Modeling Dynamic Introduction of Chikungunya Virus in the United States

Chikungunya is a mosquito-borne viral infection of humans that previously was confined to regions in central Africa. However, during this century, the virus has shown surprising potential for geographic expansion as it invaded other countries including more temperate regions. With no vaccine and no specific treatment, the main control strategy for Chikungunya remains preventive control of mosquito populations. In consideration for the risk of Chikungunya introduction to the US, we developed a model for disease introduction based on virus introduction by one individual. Our study combines a climate-based mosquito population dynamics stochastic model with an epidemiological model to identify temporal windows that have epidemic risk. We ran this model with temperature data from different locations to study the geographic sensitivity of epidemic potential. We found that in locations with marked seasonal variation in temperature there also was a season of epidemic risk matching the period of the year in which mosquito populations survive and grow. In these locations controlling mosquito population sizes might be an efficient strategy. But, in other locations where the temperature supports mosquito development all year the epidemic risk is high and (practically) constant. In these locations, mosquito population control alone might not be an efficient disease control strategy and other approaches should be implemented to complement it. Our results strongly suggest that, in the event of an introduction and establishment of Chikungunya in the US, endemic and epidemic regions would emerge initially, primarily defined by environmental factors controlling annual mosquito population cycles. These regions should be identified to plan different intervention measures. In addition, reducing vector: human ratios can lower the probability and magnitude of outbreaks for regions with strong seasonal temperature patterns. This is the first model to consider Chikungunya risk in the US and can be applied to other vector borne diseases.     

Protons at the gate: DEG/ENaC ion channels help us feel and remember

The DEG/ENaC ion channel family contributes to channels of striking functional diversity. Neuronally expressed family members include the C. elegans degenerins that mediate touch and are thought to be mechanically gated, and the mammalian ASICs, which are gated by protons. ASICs affect a range of sensory functions that includes perception of gentle touch, harsh touch, heat, sour taste, and pain. Family member ASIC1 is now implicated in long-term potentiation, suggesting that minute fluxes in synaptic pH may activate ASICs to enhance learning.     

The expression of the dodecameric ferritin in Listeria spp. is induced by iron limitation and stationary growth phase

The new discipline of Evolutionary Developmental Biology (Evo-Devo) is facing the fascinating paradox of explaining morphological evolution using conserved pieces or genes to build divergent animals. The cephalochordate amphioxus is the closest living relative to the vertebrates, with a simple, chordate body plan, and a genome directly descended from the ancestor prior to the genome-wide duplications that occurred close to the origin of vertebrates. Amphioxus morphology may have remained relatively invariant since the divergence from the vertebrate lineage, but the amphioxus genome has not escaped evolution. We report the isolation of a second Emx gene (AmphiEmxB) arising from an independent duplication in the amphioxus genome. We also argue that a tandem duplication probably occurred in the Posterior part of the Hox cluster in amphioxus, giving rise to AmphiHox14, and discuss the structure of the chordate and vertebrate ancestral clusters. Also, a tandem duplication of Evx in the amphioxus lineage produced a prototypical Evx gene (AmphiEvxA) and a divergent gene (AmphiEvxB), no longer involved in typical Evx functions. These examples of specific gene duplications in amphioxus, and other previously reported duplications summarized here, emphasize the fact that amphioxus is not the ancestor of the vertebrates but 'only' the closest living relative to the ancestor, with a mix of prototypical and amphioxus-specific features in its genome.     

Identification and molecular characterisation of CmeB, a Campylobacter jejuni multidrug efflux pump

A multidrug efflux pump gene (cmeB) was identified from the published Campylobacter jejuni genome sequence. Secondary structural analysis showed that the gene encoded a protein belonging to the resistance nodulation cell division (RND) family of efflux transporters. The gene was inactivated by insertional mutagenesis. Compared with the wild-type strain (NCTC 11168), the resultant knockout strain (NCTC 11168-cmeB::kan(r)) displayed increased susceptibility to a range of antibiotics including beta-lactams, fluoroquinolones, macrolides, chloramphenicol, tetracycline, ethidium bromide, the dye acridine orange and the detergent sodium dodecyl sulfate. Accumulation of ciprofloxacin was increased in the knockout mutant, but carbonyl cyanide m-chlorophenyl hydrazone, a proton motive force inhibitor, had less effect upon ciprofloxacin accumulation in the knockout mutant compared with NCTC 11168. These data show that the identified gene encodes an RND-type multi-substrate efflux transporter, which contributes to intrinsic resistance to a range of structurally unrelated compounds in C. jejuni. This efflux pump has been named CmeB (for Campylobacter multidrug efflux).     

Hydration effects on physiological strain of horses during exercise-heat stress

This study examined the effects ofhyperhydration, exercise-induced dehydration, and oral fluidreplacement on physiological strain of horses during exercise-heatstress. On three occasions, six horses completed a 90-min exerciseprotocol (50% maximal O₂ uptake,34.5°C, 48% relative humidity) divided into two 45-min periods(exercise I andexercise II) with a 15-min recoverybetween exercise bouts. In random order, horses receivedno fluid (NF), 10 liters of water (W), or a carbohydrate-electrolytesolution (CE) 2 h before exercise and between exercise bouts. Compared with NF, preexercise hyperhydration (W and CE) did not alter heart rate, cardiac output (), stroke volume (SV), corebody temperature, sweating rate (SR), or sweating sensitivity duringexercise I. In contrast, afterexercise II, exercise-induceddehydration in NF (decrease in body mass: NF, 5.6 ± 0.8%; W, 1.1 ± 0.4%; CE, 1.0 ± 0.2%) resulted in greater heat storage,with core body temperature ~1.0°C higher compared with W and CE.In exercise II, the greater thermalstrain in NF was associated with significant(P < 0.05) decreases in (10 ± 2%), SV (9 ± 3%), SR, and sweatingsensitivity. We concluded that 1)preexercise hyperhydration provided no thermoregulatory advantage;2) maintenance of euhydration byoral fluid replacement (~85% of sweat fluid loss) during exercise inthe heat was reflected in higher , SV, and SR withdecreased heat storage; and 3) W oran isotonic CE solution was equally effective in reducing physiological strain associated with exercise-induced dehydration and heat stress.

     

Helix induction potential of N-terminal α-methyl, α-amino acids

Summary A series of longer analogues of the C-peptide of RNAse A has been synthesized with the aim of assessing the helix induction potential in water of α-methyl, α-amino acids at the N-terminus of the chain. The circular dichroism data indicate that one isovaline residue is effective in increasing the helix content of the 13-residue peptide by about 7%.     

Interstitial cells of Cajal: mediators of communication between circular and longitudinal muscle layers of canine colon

The network of interstitial cells of Cajal associated with Auerbach’s (myenteric) plexus in the canine colon was investigated to determine its role in facilitating communication between circular and longitudinal muscle layers. Electrical coupling between the muscle layers was demonstrated by propagating extracellularly evoked electrotonic pulses from circular muscle cells to nearby longitudinal muscle cells. The likelihood of cytoplasmic continuity across Auerbach’s plexus was further demonstrated by the ability of neurobiotin to spread between the interstitial cells and the circular and longitudinal muscle cells. Importantly, direct neurobiotin spread between circular and longitudinal muscle cells was not observed even when they were in close proximity as determined by confocal microscopy. When neurobiotin did spread across the two muscle layers, the intervening interstitial cells were always neurobiotin-positive. In regions where circular and longitudinal muscle cells approach each other closely, electron microscopy revealed the presence of close appositions between interstitial cells and smooth muscle cells. Gap junctions between interstitial cells and smooth muscle cells of both layers, as judged by electron microscopy, were extremely rare. Neither gap junctions nor close appositions were observed between longitudinal and circular muscle cells. The special arrangement for electrotonic coupling across Auerbach’s plexus through interstitial cells of Cajal suggests controlled coupling between the two muscle layers, explaining the preservation of their distinct electrical activities. Received: 21 July 1995 / Accepted: 22 April 1998     

Expression of HIV-1nefin yeast causes membrane perturbation and release of the myristylated Nef protein

The human immunodeficiency virus type 1 (HIV-1) Nef protein is essential for AIDS pathogenesis, but its function remains highly controversial. During stresses such as growth in the presence of copper or at elevated temperature, myristylated Nef is released from yeast cells and, after extended culture in stationary phase, it accumulates in the supernatant as a dense membranous material that can be centrifuged into a discrete layer above the cell pellet. This material is unique to Nef-producing cells and represents a convenient source of Nef that may have application in further biological studies. Within the yeast cell, electron microscopic examination shows that Nef localises in novel, membrane-bound bodies. These data support the evidence for a role of Nef in membrane perturbation and suggest that there may be a similar localisation for myristylated Nef in HIV-1 infected cells.     

Clinical and Molecular Characterization of Patients with Distal 11q Deletions

Jacobsen syndrome is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical features include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia, though none of these features are invariably present. To define the critical regions responsible for these abnormalities, we studied 17 individuals with de novo terminal deletions of 11q. The patients were characterized in a loss-of-heterozygosity analysis using polymorphic dinucleotide repeats. The breakpoints in the complete two-generation families were localized with an average resolution of 3.9 cM. Eight patients with the largest deletions extending from 11q23.3 to 11qter have breakpoints, between D11S924 and D11S1341. This cytogenetic region accounts for the majority of 11q⁻ patients and may be related to the FRA11B fragile site in 11q23.3. One patient with a small terminal deletion distal to D11S1351 had facial dysmorphism, cardiac defects, and thrombocytopenia, suggesting that the genes responsible for these features may lie distal to D11S1351. Twelve of 15 patients with deletion breakpoints as far distal as D11S1345 had trigonocephaly, while patients with deletions distal to D11S912 did not, suggesting that, if hemizygosity for a single gene is responsible for this dysmorphic feature, the gene may lie distal to D11S1345 and proximal to D11S912.