Invited review: Nutritional and management factors that influence colostrum production and composition in dairy cows

Colostrum is a rich source of nutritional and non-nutritional components and is recognized as essential to transfer passive immunity to newborn calves. Because of the individual and seasonal variability in colostrum yield and composition, maintaining an adequate supply of high-quality colostrum year-round remains a challenge for commercial dairy producers. In this narrative review, we described the individual, seasonal, and herd-level variability of colostrum production and summarized the association between individual animal factors such as parity, sex of the calf, calf birth weight, as well as indicators of the cow's metabolic status and the yield and composition of colostrum. Further, we reviewed the current knowledge on the influence of prepartum nutrition and management strategies on colostrum production. Research on the metabolizable energy and protein supplied in the prepartum diet as well as on the inclusion and source of vitamins, minerals, and feed additives suggests prepartum nutrition influences the yield, quality, and composition of colostrum. Furthermore, the prepartum environment and dry period length remain influential factors in the production of colostrum. However, additional research is needed to understand the mechanisms by which prepartum nutrition and management affect colostrum production. Finally, time from calving to colostrum harvest and oxytocin administration as well as the current knowledge on the effect of heat treatment and colostrum storage strategies on colostral components were discussed. To conclude, we identify critical gaps in knowledge for future focus of investigation in colostrum research

Relationship between Intracellular Concentration of S-Adenosylhomocysteine and Inhibition of Vaccinia Virus Replication and Inhibition of Murine L-929 Cell Growth

9-(trans-2',trans-3'-Dihydroxycyclopent-4'-enyl)-adenine (compound 1) and -3-deazaadenine (compound 2), which are specific inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, were reported earlier by our laboratory (M. Hasobe, J. G. McKee, D. R. Borcherding, and R. T. Borchardt, Antimicrob. Agents Chemother. 31:1849-1851, 1987) to have anti-vaccinia virus activity with reduced murine L-929 cell toxicity compared with the prototype compound neplanocin A. In this study, we showed that the antiviral and cytotoxic effects of compounds 1 and 2 can be related to intracellular concentrations of AdoHey, which are elevated in cells treated with these inhibitors of AdoHcy hydrolase. For example, concentrations of analogs 1 and 2 that produce 50% inhibition of vaccinia virus replication caused only slight elevations in intracellular levels of AdoHcy (from 50 [controls] to 100 to 125 [drug-treated cells] pmol/mg of protein) and elevations in the ratios of AdoHcy/S-adenosylmethionine (from 0.05 to 0.1 [controls] to 0.15 to 0.19 [drug-treated cells]). In contrast to the extreme susceptibility of virus replication to slight elevations in intracellular AdoHcy, cell viability was quite tolerant to higher levels of this metabolite. For example, concentrations of analogs 1 and 2 that produced 50% inhibition of L-929 cell replication caused significant increases in intracellular levels of AdoHcy (to 825 to 950 pmol/mg of protein) and elevations in AdoHcy/S-adenosylmethionine ratios (approximately 1.3). These data make it possible to assign a therapeutic index of 7 to 8 to these compounds on the basis of the comparison of intracellular levels of AdoHcy that caused 50% inhibition of vaccinia virus replication with those that caused 50% inhibition of L-929 cell replication.This work was supported by a Public Health Service grant from the National Institutes of Health (GM-29332) and a grant from Glaxo, Inc

Probing the helical content of growth hormone-releasing factor analogs using electrospray ionization mass spectrometry

AbstractA series of growth hormone-releasing factor analogs have been studied by both circular dichroism and electrospray ionization mass spectrometry (ESI/MS). The peptides are 32 residues long and are known to adopt a random-coil structure in aqueous solution but become increasing helical as the proportion of organic solvent is increased. Deuterium exchange was observed as an increase in mass of the peptide, as measured by ESI/MS. Rates of exchange were measured and half-lives calculated for analogs containing amino acid substitutions designed to promote or discourage helix formation. Exchange was slower in peptides that are helical (as shown by circular dichroism) than in randomly coiled peptides. Solution conditions that favor helix formation also produced slower exchange rates. These studies suggest that ESI/MS can provide date about the extent and stability of helix formation

A Ransomware Case for Use in the Classroom

Given the global growth in ransomware attacks, employees need to understand the risks of ransomware and how to protect against it. This paper presents a teaching case based on an actual ransomware attack on a hospital that undergraduate or graduate course can use to teach students. The case introduces students to Wildcat Hospital, a fictitious 450-bed acute-care facility in a suburban location in the Northeastern United States. A ransomware attack hit Wildcat Hospital as the workday began. Malware infected the hospital\u27s computers and demanded one bitcoin, a virtual currency that affords anonymity, as ransom to restore functionality of the information systems. The chief executive officer and the chief information officer led the organizational response to the attack. We include links to two videos, a demo of a Locky ransomware attack in action, and a National Broadcasting Company (NBC) TV network news report about a similar ransomware incident at another hospital (Hollywood Presbyterian Medical Center in California) to engage students

9-(trans-2',trans-3'-Dihydroxycyclopent-4'-Enyl)-Adenine and -3-Deazaadenine: Analogs of Neplanocin A Which Retain Potent Antiviral Activity but Exhibit Reduced Cytotoxicity

Two synthetic analogs of neplanocin A, which were shown in a separate study to be inhibitors of S-adenosylhomocysteine hydrolase and devoid of substrate activity with adenosine kinase, were found in this study to inhibit vaccinia virus replication in murine L929 cells but to have reduced cytotoxicity compared with that of the parent compound. These results confirm that S-adenosylhomocysteine hydrolase is the molecular target which mediates the antiviral effects of neplanocin A and that transformation by cellular adenosine kinase mediates its cytotoxic properties.This work was supported by Public Health Service research grant GM-29332 from the National Institutes of Health

Crystallization and preliminary X-ray analysis of human placental S-adenosylhomocysteine hydrolase

A recombinant form of human placental S-adenosylhomocysteine (AdoHcy) hydrolase expressed in E. coli, which was inactivated by a type-I mechanism-based inhibitor, has been crystallized using the hanging-drop vapour-diffusion technique. The crystals grow as fiat plates, with unit-cell dimensions a=96.2, b=173.6, c=142.9A, ct=fl=7=90 °. The crystals exhibit the symmetry of space group C222 and diffract to a minimum spacing of "-~ 2.0 A resolution at the Cornell High Energy Synchrotron Source. On the basis of density calculations two monomers of the tetrameric protein are estimated to be present in the asymmetric unit (Vm = 2.99 ,~3 Da-l). The selfrotation function clearly indicates the location of the noncrystallographic twofold axis.The authors would like to thank Steve Ealick and colleagues at CHESS for access to these facilities. This work is supported by a grant from the NIH (GM29332) to RTB