Periventricular forebrain mechanisms for blood pressure regulation

Periventricular forebrain regions participate in body fluid and cardiovascular regulatory mechanisms that are intimately related to neural participation in experimental hypertension. Ablation of preoptic-hypothalamic periventricular tissue surrounding the anteroventral third ventricle (AV3V) disrupts both angiotensin (AngII) and sodium regulatory mechanisms and prevents experimental hypertension in either renin-dependent or -independent models. When AV3V is spared, and central AngII pressor mechanisms are interrupted by subfornical organ ablation or anterior hypothalamic knife cuts, renin-dependent but not renin-independent models of hypertension are prevented. Volume-expanded models of hypertension may be mediated by a natriuretic hormone that also inhibits the sodium-potassium pump in vascular smooth muscle, resulting in increased vasoconstriction. Volume expansion-induced release of this humoral ATPase inhibitor is attenuated in rats with AV3V lesions. In the renin-independent, reduced renal mass model, development of hypertension is correlated with increased plasma levels of sodium-potassium pump inhibitor. AV3V ablation blocks both the hypertension and the increase in humoral ATPase inhibitor. Thus, Thus, central angiotensin pressor and natriuretic mechanisms overlap in AV3V, and prevention of renin-dependent and volume-dependent models of experimental hypertension by AV3V ablation appears linked to disruption of these functionally separable systems.     

Mosquitoes and West Nile virus along a river corridor from prairie to montane habitats in eastern Colorado

We conducted studies on mosquitoes and West Nile virus (WNV) along a riparian corridor following the South Platte River and Big Thompson River in northeastern Colorado and extending from an elevation of 1,215 m in the prairie landscape of the eastern Colorado plains to 1,840 m in low montane areas at the eastern edge of the Rocky Mountains in the central part of the state. Mosquito collection during June‐September 2007 in 20 sites along this riparian corridor yielded a total of 199,833 identifiable mosquitoes of 17 species. The most commonly collected mosquitoes were, in descending order: Aedes vexans, Culex tarsalis, Ae. dorsalis, Ae. trivittatus, Ae. melanimon, Cx. pipiens, and Culiseta inornata. Species richness was higher in the plains than in foothills‐montane areas, and abundances of several individual species, including the WNV vectors Cx. tarsalis and Cx. pipiens and the nuisance‐biter and potential secondary WNV vector Ae. vexans, decreased dramatically from the plains (1,215‐1,487 m) to foothills‐montane areas (1,524‐1,840 m). Ae. vexans and Cx. tarsalis had a striking pattern of uniformly high abundances between 1,200‐1,450 m followed by a gradual decrease in abundance above 1,450 m to reach very low numbers above 1,550 m. Culex species were commonly infected with WNV in the plains portion of the riparian corridor in 2007, with 14 of 16 sites yielding WNV‐infected Cx. tarsalis and infection rates for Cx. tarsalis females exceeding 2.0 per 1,000 individuals in ten of the sites. The Vector Index for abundance of WNV‐infected Cx. tarsalis females during June‐September exceeded 0.5 in six plains sites along the South Platte River but was uniformly low (0–0.1) in plains, foothills and montane sites above 1,500 m along the Big Thompson River. A population genetic analysis of Cx. tarsalis revealed that all collections from the ≈190 km riparian transect in northeastern Colorado were genetically uniform but that these collections were genetically distinct from collections from Delta County on the western slope of the Continental Divide. This suggests that major waterways in the Great Plains serve as important dispersal corridors for Cx. tarsalis but that the Continental Divide is a formidable barrier to this WNV vector.     

Cheatgrass (<Emphasis Type="Italic">Bromus tectorum</Emphasis>) distribution in the intermountain Western United States and its relationship to fire frequency,seasonality, and ignitions

Cheatgrass (Bromus tectorum) is an invasive grass pervasive across the Intermountain Western US and linked to major increases in fire frequency. Despite widespread ecological impacts associated with cheatgrass, we lack a spatially extensive model of cheatgrass invasion in the Intermountain West. Here, we leverage satellite phenology predictors and thousands of field surveys of cheatgrass abundance to create regional models of cheatgrass distribution and percent cover. We compare cheatgrass presence to fire probability, fire seasonality and ignition source. Regional models of percent cover had low predictive power (34% of variance explained), but distribution models based on a threshold of 15% cover to differentiate high abundance from low abundance had an overall accuracy of 74%. Cheatgrass achieves ≥ 15% cover over 210,000 km² (31%) of the Intermountain West. These lands were twice as likely to burn as those with low abundance, and four times more likely to burn multiple times between 2000 and 2015. Fire probability increased rapidly at low cheatgrass cover (1–5%) but remained similar at higher cover, suggesting that even small amounts of cheatgrass in an ecosystem can increase fire risk. Abundant cheatgrass was also associated with a 10 days earlier fire seasonality and interacted strongly with anthropogenic ignitions. Fire in cheatgrass was particularly associated with human activity, suggesting that increased awareness of fire danger in invaded areas could reduce risk. This study suggests that cheatgrass is much more spatially extensive and abundant than previously documented and that invasion greatly increases fire frequency, even at low percent cover.     

Food choice by white-tailed deer in relation to protein and energy content of the diet: a field experiment

Optimality models of food selection by herbivores assume that individuals are capable of assessing forage value, either directly through the currency used in the model or indirectly through other variables correlated with the currency. Although energy and protein are the two currencies most often used, controversy exists regarding their respective influence on food choice. Part of the debate is due to the difficulty of teasing apart these two nutrients, which are closely correlated in most natural forages. Here we offer a test of the assumption that energy and protein contents of the forage are both currencies that large mammalian herbivores can use when selecting their food. We observed feeding behavior of 47 wild white-tailed deer (Odocoileusvirginianus) during winter while individuals were presented with four experimental foods representing two levels of energy and protein (dry matter digestibility: 40–50%; crude protein: 12–16%). Using experimental foods allowed us to separate the influences of energy and protein and clearly distinguish between the roles of these two nutrients. Deer discriminated between foods through partial selection, and selected diets higher in energy but lower in protein. The observed choices appeared consistent with physiological needs of deer wintering at the study site, where digestible energy was in short supply in the natural environment while protein was probably not. Results are in good agreement with recent findings on domesticated ruminants. They support a basic assumption of optimality models of food selection that use energy and/or protein as a currency, although the physiological mechanisms behind the food selection process remain unclear. We urge students of food selection by herbivores to replicate our experiment with other foods and/or in other circumstances before more general conclusions are drawn. Received: 1 September 1997 / Accepted: 22 February 1998     

IFITM3 inhibits influenza A virus infection by preventing cytosolic entry

To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.     

DNMT3L Modulates Significant and Distinct Flanking Sequence Preference for DNA Methylation by DNMT3A and DNMT3B In Vivo

The DNTM3A and DNMT3B de novo DNA methyltransferases (DNMTs) are responsible for setting genomic DNA methylation patterns, a key layer of epigenetic information. Here, using an in vivo episomal methylation assay and extensive bisulfite methylation sequencing, we show that human DNMT3A and DNMT3B possess significant and distinct flanking sequence preferences for target CpG sites. Selection for high or low efficiency sites is mediated by the base composition at the −2 and +2 positions flanking the CpG site for DNMT3A, and at the −1 and +1 positions for DNMT3B. This intrinsic preference reproducibly leads to the formation of specific de novo methylation patterns characterized by up to 34-fold variations in the efficiency of DNA methylation at individual sites. Furthermore, analysis of the distribution of signature methylation hotspot and coldspot motifs suggests that DNMT flanking sequence preference has contributed to shaping the composition of CpG islands in the human genome. Our results also show that the DNMT3L stimulatory factor modulates the formation of de novo methylation patterns in two ways. First, DNMT3L selectively focuses the DNA methylation machinery on properly chromatinized DNA templates. Second, DNMT3L attenuates the impact of the intrinsic DNMT flanking sequence preference by providing a much greater boost to the methylation of poorly methylated sites, thus promoting the formation of broader and more uniform methylation patterns. This study offers insights into the manner by which DNA methylation patterns are deposited and reveals a new level of interplay between members of the de novo DNMT family.     

Expression of mutant human epidermal receptor 3 attenuates lung fibrosis and improves survival in mice.

Neuregulin-1 (NRG-1), binding to the human epidermal growth factor receptor HER2/HER3, plays a role in pulmonary epithelial cell proliferation and recovery from injury in vitro. We hypothesized that activation of HER2/HER3 by NRG-1 would also play a role in recovery from in vivo lung injury. We tested this hypothesis using bleomycin lung injury of transgenic mice incapable of signaling through HER2/HER3 due to lung-specific dominant-negative HER3 (DNHER3) expression. In animals expressing DNHER3, protein leak, cell infiltration, and NRG-1 levels in bronchoalveolar lavage fluid increased after injury, similar to that in nontransgenic littermate control animals. However, HER2/HER3 was not activated, and DNHER3 animals displayed fewer lung morphological changes at 10 and 21 days after injury (P = 0.01). In addition, they contained 51% less collagen in injured lungs (P = 0.04). Transforming growth factor-beta1 did not increase in bronchoalveolar lavage fluid from DNHER3 mice compared with nontransgenic littermate mice (P = 0.001), suggesting that a mechanism for the decreased fibrosis was lack of transforming growth factor-beta1 induction in DNHER3 mice. Severe lung injury (0.08 units bleomycin) resulted in 80% mortality of nontransgenic mice, but only 35% mortality of DNHER3 transgenic mice (P = 0.04). Thus inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival.