bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel Sec18p/NSF-dependent complex required for Golgi-to-endosome transport in yeast.
Authors: Burd C G , Peterson M , Cowles C R , Emr S D
Published: August 2013

The vacuolar protein-sorting (VPS) pathway of Saccharomyces cerevisiae mediates localization of proteins from the trans-Golgi to the vacuole via a prevacuolar endosome compartment. Mutations in class D vacuolar protein-sorting (vps) genes affect vesicle-mediated Golgi-to-endosome transport and result in secretion of vacuolar proteins. Temperature-sensitive-for-function (tsf) and dominant negative mutations in PEP12, encoding a putative SNARE vesicle receptor on the endosome, and tsf mutations in VAC1, a gene implicated in vacuole inheritance and vacuolar protein sorting, were constructed and used to demonstrate that Pep12p and Vac1p are components of the VPS pathway. The sequence of Vac1p contains two putative zinc-binding RING motifs, a zinc finger motif, and a coiled-coil motif. Site-directed mutations in the carboxyl-terminal RING motif strongly affected vacuolar protein sorting. Vac1p was found to be tightly associated with membranes as a monomer and in a large SDS-resistant complex. By using Pep12p affinity chromatography, we found that Vac1p, Vps45p (SEC1 family member), and Sec18p (yeast N-ethyl maleimide-sensitive factor, NSF) bind Pep12p. Consistent with a functional role for this complex in vacuolar protein sorting, double pep12tsfvac1tsf and pep12tsf vps45tsf mutants exhibited synthetic Vps- phenotypes, the tsf phenotype of the vac1tsf mutant was rescued by overexpression of VPS45 or PEP12, overexpression of a dominant pep12 allele in a sec18-1 strain resulted in a severe synthetic growth defect that was rescued by deletion of PEP12 or VAC1, and subcellular fractionation of vac1 delta cells revealed a striking change in the fractionation of Pep12p and Vps21p, a rab family GTPase required for vacuolar protein sorting. The functions of Pep12p, Vps45p, and Vps21p indicate that key aspects of Golgi-to-endosome trafficking are similar to other vesicle-mediated transport steps, although the role of Vac1p suggests that there are also novel components of the VPS pathway.
Ran1 functions to control the Cdc10/Sct1 complex through Puc1.
Authors: Caligiuri M , Connolly T , Beach D
Published: August 2013

We have undertaken a biochemical analysis of the regulation of the G1/S-phase transition and commitment to the cell cycle in the fission yeast Schizosaccharomyces pombe. The execution of Start requires the activity of the Cdc2 protein kinase and the Sct1/Cdc10 transcription complex. Progression through G1 also requires the Ran1 protein kinase whose inactivation leads to activation of the meiotic pathway under conditions normally inhibitory to this process. We have found that in addition to Cdc2, Sct1/Cdc10 complex formation requires Ran1. We demonstrate that the Puc1 cyclin associates with Ran1 and Cdc10 in vivo and that the Ran1 protein kinase functions to control the association between Puc1 and Cdc10. In addition, we present evidence that the phosphorylation state of Cdc10 is altered upon inactivation of Ran1. These results provide biochemical evidence that demonstrate one mechanism by which the Ran1 protein kinase serves to control cell fate through Cdc10 and Puc1.
RCC1 and nuclear organization.
Authors: Huang S , Mayeda A , Krainer A R , Spector D L
Published: August 2013

We have examined the effect of RCC1 function on the nuclear organization of pre-mRNA splicing factors and poly(A)+ RNA in the tsBN2 cells, a RCC1 temperature-sensitive mutant cell line. We have found that at 4-6 h after shifting cells from the permissive temperature (32.5 degrees C) to the restrictive temperature (39.5 degrees C), both small nuclear ribonucleoprotein particles and a general splicing factor SC35 reorganized into 4-10 large round clusters in the nucleus, as compared with the typical speckled distribution seen in cells at the permissive temperature. In situ hybridization to poly(A)+ RNA resulted in a similar pattern. Examination by double labeling demonstrated that the redistribution of splicing factors coincides with that of poly(A)+ RNA. Such changes in the nuclear organization of splicing factors and poly(A)+ RNA were not the result of the temperature shift or of chromatin condensation. Cellular transcription was not significantly altered in these cells and extracts made from both the permissive and restrictive temperature were splicing competent. Electron microscopic examination demonstrated that the large clusters containing both splicing factors and poly(A)+ RNA were fused interchromatin granule clusters. In addition, small electron-dense dot-like structures measuring approximately 80 nm in diameter were also observed, most of which are accumulated in enlarged interchromatin granule clusters in the nucleoplasm of RCC1- cells. In spite of the significant changes observed in the nucleoplasm, relatively little alteration was observed in nucleolar structure by both light and electron microscopic examination. The above observations suggest that the RCC1 protein directly or indirectly regulates the organization of splicing components and poly(A)+ RNA in the cell nucleus and that RCC1 may play a role in nuclear organization.
Palmitoylation of p59fyn is reversible and sufficient for plasma membrane association.
Authors: Wolven A , Okamura H , Rosenblatt Y , Resh M D
Published: August 2013

Members of the Src family of protein tyrosine kinases are localized to subspecialized regions of the plasma membrane. Herein we show that the N-terminal SH4 region of the Src family member p59fyn (Fyn) is both necessary and sufficient for targeting of Fyn and heterologous proteins to the plasma membrane and detergent-insoluble subdomains. Attachment of the first 16 amino acids of Fyn to a normally cytosolic protein, beta-galactosidase, resulted in distinct plasma membrane localization of the chimeric protein. Mutation of the palmitoylation site (cysteine-3) within Fyn16-beta-galactosidase or wild-type Fyn abrogated plasma membrane localization, resulting in redistribution of the mutant proteins into intracellular membranes. Substitution of the SH4 motif within Fyn with heterologous sequences from other palmitoylated proteins (G alpha o and GAP43) revealed that the presence of palmitate is sufficient to direct plasma membrane localization independent of surrounding amino acid sequences and myristate. Palmitoylated Fyn chimeras were also enriched in the Triton X-100-resistant matrix, whereas nonpalmitoylated forms of these proteins were detected in the detergent-soluble fraction. The palmitate moiety on Fyn exhibited a half-life of 1.5-2 h. In contrast, the half-life of the polypeptide backbone was 8 h, indicating that palmitoylation is a reversible modification. These studies establish that the palmitoylated SH4 sequence of Fyn can be used to specifically target proteins to the plasma membrane in a reversible manner.
Functional domains in nuclear import factor p97 for binding the nuclear localization sequence receptor and the nuclear pore.
Authors: Chi N C , Adam S A
Published: August 2013

The interaction of the nuclear protein import factor p97 with the nuclear localization sequence (NLS) receptor, the nuclear pore complex, and Ran/TC4 is important for coordinating the events of protein import to the nucleus. We have mapped the binding domains on p97 for the NLS receptor and the nuclear pore. The NLS receptor-binding domain of p97 maps to the C-terminal 60% of the protein between residues 356 and 876. The pore complex-binding domain of p97 maps to residues 152-352. The pore complex-binding domain overlaps the Ran-GTP- and Ran-GDP-binding domains on p97, but only Ran-GTP competes for docking in permeabilized cells. The N-ethylmaleimide sensitivity of the p97 for docking was investigated and found to be due to inhibition of p97 binding to the pore complex and to the NLS receptor. Site-directed mutagenesis of conserved cysteine residues in the pore- and receptor-binding domains identified two cysteines, C223 and C228, that were required for p97 to bind the nuclear pore. Inhibition studies on docking and accumulation of a NLS protein provided additional evidence that the domains identified biochemically are the functional domains involved in protein import. Together, these results suggest that Ran-GTP dissociates the receptor complex and prevents p97 binding to the pore by inducing a conformational change in the structure of p97 rather than simple competition for binding sites.
Determination of floral organ identity by Arabidopsis MADS domain homeotic proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity.
Authors: Riechmann J L , Meyerowitz E M
Published: August 2013

The MADS domain homeotic proteins APETALA1 (AP1), APETALA3 (AP3), PISTILLATA (PI), and AGAMOUS (AG) combinatorially specify the identity of Arabidopsis floral organs. AP1/AP1, AG/AG, and AP3/PI dimers bind to similar CArG box sequences; thus, differences in DNA-binding specificity among these proteins do not seem to be the origin of their distinct organ identity properties. To assess the overall contribution that specific DNA binding could make to their biological specificity, we have generated chimeric genes in which the amino-terminal half of the MADS domain of AP1, AP3, PI, and AG was substituted by the corresponding sequences of human SRF and MEF2A proteins. In vitro DNA-binding assays reveal that the chimeric proteins acquired the respective, and distinct, DNA-binding specificity of SRF or MEF2A. However, ectopic expression of the chimeric genes reproduces the dominant gain-of-function phenotypes exhibited by plants ectopically expressing the corresponding Arabidopsis wild-type genes. In addition, both the SRF and MEF2 chimeric genes can complement the pertinent ap1-1, ap3-3, pi-1, or ag-3 mutations to a degree similar to that of AP1, AP3, PI, and AG when expressed under the control of the same promoter. These results indicate that determination of floral organ identity by the MADS domain homeotic proteins AP1, AP3, PI, and AG is independent of their DNA-binding specificity. In addition, the DNA-binding experiments show that either one of the two MADS domains of a dimer can be sufficient to confer a particular DNA-binding specificity to the complex and that sequences outside the amino-terminal basic region of the MADS domain can, in some cases, contribute to the DNA-binding specificity of the proteins.
Yeast actin cytoskeleton mutants accumulate a new class of Golgi-derived secretary vesicle.
Authors: Mulholland J , Wesp A , Riezman H , Botstein D
Published: August 2013

Many yeast actin cytoskeleton mutants accumulate large secretory vesicles and exhibit phenotypes consistent with defects in polarized growth. This, together with actin's polarized organization, has suggested a role for the actin cytoskeleton in the vectorial transport of late secretory vesicles to the plasma membrane. By using ultrastructural and biochemical analysis, we have characterized defects manifested by mutations in the SLA2 gene (also known as the END4 gene), previously found to affect both the organization of the actin cytoskeleton and endocytosis in yeast. Defects in cell wall morphology, accumulated vesicles, and protein secretion kinetics were found in sla2 mutants similar to defects found in act1 mutants. Vesicles that accumulate in the sla2 and act1 mutants are immunoreactive with antibodies directed against the small GTPase Ypt1p but not with antibodies directed against the homologous Sec4p found on classical "late" secretory vesicles. In contrast, the late-acting secretory mutants sec1-1 and sec6-4 are shown to accumulate anti-Sec4p-positive secretory vesicles as well as vesicles that are immunoreactive with antibodies directed against Ypt1p. The late sec mutant sec4-8 is also shown to accumulate Ypt1p-containing vesicles and to exhibit defects in actin cytoskeleton organization. These results indicate the existence of at least two classes of morphologically similar, late secretory vesicles (associated with Ypt1p+ and Sec4p+, respectively), one of which appears to accumulate when the actin cytoskeleton is disorganized.
The small GTPase Cdc42 initiates an apoptotic signaling pathway in Jurkat T lymphocytes.
Authors: Chuang T H , Hahn K M , Lee J D , Danley D E , Bokoch G M
Published: August 2013

Apoptosis plays an important role in regulating development and homeostasis of the immune system, yet the elements of the signaling pathways that control cell death have not been well defined. When expressed in Jurkat T cells, an activated form of the small GTPase Cdc42 induces cell death exhibiting the characteristics of apoptosis. The death response induced by Cdc42 is mediated by activation of a protein kinase cascade leading to stimulation of c-Jun amino terminal kinase (JNK). Apoptosis initiated by Cdc42 is inhibited by dominant negative components of the JNK cascade and by reagents that block activity of the ICE protease (caspase) family, suggesting that stimulation of the JNK kinase cascade can lead to caspase activation. The sequence of morphological events observed typically in apoptotic cells is modified in the presence of activated Cdc42, suggesting that this GTPase may account for some aspects of cytoskeletal regulation during the apoptotic program. These data suggest a means through which the biochemical and morphological events occurring during apoptosis may be coordinately regulated.
Chemotaxis to cAMP and slug migration in Dictyostelium both depend on migA, a BTB protein.
Authors: Escalante R , Wessels D , Soll D R , Loomis W F
Published: August 2013

Chemotaxis in natural aggregation territories and in a chamber with an imposed gradient of cyclic AMP (cAMP) was found to be defective in a mutant strain of Dictyostelium discoideum that forms slugs unable to migrate. This strain was selected from a population of cells mutagenized by random insertion of plasmids facilitated by introduction of restriction enzyme (a method termed restriction enzyme-mediated integration). We picked this strain because it formed small misshapen fruiting bodies. After isolation of portions of the gene as regions flanking the inserted plasmid, we were able to regenerate the original genetic defect in a fresh host and show that it is responsible for the developmental defects. Transformation of this recapitulated mutant strain with a construct carrying the full-length migA gene and its upstream regulatory region rescued the defects. The sequence of the full-length gene revealed that it encodes a novel protein with a BTB domain near the N terminus that may be involved in protein-protein interactions. The migA gene is expressed at low levels in all cells during aggregation and then appears to be restricted to prestalk cells as a consequence of rapid turnover in prespore cells. Although migA- cells have a dramatically reduced chemotactic index to cAMP and an abnormal pattern of aggregation in natural waves of cAMP, they are completely normal in size, shape, and ability to translocate in the absence of any chemotactic signal. They respond behaviorally to the rapid addition of high levels of cAMP in a manner indicative of intact circuitry connecting receptor occupancy to restructuring of the cytoskeleton. Actin polymerization in response to cAMP is also normal in the mutant cells. The defects at both the aggregation and slug stage are cell autonomous. The MigA protein therefore is necessary for efficiently assessing chemical gradients, and its absence results in defective chemotaxis and slug migration.
Defining cell-type specificity at the transcriptional level in human disease
Authors: Ju Wenjun , Greene Casey S. , Eichinger Felix , Nair Viji , Hodgin Jeffrey B. , Bitzer Markus , Lee Young-suk , Zhu Qian , Kehata Masami , Li Min , Jiang Song , Rastaldi Maria Pia , Cohen Clemens D. , Troyanskaya Olga G. , Kretzler Matthias
Published: August 2013

Cell-lineage–specific transcripts are essential for differentiated tissue function, implicated in hereditary organ failure, and mediate acquired chronic diseases. However, experimental identification of cell-lineage–specific genes in a genome-scale manner is infeasible for most solid human tissues. We developed the first genome-scale method to identify genes with cell-lineage–specific expression, even in lineages not separable by experimental microdissection. Our machine-learning–based approach leverages high-throughput data from tissue homogenates in a novel iterative statistical framework. We applied this method to chronic kidney disease and identified transcripts specific to podocytes, key cells in the glomerular filter responsible for hereditary and most acquired glomerular kidney disease. In a systematic evaluation of our predictions by immunohistochemistry, our in silico approach was significantly more accurate (65% accuracy in human) than predictions based on direct measurement of in vivo fluorescence-tagged murine podocytes (23%). Our method identified genes implicated as causal in hereditary glomerular disease and involved in molecular pathways of acquired and chronic renal diseases. Furthermore, based on expression analysis of human kidney disease biopsies, we demonstrated that expression of the podocyte genes identified by our approach is significantly related to the degree of renal impairment in patients. Our approach is broadly applicable to define lineage specificity in both cell physiology and human disease contexts. We provide a user-friendly website that enables researchers to apply this method to any cell-lineage or tissue of interest. Identified cell-lineage–specific transcripts are expected to play essential tissue-specific roles in organogenesis and disease and can provide starting points for the development of organ-specific diagnostics and therapies.
Energy calibration issues in nuclear resonant vibrational spectroscopy: observing small spectral shifts and making fast calibrations
Authors: Wang Hongxin , Yoda Yoshitaka , Dong Weibing , Huang Songping D.
Published: August 2013

The conventional energy calibration for nuclear resonant vibrational spectroscopy (NRVS) is usually long. Meanwhile, taking NRVS samples out of the cryostat increases the chance of sample damage, which makes it impossible to carry out an energy calibration during one NRVS measurement. In this study, by manipulating the 14.4 keV beam through the main measurement chamber without moving out the NRVS sample, two alternative calibration procedures have been proposed and established: (i) anin situcalibration procedure, which measures the main NRVS sample at stage A and the calibration sample at stage B simultaneously, and calibrates the energies for observing extremely small spectral shifts; for example, the 0.3 meV energy shift between the 100%-57Fe-enriched [Fe4S4Cl4]=and 10%-57Fe and 90%-54Fe labeled [Fe4S4Cl4]=has been well resolved; (ii) a quick-switching energy calibration procedure, which reduces each calibration time from 3–4 h to about 30 min. Although the quick-switching calibration is notin situ, it is suitable for normal NRVS measurements.
Causal relationships between table game players' perceptions of service quality, perceived winning, and game spending
Authors: Mi Jeon Sang , Magnini Vincent P. , Kim Insin , Sean Hyun Sunghyup
Published: August 2013

Purpose

The purpose of this paper is twofold: first, to examine the roles of five drivers of service quality (tangibles, reliability, responsiveness, assurance, and empathy) and perceived winning in the gaming behavior of table game players; and second, to test the moderating effects of table game players' demographic and situational factors (gender, education level, parenting status, and proximity to a casino).

Design/methodology/approach

A review of the current literature in the above‐mentioned areas revealed 13 theoretical hypotheses, from which the authors derived a structural model. The model was tested utilizing data collected from 383 US casino patrons that primarily played table games during visits to casinos. Confirmatory factor analysis and structural equation modeling were utilized to test the proposed theoretical relationships.

Findings

The results indicate that various dimensions of perceived service quality (including tangibles, responsiveness, assurance, and empathy) in casinos, as well as casino patrons' perceived winning have considerable influence on their satisfaction. Brand affect and game spending were found to be influenced by the patron satisfaction with table games. The relationship between perceived empathy and table game satisfaction was stronger for females than for males; the relationship between perceived winning and table game satisfaction was stronger for those with lower levels of formal education; and the relationship between table game satisfaction and game spending was stronger for table game players without children and for those residing near a casino.

Originality/value

This study provides an empirical analysis of the effects of perceived service quality at table games and perceived winning on table game players' satisfaction, brand affect, and game spending. The results of this study may be utilized to aid casino operators to better tailor their marketing efforts and improve returns on investments.
The influences of collectivism in hospitality work settings
Authors: Magnini Vincent P. , Hyun Sunghyup (Sean) , Kim BeomCheol (Peter) , Uysal Muzaffer
Published: August 2013

Purpose

The purpose of this paper is to test whether a hospitality worker's degree of individualism/collectivism influences his/her organizational citizenship behavior (OCB), comfort with empowerment, and leader‐member exchange (LMX) in the workplace.

Design/methodology/approach

Hypotheses were tested through the use of a sentence completion experiment conducted on American and Korean hotel workers. To increase generalizability, results were then replicated through the use of an identical sentence completion experiment conducted on American and Korean restaurant workers.

Findings

This research first confirms the notion that hospitality workers in a collective nation are more apt to possess a collective mindset in their work environments than those in an individualistic nation. Moreover, this research finds that hospitality workers in a collective nation demonstrate more OCB, possess lower comfort levels with empowerment, and possess higher levels of LMX than hospitality workers in an individualistic nation.

Research limitations/implications

It would prove informative for future research to test these relationships in other contexts and settings.

Practical implications

These findings demonstrate the need to consider country culture when interpreting and managing OCB, employee empowerment, and LMX tendencies in hospitality settings.

Originality/value

Research that examines the influences of individualism/collectivism on OCB, comfort with empowerment, and LMX is scarce.
Pharmaceutical advertising practitioners' approach to trust and emotion
Authors: Ball Jennifer , Mackert Michael
Published: August 2013

Purpose

Studies of direct‐to‐consumer pharmaceutical advertising (DTCA) have examined the views of consumers and healthcare providers but the perspective of pharmaceutical advertisers has been largely absent. This study sought to fill that gap by exploring the perspectives of advertising professionals working on pharmaceutical brands.

Design/methodology/approach

Interviews were conducted among 22 advertising professionals regarding the use of emotion in DTCA and considerations about consumer distrust and ad credibility.

Findings

Results suggest emotion is used to gain attention, increase involvement, and enhance information processing. Consumer trust of pharmaceutical companies was recognized as an issue, and various thoughts were provided on trust‐building strategies. However, several respondents expressed doubt that negative opinions of the industry translated into negative evaluations of the specific ads or brands with which consumers were familiar.

Research limitations/implications

Based on participants' assertions, this paper poses a number of specific avenues for future research regarding the effects of emotion on response to DTCA and consumers' conflicting sense of trust within the pharmaceutical category.

Originality/value

While scholars examining the design and effects of DTCA have inferred the motivations of pharmaceutical advertisers, this study provides insight on practitioners' actual intentions behind the messages created for DTCA.
The quest for the PhD: a better metaphor for doctoral education
Authors: McCulloch Alistair
Published: August 2013

Purpose

The paper seeks to propose the adoption of an alternative metaphor to that of the “journey”, currently the most pervasive characterisation for the student's experience of doctoral education.

Design/methodology/approach

The paper adopts a conceptual and rhetorical approach.

Findings

The paper offers a critique of the journey metaphor as a characterisation of the student's doctoral experience and proposes instead the metaphor of the Quest, a cultural and literary form found in most societies. It argues that the six elements of the Quest identified by W.H. Auden resonate with the contemporary doctoral experience and emphasise the uncertainty involved in research rather than the linearity implied by the journey metaphor.

Social implications

The paper argues that the quest metaphor offers a cross‐cultural basis for both staff and student development activities through which sense can be made of the research experience, student concerns can be surfaced, and potentially difficult issues raised for discussion in an unthreatening way.

Originality/value

The paper is the first to apply the quest as a metaphor for the student's doctoral experience and offers a new way of interrogating that experience which will be of use to those involved in supporting research students.
Preparation of urea formaldehyde resin/layered silicate nanocomposites
Authors: Ateş Esin , Uyanık Nurseli , Kızılcan Nilgün
Published: August 2013

Purpose

The purpose of the research was as follows. In situ modified urea formaldehyde resins were prepared from clay (montmorillonite) and organoclay in the presence of base catalyst. Different clay contents (1 wt%, 3 wt%, 6 wt%) were used to produce clay modified nanocomposite resins. These nanocomposites were characterized with FT‐IR, XRD as structural analysis and DSC as thermal analysis and their hardness was evaluated as mechanical analysis. The thermal results was compatible with hardness measurements and showed that using clay/organoclay added resin as a surface coating material provides significant improvement.

Design/methodology/approach

During synthesis of the resin, modification was carried out using urea/formaldehyde with molar ratio of 1/1.6, under basic medium with pH=10 and with temperature of 70°C by loading pristine and organomodified layered silicates.

Findings

X‐ray diffraction (XRD) results indicate that the interlayer space of pristine clay was increased significantly by one step, seeing that one step processes are crucial for industrial applications.

Research limitations/implications

The reaction mixture must be stirred continuously. Temperature should be controlled in order to prevent the thermal curing of urea formaldehyde resin.

Practical implications

This study provides technical information for the synthesis of nanocomposite resins. The clay or organoclay modified resins may also promote the adhesive strength of coating and also inhibit corrosion effects to metal surfaces of the coated area.

Social implications

This resin will be used for the coating material.

Originality/value

As Tg‐Tm region of some nanocomposites is enhanced, and by assessing the results of hardness measurements, it is concluded that these samples have further improved mechanical properties as a coating material than urea formaldehyde resin has.
Antifungal activity of aluminium‐containing salts against the development of carrot cavity spot and potato dry rot
Authors: Kolaei E.A. , Cenatus C. , Tweddell R.J. , Avis T.J.
Published: August 2013

As an alternative to the use of synthetic chemical fungicides to control plant disease, aluminium‐containing salts were evaluated for their effects on the mycelial growth of various fungal or fungus‐like pathogens and their ability to control carrot cavity spot (Pythium sulcatum) and potato dry rot (Fusarium sambucinum). Results showed that various aluminium‐containing salts provided strong inhibition of all the tested pathogens (Alternaria solani, Botrytis cinerea, F. sambucinum, P. sulcatum and Rhizopus stolonifer) with minimal inhibitory concentration of 1–10 mM. Aluminium chloride and aluminium sulphate were generally the most effective, inhibiting mycelial growth of pathogens by as much as 47% and 100%, respectively, at a salt concentration of 1 mM. Applied at 5 mM, aluminium sulphate also provided 28% and 100% inhibition of dry rot and cavity spot, respectively. Aluminium chloride (5 mM) reduced dry rot by 25% whereas aluminium lactate (5 mM) decreased cavity spot lesions by 86%. These results indicate that various aluminium‐containing salts may provide an alternative to the use of synthetic fungicides to control these pathogens.
Characterization and pathogenicity of Fusarium proliferatum causing stem rot of Hylocereus polyrhizus in Malaysia
Authors: Masratul Hawa M. , Salleh B. , Latiffah Z.
Published: August 2013

During a series of sampling in 2008 and 2009, stem rot disease was detected in Hylocereus polyrhizus plantations in Malaysia, with symptom appeared as circular, brown sunken lesion with orange sporodochia and white mycelium formation on the lesion surface. Eighty‐three isolates of Fusarium were isolated from 20 plantations and were morphologically identified as F. proliferatum based on the variability of colony appearance, pigmentation, growth rate, length of chains, production of bluish sclerotia, concentric ring aerial mycelium and sporodochia. Three species‐specific primers, namely ITS1/proITS‐R, PRO1/2 and Fp3‐F/4‐R successfully produced PCR products and confirmed that the isolates from stem rot of H. polyrhizus were F. proliferatum isolates. From BLAST search of translation elongation factor 1‐alpha (TEF1‐α) sequences, the isolates showed 99–100% similarity with F. proliferatum deposited in GenBank which further confirmed that the isolates were F. proliferatum. The results from amplification of MAT‐allele specific primers indicated that 14.5% of F. proliferatum isolates carried MAT‐1 allele and 85.5% carried MAT‐2. Crossing results showed that all 83 F. proliferatum isolates were male fertile showing positive crosses with the tester strains of MATD‐1 and MATD‐2. Perithecia oozing ascospore were produced. Forty isolates as representative were evaluated for pathogenicity test, produced rot symptoms similar to those observed in the fields which confirmed the isolates as the causal agent of stem rot of H. polyrhizus. To our knowledge, this is the first report of stem rot of H. polyrhizus caused by F. proliferatum in Malaysia.
Stock Returns, Housing Returns and Inflation: Is There an Inflation Illusion?
Authors: Hong Gwangheon , Khil Jaeuk , Lee Bong‐Soo
Published: August 2013

The inflation illusion hypothesis of Modigliani and Cohn () has received renewed attention in explaining a negative relation not only between stock returns and inflation but also between housing returns and inflation. We reexamine the empirical relation in general and the validity of the inflation illusion hypothesis in particular using data from the US, the UK and Korea. We find three key results. (1) The negative relation is particularly strong in recession periods, indicating that the relation is sensitive to business cycles. (2) There are two regimes with positive and negative asset returns and inflation relations for all three countries, and the two‐regime relation is found not only for the stock return–inflation relation but also for the housing return–inflation relation. This finding is at odds with the inflation illusion hypothesis because the hypothesis anticipates only a negative relation for both positive inflation and negative inflation. (3) Housing returns Granger‐cause inflation, and their dynamic net effect on inflation is significantly positive for all three countries. This is at odds with the inflation illusion hypothesis, which anticipates inflation being related to negative returns. Overall, we find limited evidence for the inflation illusion hypothesis. If there is inflation illusion, only a small fraction of investors suffer from it.
Evaluating gene expression profiling by quantitative polymerase chain reaction to develop a clinically feasible test for outcome prediction in multiple myeloma
Authors: Sarasquete María E. , Martínez‐López Joaquín , Chillón María C. , Alcoceba Miguel , Corchete Luis A. , Paiva Bruno , Puig Noemi , Sebastián Elena , Jiménez Cristina , Mateos Maria‐Victoria , Oriol Albert , Rosiñol Laura , Palomera Luis , Teruel Ana I. , González Yolanda , Lahuerta Juan J. , Bladé Joan , Gutiérrez Norma C. , Fernández‐Redondo Elena , González Marcos , San Miguel Jesús F. , García‐Sanz Ramón
Published: August 2013

The gene expression profiles (GEPs) of 96 selected genes were analysed by real‐time quantitative polymerase chain reaction (qPCR) with a TaqMan low‐density array card in isolated tumour plasma cells (PCs) from 157 newly diagnosed multiple myeloma (MM) patients. This qPCR‐based GEP correctly classified cases following the Translocation‐cyclin D classification. Classic prognostic parameters and qPCR‐based GEP predicted MM patient outcome and, although multivariate analyses revealed that cytogenetic risk (standard vs. high risk) was the variable that most strongly predicted prognosis, GEP added significant information for risk stratification. Considering only the standard risk cytogenetic patients, multivariate analyses revealed that high β2‐microglobulin, low CDKN1A and high SLC19A1 gene expression levels independently predicted a short time‐to‐progression (TTP), while high International Staging System stage, low CDKN2B and high TBRG4 gene expression predicted poor overall survival (OS). A gene expression risk score enabled the division of standard risk patients into two groups with different TTPs (83% vs. 38% at 3 years, P < 0·0001) and OS rates (88% vs. 61% at 5 years; P = 0·003). This study demonstrates that quantitative PCR is a robust, accurate and feasible technique for implementing in the daily routine as a surrogate for GEP‐arrays.
The future in clinical genetics: affective forecasting biases in patient and clinician decision making
Authors: Peters S.A. , Laham S.M. , Pachter N. , Winship I.M.
Published: August 2013

When clinicians facilitate and patients make decisions about predictive genetic testing, they often base their choices on the predicted emotional consequences of positive and negative test results. Research from psychology and decision making suggests that such predictions may often be biased. Work on affective forecasting—predicting one's future emotional states—shows that people tend to overestimate the impact of (especially negative) emotional events on their well‐being; a phenomenon termed the impact bias. In this article, we review the causes and consequences of the impact bias in medical decision making, with a focus on applying such findings to predictive testing in clinical genetics. We also recommend strategies for reducing the impact bias and consider the ethical and practical implications of doing so.
Occupational allergic contact dermatitis diagnosed by a systematic stepwise exposure assessment of allergens in the work environment
Authors: Friis Ulrik F. , Menné Torkil , Flyvholm Mari‐Ann , Bonde Jens Peter E. , Johansen Jeanne D.
Published: August 2013

Background

Information on the presence of contact allergens and irritants is crucial for the diagnosis of occupational contact dermatitis. Ingredient lists and Material Safety DataSheets (MSDSs) may be incomplete.

Objectives

To evaluate the workability of a systematic exposure assessment in consecutive patients with suspected occupational contact dermatitis, and to study how it could potentially aid correct diagnostic classification.

Methods

A tool for systematic stepwise assessment of exposures in the work environment was developed, consisting of six steps spanning medical history and workplace visits. The programme included 228 consecutive patients diagnosed with occupational contact dermatitis; all patients underwent a clinical examination, the stepwise exposure assessment, and extensive patch and prick testing.

Results

Of the participants, 48.2% were classified as having occupational allergic contact dermatitis. The diagnosis was made at the stepwise exposure assessment for 50.0% of patients at Step 1 (medical history) and for 34.5% at Step 2 (ingredient labelling/MSDS). We found 132 different occupational allergens of relevance to the patients' eczema, of these, 78.0% were allergens not included in the European baseline series.

Conclusions

Systematic stepwise exposure assessment provides information that results in the identification of occupational allergies caused by allergens not included in the European baseline series in a substantial number of patients.
What causes alopecia areata?
Authors: McElwee K. J. , Gilhar A. , Tobin D. J. , Ramot Y. , Sundberg J. P. , Nakamura M. , Bertolini M. , Inui S. , Tokura Y. , King L. E. , Duque‐Estrada B. , Tosti A. , Keren A. , Itami S. , Shoenfeld Y. , Zlotogorski A. , Paus R.
Published: August 2013

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8+ T cells, CD4+ T cells and NKGD2+ NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA‐related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re‐evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.
The metabolic modulator trimetazidine triggers autophagy and counteracts stress‐induced atrophy in skeletal muscle myotubes
Authors: Ferraro Elisabetta , Giammarioli Anna Maria , Caldarola Sara , Lista Pasquale , Feraco Alessandra , Tinari Antonella , Salvatore Anna Maria , Malorni Walter , Berghella Libera , Rosano Giuseppe
Published: August 2013

It has recently been demonstrated that trimetazidine (TMZ), an anti‐ischemic antianginal agent, is also able to improve exercise performance in patients with peripheral arterial disease. TMZ is a metabolic modulator, and the mechanisms underlying its cytoprotective anti‐ischemic activity could be ascribed, at least in cardiomyocytes, to optimization of metabolism. However, regarding the cytoprotection exerted by TMZ on skeletal muscle and allowing the improvement of exercise performance, no information is yet available. In the present study, we investigated in detail the protective effects of this drug on in vitro skeletal muscle models of atrophy. Experiments carried out with murine C2C12 myotubes treated with TMZ revealed that this drug could efficiently counteract the cytopathic effects induced by the proinflammatory cytokine tumor necrosis factor‐α and by the withdrawal of growth factors. Indeed, TMZ significantly counteracted the reduction in myotube size induced by these treatments. TMZ also increased myosin heavy chain expression and induced hypertrophy in C2C12 myotubes, both effects strongly suggesting a role of TMZ in counteracting atrophy in vitro. In particular, we found that TMZ was able to activate the phosphoinositide 3‐kinase–Akt–mammalian target of rapamycin 2 pathway and to reduce the stress‐induced transcriptional upregulation of atrogin‐1, muscle ring finger protein 1, and myostatin, all of which are key molecules involved in muscle wasting. Moreover, this is the first demonstration that TMZ induces autophagy, a key mechanism involved in muscle mass regulation. On the basis of these results, it can be hypothesized that the improvement in exercise performance previously observed in patients could be ascribed to a cytoprotective mechanism exerted by TMZ on skeletal muscle integrity.
Microeukaryote community composition assessed by pyrosequencing is associated with light availability and phytoplankton primary production along a lowland river
Authors: Bradford Tessa M. , Morgan Matthew J. , Lorenz Zygmunt , Hartley Diana M. , Hardy Christopher M. , Oliver Roderick L.
Published: August 2013

The importance of microeukaryotes (protists, ciliates, fungi, algae and small invertebrates) in riverine food webs is well recognised, but the difficulty in surveying these taxa has meant that monitoring of biodiversity in rivers has focused on larger organisms.

Microeukaryote biodiversity was assessed by pyrosequencing of the conserved 18S rRNA gene during summer and autumn at two river sites and a weir pool site that form a flow gradient in the Murray River, Australia.

Concurrent measurements were made of phytoplankton concentrations, irradiance conditions, river metabolism and associated water quality attributes.

Based on operational taxonomic units derived from the molecular analyses, significant differences were identified in eukaryotes between the river and the weir pool.

Taxonomic assignment was possible for 66% of the operational taxonomic units, reflecting the large amount of unsurveyed diversity present.

Visual identification of algae corroborated the orders identified in the molecular data set, and more orders were detected using pyrosequencing.

Day length, depth of light penetration and phytoplankton biomass and primary productivity were strongly linked to eukaryote community composition suggesting the importance of algae as an energy source.

Our finding that microeukaryote biodiversity is linked with environmental characteristics demonstrates the potential of 18S rRNA pyrosequencing for more comprehensive assessment of the condition of an aquatic ecosystem, but further data are required to confirm this potential.
Land‐sharing versus land‐sparing logging: reconciling timber extraction with biodiversity conservation
Authors: Edwards David P. , Gilroy James J. , Woodcock Paul , Edwards Felicity A. , Larsen Trond H. , Andrews David J. R. , Derhé Mia A. , Docherty Teegan D. S. , Hsu Wayne W. , Mitchell Simon L. , Ota Takahiro , Williams Leah J. , Laurance William F. , Hamer Keith C. , Wilcove David S.
Published: August 2013

Selective logging is a major driver of rainforest degradation across the tropics. Two competing logging strategies are proposed to meet timber demands with the least impact on biodiversity: land sharing, which combines timber extraction with biodiversity protection across the concession; and land sparing, in which higher intensity logging is combined with the protection of intact primary forest reserves. We evaluate these strategies by comparing the abundances and species richness of birds, dung beetles and ants in Borneo, using a protocol that allows us to control for both timber yield and net profit across strategies. Within each taxonomic group, more species had higher abundances with land‐sparing than land‐sharing logging, and this translated into significantly higher species richness within land‐sparing concessions. Our results are similar when focusing only on species found in primary forest and restricted in range to Sundaland, and they are independent of the scale of sampling. For each taxonomic group, land‐sparing logging was the most promising strategy for maximizing the biological value of logging operations.
Myeloid‐derived suppressor cells: the dark knight or the joker in viral infections?
Authors: Goh Celeste , Narayanan Sowmya , Hahn Young S.
Published: August 2013

Myeloid derived suppressor cells (MDSCs) are immature cells of myeloid origin, frequently found in tumor microenvironments and in the blood of cancer patients. In recent years, MDSCs have also been found in non‐cancer settings, including a number of viral infections. The evasion of host immunity employed by viruses to establish viral persistence strikingly parallels mechanisms of tumor escape, prompting investigations into the generation and function of MDSCs in chronic viral infections. Importantly, analogous to the tumor microenvironment, MDSCs effectively suppress antiviral host immunity by limiting the function of several immune cells including T cells, natural killer cells, and antigen‐presenting cells. In this article, we review studies on the mechanisms of MDSC generation, accumulation, and survival in an effort to understand their emergent importance in viral infections. We include a growing list of viral infections in which MDSCs have been reported. Finally, we discuss how MDSCs might play a role in establishing chronic viral infections and identify potential therapeutics that target MDSCs.
Antiviral memory phenotype T cells in unexposed adults
Authors: Su Laura F. , Davis Mark M.
Published: August 2013

αβ T cells are an integral part of protective immunity against pathogens. After precursor cells arise in the adult bone marrow or fetal liver, they migrate to the thymus where they rearrange their T‐cell receptor genes (TCR) and undergo selection on the basis of their interactions with ligands expressed by thymic stroma and other cells. Those that survive then exit the thymus to populate the peripheral immune compartment, where they patrol the blood and lymphoid systems. The composition of this pre‐immune peripheral repertoire is critically important in determining the robustness of an immune response. In both mice and humans, the magnitude and diversity of a response are directly correlated with the frequency of precursor T cells. Equally relevant are the functional characteristics of these lymphocytes. Engagement of a specific antigen to the TCR activates signaling pathways in the naive T cell that result in cellular proliferation and the acquisition of particular effector functions. A portion of these persist following the resolution of infection and become memory cells. These memory cells can mount a faster and stronger response when they encounter the same antigen at a later time. As the molecular basis for TCR ligand interaction has become better defined, it is clear that some T cells can recognize multiple distinct ligands and therefore T‐cell memory developed by exposure to one ligand may play a significant role in the response to a different antigen. Thus, there is an increasing focus on understanding how exposure to related or unrelated antigens influences the T‐cell repertoire and impacts subsequent immunity. In this review, we discuss the issue of TCR cross‐reactivity in the development of memory phenotype CD4+ T cells and the implications for pathogen‐specific responses. We review both the human and mouse data and discuss the therapeutic implications of these findings in the contexts of infection and vaccination.