Homeotic transformation induced by protein transduction

One of the most fundamental features of living organisms is that cells are separated from their external environment by a thin, but highly complex plasma membrane constituted of a lipid bilayer. Although, the lipid bilayer is only a few nanometers in width, it is impermeable to most molecules apart from small hydrophobic ones. The ability of small molecules to diffuse through a lipid bilayer is related to their lipid solubility. Hydrophilic macromolecular Antennapedia homeodomain peptide has been shown to be able to translocate from extracellular space into the cytoplasm of cells in a receptor-independent manner. Its third α-helix domain, designated as “Penetratin”, was proposed to be the functional transduction domain that is responsible for the translocation, and it is widely used for intracellular delivery of various exogenous proteins. Although Penetratin has been regarded to be the only element conferring the capacity of its parent polypeptide to penetrate through the plasma membrane, we found that the complete Antennapedia homeodomain exhibits an appreciably higher level of translocation efficiency as compared to Penetratin. Pharmacological analysis demonstrated that macropinocytic endocytosis plays a significant role underlying the process of the homeodomain internalization, and this is consistent with the observation that internalized polypeptide co-localizes with a fluid phase dye. Our studies identify macropinocytosis as a major mechanism by which Antennapedia homeodomain obtains the access to the interior of cells. In the process of macropinocytosis, signaling from the plasma membrane is required for actin remodeling to generate mechanical deformation forces; the interaction between positively charged Antennapedia homeodomain and negatively charged extracellular heparan sulfate could trigger the signaling cascade for fluid phase endocytosis. This would presumably explain why positively charged peptides, polymers, and liposomes are able to penetrate cells. As a fluid phase macropinocytosis provides cells with a way to non-selectively internalize large quantities of solute, it represents an effective means for drug delivery into cells. Both of “Penetratin” and Antennapedia homeodomain exploit macropinocytosis to a certain extent, the comparison between them may advance our understanding of the mechanisms triggering macropinocytotic endocytosis

Dynamic spatiotemporal trends of imported dengue fever in Australia.

Dengue fever (DF) epidemics in Australia are caused by infected international travellers and confined to Northern Queensland where competent vectors exist. Recent analyses suggest that global trade and climate change could lead to the re-establishment of Ae. aegypti across the country and promote the spread of dengue nationally. This study aimed to describe the dynamic spatiotemporal trends of imported DF cases and their origins, identify the current and potential future high-risk regions and locate areas that might be at particular risk of dengue transmission should competent mosquito vectors expand their range. Our results showed that the geographical distribution of imported DF cases has significantly expanded in mainland Australia over the past decade. In recent years, the geographical distribution of source countries of DF has expanded from the Pacific region and Asia to include Africa and the Americas. Australia is now exposed to dengue importations from all of the regions involved in the current global pandemic. The public health implications of a range expansion of dengue mosquito vectors are severe. Enhanced mosquito surveillance in those areas that have high imported cases is called for to reduce emerging threats from this globally expanding pathogen

An expressed sequence tag (EST) library for Drosophila serrata, a model system for sexual selection and climatic adaptation studies

The native Australian fly Drosophila serrata belongs to the highly speciose montium subgroup of the melanogaster species group. It has recently emerged as an excellent model system with which to address a number of important questions, including the evolution of traits under sexual selection and traits involved in climatic adaptation along latitudinal gradients. Understanding the molecular genetic basis of such traits has been limited by a lack of genomic resources for this species. Here, we present the first expressed sequence tag (EST) collection for D. serrata that will enable the identification of genes underlying sexually-selected phenotypes and physiological responses to environmental change and may help resolve controversial phylogenetic relationships within the montium subgroup

Projecting the future of dengue under climate change scenarios: Progress, uncertainties and research needs.

BACKGROUND: Dengue is a mosquito-borne viral disease and its transmission is closely linked to climate. We aimed to review available information on the projection of dengue in the future under climate change scenarios. METHODS: Using five databases (PubMed, ProQuest, ScienceDirect, Scopus and Web of Science), a systematic review was conducted to retrieve all articles from database inception to 30th June 2019 which projected the future of dengue under climate change scenarios. In this review, "the future of dengue" refers to disease burden of dengue, epidemic potential of dengue cases, geographical distribution of dengue cases, and population exposed to climatically suitable areas of dengue. RESULTS: Sixteen studies fulfilled the inclusion criteria, and five of them projected a global dengue future. Most studies reported an increase in disease burden, a wider spatial distribution of dengue cases or more people exposed to climatically suitable areas of dengue as climate change proceeds. The years 1961-1990 and 2050 were the most commonly used baseline and projection periods, respectively. Multiple climate change scenarios introduced by the Intergovernmental Panel on Climate Change (IPCC), including B1, A1B, and A2, as well as Representative Concentration Pathway 2.6 (RCP2.6), RCP4.5, RCP6.0 and RCP8.5, were most widely employed. Instead of projecting the future number of dengue cases, there is a growing consensus on using "population exposed to climatically suitable areas for dengue" or "epidemic potential of dengue cases" as the outcome variable. Future studies exploring non-climatic drivers which determine the presence/absence of dengue vectors, and identifying the pivotal factors triggering the transmission of dengue in those climatically suitable areas would help yield a more accurate projection for dengue in the future. CONCLUSIONS: Projecting the future of dengue requires a systematic consideration of assumptions and uncertainties, which will facilitate the development of tailored climate change adaptation strategies to manage dengue

Effect of Serotype and Strain Diversity on Dengue Virus Replication in Australian Mosquito Vectors

Dengue virus (DENV) is the most important mosquito-borne viral pathogen of humans, comprising four serotypes (DENV-1 to -4) with a myriad of genotypes and strains. The kinetics of DENV replication within the mosquito following ingestion of a blood meal influence the pathogen’s ability to reach the salivary glands and thus the transmission potential. The influence of DENV serotype and strain diversity on virus kinetics in the two main vector species, Aedes aegypti and Ae. albopictus, has been poorly characterized. We tested whether DENV replication kinetics vary systematically among serotypes and strains, using Australian strains of the two vectors. Mosquitoes were blood fed with two strains per serotype, and sampled at 3, 6, 10 and 14-days post-exposure. Virus infection in mosquito bodies, and dissemination of virus to legs and wings, was detected using qRT-PCR. For both vectors, we found significant differences among serotypes in proportions of mosquitoes infected, with higher numbers for DENV-1 and -2 versus other serotypes. Consistent with this, we observed that DENV-1 and -2 generally replicated to higher RNA levels than other serotypes, particularly at earlier time points. There were no significant differences in either speed of infection or dissemination between the mosquito species. Our results suggest that DENV diversity may have important epidemiological consequences by influencing virus kinetics in mosquito vectors

Does Bangkok have a central role in the dengue dynamics of Thailand?

BACKGROUND: Bangkok plays a central role in the commerce of Thailand. This study aimed to characterize the district-level spatial-temporal patterns of dengue in Thailand and explore if a dengue peak in Bangkok led the peaks of dengue in other Thai provinces. METHODS: Monthly dengue data at district level in Thailand from January 2004 to December 2017 were obtained and used to assess the spatial and seasonal patterns of dengue in Thailand. As our seasonal decomposition and cross-correlation analyses showed that dengue in Bangkok peaked in November, which was a few months after the dengue peak in most other provinces, we used a time-series generalized linear model to explore if there was another province in which the dengue case number was most predictive of dengue case numbers in other Thai provinces. RESULTS: The highest district-level annual dengue incidence rates (per 10,000) in the three time periods (i.e. 2004-2008, 2009-2013 and 2014-2017) were 58.08 (Samphanthawong), 85.93 (Mueang Krabi), and 66.60 (Mae Sariang), respectively. Dengue incidence rates in the western part of Northern Thailand, southern part of Central Thailand, southern part of Eastern Thailand, and Southern Thailand were higher than in other regions. Dengue in most districts of Thailand peaked in June, July or August, but dengue peaks in all districts of Bangkok occurred in November. The number of dengue cases in Nakhon Ratchasima was most predictive of the number of dengue cases in other provinces in Thailand by a one-month lag. CONCLUSIONS: Our results suggest that the dengue peak in Bangkok did not lead the peaks of dengue in other Thai provinces. Future research exploring how changes in socio-ecological factors (e.g. road network and climate factors) in Nakhon Ratchasima have affected the transmission of dengue in Thailand might shed some new light on the prevention and control of dengue

Heatwaves and dengue outbreaks in Hanoi, Vietnam: New evidence on early warning.

BACKGROUND: Many studies have shown associations between rising temperatures, El Niño events and dengue incidence, but the effect of sustained periods of extreme high temperatures (i.e., heatwaves) on dengue outbreaks has not yet been investigated. This study aimed to compare the short-term temperature-dengue associations during different dengue outbreak periods, estimate the dengue cases attributable to temperature, and ascertain if there was an association between heatwaves and dengue outbreaks in Hanoi, Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: Dengue outbreaks were assigned to one of three categories (small, medium and large) based on the 50th, 75th, and 90th percentiles of distribution of weekly dengue cases during 2008-2016. Using a generalised linear regression model with a negative binomial link that controlled for temporal trends, temperature variation, rainfall and population size over time, we examined and compared associations between weekly average temperature and weekly dengue incidence for different outbreak categories. The same model using weeks with or without heatwaves as binary variables was applied to examine the potential effects of extreme heatwaves, defined as seven or more days with temperatures above the 95th percentile of daily temperature distribution during the study period. This study included 55,801 dengue cases, with an average of 119 (range: 0 to 1454) cases per week. The exposure-response relationship between temperature and dengue risk was non-linear and differed with dengue category. After considering the delayed effects of temperature (one week lag), we estimated that 4.6%, 11.6%, and 21.9% of incident cases during small, medium, and large outbreaks were attributable to temperature. We found evidence of an association between heatwaves and dengue outbreaks, with longer delayed effects on large outbreaks (around 14 weeks later) than small and medium outbreaks (4 to 9 weeks later). Compared with non-heatwave years, dengue outbreaks (i.e., small, moderate and large outbreaks combined) in heatwave years had higher weekly number of dengue cases (p<0.05). Findings were robust under different sensitivity analyses. CONCLUSIONS: The short-term association between temperature and dengue risk varied by the level of outbreaks and temperature seems more likely affect large outbreaks. Moreover, heatwaves may delay the timing and increase the magnitude of dengue outbreaks

Comparative susceptibility of mosquito populations in North Queensland, Australia to oral infection with dengue virus.

Dengue is the most prevalent arthropod-borne virus, with at least 40% of the world's population at risk of infection each year. In Australia, dengue is not endemic, but viremic travelers trigger outbreaks involving hundreds of cases. We compared the susceptibility of Aedes aegypti mosquitoes from two geographically isolated populations to two strains of dengue virus serotype 2. We found, interestingly, that mosquitoes from a city with no history of dengue were more susceptible to virus than mosquitoes from an outbreak-prone region, particularly with respect to one dengue strain. These findings suggest recent evolution of population-based differences in vector competence or different historical origins. Future genomic comparisons of these populations could reveal the genetic basis of vector competence and the relative role of selection and stochastic processes in shaping their differences. Lastly, we show the novel finding of a correlation between midgut dengue titer and titer in tissues colonized after dissemination

High relative humidity might trigger the occurrence of the second seasonal peak of dengue in the Philippines.

BACKGROUND: Dengue in some regions has a bimodal seasonal pattern, with a first big seasonal peak followed by a second small seasonal peak. The factors associated with the second small seasonal peak remain unclear. METHODS: Monthly data on dengue cases in the Philippines and its 17 regions from 2008 to 2017 were collected and underwent a time series seasonal decomposition analysis. The associations of monthly average mean temperature, average relative humidity, and total rainfall with dengue in 19 provinces were assessed with a generalized additive model. Logistic regression and a classification and regression tree (CART) model were used to identify the factors associated with the second seasonal peak of dengue. RESULTS: Dengue incidence rate in the Philippines increased substantially in the period 2013-2017, particularly for the regions in south Philippines. Dengue peaks in south Philippines predominantly occurred in August, with the peak in the national capital region (NCR) (i.e., Metropolitan Manila) occurring in September. The association between mean temperature and dengue appeared J-shaped or upside-down-V-shaped, and the association between relative humidity (or rainfall) and dengue was heterogeneous across different provinces (e.g., J shape, reverse J shape, or upside-down V shape, etc). Relative humidity was the only factor associated with the second seasonal peak of dengue (odds ratio: 1.144; 95% confidence interval: 1.023-1.279; threshold: 77%). CONCLUSIONS: Dengue control and prevention resources are increasingly required in regions beyond the NCR, and relative humidity can be used as a predictor of the second seasonal peak of dengue in the Philippines

Spatiotemporal patterns and climatic drivers of severe dengue in Thailand.

OBJECTIVES: The burden of dengue fever in Thailand is considerable, yet there are few large-scale studies exploring the drivers of transmission. This study aimed to investigate the spatiotemporal patterns and climatic drivers of severe dengue in Thailand. METHODS: Geographic Information System (GIS) techniques and spatial cluster analysis were used to visualize the spatial distribution and detect high-risk clusters of severe dengue in 76 provinces of Thailand from January 1999 to December 2014. The seasonal patterns of severe dengue cases in different provinces were identified. A two-stage modelling approach combining a generalized linear model with a distributed lag non-linear model was used to quantify the effects of monthly mean temperature and relative humidity on the occurrence of severe dengue cases in 51 provinces of Thailand. RESULTS: Significant severe dengue clustering was detected, especially during epidemic years, and the location of these clusters showed substantial inter-annual variation. Severe dengue cases in Northern and Northeastern Thailand peaked in June to August and this pattern was stable across the study period, whereas the seasonality of severe dengue cases in other regions (especially Central Thailand) was less predictable. The risk of the occurrence of severe dengue cases increased with an increase in mean temperature in Northeastern Thailand, Central Thailand, and Southern Thailand, with peaks occurring between 24 °C to 30 °C in Northeastern Thailand and 27 °C to 29 °C in Southern Thailand West Coast, respectively. Relative humidity significantly affected the occurrence of severe dengue cases in Northeastern and Central Thailand, with optimal ranges observed for each region. CONCLUSIONS: Our findings substantiate the potential for developing climate-based dengue early warning systems for Thailand, and have implications for informing pre-emptive vector control