasts, resulted in dysfunctional cellular respiration.

Conclusions

The data demonstrate that fibroblasts can act as cellular models for ALS and PLS, by establishing the transcriptional changes in known pathogenic pathways that confer subsequent functional effects and potentially highlight targets for therapeutic intervention.
Loss of nuclear TDP‐43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones
Authors: Highley J. Robin , Kirby Janine , Jansweijer Joeri A. , Webb Philip S. , Hewamadduma Channa A. , Heath Paul R. , Higginbottom Adrian , Raman Rohini , Ferraiuolo Laura , Cooper‐Knock Johnathan , McDermott Christopher J. , Wharton Stephen B. , Shaw Pamela J. , Ince Paul G.
Published: April 2014

Aims

Loss of nuclear TDP‐43 characterizes sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP‐43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether (1) RNA splicing dysregulation is present in lower motor neurones in ALS and in a motor neurone‐like cell model; and (2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient‐derived fibroblasts.

Methods

Affymetrix exon arrays were used to study mRNA expression and splicing in lower motor neurones obtained by laser capture microdissection of autopsy tissue from individuals with sporadic ALS and TDP‐43 proteinopathy. Findings were confirmed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and in NSC34 motor neuronal cells following shRNA‐mediated TDP‐43 depletion. Exon arrays and immunohistochemistry were used to study mRNA splicing and TDP‐43 expression in fibroblasts from patients with mtTARDBP‐associated, sporadic and mutant SOD1‐associated ALS.

Results

We found altered expression of spliceosome components in motor neurones and widespread aberrations of mRNA splicing that specifically affected genes involved in ribonucleotide binding. This was confirmed in TDP‐43‐depleted NSC34 cells. Fibroblasts with mtTARDBP showed loss of nuclear TDP‐43 protein and demonstrated similar changes in splicing and gene expression, which were not present in fibroblasts from patients with sporadic or SOD1‐related ALS.

Conclusion

Loss of nuclear TDP‐43 is associated with RNA processing abnormalities in ALS motor neurones, patient‐derived cells with mtTARDBP, and following artificial TDP‐43 depletion, suggesting that splicing dysregulation directly contributes to disease pathogenesis. Key functional pathways affected include those central to RNA metabolism.
Mitochondrial and inflammatory changes in sporadic inclusion body myositis
Authors: Rygiel Karolina A. , Miller James , Grady John P. , Rocha Mariana C. , Taylor Robert W. , Turnbull Doug M.
Published: April 2014

Aims

Sporadic inclusion body myositis (sIBM) is the most common late onset muscle disease causing progressive weakness. In light of the lack of effective treatment, we investigated potential causes underlying muscle wasting. We hypothesized that accumulation of mitochondrial respiratory deficiency in muscle fibres may lead to fibre atrophy and degeneration, contributing to muscle mass reduction.

Methods

Histochemical and immunohistochemical analyses were performed on muscle biopsies from 16 sIBM patients to detect activity of mitochondrial enzymes and expression of mitochondrial respiratory chain proteins along with inflammatory markers respectively. Mitochondrial DNA mutations were assessed in single muscle fibres using real‐time PCR.

Results

We identified respiratory‐deficient fibres at different stages of mitochondrial dysfunction, with downregulated expression of complex I of mitochondrial respiratory chain being the initial feature. We detected mitochondrial DNA rearrangements in the majority of individual respiratory‐deficient muscle fibres. There was a strong correlation between number of T lymphocytes and macrophages residing in muscle tissue and the abundance of respiratory‐deficient fibres. Moreover, we found that respiratory‐deficient muscle fibres were more likely to be atrophic compared with respiratory‐normal counterparts.

Conclusions

Our findings suggest that mitochondrial dysfunction has a role in sIBM progression. A strong correlation between the severity of inflammation, degree of mitochondrial changes and atrophy implicated existence of a mechanistic link between these three parameters. We propose a role for inflammatory cells in the initiation of mitochondrial DNA damage, which when accumulated, causes respiratory dysfunction, fibre atrophy and ultimately degeneration of muscle fibres.
Immune‐mediated monofocal motor neuropathy: Report of two cases with long‐term follow up and review of six published cases
Authors: Adeyemo Bamidele O , Andriotakis James , Dreyer Michael , Pavlakis Pantelis P , Siao Peter
Published: April 2014

Background and Aim

There are rare cases of multifocal motor neuropathy (MMN) with single nerve involvement published. The aim of the present study was to describe two cases of MMN with single nerve involvement and long‐term follow up. The first consisted of an isolated wrist drop, which developed conduction block later in the course of the disease. The second presented with longstanding left thumb weakness and near complete radial conduction block. Both responded to intravenous immunoglobulin.

Methods

The clinical and electrodiagnostic findings of two cases with long–term follow up are discussed, and six cases published in the literature are reviewed.

Results

Both patients responded to intravenous immunoglobulin. One developed conduction block later in the course of the disease.

Conclusion

Monofocal motor neuropathy, a pure motor immune–mediated mononeuropathy, is a rare disorder, which responds to intravenous immunoglobulin. Although it might resemble MMN, some of its features lead us to consider it as a distinct entity.
Pain in the acute phase of Guillain–Barré syndrome
Authors: Kinboshi Masato , Inoue Manabu , Kojima Yasuhiro , Ono Michio , Nakagawa Tomokazu , Kanda Masutaro , Shibasaki Hiroshi
Published: April 2014

Background and Aim

Pain has not been recognized as a main feature of Guillain–Barré syndrome (GBS) in its acute phase. The pathophysiology of pain and its effect on the prognostic outcome of GBS have not been fully evaluated. The aim of the present study was to report the clinical features and prognosis of GBS patients presenting with pain in the acute phase.

Methods

This was a retrospective study of 34 consecutive patients with GBS. We compared clinical profiles and laboratory findings between the GBS patients with pain and those without pain.

Results

A total of 29% of GBS patients had pain in the acute phase. Among others, low back pain was most common. GBS patients with pain were significantly younger than those without pain. In GBS patients with pain, the time of admission, the time for starting treatment and the time of discharge from the hospital were significantly delayed as compared with those without pain. However, there was no difference in the preceding infections, laboratory findings, or disability at the time of nadir and discharge.

Conclusion

Pain is relatively common in the acute phase of GBS. Young GBS patients are especially susceptible to pain. Pain in the acute phase of GBS delays the time for reaching the correct diagnosis, and prolongs the duration of hospital stay and recovery, although it does not influence the functional prognosis.
Selenium deficiency presenting visual disturbance and myelopathy
Authors: Fujita Koji , Furukawa Takahiro , Matsuoka Takashi , Osaki Yusuke , Izumi Yuishin , Kaji Ryuji
Published: April 2014

The neurological features of selenium deficiency are poorly understood, and deserve more recognition for early diagnosis and treatment. Here, we report a 63‐year‐old parenteral nutrition‐dependent woman with Crohn's disease who presented with visual loss, myelopathy and macrocytic anemia. It was found that the selenium level was below the sensitivity limit in the serum. On selenium supplementation, which ameliorated anemia, her consciousness slightly improved, but vision and sensation did not. We suggest that visual disturbance and myelopathy after anemia can be warning signs of selenium deficiency.
Ultra‐early intravenous thrombolytic therapy for recurrent ischemic stroke after transient ischemic attack
Authors: Kobayashi Junpei , Ohara Tomoyuki , Sato Kazuaki , Uehara Toshiyuki , Minematsu Kazuo , Toyoda Kazunori
Published: April 2014

An 89‐year‐old woman was admitted to our stroke care unit because of transient ischemic attack caused by cardioembolic occlusion of the right internal carotid artery. She developed recurrent ischemic stroke shortly after hospitalization. She was very quickly treated with intravenous tissue plasminogen activator, because she had been just hospitalized, and had a favorable outcome. Earlier thrombolysis to patients with ischemic stroke is associated with better outcomes. Hospitalization in a stroke care unit is useful for close observation of patients with transient ischemic attack, and allows timely administration of tissue plasminogen activator.
Meralgia paresthetica secondary to abdominal desmoid tumor
Authors: Rattray Kyle , Schaeffer John
Published: April 2014

Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous nerve that supplies sensation to the anterolateral portion of the thigh. Compression of this nerve can lead to paresthesias and neuropathic pain. It is commonly associated with pregnancy, obesity, trauma or diabetes mellitus. Here we present a case of meralgia paresthetica in a 26‐year‐old woman secondary to nerve compression by a desmoid tumor within the internal oblique muscle tissue. Desmoid tumors are fibrous neoplasms originating from musculoaponeurotic structures, and can be locally aggressive and recurrent.
Expression of Niban in renal interstitial fibrosis
Authors: Liu Jishi , Qin Jiao , Mei Wenjuan , Zhang Hao , Yuan Qiongjing , Peng Zhangzhe , Luo Renna , Yuan Xiangning , Huang Ling , Tao Lijian
Published: April 2014

Aim

Apoptosis is one of the most important mechanisms underlying renal interstitial fibrosis. We identified the role of protein Niban in apoptosis of tumour cells. The purpose of this study was to assess the expression of Niban in renal interstitial fibrosis of humans and rats.

Methods

Immunohistochemistry was used to detect Niban in patients with obstructive nephropathy. Proteomics and gene array analysis were performed to screen different molecules involved in the pathophysiology of unilateral‐ureteral obstruction rats. We confirmed Niban using immunohistochemistry and Western blot in renal cortex of UUO rats and HK‐2 cells. TUNEL assay and flow cytometry revealed apoptosis of renal tubular cells. siRNA and overexpression plasmid were transfected specifically to study the possible function of Niban.

Results

Niban was decreased apparently in renal tubular cells of patients with obstructive nephropathy, compared with controls. Niban decreased in renal cortex of UUO rats and transforming growth factor‐β1 (TGF‐β1)‐stimulated HK‐2 cells. siRNA of Niban increased apoptosis of HK‐2 cells. TGF‐β1 also increased apoptosis of HK‐2 cells. Overexpression of Niban failed to diminish apoptosis of HK‐2 cells induced by TGF‐β1.

Conclusions

Niban decreased in renal tubular cells of patients of obstructive nephropathy, UUO rats and TGF‐β1 stimulated HK‐2 cells. Suppressing Niban increases apoptosis in HK‐2 cells. Niban may be associated with apoptosis of HK‐2 cells.
Nanomedicines: addressing the scientific and regulatory gap
Authors: Tinkle Sally , McNeil Scott E. , Mühlebach Stefan , Bawa Raj , Borchard Gerrit , Barenholz Yechezkel (Chezy) , Tamarkin Lawrence , Desai Neil
Published: April 2014

Nanomedicine is the application of nanotechnology to the discipline of medicine: the use of nanoscale materials for the diagnosis, monitoring, control, prevention, and treatment of disease. Nanomedicine holds tremendous promise to revolutionize medicine across disciplines and specialties, but this promise has yet to be fully realized. Beyond the typical complications associated with drug development, the fundamentally different and novel physical and chemical properties of some nanomaterials compared to materials on a larger scale (i.e., their bulk counterparts) can create a unique set of opportunities as well as safety concerns, which have only begun to be explored. As the research community continues to investigate nanomedicines, their efficacy, and the associated safety issues, it is critical to work to close the scientific and regulatory gaps to assure that nanomedicine drives the next generation of biomedical innovation.
Determination of optimum time for intravenous cannulation after induction with sevoflurane and nitrous oxide in children premedicated with midazolam
Authors: Kilicaslan Alper , Gök Funda , Erol Atilla , Okesli Selmin , Sarkilar Gamze , Otelcioglu Şeref
Published: April 2014

Background

It has been shown that early placement of an intravenous line in children administered sevoflurane anesthesia increased the incidence of laryngospasm and movement. However, the optimal time for safe cannulation after the loss of the eyelash reflex during the administration of sevoflurane and nitrous oxide is not known.

Aim

The aim of the study was to determine the optimum time for intravenous cannulation after the induction of anesthesia with sevoflurane and nitrous oxide in children premedicated with oral midazolam.

Method

We performed a prospective, observer‐blinded, up–down sequential, allocation study, and children, aged 2–6 years, ASA physical status I, scheduled for an elective procedure undergoing inhalational induction were included in the study. Anesthesia was induced with sevoflurane and nitrous oxide after premedication with oral midazolam. For the first child, 4 min after the loss of the eyelash reflex, the intravenous cannulation was attempted by an experienced anesthesiologist. The time for intravenous cannulation was considered adequate if movement, coughing, or laryngospasm did not occur. The time for cannulation was increased by 15 s if the time was inadequate in the previous patient, and conversely, the time for cannulation was decreased by 15 s if the time was adequate in the previous patient. The probit test was used in the analysis of up–down sequences.

Results

A total of 32 children were enrolled sequentially during the study period. The adequate time for effective intravenous cannulation after induction with sevoflurane and nitrous oxide in 50% and 95% of patients were 1.29 min (95% confidence interval, 0.96–1.54 min) and 1.86 min (95% confidence interval 1.58–4.35 min), respectively.

Conclusion

We recommend waiting 2 min for attempting intravenous placement following the loss of the eyelash reflex in children sedated with midazolam and receiving an inhalation induction with sevoflurane and nitrous oxide.
Effectiveness and Tolerability of a Moderate Dose of Tapentadol Prolonged Release for Managing Severe, Chronic Low Back Pain with a Neuropathic Component: An Open‐label Continuation Arm of a Randomized Phase 3b Study
Authors: Baron Ralf , Kern Uwe , Müller Matthias , Dubois Cecile , Falke Dietmar , Steigerwald Ilona
Published: April 2014

Objective

To evaluate the effectiveness and tolerability of tapentadol prolonged release (PR) for severe, chronic low back pain with a neuropathic component in a subpopulation that achieved adequate pain relief with tapentadol PR 300 mg/day in a randomized, double‐blind, phase 3b study.

Methods

Patients with painDETECT “unclear” or “positive” ratings and pain intensity ≥ 6 (11‐point NRS‐3 [average 3‐day pain intensity]) were titrated to tapentadol PR 300 mg/day over 3 weeks. A subpopulation with pain intensity < 4 continued receiving tapentadol PR 300 mg/day during an 8‐week, open‐label continuation arm. For the primary study population, patients with ≥ 1‐point decrease from baseline and pain intensity ≥ 4 were randomized to tapentadol PR 500 mg/day or tapentadol PR 300 mg/day plus pregabalin 300 mg/day during a concurrent 8‐week, double‐blind comparative period.

Results

From baseline to end of titration and to final evaluation, significant improvements were observed in pain intensity (mean [SD] changes from baseline to: end of titration; − 5.3 [1.78]; final evaluation; − 5.2 [2.39]; both P < 0.0001), neuropathic pain symptoms, and quality‐of‐life measures in the open‐label continuation arm, with greater improvements in this selected subpopulation than in either group in the primary study population. A favorable tolerability profile was observed, with incidences of all individual treatment‐emergent adverse events ≤ 5.1% during the continuation period.

Conclusions

A subpopulation of patients with low back pain with a neuropathic component responded very well to tapentadol PR 300 mg/day, with significant improvements in pain intensity, neuropathic pain‐related symptoms, and quality of life. Further research is needed to identify factors associated with a very positive treatment response.
On the Role of Exponential Smoothing in Circadian Dosimetry
Authors: Price Luke L. A.
Published: April 2014

The effects lighting has on health through modulation of circadian rhythms are becoming increasingly well documented. Data are still needed to show how light exposures are influenced by architecture and lighting design and circadian dosimetry analyses should provide duration, phase and amplitude measures of 24 h exposure profiles. Exponential smoothing is used to derive suitable metrics from 24 h light measurements collected from private dwellings. A further application of these modified exposure time series as physiological models of the light drive is discussed. Unlike previous light drive models, the dose rate persists into periods of darkness following exposures. Comparisons to long duration exposure studies suggest this type of persistent light drive model could be incorporated into contemporary physiological models of the human circadian oscillator.
Inclusion of urea in a 59FeEDTA solution stimulated leaf penetration and translocation of 59Fe within wheat plants
Authors: Aciksoz Seher Bahar , Ozturk Levent , Yazici Atilla , Cakmak Ismail
Published: April 2014

The role of urea in the translocation of 59Fe from 59FeEDTA‐treated leaves was studied in durum wheat (Triticum durum) grown for 2 weeks in nutrient solution and until grain maturation in soil culture. Five‐cm long tips of the first leaf of young wheat seedlings or flag leaves at the early milk stage were immersed twice daily for 10 s in 59FeEDTA solutions containing increasing amounts of urea (0, 0.2, 0.4 and 0.8% w/v) over 5 days. In the experiment with young wheat seedlings, urea inclusion in the 59FeEDTA solution increased significantly translocation of 59Fe from the treated leaf into roots and the untreated part of shoots. When 59Fe‐treated leaves were induced into senescence by keeping them in the dark, there was a strong 59Fe translocation from these leaves. Adding urea to the 59Fe solution did not result in an additional increase in Fe translocation from the dark‐induced senescent leaves. In the experiment conducted in the greenhouse in soil culture until grain maturation, translocation of 59Fe from the flag leaves into grains was also strongly promoted by urea, whereas 59Fe translocation from flag leaves into the untreated shoot was low and not affected by urea. In conclusion, urea contributes to transportation of the leaf‐absorbed Fe into sink organs. Probably, nitrogen compounds formed after assimilation of foliar‐applied urea (such as amino acids) contributed to Fe chelation and translocation to grains in wheat.
Sterol partitioning by HMGR and DXR for routing intermediates toward withanolide biosynthesis
Authors: Singh Shefali , Pal Shaifali , Shanker Karuna , Chanotiya Chandan Singh , Gupta Madan Mohan , Dwivedi Upendra Nath , Shasany Ajit Kumar
Published: April 2014

Withanolides biosynthesis in the plant Withania somnifera (L.) Dunal is hypothesized to be diverged from sterol pathway at the level of 24‐methylene cholesterol. The conversion and translocation of intermediates for sterols and withanolides are yet to be characterized in this plant. To understand the influence of mevalonate (MVA) and 2‐C‐methyl‐d‐erythritol‐4‐phosphate (MEP) pathways on sterols and withanolides biosynthesis in planta, we overexpressed the WsHMGR2 and WsDXR2 in tobacco, analyzed the effect of transient suppression through RNAi, inhibited MVA and MEP pathways and fed the leaf tissue with different sterols. Overexpression of WsHMGR2 increased cycloartenol, sitosterol, stigmasterol and campesterol compared to WsDXR2 transgene lines. Increase in cholesterol was, however, marginally higher in WsDXR2 transgenic lines. This was further validated through transient suppression analysis, and pathway inhibition where cholesterol reduction was found higher due to WsDXR2 suppression and all other sterols were affected predominantly by WsHMGR2 suppression in leaf. The transcript abundance and enzyme analysis data also correlate with sterol accumulation. Cholesterol feeding did not increase the withanolide content compared to cycloartenol, sitosterol, stigmasterol and campesterol. Hence, a preferential translocation of carbon from MVA and MEP pathways was found differentiating the sterols types. Overall results suggested that MVA pathway was predominant in contributing intermediates for withanolides synthesis mainly through the campesterol/stigmasterol route in planta.
What is and what could have been: An ERP study on counterfactual comparisons
Authors: Osinsky Roman , Walter Helen , Hewig Johannes
Published: April 2014

Prior research indicates that the feedback‐related negativity (FRN) reflects a good versus bad evaluation of decision outcomes, which is insensitive to the local utilitarian relation between chosen and unchosen outcomes. We tested whether this negative finding holds when the chosen outcome has an objective value of zero and therefore a comparison with the unchosen outcome is needed to identify overall choice valence. Participants completed a gambling task in which chosen and unchosen options could result in monetary wins, losses, or breaking even. Results show that the FRN does not reflect local favorableness but rather a dichotomy of gain versus no‐gain for both chosen and unchosen outcomes. In contrast, P300 amplitude appears to reflect motivational salience derived from counterfactual comparisons of chosen and unchosen outcomes. Based on our and prior findings, we propose a threefold taxonomy of contextual factors and their relation to the FRN.
Localization and overseas R&D activity: the case of Taiwanese multinational enterprises in China
Authors: Yang Chih‐Hai , Hayakawa Kazunobu
Published: April 2014

This study investigates the determinants of overseas research and development (R&D) and the influences of various aspects of localization on affiliates' R&D intensity. Using a dataset of Taiwanese multinational enterprises (MNEs) in China, the empirical estimations find that MNEs with a larger firm size, more R&D expenditure, and a higher outward foreign direct investments intensity tend to undertake R&D. Host regions' characteristics, particularly market size and R&D resources, do matter for attracting MNEs to conduct R&D locally. Crucially, affiliates' R&D intensity is related to the degree of localization. The degree of market localization and localization of the R&D network has a positive association with affiliates' R&D intensity. From the perspective of R&D policy, a country with healthy R&D infrastructures helps attract the establishment of R&D labs of MNEs.
Communities and managerial competencies supporting SMEs innovation networking: a longitudinal case study
Authors: Muzzi Caterina , Albertini Sergio
Published: April 2014

Over the last few decades, the need for small and medium‐sized enterprises (SMEs) to rely on networking to get access to innovation and larger knowledge bases has become evident. This paper analyzes the birth and evolution of an Italian innovation community created by a group of SMEs searching for innovation. Coming from quite different fields, these SMEs converged around a challenging project in the field of biomedical and rehabilitation devices. The aim of the paper is twofold: (1) to investigate what type of competences and tasks have to be accomplished to effectively manage an innovation community (IC) and what managerial roles (promotors) emerge by crossing competences and tasks; and (2) to what extent community members' absorptive capacity (ACAP) influences their ability to acquire and exploit innovation generated by the community. Using an in‐depth longitudinal case study analysis, we identified three different stages in community evolution. We also studied which promotors' roles that emerged in each stage and determined their relationship both between each other and to community performance. Furthermore, we investigated to what extent an existing knowledge base in a specific domain and previous experiences in networking influenced community members' ability to exploit innovation. We found that a specific correspondence among competences and tasks is needed to guarantee community performance and that promotors should interact among themselves to enable the community to reach its goal. Concerning ACAP, we found that prior experience and familiarity in networking are not predictive of new knowledge exploitation.
The work motivation of research scientists and its effect on research performance
Authors: Ryan James C.
Published: April 2014

This research examines the work motivation profile of research scientists and the effect of work motivation on research performance. A sample of United Kingdom‐based research scientists (N = 405) working in the chemical, biological and biomedical research domains took part in the study. Participants completed a survey based measure of motivational sources and self‐report research performance evaluation. The motivational sources of internal self‐concept motivation and instrumental motivation were found to be the strongest and weakest respectively for research scientists. External self‐concept motivation was found to be significantly higher among younger scientists. No gender differences were found in the motivational profile of scientists. While controlling for the influences of age and gender, internal self‐concept motivation was found to have a significant positive effect on research performance, and instrumental motivation was found to have a significant negative effect on research performance. Consistent with prior research, differences in research performance across age and gender were also identified. The implications of these findings for our understanding of the effective management of scientific research are discussed.
Understanding commercialization of technological innovation: taking stock and moving forward
Authors: Datta Avimanyu , Mukherjee Debmalya , Jessup Len
Published: April 2014

The commercialization of technological innovation, which is key to entrepreneurial success, represents a combination of several entrepreneurial activities. Building on research in management, strategy, entrepreneurship, and economics, this research summarizes 194 articles from 62 journals, categorizing them into six broad entrepreneurial activity themes: sources of innovations, types of innovation, market entry competence and feasibility, protection, development, and deployment. This review and synthesis suggest a framework of commercialization and an agenda for future research along with recommendations and guidance for future research. The proposed agenda provides topics and research questions for research, as well as related recommendations regarding the study and practice of the commercialization of innovation.
Knowing Other People: A Second‐Person Framework
Authors: Talbert Bonnie M.
Published: April 2014

What does it mean to know another person, and how is such knowledge different from other kinds of knowledge? These questions constitute an important part of what I call ‘second‐person epistemology’ – the study of how we know other people. I claim that knowledge of other people is not only central to our everyday lives, but it is a kind of knowledge that is unlike other kinds of knowledge. In general, I will argue that second‐person knowledge arises from repeated interactions with another person, and that it also requires employment of certain cognitive abilities and a unique kind of second‐order knowledge.

This paper provides the framework for a second‐person epistemology by examining some of our ordinary claims about what it means to know another person. I describe four conditions that typically characterize knowing another person. Then I describe the psychological grounds of knowing a person. Finally, I conclude with some thoughts about the unique symmetries of second person knowledge and the role of such knowledge in our broader epistemological endeavours.
Integrated Evaluation of Scrotal Temperature and Testosteronemia after GnRH Administration in Young Bulls with Low Semen Production
Authors: Vencato J , Cestaro L , Vazzana I , Carrer G , Carlo E , Dara S , Stelletta C
Published: April 2014

Contents

The aim of this study was to determine the suitability of thermographic monitoring of scrotal surface temperature (SST) as a method to monitor testicular function. Yearling bulls (n = 23) with low semen production were selected. Scrotal surface temperature and serum testosterone (T) concentrations were evaluated before and after administration of 10.5 μg buserelin acetate IV. Thermographic images of scrotum were recorded at 0, 15, 30, 45 and 60 min post‐GnRH, while blood sampling was only performed at 60 min post‐GnRH. Bulls were divided in two groups: LowTemp bulls (n = 10) had a decreased SST at 60 min; HighTemp bulls (n = 13) had an increased SST. After 60 min, LowTemp bulls had higher T concentrations compared to HighTemp bulls: 14.32 ng/ml ± 0.53 vs 10.30 ± 1.37 ng/ml (mean ± SEM; p < 0.05), respectively. Reproductive performances in both groups improved after GnRH administration, resulting in an increased number of inseminating doses from each collection, which was higher in LowTemp bulls. Pearson correlation test showed a negative relationship between T and SST (r = −0.554). In conclusion, a decreased scrotal surface temperature 60 min after GnRH treatment was associated with improved semen production.