605 research outputs found
Tracking elusive cargo: Illuminating spatio-temporal type 3 effector protein dynamics using reporters
Type 3 secretion systems (T3SS) form an integral part of the arsenal of many pathogenic bacteria. These injection machines, together with their cargo of subversive effector proteins are capable of manipulating the cellular environment of the host in order to ensure persistence of the pathogen. In order to fully appreciate the functions of Type 3 effectors it is necessary to gain spatio-temporal knowledge of each effector during the process of infection. A number of genetic modifications have been exploited in order to reveal effector protein secretion, translocation and subsequent activity and localisation within host cells. In this review, we will discuss the many available approaches for tracking effector protein dynamics and discuss the challenges faced to improve the current technologies and gain a clearer picture of effector protein function
CONTROL OF XENON INSTABILITIES IN LARGE PWR'S. Quarterly Progress Report for the Period Ending December 31, 1968.
The miRNAome of the postpartum dairy cow liver in negative energy balance
peer-reviewedBackground: Negative energy balance (NEB) is an altered metabolic state in high yielding cows that occurs during the first few weeks postpartum when energy demands for lactation and maintenance exceed the energy supply from dietary intake. NEB can, in turn, lead to metabolic disorders and to reduced fertility. Alterations in the expression of more than 700 hepatic genes have previously been reported in a study of NEB in postpartum dairy cows. miRNAs (microRNA) are known to mediate many alterations in gene expression post transcriptionally. To study the hepatic miRNA content of postpartum dairy cows, including their overall abundance and differential expression, in mild NEB (MNEB) and severe NEB (SNEB), short read RNA sequencing was carried out. To identify putative targets of differentially expressed miRNAs among differentially expressed hepatic genes reported previously in dairy cows in SNEB computational target identification was employed.
Results: Our results indicate that the dairy cow liver expresses 53 miRNAs at a lower threshold of 10 reads per million. Of these, 10 miRNAs accounted for greater than 95% of the miRNAome (miRNA content). Of the highly expressed miRNAs, miR-122 constitutes 75% followed by miR-192 and miR-3596. Five out of thirteen let-7 miRNA family members are also among the highly expressed miRNAs. miR-143, down-regulated in SNEB, was found to have 4 putative up-regulated gene targets associated with SNEB including LRP2 (low density lipoprotein receptor-related protein 2), involved in lipid metabolism and up-regulated in SNEB.
Conclusions: This is the first liver miRNA-seq profiling study of moderate yielding dairy cows in the early postpartum period. Tissue specific miR-122 and liver enriched miR-192 are two of the most abundant miRNAs in the postpartum dairy cow liver. miR-143 is significantly down-regulated in SNEB and putative targets of miRNA-143 which are up-regulated in SNEB, include a gene involved in lipid metabolism.Teagasc Walsh Fellowship Programm
Associations between the K232A polymorphism in the diacylglycerol-O-transferase 1 (DGAT1) gene and performance in Irish Holstein-Friesian dairy cattle
peer-reviewedSelection based on genetic polymorphisms requires accurate quantification of the
effect or association of the polymorphisms with all traits of economic importance.
The objective of this study was to estimate, using progeny performance data on 848
Holstein-Friesian bulls, the association between a non-conservative alanine to lysine
amino acid change (K232A) in exon 8 of the diacylglycerol-O-transferase 1 (DGAT1)
gene and milk production and functionality in the Irish Holstein-Friesian population.
The DGAT1 gene encodes the diacylglycerol-O-transferase microsomal enzyme
necessary to catalyze the final step in triglyceride synthesis. Weighted mixed model
methodology, accounting for the additive genetic relationships among animals, was
used to evaluate the association between performance and the K232A polymorphism.
The minor allele frequency (K allele) was 0.32. One copy of the K allele was associated
(P < 0.001) with 77 kg less milk yield, 4.22 kg more fat yield, 0.99 kg less protein
yield, and 1.30 and 0.28 g/kg greater milk fat and protein concentration, respectively;
all traits were based on predicted 305-day production across the first five lactations.
The K232A polymorphism explained 4.8%, 10.3% and 1.0% of the genetic variance in
milk yield, fat yield and protein yield, respectively. There was no association between
the K232A polymorphism and fertility, functional survival, calving performance,
carcass traits, or any conformation trait with the exception of rump width and carcass
conformation. Using the current economic values for the milk production traits
in the Irish total merit index, one copy of the K allele is worth €5.43 in expected
profitability of progeny. Results from this study will be useful in quantifying the
cost-benefit of including the K232A polymorphism in the Irish national breeding programme
The effect of body mass index and melphalan dose adjustments on outcomes in patients undergoing autologous haematopoietic cell transplantation for multiple myeloma: a single-centre retrospective study
Neural Architecture Search as Program Transformation Exploration
Improving the performance of deep neural networks (DNNs) is important to both
the compiler and neural architecture search (NAS) communities. Compilers apply
program transformations in order to exploit hardware parallelism and memory
hierarchy. However, legality concerns mean they fail to exploit the natural
robustness of neural networks. In contrast, NAS techniques mutate networks by
operations such as the grouping or bottlenecking of convolutions, exploiting
the resilience of DNNs. In this work, we express such neural architecture
operations as program transformations whose legality depends on a notion of
representational capacity. This allows them to be combined with existing
transformations into a unified optimization framework. This unification allows
us to express existing NAS operations as combinations of simpler
transformations. Crucially, it allows us to generate and explore new tensor
convolutions. We prototyped the combined framework in TVM and were able to find
optimizations across different DNNs, that significantly reduce inference time -
over 3 in the majority of cases.
Furthermore, our scheme dramatically reduces NAS search time. Code is
available
at~\href{https://github.com/jack-willturner/nas-as-program-transformation-exploration}{this
https url}
MACiE: a database of enzyme reaction mechanisms.
SUMMARY: MACiE (mechanism, annotation and classification in enzymes) is a publicly available web-based database, held in CMLReact (an XML application), that aims to help our understanding of the evolution of enzyme catalytic mechanisms and also to create a classification system which reflects the actual chemical mechanism (catalytic steps) of an enzyme reaction, not only the overall reaction. AVAILABILITY: http://www-mitchell.ch.cam.ac.uk/macie/.EPSRC (G.L.H. and J.B.O.M.), the BBSRC (G.J.B. and J.M.T.—CASE studentship in association with Roche Products Ltd; N.M.O.B. and J.B.O.M.—grant BB/C51320X/1), the Chilean Government’s Ministerio de Planificacio´n y Cooperacio´n and
Cambridge Overseas Trust (D.E.A.) for funding and Unilever for supporting the Centre for Molecular Science Informatics.application note restricted to 2 printed pages web site: http://www-mitchell.ch.cam.ac.uk/macie
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