How does habitat diversity affect the species–area relationship?

Aim   To examine the way in which 'area' and 'habitat diversity' interact in shaping species richness and to find a simple and valid way to express this interaction.
Location   The Natura 2000 network of terrestrial protected areas in Greece, covering approximately 16% of the national territory.
Methods   We used the Natura 2000 framework, which provides a classification scheme for natural habitat types, to quantify habitat heterogeneity. We analysed data for the plant species composition in 16,143 quadrats in which 5044 species and subspecies of higher plants were recorded. We built a simple mathematical model that incorporates the effect of habitat diversity on the species–area relationship (SAR).
Results   Our analysis showed that habitat diversity was correlated with area. However, keeping habitat diversity constant, species richness was related to area; while keeping area constant, species richness was related to habitat diversity. Comparing the SAR of the 237 sites we found that the slope of the species–area curve was related to habitat diversity.
Main conclusions   Discussion of the causes of the SAR has often focused on the primacy of area per se versus habitat heterogeneity, even though the two mechanisms are not mutually exclusive and should be considered jointly. We find that increasing habitat diversity affects the SAR in different ways, but the dominant effect is to increase the slope of the SAR. While a full model fit typically includes a variety of terms involving both area and habitat richness, we find that the effect of habitat diversity can be reduced to a linear perturbation of the slope of the species accumulation curve.     

Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases

HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.     

New, miniaturized breath analyser for applications on Earth and in space

The present article deals with the development and application of an innovative breath analyser for metabolic stress testing and cardio respiratory measurements. The system is based on new, miniaturized ceramic gas sensors, which have the unique ability to measure simultaneously oxygen and carbon dioxide concentrations as well as flow rates. The small size of just a few millimetres allows the operation of the sensor directly in a breathing mask, minimizing dead space and breath resistance. Due to these properties and the fast response time of the measurement, it will be possible to perform a breath-by-breath analysis, in both stationary and mobile mode, with low environmental and psychological influences of the experimental circumstances to the tested person. The current development status and the most interesting technical data, experimental results, and benefits of the new breath analyser are described in the article.     

Bicarbonate attenuates arterial desaturation during maximal exercise in humans.

The contribution of pH to exercise-induced arterial O2 desaturation was evaluated by intravenous infusion of sodium bicarbonate (Bic, 1 M; 200-350 ml) or an equal volume of saline (Sal; 1 M) at a constant infusion rate during a "2,000-m" maximal ergometer row in five male oarsmen. Blood-gas variables were corrected to the increase in blood temperature from 36.5 +/- 0.3 to 38.9 +/- 0.1 degrees C (P < 0.05; means +/- SE), which was established in a pilot study. During Sal exercise, pH decreased from 7.42 +/- 0.01 at rest to 7.07 +/- 0.02 but only to 7.34 +/- 0.02 (P < 0.05) during the Bic trial. Arterial PO2 was reduced from 103.1 +/- 0.7 to 88.2 +/- 1.3 Torr during exercise with Sal, and this reduction was not significantly affected by Bic. Arterial O2 saturation was 97.5 +/- 0.2% at rest and decreased to 89.0 +/- 0.7% during Sal exercise but only to 94.1 +/- 1% with Bic (P < 0.05). Arterial PCO2 was not significantly changed from resting values in the last minute of Sal exercise, but in the Bic trial it increased from 40.5 +/- 0.5 to 45.9 +/- 2.0 Torr (P < 0.05). Pulmonary ventilation was lowered during exercise with Bic (155 +/- 14 vs. 142 +/- 13 l/min; P < 0.05), but the exercise-induced increase in the difference between the end-tidal O2 pressure and arterial PO2 was similar in the two trials. Also, pulmonary O2 uptake and changes in muscle oxygenation as determined by near-infrared spectrophotometry during exercise were similar. The enlarged blood-buffering capacity after infusion of Bic attenuated acidosis and in turn arterial desaturation during maximal exercise.     

3'-Azido-3'-deoxythymidine-(5')-tetraphospho-(5')-adenosine, the product of ATP-mediated excision of chain-terminating AZTMP, is a potent chain-terminating substrate for HIV-1 reverse transcriptase

The resistance of HIV-1 to 3'-azido-3'-deoxythymidine (AZT) involves phosphorolytic excision of chain-terminating AZT-5'-monophosphate (AZTMP). Both pyrophosphate (PPi) and ATP act as excision substrates in vitro, but the intracellular substrate used during replication of AZT-resistant HIV is still unknown. PPi-mediated excision produces AZT-5'-triphosphate (AZTTP), which could be immediately re-used as a substrate for viral DNA chain termination. In contrast, ATP-mediated excision produces the novel compound AZT-(5')-tetraphospho-(5')-adenosine (AZTp4A). Since little is known of the interaction of AZTp4A with HIV-1 RT, we carried out kinetic and molecular modeling studies to probe this. AZTp4A was found to be a potent inhibitor of HIV-1 RT-catalyzed DNA synthesis and of both ATP- and PPi-mediated AZTMP excision. AZTp4A is in fact an excellent chain-terminating substrate for AZT-resistant RT-catalyzed DNA synthesis, better than AZTTP (k(pol)/Kd = 6.2 and 11.9 for AZTTP and AZTp4A, respectively). The affinity of AZT-resistant HIV-1 RT for AZTp4A is at least 30,000-fold greater than that for the excision substrate ATP and approximately 10-fold greater than that for AZTTP. Dissociation of newly formed AZTp4A from RT may therefore provide a significant rate-limiting step for continued HIV-1 DNA synthesis. Our studies show that the products of PPi- and ATP-mediated excision of chain-terminating AZTMP (AZTTP and AZTp4A, respectively) are both potent chain-terminating substrates for HIV-1 RT, suggesting that there is no obvious benefit to HIV using ATP instead of PPi as the excision substrate.     

Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor,CXCR4

Rev, a viral regulatory protein of HIV-1, binds through its arginine-rich domain to the Rev-responsive element (RRE), a secondary structure in transcribed HIV-1 RNA. Binding of Rev to RRE mediates export of singly spliced or unspliced mRNAs from the nucleus to the cytoplasm. It has been previously shown that a certain arginine-rich peptide exhibits not only RRE-binding ability but also cell permeability and antagonism of CXCR4, one of the major coreceptors of HIV-1. Here we designed and synthesized arginine-rich peptides derived from the RNA-binding domain of Rev (Rev_34-50) and evaluated their anti-HIV-1 activities. Rev_34-50-A₄C, comprising Rev_34-50 with AAAAC at the C-terminus to increase the α-helicity, inhibited HIV-1 entry by CXCR4 antagonism and virus production in persistently HIV-1-infected PM1-CCR5 cells. Interestingly, similar motif of human lymphotropic virus type I Rex (Rex_1-21) also exerted moderate anti-HIV-1 activity. These results indicate that arginine-rich peptide, Rev_34-50-A₄C exerts dual antagonism against CXCR4 and Rev.     

Involvement of Na/H exchanger and respiratory burst enzymes NADPH oxidase and NO synthase,in Cd-induced lipid peroxidation and DNA damage in haemocytes of mussels

This study investigated cadmium-induced oxidative and genotoxic effects, such as lipid peroxidation and disturbance of DNA integrity (DNA damage) in haemocytes of mussel Mytilus galloprovincialis and the possible involvement of Na⁺/H⁺ exchanger (NHE), and/or the main enzymes of respiratory burst, NADPH oxidase and nitric oxide (NO) synthase, in the induction of Cd toxic effects. In order to verify the role of either NHE, or NADPH oxidase and NO synthase in Cd-mediated toxicity, inhibitors such as ethyl-N-isopropyl-amiloride (EIPA), diphenyleneiodonium chloride (DPI) and N^G-nitro-l-arginine methyl ester (L-NAME) were used in each case. Moreover, phorbol-myristate acetate (PMA), a well-known protein kinase C (PKC)-mediated NADPH oxidase and NO synthase stimulator, as well as hydrogen peroxide (H₂O₂), a well-known genotoxic agent, was also used for elucidating the modulation of signaling molecules within cells, thus leading to the induction of lipid peroxidation and DNA damage. The results of the present study showed that micromolar concentrations of Cd (0.05–50 μΜ) could enhance both lipid peroxidation and DNA damage, possible via a PKC-mediated signaling pathway with the involvement of NHE, thus leading to the induction of NADPH oxidase and NO synthase activity, since inhibition of either NHE, or NADPH oxidase and NO synthase activity, significantly attenuates Cd-induced toxic effects in each case.