Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats

The generation of the Lew.Tg(mRen2) congenic hypertensive rat strain, developed through a backcross of the hypertensive (mRen2)27 transgenic rat with normotensive Lewis rats, provides a new model by which primary hypertension can be studied without the genetic variability found in the original strain. The purpose of this study was to characterize the Lew.Tg(mRen2) rats by dually investigating the effects of type 1 angiotensin II (ANG II) receptor (AT(1)) blockade and angiotensin-converting enzyme (ACE) activity inhibition on the ANG-(1-7)/ACE2 axis of the renin-angiotensin system in this new hypertensive model. The control of blood pressure elicited by 12-day administration of either lisinopril (mean difference change = 92 +/- 2, P < 0.05) or losartan (mean difference change = 69 +/- 2, P < 0.05) was associated with 54% and 33% increases in cardiac ACE2 mRNA and 54% and 43% increases in cardiac ACE mRNA, respectively. Lisinopril induced a 3.1-fold (P < 0.05) increase in renal cortical expression of ACE2, whereas losartan increased ACE2 mRNA 3.5-fold (P < 0.05). Both treatment regimens increased renal ACE mRNA 2.6-fold (P < 0.05). The two therapies augmented ACE2 protein activity, as well as increased cardiac and renal AT(1) receptor mRNAs. ACE inhibition reduced plasma ANG II levels (81%, P < 0.05) and increased plasma ANG-(1-7) (265%, P < 0.05), whereas losartan had no effect on the peptides. In contrast with what had been shown in normotensive rats, ACE inhibition decreased renal ANG II excretion and transiently decreased ANG-(1-7) excretion, whereas losartan treatment was associated with a consistent decrease in ANG-(1-7) urinary excretion rates. In response to the treatments, the expression of both renal cortical renin and angiotensinogen mRNAs was significantly augmented. The paradoxical effects of blockade of ANG II synthesis and activity on urinary excretion rates of the peptides and plasma angiotensins levels suggest that, in Lew.Tg(mRen2) congenic rats, a failure of compensatory ACE2 and ANG-(1-7)-dependent vasodepressor mechanisms may contribute both to the development and progression of hypertension driven by increased formation of endogenous ANG II.     

A region of calpastatin domain L that reprimes cardiac L-type Ca2+ channels

Calpastatin, an endogenous inhibitor of calpain, is composed of domain L and four repetitive homologous domains 1-4. Domains 1-4 inhibit calpain, whereas domain L partially reprimes L-type Ca2+ channels for voltage-gated activation. In the present study, the effects on Ca2+ channel activity of four isoforms and a series of fragments of calpastatin domain L were investigated in guinea-pig ventricular myocytes with the patch-clamp method. With one exception, all the isoforms and fragment peptides that contained amino acid residues 54-64 of domain L reprimed the Ca2+ channels to comparable levels (9-15% of control activity) to those observed previously with a full-length form of calpastatin. These results suggest that the region containing amino acid residues 54-64 (EGKPKEHTEPK) is responsible for the Ca2+ channel repriming function of calpastatin domain L.     

Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies

Ofatumumab is the first human anti-CD20 monoclonal antibody to be approved for patients in the United States and the European Union. Ofatumumab received accelerated approval from the U.S. Food and Drug Administration in October 2009 and was granted a conditional marketing authorization by the European Medicines Agency in April 2010 for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab, based on interim results of a pivotal phase 2 trial. Preliminary positive results for ofatumumab in combination with chemotherapy in patients with CLL are currently being confirmed in larger randomized trials in both the frontline setting and the relapsed/refractory setting. Ofatumumab has also shown potential in treating B cell non-Hodgkin's lymphoma, such as follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and Waldenstr?m's macroglobulinemia. Additional trials are ongoing to confirm activity of ofatumumab as monotherapy and in combination with chemotherapy in patients with FL or DLBCL.     

Survival patterns in white-tailed and mule deer after oral inoculation with a standardized, conspecific prion dose

We orally inoculated white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) with a standardized, conspecific prion dose and collected biologic samples throughout the disease course. Mule deer (PRNP genotype 225SS) and PRNP genotype 96GG white-tailed deer succumbed along similar trajectories, but 96GS- and 96SS-genotype individuals tended to survive longer.     

Global Coverage of Cetacean Line-Transect Surveys: Status Quo, Data Gaps and Future Challenges

Knowledge of abundance, trends and distribution of cetacean populations is needed to inform marine conservation efforts, ecosystem models and spatial planning. We compiled a geo-spatial database of published data on cetacean abundance from dedicated visual line-transect surveys and encoded >1100 abundance estimates for 47 species from 430 surveys conducted worldwide from 1975–2005. Our subsequent analyses revealed large spatial, temporal and taxonomic variability and gaps in survey coverage. With the exception of Antarctic waters, survey coverage was biased toward the northern hemisphere, especially US and northern European waters. Overall, <25% of the world''s ocean surface was surveyed and only 6% had been covered frequently enough (≥5 times) to allow trend estimation. Almost half the global survey effort, defined as total area (km²) covered by all survey study areas across time, was concentrated in the Eastern Tropical Pacific (ETP). Neither the number of surveys conducted nor the survey effort had increased in recent years. Across species, an average of 10% of a species'' predicted range had been covered by at least one survey, but there was considerable variation among species. With the exception of three delphinid species, <1% of all species'' ranges had been covered frequently enough for trend analysis. Sperm whales emerged from our analyses as a relatively data-rich species. This is a notoriously difficult species to survey visually, and we use this as an example to illustrate the challenges of using available data from line-transect surveys for the detection of trends or for spatial planning. We propose field and analytical methods to fill in data gaps to improve cetacean conservation efforts.     

Modulation of social interactions by immune stimulation in honey bee, <Emphasis Type="Italic">Apis mellifera</Emphasis>, workers

Background  

Immune response pathways have been relatively well-conserved across animal species, with similar systems in both mammals and invertebrates. Interestingly, honey bees have substantially reduced numbers of genes associated with immune function compared with solitary insect species. However, social species such as honey bees provide an excellent environment for pathogen or parasite transmission with controlled environmental conditions in the hive, high population densities, and frequent interactions. This suggests that honey bees may have developed complementary mechanisms, such as behavioral modifications, to deal with disease.     

Flying lemurs – The 'flying tree shrews'? Molecular cytogenetic evidence for a Scandentia-Dermoptera sister clade

Background  

Flying lemurs or Colugos (order Dermoptera) represent an ancient mammalian lineage that contains only two extant species. Although molecular evidence strongly supports that the orders Dermoptera, Scandentia, Lagomorpha, Rodentia and Primates form a superordinal clade called Supraprimates (or Euarchontoglires), the phylogenetic placement of Dermoptera within Supraprimates remains ambiguous.