Manipulation of plasma myo-inositol in broiler chickens: effect on growth performance, dietary energy, nutrient availability, and hepatic function

This study investigated the effects of graded levels of myo-inositol (INS) in diets containing 2 levels of available P on growth performance, nutrient retention, liver N, fat and Vitamin E contents, INS and alkaline phosphatase (ALP) concentrations in blood plasma. A total of 120 male Ross 308 broilers were allocated to 60 small floor pens each holding 2 birds. Two basal mash diets were formulated to be nutritionally adequate for chicks at that age, with one diet designed to have the recommended available P content (RP) (4.8 g/kg non-phytate P) and the other diet containing low available P (LP) (2.5 g/kg non-phytate P). The 2 basal diets were split in 3 batches each and 2 of the batches were supplemented with INS at 3.0 and 30 g/kg diet, with the remaining batch of each basal diet not supplemented, giving a total of 6 experimental diets. Diets were fed ad libitum to 10 pens from 7 to 21 d age following randomization. Feeding RP diets improved (P 0.05) influence bird growth, dietary AME, or nutrient retention coefficients. Feeding INS linearly increased (P 0.05) the endogenous losses (measured as sialic acid concentration) in excreta. Dietary INS did not influence (P > 0.05) the hepatic Vitamin E concentration but increased (P < 0.001) the ALP in the blood of birds fed 30 g/kg INS. In conclusion, highlevel dietary INS supplementation did not affect bird growth performance, mineral availability, and endogenous losses, and there were no interactions between INS and P

Development of hepatic pathology in GBV‐B‐infected red‐bellied tamarins (Saguinus labiatus)

GB virus B (GBV‐B) is a new world monkey‐associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post‐infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver‐associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV‐B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology

UK science press officers, professional vision and the generation of expectations

Science press officers can play an integral role in helping promote expectations and hype about biomedical research. Using this as a starting point, this article draws on interviews with 10 UK-based science press officers, which explored how they view their role as science reporters and as generators of expectations. Using Goodwin’s notion of ‘professional vision’, we argue that science press officers have a specific professional vision that shapes how they produce biomedical press releases, engage in promotion of biomedical research and make sense of hype. We discuss how these insights can contribute to the sociology of expectations, as well as inform responsible science communication.This project was funded by the Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034)

Ramified rectilinear polygons: coordinatization by dendrons

Simple rectilinear polygons (i.e. rectilinear polygons without holes or cutpoints) can be regarded as finite rectangular cell complexes coordinatized by two finite dendrons. The intrinsic $l_1$-metric is thus inherited from the product of the two finite dendrons via an isometric embedding. The rectangular cell complexes that share this same embedding property are called ramified rectilinear polygons. The links of vertices in these cell complexes may be arbitrary bipartite graphs, in contrast to simple rectilinear polygons where the links of points are either 4-cycles or paths of length at most 3. Ramified rectilinear polygons are particular instances of rectangular complexes obtained from cube-free median graphs, or equivalently simply connected rectangular complexes with triangle-free links. The underlying graphs of finite ramified rectilinear polygons can be recognized among graphs in linear time by a Lexicographic Breadth-First-Search. Whereas the symmetry of a simple rectilinear polygon is very restricted (with automorphism group being a subgroup of the dihedral group $D_4$), ramified rectilinear polygons are universal: every finite group is the automorphism group of some ramified rectilinear polygon.Comment: 27 pages, 6 figure

Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20-37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1-2 (n = 27) and non-responders classified as TRG4-5 (n =38). We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs. 1.70/Mb, p = 0.036) and elevated copy number variation in non-responders (282 vs. 136/patient, p < 0.001). We identified copy number variants unique to each group in our cohort, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC

A Freeze Frame View of Vesicular Stomatitis Virus Transcription Defines a Minimal Length of RNA for 5′ Processing

The RNA synthesis machinery of vesicular stomatitis virus (VSV) comprises the genomic RNA encapsidated by the viral nucleocapsid protein (N) and associated with the RNA dependent RNA polymerase, the viral components of which are a large protein (L) and an accessory phosphoprotein (P). The 241 kDa L protein contains all the enzymatic activities necessary for synthesis of the viral mRNAs, including capping, cap methylation and polyadenylation. Those RNA processing reactions are intimately coordinated with nucleotide polymerization such that failure to cap results in termination of transcription and failure to methylate can result in hyper polyadenylation. The mRNA processing reactions thus serve as a critical check point in viral RNA synthesis which may control the synthesis of incorrectly modified RNAs. Here, we report the length at which viral transcripts first gain access to the capping machinery during synthesis. By reconstitution of transcription in vitro with highly purified recombinant polymerase and engineered templates in which we omitted sites for incorporation of UTP, we found that transcripts that were 30-nucleotides in length were uncapped, whereas those that were 31-nucleotides in length contained a cap structure. The minimal RNA length required for mRNA cap addition was also sufficient for methylation since the 31-nucleotide long transcripts were methylated at both ribose-2′-O and guanine-N-7 positions. This work provides insights into the spatial relationship between the active sites for the RNA dependent RNA polymerase and polyribonucleotidyltransferase responsible for capping of the viral RNA. We combine the present findings with our recently described electron microscopic structure of the VSV polymerase and propose a model of how the spatial arrangement of the capping activities of L may influence nucleotide polymerization

The association of homeobox gene expression with stem cell formation and morphogenesis in cultured Medicago truncatula

Somatic embryogenesis (SE) is induced in vitro in Medicago truncatula 2HA by auxin and cytokinin but rarely in wild type Jemalong. The putative WUSCHEL (MtWUS), CLAVATA3 (MtCLV3) and the WUSCHEL-related homeobox gene WOX5 (MtWOX5) were investigated in M. truncatula (Mt) and identified by the similarity to Arabidopsis WUS, CLV3 and WOX5 in amino acid sequence, phylogeny and in planta and in vitro expression patterns. MtWUS was induced throughout embryogenic cultures by cytokinin after 24–48 h and maximum expression occurred after 1 week, which coincides with the induction of totipotent stem cells. During this period there was no MtCLV3 expression to suppress MtWUS. MtWUS expression, as illustrated by promoter-GUS studies, subsequently localised to the embryo, and there was then the onset of MtCLV3 expression. This suggests that the expression of the putative MtCLV3 coincides with the WUS-CLAVATA feedback loop becoming operational. RNAi studies showed that MtWUS expression is essential for callus and somatic embryo production. Based on the presence of MtWUS promoter binding sites, MtWUS may be required for the induction of MtSERF1, postulated to have a key role in the signalling required for SE induced in 2HA. MtWOX5 expressed in auxin-induced root primordia and root meristems and appears to be involved in pluripotent stem cell induction. The evidence is discussed that the homeobox genes MtWUS and MtWOX5 are “hijacked” for stem cell induction, which is key to somatic embryo and de novo root induction. In relation to SE, a role for WUS in the signalling involved in induction is discussed