171 research outputs found
Alcohol tolerance and Adh gene frequencies in European and African populations of Drosophila melanogaster
International audienc
Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide
BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored
Secure Code Updates for Smart Embedded Devices based on PUFs
Code update is a very useful tool commonly used in low-end embedded devices to improve the existing functionalities or patch discovered bugs or vulnerabilities. If the update protocol itself is not secure, it will only bring new threats to embedded systems. Thus, a secure code update mechanism is required. However, existing solutions either rely on strong security assumptions, or result in considerable storage and computation consumption, which are not practical for resource-constrained embedded devices (e.g., in the context of Internet of Things). In this work, we propose to use intrinsic device characteristics (i.e., Physically Unclonable Functions or PUF) to design a practical and lightweight secure code update scheme. Our scheme can not only ensure the freshness, integrity, confidentiality and authenticity of code update, but also verify that the update is installed correctly on a specific device without any malicious software. Cloned or counterfeit devices can be excluded as the code update is bound to the unpredictable physical properties of underlying hardware. Legitimate devices in an untrustworthy software state can be restored by filling suspect memory with PUF-derived random numbers. After update installation, the initiator of the code update is able to obtain the verifiable software state from device, and the device can maintain a sustainable post-update secure check by enforcing a secure call sequence. To demonstrate the practicality and feasibility, we also implement the proposed scheme on a low-end MCU platform (TI MSP430) by using onboard SRAM and Flash resources
A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila
Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2)) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses
Potent Nonnucleoside Reverse Transcriptase Inhibitors Target HIV-1 Gag-Pol
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation
Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture
(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D.
melanogaster, representing 22 population samples from the sub-Saharan ancestral
range of this species, along with one European population. Most genomes were
sequenced above 25X depth from haploid embryos. Results indicated a pervasive
influence of non-African admixture in many African populations, motivating the
development and application of a novel admixture detection method. Admixture
proportions varied among populations, with greater admixture in urban
locations. Admixture levels also varied across the genome, with localized peaks
and valleys suggestive of a non-neutral introgression process. Genomes from the
same location differed starkly in ancestry, suggesting that isolation
mechanisms may exist within African populations. After removing putatively
admixed genomic segments, the greatest genetic diversity was observed in
southern Africa (e.g. Zambia), while diversity in other populations was largely
consistent with a geographic expansion from this potentially ancestral region.
The European population showed different levels of diversity reduction on each
chromosome arm, and some African populations displayed chromosome arm-specific
diversity reductions. Inversions in the European sample were associated with
strong elevations in diversity across chromosome arms. Genomic scans were
conducted to identify loci that may represent targets of positive selection. A
disproportionate number of candidate selective sweep regions were located near
genes with varied roles in gene regulation. Outliers for Europe-Africa FST were
found to be enriched in genomic regions of locally elevated cosmopolitan
admixture, possibly reflecting a role for some of these loci in driving the
introgression of non-African alleles into African populations
A Fourier Analysis Based Attack against Physically Unclonable Functions
Electronic payment systems have leveraged the advantages offered by the RFID technology, whose security is promised to be improved by applying the notion of Physically Unclonable Functions (PUFs). Along with the evolution of PUFs, numerous successful attacks against PUFs have been proposed in the literature. Among these are machine learning (ML) attacks, ranging from heuristic approaches to provable algorithms, that have attracted great attention. Our paper pursues this line of research by introducing a Fourier analysis based attack against PUFs. More specifically, this paper focuses on two main aspects of ML attacks, namely being provable and noise tolerant. In this regard, we prove that our attack is naturally integrated into a provable Probably Approximately Correct (PAC) model. Moreover, we show that our attacks against known PUF families are effective and applicable even in the presence of noise. Our proof relies heavily on the intrinsic properties of these PUF families, namely arbiter, Ring Oscillator (RO), and Bistable Ring (BR) PUF families. We believe that our new style of ML algorithms, which take advantage of the Fourier analysis principle, can offer better measures of PUF security
Setting the stage: host invasion by HIV.
For more than two decades, HIV has infected millions of people worldwide each year through mucosal transmission. Our knowledge of how HIV secures a foothold at both the molecular and cellular levels has been expanded by recent investigations that have applied new technologies and used improved techniques to isolate ex vivo human tissue and generate in vitro cellular models, as well as more relevant in vivo animal challenge systems. Here, we review the current concepts of the immediate events that follow viral exposure at genital mucosal sites where most documented transmissions occur. Furthermore, we discuss the gaps in our knowledge that are relevant to future studies, which will shape strategies for effective HIV prevention
HIV interactions with monocytes and dendritic cells: viral latency and reservoirs
HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4+ T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis
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