716 research outputs found
A longitudinal analysis of motivation profiles at work
This paper examines the multidimensional nature of workplace motivation and the importance of a continuum structure in self-determination theory through application of complementary variable- and person-centered approaches. This approach is taken to simultaneously model the complexity of motivation and highlight interactions between motivational factors. Additionally, this study represents an initial test of the temporal stability of work motivation profiles. A sample of 510 full-time employees were recruited from a range of occupations. Results support the central importance of a general factor representing self-determination as the most influential factor in an employee’s motivation profile. However, smaller effects associated with the motivation subscales, especially identified regulation, were also noticed. Importantly, motivation profiles were found to be highly stable over the 4-month duration of this study. Results lend support to the theoretical position that while general self-determination is an essential component of motivation, it alone does not fully describe an employee’s motivation
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Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA
DNA resection in eukaryotes: deciding how to fix the break
DNA double-strand breaks are repaired by different mechanisms, including homologous
recombination and nonhomologous end-joining. DNA-end resection, the first step in
recombination, is a key step that contributes to the choice of DSB repair. Resection, an
evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint
activation and is critical for survival. Failure to regulate and execute this process results in
defective recombination and can contribute to human disease. Here, I review recent findings on
the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the
regulatory strategies that control it, and highlight the consequences of both its impairment and its
deregulation
Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation
The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi
Cavity Induced Interfacing of Atoms and Light
This chapter introduces cavity-based light-matter quantum interfaces, with a
single atom or ion in strong coupling to a high-finesse optical cavity. We
discuss the deterministic generation of indistinguishable single photons from
these systems; the atom-photon entanglement intractably linked to this process;
and the information encoding using spatio-temporal modes within these photons.
Furthermore, we show how to establish a time-reversal of the aforementioned
emission process to use a coupled atom-cavity system as a quantum memory. Along
the line, we also discuss the performance and characterisation of cavity
photons in elementary linear-optics arrangements with single beam splitters for
quantum-homodyne measurements.Comment: to appear as a book chapter in a compilation "Engineering the
Atom-Photon Interaction" published by Springer in 2015, edited by A.
Predojevic and M. W. Mitchel
Wnt signalling in adenomas of familial adenomatous polyposis patients
BACKGROUND: Epigenetic silencing of Wnt antagonists and expression changes in genes associated with Wnt response pathways occur
in early sporadic colorectal tumourigenesis, indicating that tumour cells are more sensitive to Wnt growth factors and respond
differently. In this study, we have investigated whether similar changes occur in key markers of the Wnt response pathways in the
genetic form of the disease, familial adenomatous polyposis (FAP).
METHODS: We investigated epigenetic and expression changes using pyrosequencing and real-time RT-PCR in samples from seven
patients without neoplasia, and matched normal and tumour tissues from 22 sporadic adenoma and 14 FAP patients.
RESULTS: We found that 17 out of 24 (71%) FAP adenomas were hypermethylated at sFRP1, compared with 20 out of 22 (91%) of
sporadic cases. This was reflected at the level of sFRP1 transcription, where 73% of FAP and 100% of sporadic cases were downregulated.
Increased expression levels of c-myc and FZD3 were less common in FAP (35 and 46% respectively) than sporadic tumours
(78 and 67% respectively).
CONCLUSION: Overall, the changes in expression and methylation were comparable, although the degree of change was generally
lower in the FAP adenomas. Molecular heterogeneity between multiple adenomas from individual FAP patients may reflect different
developmental fates for these premalignant tumours
Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy
Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy
TRIPS implementation and secondary pharmaceutical patenting in Brazil and India
This article compares national approaches toward secondary pharmaceutical patents. Because secondary patents can extend periods of exclusivity and delay generic competition, they can raise prices and reduce access to medicines. Little is known about what measures countries have enacted policies to address applications for secondary pharmaceutical patents, how they function, and whether, in practice, these measures limit secondary patents. We analyze the cases of India and Brazil. We assemble data on pharmaceutical patent applications filed in the two countries, code each application to identify which constitute secondary applications, and examine outcomes for each application in both countries. The data indicate that Brazil is less likely to grant applications than India, but in both countries the measures designed to limit secondary patents are having little direct effect. This suggests, on the one hand, that critics of these policies, such as the transnational pharmaceutical sector and foreign governments, may be more worried than they should be. On the other hand, champions of the policies, such as NGOs and international organizations, may have cause for concern that laws on the books are not having the expected impact on patent outcomes in practice. Our findings also suggest that, at the drug level, the effects of countries’ approaches toward secondary patents need to be understood in the context of their broader approaches toward TRIPS implementation, including when and how they introduced pharmaceutical patents in the 1990s and 2000s
Altered Intracellular Localization and Mobility of SBDS Protein upon Mutation in Shwachman-Diamond Syndrome
Shwachman-Diamond Syndrome (SDS) is a rare inherited disease caused by mutations in the SBDS gene. Hematopoietic defects, exocrine pancreas dysfunction and short stature are the most prominent clinical features. To gain understanding of the molecular properties of the ubiquitously expressed SBDS protein, we examined its intracellular localization and mobility by live cell imaging techniques. We observed that SBDS full-length protein was localized in both the nucleus and cytoplasm, whereas patient-related truncated SBDS protein isoforms localize predominantly to the nucleus. Also the nucleo-cytoplasmic trafficking of these patient-related SBDS proteins was disturbed. Further studies with a series of SBDS mutant proteins revealed that three distinct motifs determine the intracellular mobility of SBDS protein. A sumoylation motif in the C-terminal domain, that is lacking in patient SBDS proteins, was found to play a pivotal role in intracellular motility. Our structure-function analyses provide new insight into localization and motility of the SBDS protein, and show that patient-related mutant proteins are altered in their molecular properties, which may contribute to the clinical features observed in SDS patients
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