Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

CNS mastitis: nothing to worry about?

In this paper, we analyzed a very large field data set on intramammary infections (IMI) and the associated somatic cell count (SCC) in dairy cows. The objective of the study was to analyze the impact of coagulase-negative staphylococci (CNS) IMI on cow SCC, both mean and variability, and on the potential of these infections to have a major impact on the bulk milk SCC (BMSCC). Data and milk samples for bacterial culture were collected by Quality Milk Production Services (QMPS) between 1992 and March of 2007. The QMPS program services dairy farms in New York State and other states in the Northeastern USA and operates in conjunction with Cornell University. Only records from cows where SCC and milk production data were available, and where only one organism was isolated from bacterial cultures of milk samples (or where culture was negative) were used for this analysis. A total of 352,614 records from 4200 whole herd mastitis screening sampling qualified for this study. Within herds an average of 15% (S.D. 12%) of cows sampled were infected with CNS, ranging between 0 and 100%. Average within herd prevalence of cows with a CNS IMI and an SCC over 200,000 cells/ml was 2% (S.D. 4%) with a minimum of 0% and a maximum of 50%. Results of linear mixed models showed three distinct populations of IMI statuses: negative cultures with the lowest SCC; CNS and Corynebacterium bovis with a moderate increase in SCC, and Streptococcus agalactiae, Streptococcus spp. and Staphylococcus aureus showing an important increase in SCC. Surprisingly, milk production was slightly but significantly higher in CNS infected cows compared to culture-negative cows, whereas it was strongly reduced in cows with a major pathogen IMI. The percentage contribution of CNS infections to the BMSCC was 17.9% in herds with a BMSCC less than 200,000 cells/ml. This value decreased to 11.9 and 7.9% in herds with bulk milk SCC between 200,000 and 400,000 and over 400,000 cells/ml, respectively. We concluded that very few herds with milk quality problems would have an important increase in BMSCC that could be mostly attributed to CNS infections. On the other hand, in herds with low BMSCC, CNS infections may be an important contributor to the total number of somatic cells in the bulk milk.     

Biochemical genetics of oxidative resistance to diazinon in the house fly

The genetics and biochemistry of oxidative resistance to diazinon were investigated in a diazinon-resistant strain of the house fly, Musca domestica L. The resistant strain was crossed with a multimarker susceptible strain and substrains containing portions of the resistant strain genome were prepared. Resistance, microsomal oxidase, and cytochrome P-450 spectral characteristics were then compared in the different strains. The major gene for resistance to diazinon is semidominant and is located on chromosome II, 13 crossing over units from the recessive mutant stubby wing. Additional resistance genes occur on chromosome II and on other chromosomes as well. Resistance to diazinon was introduced into a susceptible mutant-marked strain via genetic crossing over. Increases in parathion oxidase, total and P-450-specific N- and O-demethylase activity, and resistant strain type I binding spectrum were introduced along with resistance, indicating genes controlling these parameters and resistance are either identical or closely linked. No increase in activity of cytochrome P-450 itself was introduced into the mutant strain. Additional genes controlling the amount of cytochrome P-450 and several spectral changes characteristic of the resistant strains are apparently controlled by genes located at different loci on chromosome II. Resistance factors on other chromosomes are also present, but were not characterized.     

Evaluation of hemostatic defects secondary to vascular tumors in dogs: 11 cases (1983-1988)

Two populations of dogs with cutaneous hemangiomas and hemangiosarcomas were evaluated retrospectively. One population consisted of 96 dogs seen at the Veterinary Medical Teaching Hospital at the University of California, Davis. The second population consisted of 116 dogs that had skin biopsy specimens submitted to a private veterinary diagnostic laboratory for histologic diagnosis. Nine dogs from the teaching hospital and 2 dogs, from which samples had been submitted to the veterinary diagnostic laboratory, developed hemostatic defects in association with the tumors. Hemostatic defects included hemorrhage directly from the tumor, thrombocytopenia, hypofibrinogenemia, and findings associated with disseminated intravascular coagulation. Because bleeding during surgery can develop in animals with hemostatic defects, dogs with one or more tumors suspected of being vascular in origin should have platelet numbers and hemostatic analytes evaluated prior to surgery, especially if petechiae or ecchymoses are evident.     

The effect of feeding level and physiological status on total flow and amino acid composition of endogenous protein at the distal ileum in swine.

An experiment was conducted to investigate the effects of BW, feed intake, and the physiological condition of the animal on the loss and amino acid composition of endogenous protein in swine. Ten growing barrows and five multiparous sows were equipped with a T-cannula in the distal ileum for digesta collection. A protein-free diet was fed to all animals. The barrows were given free access to the experimental diet. The sows also were allowed to consume the diet on an ad libitum basis, and digesta were collected during lactation and in the following gestation period. In addition, digesta from the gravid sows were collected after restricting the sows to 2 kg of feed per day. For each animal group, the endogenous losses of protein and amino acids were calculated in relation to DMI, and the amino acid composition of endogenous protein was calculated. The total endogenous gut protein loss at the distal ileum of growing pigs, lactating sows, and gestating sows, given free access to feed, was 12.4, 9.4, and 11.2 g/kg DMI, respectively. These values were not different (P > .10). However, when gestating sows were fed only 2 kg/d, 17.8 g of endogenous protein was lost per kilogram of DMI, which was higher (P < .05) than for any of the other groups. This difference was mainly caused by higher (P < .05) losses of glycine, proline, and serine. There were no differences (P > .05) in amino acid composition of endogenous protein between growing pigs, lactating sows, and gestating sows given free access to feed, but restricted-fed gestating sows had an amino acid composition of endogenous protein that was significantly different from that of the other groups. The results from the experiment showed that age, BW, and the physiological condition of the animal have little or no effect on the amount of endogenous protein and amino acids lost at the distal ileum of hogs if calculated in relation to DMI. Likewise, the amino acid composition was not affected by the BW or physiological condition of the animal. However, DMI had a significant effect on endogenous protein losses in sows as well as on amino acid composition of endogenous protein.     

Cultivation of Pen Shells: An Example with Atrina maura in Northwestern Mexico

Pen shells are economically important and most are threatened by overexploitation and habitat degradation. Cultivation represents an alternative for preserving the resource and increasing the production. Atrina maura was cultivated in a suspension system which was followed by a bottom phase. Samples of pen shells and tissues were collected monthly to measure absolute growth, shell height increase, and an adductor muscle index. After the trials, adults shell height was 195 ± 10 mm, total weight was 223 ± 28 g, and mean shell height increase was 0.81 cm/mo. Protective devices were vital to avoid predation by crabs and fish; survival was 90% in the suspension phase and 70% in the bottom phase. Variations in the muscle index were apparently related to reproduction, suggesting activity (partial spawning) from August 2008 to April 2009 in juveniles and a major spawning in adults during August 2009. Adductor muscles reached a mean of 21 g after 20 mo of cultivation, but muscle weights decreased significantly after reproduction (August to November 2009). Results indicated that A. maura is suitable for aquaculture and the cultivation system adopted here should be tested in pilot‐scale ventures. This system may work with other species of pen shells.     

Dietary plasticity in Arctic charr (Salvelinus alpinus) in response to long‐term environmental change

Corrigan LJ, Winfield IJ, Hoelzel AR, Lucas MC. Dietary plasticity in Arctic charr (Salvelinus alpinus) in response to long‐term environmental change.
Ecology of Freshwater Fish 2011: 20: 5–13. © 2010 John Wiley & Sons A/S Abstract –  In the face of widespread environmental change impacts, there is a need to better understand mechanisms promoting flexibility and resilience of ecosystem components to such change to inform strategies for conservation. Glacial relict species are especially vulnerable to such changes. We investigated the behavioural responses of a native, glacial relict species, Arctic charr (Salvelinus alpinus) to long‐term environmental changes. It was hypothesised that changes in feeding behaviour would occur as a key intermediary to reduction in habitat availability (through climate change and eutrophication) or competitive interactions [with introduced roach (Rutilus rutilus)]. Stomach content analysis was used to assess the diet of 199 charr caught from Windermere, United Kingdom, in the months of March, June, September and November 2003–2007. The results were compared to data from 1940 to 1951 prior to the environmental changes and revealed a marked increase in the contribution of benthic invertebrates in the present diet. Stable isotope analysis confirms the results of the stomach analysis, suggesting that the charr have switched their diet from zooplanktivory towards benthivory. We discuss the possibility that habitat modification and roach population expansion in Windermere have contributed to changes in charr diet. Complementary studies suggest that this diet shift is more likely to be a response to the increasing roach population than to habitat modification; however, further study in Windermere would be required to elucidate the exact mechanism. Long‐term data sets such as these provide information that is useful for determining the directivity of ecological change and the capability of species to respond to change.     

Effect of ammonia and nitrite on vigour,survival rate,moulting rate of the blue swimming crab <Emphasis Type=Italic>Portunus pelagicus</Emphasis> zoea

The effects of ammonia and nitrite on vigour, survival rate, moulting rate of zoea of blue swimming crab, Portunus pelagicus, were studied. A total of five nitrite-N treatments (26.67, 53.34, 106.68, 213.36, 426.72 mg/l) and a control (no nitrite-N added) were set up for the acute nitrite-N toxicity experiment; a total of five ammonia-N treatments (8.43, 16.86, 33.72, 67.44, 134.88 mg/l) and a control (no ammonia-N added) were set up for the acute ammonia-N toxicity experiment. The results showed that the vigour, survival rate and moulting rate of zoea of the blue swimming crabs exposed to over 53.34 mg/l were significantly different (P < 0.05) from the control group. The zoea LC₅₀ values (mg/l) of nitrite-N were 179.47, 76.56, 66.70, 37.49, 25.01, 25.35, 25.34 mg/l for 24, 36, 48, 60, 72, 84, 96 h, respectively. The vigour, survival rate and moulting rate of zoea of the blue swimming crabs exposed to over 16.86 mg/l were significantly different (P < 0.05) from the control group. The zoea LC₅₀ values (mg/l) of ammonia-N were 51.04, 39.62, 38.72, 24.43, 16.90, 13.42, 11.16 mg/l for 24, 36, 48, 60, 72, 84, 96 h, respectively. The zoeae are highly sensitive to ammonia and nitrite, and the toxicity of ammonia and nitrite on Portunus pelagicus decrease with development of this crab.