bluuebunny/crossref_metadata_2025 huggingface dataset:
Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients?
Authors: Brandi Giovanni , de Rosa Francesco , Calzà Laura , Girolamo Stefania Di , Tufoni Manuel , Ricci Carmen Serena , Cirignotta Fabio , Caraceni Paolo , Biasco Guido
Published: December 2012

Background

Sorafenib is the standard treatment of advanced hepatocarcinoma (HCC) in cirrhotic patients with preserved liver function. It shares many adverse effects with other tyrosine‐kinase (TK) inhibitors and antiangiogenic drugs. TK inhibitors could have a direct toxicity on CNS, both by interfering with TK‐related pathways and by inhibiting angiogenesis.

Aims

The aim of this study was to investigate whether sorafenib administration can be associated to metabolic encephalopathy in patients with cirrhosis.

Methods

We retrospectively reviewed medical records of all cirrhotic patients treated with sorafenib for HCC afferent at our Department from January 2009 to December 2011.

Results

Among 62 patients, we identified 10 patients with clinically significant cognitive impairment. Seven of these were clearly diagnosed with overt hepatic encephalopathy (HE), one with brain metastases and two with drug‐related toxic‐metabolic encephalopathy. These last two cases were characterized by severe cognitive impairment, mood alteration and memory deficit. Clinical exam, blood tests and brain CT excluded organic causes of encephalopathy and precipitating factors of HE. Sorafenib discontinuation was associated with complete reversal of the syndrome, which recurred on drug re‐administration in one case.

Conclusions

Our study suggests that sorafenib may be a precipitating factor of metabolic encephalopathy in cirrhotic patients with advanced HCC. This neurological syndrome appears to be not responsive to the conventional treatment for HE, but it is fully reversible by drug discontinuation. It can be speculated that the potential direct neuronal action of sorafenib may represent a trigger for the onset of metabolic encephalopathy in a subset of cirrhotic patients.
Second primary cancers in patients with hepatocellular carcinoma: a nationwide cohort study in Taiwan
Authors: Wu Wen‐Chieh , Chen Yung‐Tai , Hwang Chian‐Yaw , Su Chien‐Wei , Li Szu‐Yuan , Chen Tzeng‐Ji , Liu Chia‐Jen , Kao Wei‐Yu , Chao Yee , Lin Han‐Chieh , Wu Jaw‐Ching
Published: December 2012

Background

There has been no large‐scale population‐based study on the incidence and clinical manifestations of second primary cancer (SPC) after diagnosis of hepatocellular carcinoma (HCC).

Aims

This study aimed to evaluate the incidence and the risk factors of SPC following HCC diagnosis.

Method

This study used data from the National Health Insurance Research Database of Taiwan to identify all HCC patients from 1 January 1997 to 31 December 2006. Cases of SPC were gathered using the ICD9‐CM codes of 140–208.91. Standardized incidence ratios (SIRs) were conducted for incidence of SPC in HCC survivors. Competing‐risks regression with adjustment of death was used to analyse the risk factors of SPC.

Results

From 45 976 HCC patients, 749 (1.6%) developed SPC after 90 days of HCC diagnosis. Male HCC patients had higher risks of gastric, biliary, urinary bladder, kidney and haematological cancers compared to the general male population. Female patients had higher incidences of biliary tract, kidney and bone and soft tissue cancers. Older age and chronic kidney disease (CKD) were independent factors predicting SPC.

Conclusions

SPC in patients with HCC is not rare in Taiwan. Urinary bladder cancer and renal cancer are more specific SPC for HCC patients. Better surveillance strategies for SPC should be established for HCC survivors, especially in the elderly or those with CKD.
A novel approach to parasite population genetics: Experimental infection reveals geographic differentiation, recombination and host‐mediated population structure in Pasteuria ramosa, a bacterial parasite of Daphnia
Authors: Andras J. P. , Ebert D.
Published: December 2012

The population structure of parasites is central to the ecology and evolution of host‐parasite systems. Here, we investigate the population genetics of Pasteuria ramosa, a bacterial parasite of Daphnia. We used natural P. ramosa spore banks from the sediments of two geographically well‐separated ponds to experimentally infect a panel of Daphnia magna host clones whose resistance phenotypes were previously known. In this way, we were able to assess the population structure of P. ramosa based on geography, host resistance phenotype and host genotype. Overall, genetic diversity of P. ramosa was high, and nearly all infected D. magna hosted more than one parasite haplotype. On the basis of the observation of recombinant haplotypes and relatively low levels of linkage disequilibrium, we conclude that P. ramosa engages in substantial recombination. Isolates were strongly differentiated by pond, indicating that gene flow is spatially restricted. Pasteuria ramosa isolates within one pond were segregated completely based on the resistance phenotype of the host—a result that, to our knowledge, has not been previously reported for a nonhuman parasite. To assess the comparability of experimental infections with natural P. ramosa isolates, we examined the population structure of naturally infected D. magna native to one of the two source ponds. We found that experimental and natural infections of the same host resistance phenotype from the same source pond were indistinguishable, indicating that experimental infections provide a means to representatively sample the diversity of P. ramosa while reducing the sampling bias often associated with studies of parasite epidemics. These results expand our knowledge of this model parasite, provide important context for the large existing body of research on this system and will guide the design of future studies of this host‐parasite system.
Progressive genome‐wide introgression in agricultural Campylobacter coli
Authors: Sheppard Samuel K. , Didelot Xavier , Jolley Keith A. , Darling Aaron E. , Pascoe Ben , Meric Guillaume , Kelly David J. , Cody Alison , Colles Frances M. , Strachan Norval J. C. , Ogden Iain D. , Forbes Ken , French Nigel P. , Carter Philip , Miller William G. , McCarthy Noel D. , Owen Robert , Litrup Eva , Egholm Michael , Affourtit Jason P. , Bentley Stephen D. , Parkhill Julian , Maiden Martin C. J. , Falush Daniel
Published: December 2012

Hybridization between distantly related organisms can facilitate rapid adaptation to novel environments, but is potentially constrained by epistatic fitness interactions among cell components. The zoonotic pathogens Campylobacter coli and C. jejuni differ from each other by around 15% at the nucleotide level, corresponding to an average of nearly 40 amino acids per protein‐coding gene. Using whole genome sequencing, we show that a single C. coli lineage, which has successfully colonized an agricultural niche, has been progressively accumulating C. jejuni DNA. Members of this lineage belong to two groups, the ST‐828 and ST‐1150 clonal complexes. The ST‐1150 complex is less frequently isolated and has undergone a substantially greater amount of introgression leading to replacement of up to 23% of the C. coli core genome as well as import of novel DNA. By contrast, the more commonly isolated ST‐828 complex bacteria have 10–11% introgressed DNA, and C. jejuni and nonagricultural C. coli lineages each have <2%. Thus, the C. coli that colonize agriculture, and consequently cause most human disease, have hybrid origin, but this cross‐species exchange has so far not had a substantial impact on the gene pools of either C. jejuni or nonagricultural C. coli. These findings also indicate remarkable interchangeability of basic cellular machinery after a prolonged period of independent evolution.
The simulation game: an analysis of interactions between students and simulated patients
Authors: de la Croix Anne , Skelton John
Published: December 2012

Context Institutional interactions are often asymmetrical in that the professional has more control over the conversation. It is difficult to say who the professional is in simulated consultations between simulated patients (SPs) and medical students because these feature a real (educational) institutional context and a simulated (medical) institutional context. This study describes this asymmetry and makes educational recommendations based on the description.

Methods One hundred assessed conversations between SPs and Year 3 students were transcribed and analysed using discourse analysis (DA). We aimed to find linguistic patterns in predefined parts of the conversations (questions, topic initiations, openings, closings) that might suggest conversational dominance.

Results The SP is conversationally more dominant, despite performing the role of the patient, in that he or she asks more direct questions, is more likely to initiate topics, is more likely not to follow topic changes by students, and closes the consultation. The student is likely to follow topics initiated by the SP and to seek permission to pre‐close the consultation.

Conclusions The apparently greater dominance of the SP indicates that the simulated consultation differs from the doctor–patient consultation in certain key aspects. It is in that sense unrealistic. We argue, however, that ‘realism’ ought not to be a goal of simulated consultation and that what matters is that such consultations are sufficiently realistic for their educational purpose. We discuss the educational implications that follow from this.
Stoichiometry and perturbation studies of the LiaFSR system of Bacillus subtilis
Authors: Schrecke Karen , Jordan Sina , Mascher Thorsten
Published: December 2012

The response regulator/histidine kinase pair LiaRS of Bacillus subtilis, together with its membrane‐bound inhibitor protein LiaF, constitutes an envelope stress‐sensing module that is conserved in Firmicutes bacteria. LiaR positively autoregulates the expression of the liaIH‐liaGFSR operon from a strictly LiaR‐dependent promoter (PliaI). A comprehensive perturbation analysis revealed that the functionality of the LiaFSR system is very susceptible to alterations of its protein composition and amounts. A genetic analysis indicates a LiaF:LiaS:LiaR ratio of 18:4:1. An excess of LiaS over LiaR was subsequently verified by quantitative Western analysis. This stoichiometry, which is crucial to maintain a functional Lia system, differs from any other two‐component system studied to date, in which the response regulator is present in excess over the histidine kinase. Moreover, we demonstrate that LiaS is a bifunctional histidine kinase that acts as a phosphatase on LiaR in the absence of a suitable stimulus. An increased amount of LiaR – both in the presence and in the absence of LiaS – leads to a strong induction of PliaI activity due to phosphorylation of the response regulator by acetyl phosphate. Our data demonstrate that LiaRS, in contrast to other two‐component systems, is non‐robust with regard to perturbations of its stoichiometry.
Membrane sequestration by the EIIB domain of the mannitol permease MtlA activates the Bacillus subtilismtl operon regulator MtlR
Authors: Bouraoui Houda , Ventroux Magali , Noirot‐Gros Marie‐Françoise , Deutscher Josef , Joyet Philippe
Published: December 2012

In most firmicutes expression of the mannitol operon is regulated by MtlR. This transcription activator is controlled via phosphorylation of its regulatory domains by components of the phosphoenolpyruvate : carbohydrate phosphotransferase system (PTS). We found that activation of Bacillus subtilis MtlR also requires an interaction with the EIIBMtl domain of the mannitol permease MtlA (EIICBMtl). The constitutive expression of the mtlAFD operon in an mtlF mutant was prevented when entire mtlA or only its 3′ part (EIIBMtl) were deleted. Yeast two‐hybrid experiments revealed a direct interaction of the EIIBMtl domain with the two C‐terminal domains of MtlR. Complementation of the Δ3′‐mtlA ΔmtlF or ΔmtlAFD mutants with mtlA restored constitutive MtlR activity, whereas complementation with only 3′‐mtlA had no effect. Moreover, synthesis of EIIBMtl in strains producing constitutively active MtlR caused MtlR inactivation. Interestingly, EIIBMtl fused to the trans‐membrane protein YwqC restored constitutive MtlR activity in the above mutants. Replacing the phosphorylatable Cys with Asp in MtlA or soluble EIIBMtl lowered MtlR activation, indicating that MtlR does not interact with phosphorylatyed EIIBMtl. Induction of the B. subtilis mtl operon therefore follows a novel regulation mechanism where the transcription activator needs to be sequestered to the membrane by unphosphorylated EIICBMtl in order to be functional.
The C‐terminal portion of the cleaved HT motif is necessary and sufficient to mediate export of proteins from the malaria parasite into its host cell
Authors: Tarr Sarah J. , Cryar Adam , Thalassinos Konstantinos , Haldar Kasturi , Osborne Andrew R.
Published: December 2012

The malaria parasite exports proteins across its plasma membrane and a surrounding parasitophorous vacuole membrane, into its host erythrocyte. Most exported proteins contain a Host Targeting motif (HT motif) that targets them for export. In the parasite secretory pathway, the HT motif is cleaved by the protease plasmepsin V, but the role of the newly generated N‐terminal sequence in protein export is unclear. Using a model protein that is cleaved by an exogenous viral protease, we show that the new N‐terminal sequence, normally generated by plasmepsin V cleavage, is sufficient to target a protein for export, and that cleavage by plasmepsin V is not coupled directly to the transfer of a protein to the next component in the export pathway. Mutation of the fourth and fifth positions of the HT motif, as well as amino acids further downstream, block or affect the efficiency of protein export indicating that this region is necessary for efficient export. We also show that the fifth position of the HT motif is important for plasmepsin V cleavage. Our results indicate that plasmepsin V cleavage is required to generate a new N‐terminal sequence that is necessary and sufficient to mediate protein export by the malaria parasite.
Obesity and its relation to chronic kidney disease: A population‐based, cross‐sectional study of a Thai army population and relatives
Authors: Satirapoj Bancha , Supasyndh Ouppatham , Mayteedol Natee , Punpanich Dollapas , Chaiprasert Amnart , Nata Naowanit , Ruangkanchanasetr Prajej , Kanjanakul Inseey , Choovichian Panbubpa
Published: December 2012

Aim

Obesity represents a significant problem in patients with cardiovascular disease and chronic kidney disease (CKD). The aim of the present study was to investigate the association between body mass index (BMI) and CKD in Thai individuals.

Methods

Participants underwent general health screening. Overweight, weight at risk, obese I and obese II were defined as having a BMI ≥23 kg/m2, 23–24.9 kg/m2, 25–29.9 kg/m2 and ≥30 kg/m2, respectively. Waist circumference ≥ 90 cm for men and > 80 cm for women were represented by abdominal obesity. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min per 1.73 m2. An estimate of the GFR was obtained by the four‐variable Modification of Diet in Renal Disease (MDRD) equation.

Results

The study population had 12 348 males and 3009 females. The survey population had a 7.5% prevalence of CKD. There was also a significant graded relationship between the degrees of overweight with the prevalence of CKD. Mean BMI were 25.36 ± 3.29 kg/m2 for CKD subjects and 24.04 ± 3.13 kg/m2 for non‐CKD subjects (P < 0.001). Prevalence of overweight and abdominal obesity in the participants with CKD were found to be higher than in those without CKD (overweight, 77.6% vs. 61.6%, P < 0.001; abdominal obesity, 35.7% vs. 25.3%, P < 0.001). In a multivariate logistic regression analysis, weight at risk (adjusted odds ratio 1.29; 95% CI 1.07–1.54), obese I (adjusted odds ratio 1.58; 95% CI 1.33–1.87) and obese II (adjusted odds ratio 1.65; 95% CI 1.24–2.19) were associated with CKD.

Conclusion

Our data showed that overweight and obesity were associated with CKD in Thai members of the army population and their relatives undergoing a general health screening, independently of age, gender, blood pressure, serum lipid, uric acid and glucose levels.
Malignant peripheral nerve sheath tumor of the trigeminal nerve: Clinicopathologic features in a young adult patient
Authors: Nakayama Yoko , Watanabe Masatoshi , Suzuki Kenji , Usuda Hiroyuki , Emura Iwao , Ogura Ryosuke , Shiga Atsushi , Toyoshima Yasuko , Takahashi Hitoshi , Kawaguchi Tadashi , Kakita Akiyoshi
Published: December 2012

Malignant peripheral nerve sheath tumors (MPNSTs) arising from cranial nerves are rare and usually affect adults. Here we report the clinicopathologic features of a young adult patient with a trigeminal nerve MPNST, in whom another tumor involving the oculomotor nerve on the contralateral side was evident. The patient, an 18‐year‐old woman, had suffered recurrent paroxysmal sharp stabbing pain over her cheek and forehead on the right side for 1 month. A brain MRI study disclosed a mass, 35 mm in diameter, in the right Meckel's cave, and another mass, 10 mm in diameter, involving the intracranial portion of the left oculomotor nerve. Following gadolinium administration, the former and latter tumors exhibited strong and weak enhancement, respectively. The patient had no clinical stigmata characteristic of neurofibromatosis type 1. Following a tentative diagnosis of schwannoma, total resection of the trigeminal nerve tumor was performed. Histologically, the tumor consisted of highly cellular, spindle‐shaped cells arranged in a fascicular pattern, with occasional mitotic figures, nuclear pleomorphism and necrosis. Immunohistochemically, the tumor cells showed variable intensities and frequencies of reactivity for S‐100 protein, myelin basic protein, CD34, podoplanin and p53, but no reactivity for Smarcb1. Thus, the tumor exhibited features of MPNST. This case appears to provide information that is useful for accurate diagnosis and surgical planning in patients with bilateral or multiple cranial nerve tumors.
Epstein‐Barr virus‐associated primary central nervous system cytotoxic T‐cell lymphoma
Authors: Ogura Ryosuke , Aoki Hiroshi , Natsumeda Manabu , Shimizu Hiroshi , Kobayashi Tsutomu , Saito Tomohisa , Takizawa Jun , Okamoto Kouichirou , Hasegawa Go , Umezu Hajime , Ohshima Kouichi , Takahashi Hitoshi , Fujii Yukihiko , Kakita Akiyoshi
Published: December 2012

Primary central nervous system lymphoma (PCNSL) expressing T‐cell markers is rare, among which nasal‐type extranodal NK/T‐cell lymphoma is an extremely rare subtype associated with Epstein‐Barr virus (EBV) infection. Here we report the clinicopathologic features of a case of EBV‐associated PCNSL showing a cytotoxic T‐cell phenotype. The patient, a 73‐year‐old woman, presented with rapidly progressive mental deterioration. Brain MRI revealed multiple lesions with swelling in the bilateral cerebral hemispheres, which were hypointense on T1‐weighted images, hyperintense on T2‐weighted and fluid‐attenuated inversion recovery images, and slightly hyperintense on diffusion‐weighted images. Biopsy specimens from the temporal region showed many medium‐sized anaplastic lymphocytic cells with perivascular and angio‐invasive patterns in the cortex. Immunohistochemically, the cells were positive for CD3, CD8, T‐cell‐restricted intracellular antigen‐1 (TIA‐1), granzyme B and perforin, but negative for CD56 and CD20. In situ hybridization revealed EBV‐encoded RNAs in the tumor cell nuclei. A rearrangement study showed T‐cell receptor γ–chain gene rearrangement with a clonal appearance. The patient died 6 months after surgery, and a general autopsy revealed no lymphoma cells outside the brain. These cellular profiles are inconsistent with those of extranodal NK/T‐cell lymphoma, and have not been previously described. This case appears to represent an unusual CNS manifestation of EBV‐associated T‐cell lymphoma.
Primary granulomatous angiitis of the CNS preferentially involving small veins with a granulomatous leukoencephalitis‐like lesion in the cerebrum
Authors: Okeda Riki , Ito Keisuke , Tsumura Koutaro , Eishi Yoshinobu
Published: December 2012

We have reported an autopsy case of primary granulomatous angiitis of the CNS preferentially involving the small veins with a granulomatous leukoencepalitis‐like lesion in the cerebral white matter of a 48‐year‐old man. The latter lesion was ischemic necrosis due to circumferential multiple perivenous granulomas in the adjacent Virchow‐Robin space. Multifocal progressive involvement of venular adventitia by granulomas, leaving behind mural fibrosis and luminal stenosis, was related clinically to the prolonged stepwise deterioration observed in the patient, and pathologically to diffuse loosening with dilated veins in the deep cerebral white matter and subcortical hemorrhagic infarction in the left parietal lobe through chronic venous stagnation. PCR demonstrated negativity for Mycobacterium tuberculosis and Propionibacterium acnes, and in situ hybridization with EBV‐encoded small nuclear RNA probe was also negative. The possibility of subarachnoidal latent infection with an unknown avirulent agent causing exclusively perivascular granulomas is proposed. It will be necessary to examine by autopsy whether the type (artery or vein) and size of the involved vessels and the pathological subtype of angiitis is related to the etiopathogenesis and prognosis. It is also pointed out that the entity of lymphocytic angiitis is problematic.
Populus trichocarpa cell wall chemistry and ultrastructure trait variation, genetic control and genetic correlations
Authors: Porth Ilga , Klápště Jaroslav , Skyba Oleksandr , Lai Ben S. K. , Geraldes Armando , Muchero Wellington , Tuskan Gerald A. , Douglas Carl J. , El‐Kassaby Yousry A. , Mansfield Shawn D.
Published: December 2012

The increasing ecological and economical importance of Populus species and hybrids has stimulated research into the investigation of the natural variation of the species and the estimation of the extent of genetic control over its wood quality traits for traditional forestry activities as well as the emerging bioenergy sector. A realized kinship matrix based on informative, high‐density, biallelic single nucleotide polymorphism (SNP) genetic markers was constructed to estimate trait variance components, heritabilities, and genetic and phenotypic correlations.

Seventeen traits related to wood chemistry and ultrastructure were examined in 334 9‐yr‐old Populus trichocarpa grown in a common‐garden plot representing populations spanning the latitudinal range 44° to 58.6°. In these individuals, 9342 SNPs that conformed to Hardy–Weinberg expectations were employed to assess the genomic pair‐wise kinship to estimate narrow‐sense heritabilities and genetic correlations among traits.

The range‐wide phenotypic variation in all traits was substantial and several trait heritabilities were > 0.6. In total, 61 significant genetic and phenotypic correlations and a network of highly interrelated traits were identified.

The high trait variation, the evidence for moderate to high heritabilities and the identification of advantageous trait combinations of industrially important characteristics should aid in providing the foundation for the enhancement of poplar tree breeding strategies for modern industrial use.
Polymorphic simple sequence repeat (SSR) loci within cellulose synthase (PtoCesA) genes are associated with growth and wood properties in Populus tomentosa
Authors: Du Qingzhang , Pan Wei , Xu Baohua , Li Bailian , Zhang Deqiang
Published: December 2012

Chinese white poplar (Populus tomentosa), an important commercial tree species for timber and pulp production in northern China, has been used to examine the individual genes and allelic diversity responsible for complex traits controlling growth and lignocellulosic biosynthesis. Taking advantage of the low degree of linkage disequilibrium (LD) within P. tomentosa association populations, we examined associations between 15 cellulose synthase (PtoCesA) genes and traits including growth and wood properties.

Thirty‐six novel simple sequence repeat (SSR) markers within PtoCesA genes were detected by re‐sequencing and genotyped in an association population (460 individuals). Single‐marker and haplotype‐based LD approaches were used to identify significant marker–trait associations. Family‐based linkage studies and real‐time PCR testing were conducted to validate the functional significance of SSR variation.

Fifteen single‐marker associations from seven PtoCesA genes and nine haplotype‐based associations within six genes were identified in the association population (false discovery rate Q < 0.05). Next, five SSR marker–trait associations (Q < 0.05) from four PtoCesA genes were successfully validated in a linkage mapping population (1200 individuals).

The results imply a functional role for these genes in mediating wood properties, demonstrating the potential of combining single‐marker and haplotype‐based LD approaches to detect functional allelic variation underlying quantitative traits in a low‐LD population.
Root stress and nitrogen deposition: consequences and research priorities
Authors: Smithwick Erica A. H. , Eissenstat David M. , Lovett Gary M. , Bowden Richard D. , Rustad Lindsey E. , Driscoll Charles T.
Published: December 2012

Stress within tree roots may influence whole‐tree responses to nutrient deficiencies or toxic ion accumulation, but the mechanisms that govern root responses to the belowground chemical environment are poorly quantified. Currently, root production is modeled using rates of forest production and stoichiometry, but this approach alone may be insufficient to forecast variability in forest responses when physical and chemical stressors alter root lifespan, rooting depth or mycorrhizal colonization directly. Here, we review key research priorities for improving predictions of tree responses to changes in the belowground biogeochemical environment resulting from nitrogen deposition, including: limits of the optimum allocation paradigm, root physiological stress and lifespan, contingency effects that determine threshold responses across broad gradients, coupled water‐biogeochemical interactions on roots, mycorrhizal dynamics that mediate root resilience and model frameworks to better simulate root feedbacks to aboveground function. We conclude that models incorporating physiological feedbacks, dynamic responses to coupled stressors, mycorrhizal interactions, and which challenge widely‐accepted notions of optimum allocation, can elucidate potential thresholds of tree responses to biogeochemical stressors. Emphasis on comparative studies across species and environmental gradients, and which incorporates insights at the cellular and ecosystem level, is critical for forecasting whole‐tree responses to altered biogeochemical landscapes.
Vessel diameter–stem diameter scaling across woody angiosperms and the ecological causes of xylem vessel diameter variation
Authors: Olson Mark E. , Rosell Julieta A.
Published: December 2012

Variation in angiosperm vessel diameter is of major functional significance. In the light of recent models predicting optimal vessel taper given resistance imposed by conductive path length, we tested the prediction that plant size should predict vessel diameter, with dryland plants having narrower vessels for their stem sizes.

We assembled a comparative dataset including vessel and stem diameter measurements from 237 species from over 40 angiosperm orders across a wide range of habits and habitats.

Stem diameter predicted vessel diameter across self‐supporting plants (slope 0.36, 95% CI 0.32–0.39). Samples from 142 species from five communities of differing water availability showed no tendency for dryland plants to have narrower vessels. Predictable relationships between vessel diameter and stem diameter mirrored predictable relationships between stem length and diameter across self‐supporting species.

That vessels are proportional to stem diameter and stem diameter is proportional to stem length suggests that taper in relation to conductive path length gives rise to the vessel diameter–stem diameter relationship. In turn, plant size is related to climate, leading indirectly to the vessel–climate relationship: vessels are likely narrower in drier communities because dryland plants are on average smaller, not because they have narrow vessels for their stem sizes.
Elevated night‐time temperatures increase growth in seedlings of two tropical pioneer tree species
Authors: Cheesman Alexander W. , Winter Klaus
Published: December 2012

Increased night‐time temperatures, through their influence on dark respiration, have been implicated as a reason behind decreasing growth rates in tropical trees in the face of contemporary climate change.

Seedlings of two neo‐tropical tree species (Ficus insipida and Ochroma pyramidale) were grown in controlled‐environment chambers at a constant daytime temperature (33°C) and a range of increasing night‐time temperatures (22, 25, 28, 31°C) for between 39 d and 54 d. Temperature regimes were selected to represent a realistic baseline condition for lowland Panama, and a rise in night‐time temperatures far in excess of those predicted for Central America in the coming decades. Experiments were complemented by an outdoor open‐top chamber study in which night‐time temperatures were elevated by 2.4°C above ambient.

Increasing night‐time temperatures resulted in > 2‐fold increase in biomass accumulation in growth‐chamber studies despite an increase in leaf‐level dark respiration. Similar trends were seen in open‐top chambers, in which elevated night‐time temperatures resulted in stimulation of growth.

These findings challenge simplistic considerations of photosynthesis‐directed growth, highlighting the role of temperature‐dependent night‐time processes, including respiration and leaf development as drivers of plant performance in the tropics.
Prevalence of gene expression additivity in genetically stable wheat allohexaploids
Authors: Chelaifa Houda , Chagué Véronique , Chalabi Smahane , Mestiri Imen , Arnaud Dominique , Deffains Denise , Lu Yunhai , Belcram Harry , Huteau Virginie , Chiquet Julien , Coriton Olivier , Just Jérémy , Jahier Joseph , Chalhoub Boulos
Published: December 2012

The reprogramming of gene expression appears as the major trend in synthetic and natural allopolyploids where expression of an important proportion of genes was shown to deviate from that of the parents or the average of the parents.

In this study, we analyzed gene expression changes in previously reported, highly stable synthetic wheat allohexaploids that combine the D genome of Aegilops tauschii and the AB genome extracted from the natural hexaploid wheat Triticum aestivum. A comprehensive genome‐wide analysis of transcriptional changes using the Affymetrix GeneChip Wheat Genome Array was conducted.

Prevalence of gene expression additivity was observed where expression does not deviate from the average of the parents for 99.3% of 34 820 expressed transcripts. Moreover, nearly similar expression was observed (for 99.5% of genes) when comparing these synthetic and natural wheat allohexaploids. Such near‐complete additivity has never been reported for other allopolyploids and, more interestingly, for other synthetic wheat allohexaploids that differ from the ones studied here by having the natural tetraploid Triticum turgidum as the AB genome progenitor.

Our study gave insights into the dynamics of additive gene expression in the highly stable wheat allohexaploids.
Synaptic dysfunction in congenital myasthenic syndromes
Authors: Beeson David
Published: December 2012

Congenital myasthenic syndromes (CMS) are hereditary disorders of neuromuscular transmission characterized by fatigable muscle weakness. The number of cases recognized is increasing with improved diagnosis. To date we have identified over 300 different mutations present in over 350 unrelated kinships. The underlying genetic defects are diverse, involving a series of different genes with a variety of different phenotypes. The type of treatment and its effectiveness will depend on the underlying pathogenic mechanism. We aim to define the molecular mechanism for each mutation identified and feed this information back to the clinic as a basis to tailor patient treatment. Here, we describe some of the methods that can be used to define if a DNA sequence variant is pathogenic with reference to variants in DOK7. We highlight a new mechanism for disruption of AChR function, where a mutation in the AChR ɛ‐subunit gene causes reduced ion channel conductance and discuss new methods for identifying gene mutations. The study of these disorders is proving highly informative for understanding the diverse molecular mechanisms that can underlie synaptic dysfunction.
Dynamic Factor Models with Jagged Edge Panel Data: Taking on Board the Dynamics of the Idiosyncratic Components
Authors: Pinheiro Maximiano , Rua António , Dias Francisco
Published: December 2012

As macroeconomic data are released with different delays, one has to handle unbalanced panel data sets with missing values at the end of the sample period when estimating dynamic factor models. We propose an EM algorithm which copes with such data sets while accounting for autoregressive common factors and allowing for serial correlation in the idiosyncratic components. Based on Monte Carlo simulations, we find that taking on board the dynamics of the idiosyncratic components improves significantly the accuracy of the estimation of both the missing values and the common factors at the end of the sample period.
Differential interactions of Streptococcus gordonii and Staphylococcus aureus with cultured osteoblasts
Authors: Jauregui C.E. , Mansell J.P. , Jepson M.A. , Jenkinson H.F.
Published: December 2012

The impedance of normal osteoblast function by microorganisms is at least in part responsible for the failure of dental or orthopedic implants. Staphylococcus aureus is a major pathogen of bone, and exhibits high levels of adhesion and invasion of osteoblasts. In this article we show that the commensal oral bacterium Streptococcus gordonii also adheres to and is internalized by osteoblasts. Entry of S. gordonii cells had typical features of phagocytosis, similar to S. aureus, with membrane protrusions characterizing initial uptake, and closure of the osteoblast membrane leading to engulfment. The sensitivities of S. gordonii internalization to inhibitors cytochalasin D, colchicine and monensin indicated uptake through endocytosis, with requirement for actin accumulation. Internalization levels of S. gordonii were enhanced by expression of S. aureus fibronectin‐binding protein A (FnBPA) on the S. gordonii cell surface. Lysosomal‐associated membrane protein‐1 phagosomal membrane marker accumulated with intracellular S. aureus and S. gordonii FnBPA, indicating trafficking of bacteria into the late endosomal/lysosomal compartment. Streptococcus gordonii cells did not survive intracellularly for more than 12 h, unless expressing FnBPA, whereas S. aureus showed extended survival times (>48 h). Both S. aureus and S. gordonii DL‐1 elicited a rapid interleukin‐8 response by osteoblasts, whereas S. gordonii FnBPA was slower. Only S. aureus elicited an interleukin‐6 response. Hence, S. gordonii invades osteoblasts by a mechanism similar to that exhibited by S. aureus, and elicits a proinflammatory response that may promote bone resorption.
Sustainable plant breeding
Authors: Cowling Wallace A.
Published: December 2012

Plant breeders disrupt Hardy–Weinberg equilibrium through selection, non‐random mating, drift, migration and mutation. Sustainable plant breeding can be defined as productive and competitive breeding that is achieved without loss of genetic diversity in the elite breeding population during the professional career of the breeder. Breeding is often productive but not sustainable. From 1974 to 2000, the animal breeding programme Meatlinc in the United Kingdom had effective population size of 95, population inbreeding of 0.19% per year and generation interval of 2.15 years. Genetic progress in Meatlinc tripled in the 8 years following introduction of best linear unbiased prediction (BLUP) selection (based on the information from relatives) in 1992. Canola breeding in Australia from 1970 to 2000 had longer generation interval (6 years), smaller effective population size (<11) and higher rates of inbreeding (>0.7% per year). BLUP selection in canola was first reported in 2010. Neither programme replaced genetic diversity lost through selection and drift. Most breeding programmes violate conditions of the infinitesimal model, thereby reducing predictability of selection, but breeders can minimize these limitations to sustainable plant breeding.
Structure‐function relationships during transgenic telomerase expression in Arabidopsis
Authors: Zachová Dagmar , Fojtová Miloslava , Dvořáčková Martina , Mozgová Iva , Lermontova Inna , Peška Vratislav , Schubert Ingo , Fajkus Jiří , Sýkorová Eva
Published: December 2012

Although telomerase (EC 2.7.7.49) is important for genome stability and totipotency of plant cells, the principles of its regulation are not well understood. Therefore, we studied subcellular localization and function of the full‐length and truncated variants of the catalytic subunit of Arabidopsis thaliana telomerase, AtTERT, in planta. Our results show that multiple sites in AtTERT may serve as nuclear localization signals, as all the studied individual domains of the AtTERT were targeted to the nucleus and/or the nucleolus. Although the introduced genomic or cDNA AtTERT transgenes display expression at transcript and protein levels, they are not able to fully complement the lack of telomerase functions in tert −/− mutants. The failure to reconstitute telomerase function in planta suggests a more complex telomerase regulation in plant cells than would be expected based on results of similar experiments in mammalian model systems.
Genetic identity of free‐living Symbiodinium obtained over a broad latitudinal range in the Japanese coast
Authors: Yamashita Hiroshi , Koike Kazuhiko
Published: December 2012

The dinoflagellate Symbiodinium is well known to engage symbiosis with various marine animals, including corals. Recent records of environmental Symbiodinium (occurring in the environment and separately from host animals; usually referred to as ‘free‐living’ Symbiodinium) are of special interest, since these environmental populations are essential as symbiont sources for many host animals. In the present study, we carried out a phylogenetic analysis of environmental Symbiodinium isolates (culture strains) from sand, tide pools, or macroalgal surfaces, and environmental DNA clones extracted from the water‐column, at numerous sites around Japan. Our phylogenetic analysis based on the nuclear rRNA gene (internal transcribed spacers ‐1, ‐2, and 5.8S), indicated that most of the environmental isolates form monophyletic subclades within the Clade‐A lineage, and separate from a host‐associated Clade‐A population with high bootstrap values. Results of the partial nuclear 28S rDNA phylogeny and thecal‐plate observations revealed that these environmental isolates were closely related to a previously‐described ‘planktonic species’, Symbiodinium natans Gert Hansen et Daugbjerg, which was isolated from a plankton‐net sample from the Northeast‐Atlantic Ocean. On the other hand, the environmental DNA clones were also noted to be mostly nested within host‐associated Symbiodinium groups scattered in various clades. These results led to the assumption that the environmental Symbiodinium can be divided into two groups. One group, as typified by environmental isolates in the present study and previous reports, may be exclusively free‐living; the other group exists transiently in free‐living forms, possibly having been expelled from animal hosts. The populations within the latter group probably represent environmental sources of viable symbionts, because these are normally host‐associated. However, the Symbiodinium in the former group are not expected to engage in stable symbioses with host cnidarians.
“The Big Society,” Public Expenditure, and Volunteering
Authors: Bartels Koen P. R. , Cozzi Guido , Mantovan Noemi
Published: December 2012

The debate on volunteering has paid insufficient attention to the relationship between public spending and volunteering. The importance of this relationship is highlighted by the British government's “Big Society” plan, which asserts that an increase in volunteering will compensate for the withdrawal of public agencies and spending. This idea is based on the widely held belief that a high degree of government intervention decreases voluntary activities. This article uses a multidisciplinary approach to improve understanding of how public spending affects the decision to volunteer. A theoretical model conceptualizes this relationship in terms of time donation by employed individuals. The model is tested empirically through an econometric analysis of two survey data sets and interpretative analysis of narratives of local volunteers and public professionals. The results suggest that volunteering is likely to decline when government intervention decreases and that a collaborative approach to sustaining volunteering is needed.
Vital capacity and oxygen saturation at rest and after exercise predict hypoxaemia during hypoxic inhalation test in patients with respiratory disease
Authors: Ling Ivan T. , Singh Bhajan , James Alan L. , Hillman David R.
Published: December 2012

Background and objective

The hypoxic inhalation test (HIT) accurately predicts air travel hypoxaemia, but availability is limited. We assessed whether oxygen saturation (SpO2) during HIT can be predicted by simple measures of lung function and exercise‐induced hypoxaemia.

Methods

Analysis of all patients who had HIT and lung function testing performed between January 2005 and April 2010. Prior to HIT, SpO2 on room air was measured at rest and after 2 min of moderate exercise. HIT was conducted using fractional inspired oxygen concentration 0.14 and SpO2 was measured after equilibration of ≥ 5 min. The relationships between SpO2 during HIT (HIT SpO2) and resting SpO2, post‐exercise SpO2, gas exchange (diffusing capacity for carbon monoxide) and ventilatory capacity were examined. Linear regression was performed to identify significant predictors of HIT SpO2.

Results

137 patients were studied: 70 had chronic obstructive pulmonary disease, 43 interstitial lung disease and 20 extra‐pulmonary restriction. All patients with HIT SpO2 ≤ 85% had post‐exercise SpO2 < 95% (n = 24 (18%)). HIT SpO2 correlated best with post‐exercise SpO2 overall (r = 0.69, P < 0.01). Linear regression identified forced vital capacity % predicted, resting SpO2 and post‐exercise SpO2 as independent predictors of HIT SpO2.

Conclusions

In patients with respiratory disease, post‐exercise SpO2 ≥ 95% on room air may be used to exclude the need for HIT to assess oxygen requirement for air travel. HIT SpO2 can be estimated from forced vital capacity % predicted, resting SpO2 and post‐exercise SpO2 using a linear regression model.
Analysis of Repair Distribution, Error Correction Rates And Repair Successfulness In L2*
Authors: Matea Kovač Mirjana , Milatović Biljana
Published: December 2012

Abstract.  The study reported in this paper investigated the repair distribution, the error correction rates and the repair successfulness in the speech of L2 learners, with the goal to find out more information on the monitoring skills and repair behaviour. The research also included a detailed subcategory analysis within syntactic, lexical and morphological categories which have not been investigated so far. The lowest correction rates were observed in the case of morphological subcategories, showing that the speakers’ attention was not oriented towards grammatical accuracy. The findings of this study may find practical application in foreign language teaching, suggesting possible reviews of formal teaching methods, aiming at more efficient linking of grammatical development to the ability to communicate.
Language ideology in discourses of resistance to dominant hierarchies of linguistic worth: MandarinChinese andChinese ‘dialects’ inSingapore
Authors: Tan Sherman
Published: December 2012

In Singapore, government language policy promotesMandarin as the official Chinese variety, while discouraging the use of otherChinese ‘dialects’. This article examines Singaporean citizens' comments in blogs and discussion forums about the value and relevance of these stigmatised languages. Although these online discourses overtly contrast with state discourses in their positive evaluations of the non‐Mandarin languages, both bodies of discourse presuppose a common ground of language ideology: namely, that a language is an alienable commodity that can be actively manipulated and that it possesses a specific value. The discourses also follow shared patterns of constructing sociolinguistic difference through semiotic processes of iconisation, recursivity, and erasure. My analysis distinguishes between the discourses' implicit language‐ideological presuppositions and their explicitly articulated linguistic‐evaluative content and traces the interrelation of these. The shared presuppositions are important for actors' bids to enlist (different) normative sociolinguistic hierarchies in the service of projects of hegemonic nation‐building, as well as for the purposes of politically subversive identity work.
Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation
Authors: Shah S.K. , Parto P. , Lombard G.A. , James M.A. , Beckles D.L. , Lick S. , Valentine V.G.
Published: December 2012

Lung nodules after lung transplantation most often represent infection or post‐transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation.
Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient
Authors: Osthoff M. , Chew E. , Bajel A. , Kelsey G. , Panek‐Hudson Y. , Mason K. , Szer J. , Ritchie D. , Slavin M.
Published: December 2012

Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre‐transplant. We herein report a seronegative patient with acute T‐cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre‐transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.