Responses to supplementation by dairy cows given low pasture allowances in different seasons 2. Milk production

Two factorial experiments were designed to determine the effects of stage of lactation, and season of the year, on cow responses to supplementary feeding. These experiments were conducted over consecutive years with 128 high genetic merit multiparous Holstein-Friesian cows in early, mid and late lactation in spring, summer, autumn and winter. At each stage of lactation, and in each season of the year, cows were offered a restricted pasture allowance (25 to 35 kg dry matter (DM) per cow per day), either unsupplemented (control) or with supplement at 50 MJ metabolizable energy (ME) per cow per day in experiment 1 and 80 MJ ME per cow per day in experiment 2. The two supplements given in both years were rolled maize grain (MG) and a mixture of foods formulated to nutritionally balance the diet (BR). In experiment 2, another treatment, of a generous pasture allowance (60 to 75 kg DM per cow per day) (AP), was imposed on an additional group of early lactation cows during each season. Direct milk solids (MS) (milk fat plus milk protein) responses in experiment 1 to MG were 169, 279, 195 and 251 g MS per cow per day in spring, summer, autumn and winter, respectively, while those to BR were 107, 250, 192, 289 g MS per cow per day. In experiment 2, however, milk solids responses to both supplements during spring were slightly below the control treatment, with values similar to those in experiment 1 in summer and autumn for cows on the BR but not the MG supplement. Milk solids responses to supplementary foods were largest during seasons of the year when the quantity and quality of pasture on offer resulted in the lowest milk solids yield from unsupplemented cows. When carry-over effects of feeding MG and BR on milk solids production were detected, they were only about half the magnitude of the direct effects. Serum urea concentrations were higher in control cows than those offered MG with a similar effect for BR in all but summer in experiment 1, while serum glucose concentrations were highest in winter and lowest in summer. The most important factor influencing milk solids responses was the relative food deficit (RFD) represented by the decline in milk solids yield of the respective control groups after,changing from a generous pasture allowance to restricted allowance when the feeding treatments were imposed. Total milk solids responses (direct and carry-over) to supplements were greatest when severe food restrictions, relative to the cows' current food demand, resulted in large reductions in milk solids yield of the control groups. The RFD was the best predictor of milk solids response to supplementary foods. Therefore, it is likely that cows are most responsive to supplementary foods during or immediately after the imposition of a severe food restriction

Responses to supplementation by dairy cows given low pasture allowances in different seasons 1. Pasture intake and substitution

Two factorial experiments were designed to determine the effects of stage of lactation, and season of the year, on cow responses to supplementary feeding. These experiments were conducted over consecutive years with 128 high genetic merit multiparous Holstein-Friesian cows in early, mid and late lactation in spring, summer, autumn and winter. At each stage of lactation, and in each season of the year, cows were offered a restricted pasture allowance (25 to 35 kg dry matter (DM) per cow per day), either unsupplemented (control) or supplemented with 50 MJ metabolizable energy (ME) per cow per day in experiment 1 and 80 MJ ME per cow per day in experiment 2. Two different supplements were offered, namely, rolled maize grain (MG) and a mixture of foods (BR) formulated to nutritionally balance the diet. In experiment 2, a fourth treatment consisting solely of a generous pasture allowance (60 to 75 kg DM per cow per day, AP) was introduced. Offering MG and BR increased DM intake (DMI). At the restricted pasture allowance, increasing total ME allowance (MEA) by offering supplementary foods increased ME intake (MEI) by 0.68 (s.e. 0.047) MJ per extra MJ ME offered. This highly significant (P < 0.001) linear relationship was consistent across seasons, and did not diminish at higher MEA. In experiment 2, cows in early lactation had lower substitution rates than mid and late lactation cows irrespective of season. Substitution rate was higher when higher pasture allowance or quality of pasture on offer enabled the unsupplemented cows to achieve higher DMI from pasture than at other times of the year. These results suggest that one of the key factors determining the intake response to supplementary foods is pasture allowance. Within spring calving dairying systems, the largest increases in total DMI per kg of supplement offered is likely when offering supplements to early lactation cows grazing restricted allowances of high quality pasture

The Effects of Reputation and Ethics on Budgetary Slack

This experimental study tests the effects on budgetary slack of two potential controls for opportunistic self-interestóreputation and ethics. I manipulate the level of information asymmetry between the subordinate and the superior regarding productive capability and measure the subordinateís reputation and ethical concerns regarding budgetary slack. In this setting, I examine how information asymmetry affects reputation and ethical concerns, and test the effects of these concerns on budgetary slack. Consistent with prior findings, subordinates restrict the slack in their budgets to well below the maximum under a slackinducing pay scheme, even after five periods of experience. Budgetary slack is negatively associated with a measure of ethical responsibility from a pre-experiment personality questionnaire as well as reputation and ethical concerns expressed in an exit questionnaire. Subordinates express lower reputation concerns as information asymmetry regarding productive capability increases, thereby reducing the superiorís ability to monitor the slack in their budget. Ethical concerns, however, are not diminished with increases in information asymmetry. These results suggest that reputation is a socially mediated control, whereas ethics is an internally mediated control for opportunistic self-interest

A major electronics upgrade for the H.E.S.S. Cherenkov telescopes 1-4

The High Energy Stereoscopic System (H.E.S.S.) is an array of imaging atmospheric Cherenkov telescopes (IACTs) located in the Khomas Highland in Namibia. It consists of four 12-m telescopes (CT1-4), which started operations in 2003, and a 28-m diameter one (CT5), which was brought online in 2012. It is the only IACT system featuring telescopes of different sizes, which provides sensitivity for gamma rays across a very wide energy range, from ~30 GeV up to ~100 TeV. Since the camera electronics of CT1-4 are much older than the one of CT5, an upgrade is being carried out; first deployment was in 2015, full operation is planned for 2016. The goals of this upgrade are threefold: reducing the dead time of the cameras, improving the overall performance of the array and reducing the system failure rate related to aging. Upon completion, the upgrade will assure the continuous operation of H.E.S.S. at its full sensitivity until and possibly beyond the advent of CTA. In the design of the new components, several CTA concepts and technologies were used and are thus being evaluated in the field: The upgraded read-out electronics is based on the NECTAR readout chips; the new camera front- and back-end control subsystems are based on an FPGA and an embedded ARM computer; the communication between subsystems is based on standard Ethernet technologies. These hardware solutions offer good performance, robustness and flexibility. The design of the new cameras is reported here.Comment: Proceedings of the 34th International Cosmic Ray Conference, 30 July- 6 August, 2015, The Hague, The Netherland

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract

Structural, mechanistic and regulatory studies of serine palmitoyltransferase

SLs (sphingolipids) are composed of fatty acids and a polar head group derived from l-serine. SLs are essential components of all eukaryotic and many prokaryotic membranes but S1P (sphingosine 1-phosphate) is also a potent signalling molecule. Recent efforts have sought to inventory the large and chemically complex family of SLs (LIPID MAPS Consortium). Detailed understanding of SL metabolism may lead to therapeutic agents specifically directed at SL targets. We have studied the enzymes involved in SL biosynthesis; later stages are species-specific, but all core SLs are synthesized from the condensation of l-serine and a fatty acid thioester such as palmitoyl-CoA that is catalysed by SPT (serine palmitoyltransferase). SPT is a PLP (pyridoxal 5'-phosphate)-dependent enzyme that forms 3-KDS (3-ketodihydrosphingosine) through a decarboxylative Claisen-like condensation reaction. Eukaryotic SPTs are membrane-bound multi-subunit enzymes, whereas bacterial enzymes are cytoplasmic homodimers. We use bacterial SPTs (e. g. from Sphingomonas) to probe their structure and mechanism. Mutations in human SPT cause a neuropathy [HSAN1 (hereditary sensory and autonomic neuropathy type 1)], a rare SL metabolic disease. How these mutations perturb SPT activity is subtle and bacterial SPT mimics of HSAN1 mutants affect the enzyme activity and structure of the SPT dimer. We have also explored SPT inhibition using various inhibitors (e. g. cycloserine). A number of new subunits and regulatory proteins that have a direct impact on the activity of eukaryotic SPTs have recently been discovered. Knowledge gained from bacterial SPTs sheds some light on the more complex mammalian systems. In the present paper, we review historical aspects of the area and highlight recent key developments.</p

Characterization of the Promoter, MxiE Box and 5′ UTR of Genes Controlled by the Activity of the Type III Secretion Apparatus in Shigella flexneri

Activation of the type III secretion apparatus (T3SA) of Shigella flexneri, upon contact of the bacteria with host cells, and its deregulation, as in ipaB mutants, specifically increases transcription of a set of effector-encoding genes controlled by MxiE, an activator of the AraC family, and IpgC, the chaperone of the IpaB and IpaC translocators. Thirteen genes carried by the virulence plasmid (ospB, ospC1, ospD2, ospD3, ospE1, ospE2, ospF, ospG, virA, ipaH1.4, ipaH4.5, ipaH7.8 and ipaH9.8) and five genes carried by the chromosome (ipaHa-e) are regulated by the T3SA activity. A conserved 17-bp MxiE box is present 5′ of most of these genes. To characterize the promoter activity of these MxiE box-containing regions, similar ∼67-bp DNA fragments encompassing the MxiE box of 14 MxiE-regulated genes were cloned 5′ of lacZ in a promoter probe plasmid; β-galactosidase activity detected in wild-type and ipaB strains harboring these plasmids indicated that most MxiE box-carrying regions contain a promoter regulated by the T3SA activity and that the relative strengths of these promoters cover an eight-fold range. The various MxiE boxes exhibiting up to three differences as compared to the MxiE box consensus sequence were introduced into the ipaH9.8 promoter without affecting its activity, suggesting that they are equally efficient in promoter activation. In contrast, all nucleotides conserved among MxiE boxes were found to be involved in MxiE-dependent promoter activity. In addition, we present evidence that the 5′ UTRs of four MxiE-regulated genes enhance expression of the downstream gene, presumably by preventing degradation of the mRNA, and the 5′ UTRs of two other genes carry an ancillary promoter