Reply to S Riehl and K Pustovoytov (Journal of Archaeological Science 33 (2006) 143-144)

We appreciate the interest of Simone Riehl and Konstantin Pustovoytov (hereafter R&P) in our publication and here we answer their critical remarks and questions. R&P criticise two aspects: (1) our interpretation of the pollen record from Kutuzhekovo Lake and (2) the information we derived from the St. Petersburg radiocarbon database. We discuss the questions and we show that these do not really affect our earlier conclusions.

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

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

Chronological studies of the Arzhan-2 Scythian monument in Tuva (Russia)

The first radiocarbon dates from the unique early Scythian monument Arzhan-2, discovered in 2001, are presented. The monument contained a royal burial (grave nr 5). Unfortunately, precise dating is hampered by the Hallstatt plateau in the calibration curve. However, using both accelerator mass spectrometry measurements from buried materials and conventional dates for floating tree rings from the burial chamber, we were able to date the construction of the monument to the 7th century BC. This is consistent with archaeological expectations. Other graves located inside the barrow were also dated. Grave nr 11, located on the edge of the barrow, is younger, showing that the monument was a place of burial ritual for many years for this ancient population.

Chronology and possible links between climatic and cultural change during the first millennium BC in southern Siberia and Central Asia

We reconstructed climate change during the second half of the Holocene for the Minusinsk (southern Siberia) and the Uyuk (Central Asia) valleys in the Eurasian steppe zone. Sediment cores from 2 lakes and a soil profile from the Arzhan-2 burial mount were investigated. We combined pollen and geochemical analyses and radiocarbon dating with the archaeological record. A sharp increase of human population density occurred at the transition from the Bronze Age to Iron Age (about 2700 cal BP). The most representative Scythian culture started in the Uyuk and the Minusinsk valleys after increased humidity and occupation capacity of the steppe zone during the 9th century BC