Assessment of the stream invertebrate β‐diversity along an elevation gradient using a bidimensional null model analysis

β‐Diversity, commonly defined as the compositional variation among localities that links local diversity (α‐diversity) and regional diversity (γ‐diversity), can arise from two different ecological phenomena, namely the spatial species turnover (i.e., species replacement) and the nestedness of assemblages (i.e., species loss). However, any assessment that does not account for stochasticity in community assembly could be biased and misinform conservation management. In this study, we aimed to provide a better understanding of the overall ecological phenomena underlying stream β‐diversity along elevation gradients and to contribute to the rich debate on null model approaches to identify nonrandom patterns in the distribution of taxa. Based on presence‐absence data of 78 stream invertebrate families from 309 sites located in the Swiss Alpine region, we analyzed the effect size of nonrandom spatial distribution of stream invertebrates on the β‐diversity and its two components (i.e., turnover and nestedness). We used a modeling framework that allows exploring the complete range of existing algorithms used in null model analysis and assessing how distribution patterns vary according to an array of possible ecological assumptions. Overall, the turnover of stream invertebrates and the nestedness of assemblages were significantly lower and higher, respectively, than the ones expected by chance. This pattern increased with elevation, and the consistent trend observed along the altitudinal gradient, even in the most conservative analysis, strengthened our findings. Our study suggests that deterministic distribution of stream invertebrates in the Swiss Alpine region is significantly driven by differential dispersal capacity and environmental stress gradients. As long as the ecological assumptions for constructing the null models and their implications are acknowledged, we believe that they still represent useful tools to measure the effect size of nonrandom spatial distribution of taxa on β‐diversity.     

An assessment of macroinvertebrate functional feeding groups as water quality indicators in the Buffalo River, eastern Cape Province, South Africa

The aim of this paper was to investigate the potential for using functional feeding groups (FFGs) as indicators of water quality conditions in rivers, using the Buffalo River, South Africa, as a specific example. Multivariate classification and ordination techniques were used to investigate species and FFG distributions in relation to a number of physico-chemical variables at 16 sites from the headwaters to the estuary of the Buffalo River.Two-way indicator species analysis (TWINSPAN) of species composition ranked most of the sites sequentially down the river, irrespective of water quality conditions. Ordination of FFGs from a set of riffle samples collected in mid-late summer showed only weak relationships between FFG distribution and water quality changes, except where variables changed sequentially down the river (e.g. pH and temperature). Individual species responses to water quality gradients were examined for nine riffle-dwelling species representing diverse FFGs. Following correspondence analysis of a matrix of environmental variables and species frequencies, some species showed strong associations with defined ranges of some variables. In particular, Adenophlebia auriculata (Leptophlebiidae, Ephemeroptera) from the headwater sampling site, was associated with low pH and low temperature. Simulium damnosum occurred under conditions of high turbidity, while Afronurus harrisoni was found under high concentrations of potassium, ammonium and nitrite ions.We conclude that although there was a distinct headwaters fauna in the Buffalo River, and sequential downstream changes in species composition, most FFGs (apart from shredders) were represented down the whole length of the river. FFG classifications are therefore unlikely to provide useful indications of water quality conditions in the Buffalo River.Using a categorical approach to classifying water quality variables, and by applying correspondence analysis to the resulting matrix, we recognised nine species that could be used to define water quality. These indicator species can be used to define tolerance ranges of the fauna for water quality conditions in different parts of the Buffalo river.     

HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission

HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to ‘purge’ the reservoir of latently infected cells in order to either eliminate infection completely, or significantly delay the time to viral recrudescence after therapy interruption. A fundamental question in HIV research is how frequently the virus reactivates from latency, and thus how much the reservoir might need to be reduced to produce a prolonged antiretroviral-free HIV remission. Here we provide the first direct estimates of the frequency of viral recrudescence after ART interruption, combining data from four independent cohorts of patients undergoing treatment interruption, comprising 100 patients in total. We estimate that viral replication is initiated on average once every ≈6 days (range 5.1- 7.6 days). This rate is around 24 times lower than previous thought, and is very similar across the cohorts. In addition, we analyse data on the ratios of different ‘reactivation founder’ viruses in a separate cohort of patients undergoing ART-interruption, and estimate the frequency of successful reactivation to be once every 3.6 days. This suggests that a reduction in the reservoir size of around 50-70-fold would be required to increase the average time-to-recrudescence to about one year, and thus achieve at least a short period of anti-retroviral free HIV remission. Our analyses suggests that time-to-recrudescence studies will need to be large in order to detect modest changes in the reservoir, and that macaque models of SIV latency may have much higher frequencies of viral recrudescence after ART interruption than seen in human HIV infection. Understanding the mean frequency of recrudescence from latency is an important first step in approaches to prolong antiretroviral-free viral remission in HIV.     

Beyond ecosystem modeling: A roadmap to community cyberinfrastructure for ecological data‐model integration

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, and transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundations of community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is a key to meeting the pressing needs of science and society in the 21st century.     

Role of MGMT in protecting against cyclophosphamide-induced toxicity in cells and animals

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that protects cells from the biological consequences of alkylating agents by removing alkyl groups from the O(6)-position of guanine. Cyclophosphamide and ifosfamide are oxazaphosphorines used clinically to treat a wide variety of cancers; however, the role of MGMT in recognizing DNA damage induced by these agents is unclear. In vitro evidence suggests that MGMT may protect against the urotoxic oxazaphosphorine metabolite, acrolein. Here, we demonstrate that Chinese hamster ovary cells transfected with MGMT are protected against cytotoxicity following treatment with chloroacetaldehyde (CAA), a neuro- and nephrotoxic metabolite of cyclophosphamide and ifosfamide. The mechanism by which MGMT recognizes damage induced by acrolein and CAA is unknown. CHO cells expressing a mutant form of MGMT (MGMT(R128A)), known to have >1000-fold less repair activity towards alkylated DNA while maintaining full active site transferase activity towards low molecular weight substrates, exhibited equivalent CAA- and acrolein-induced cytotoxicity to that of CHO cells transfected with plasmid control. These results imply that direct reaction of acrolein or CAA with the active site cysteine residue of MGMT, i.e. scavenging, is unlikely a mechanism to explain MGMT protection from CAA and acrolein-induced toxicity. In vivo, no difference was detected between Mgmt-/- and Mgmt+/+ mice in the lethal effects of cyclophosphamide. While MGMT may be important at the cellular level, mice deficient in MGMT are not significantly more susceptible to cyclophosphamide, acrolein or CAA. Thus, our data does not support targeting MGMT to improve oxazaphosphorine therapy.     

Plasma-initiated graft polymerization as an immobilization platform for metal free Russian propolis ethanol extracts designed specifically for biomaterials

The antibacterial and anti-biofilm activities of propolis have been intensively reported. However, the application of this folk remedy as a means to prevent biomedical implant contamination has yet to be completely evaluated. In response to the significant resistant and infectious attributes of biofilms, biomaterials engineered to possess specific chemical and physical properties were immobilized with metal free Russian propolis ethanol extracts (MFRPEE), a known antibacterial agent. The results obtained from this study begin to examine the application of MFRPEE as a novel alternative method for the prevention of medical and biomedical implant infections. When constructed under specific experimental conditions, immobilized biomaterials showed excellent stability when subjected to simulated body fluid and fetal bovine serum. The ability of immobilized biomaterials to specifically target pathogens (both Gram-positive and Gram-negative biofilm forming bacteria), while promoting tissue cell growth, renders these biomaterials as potential candidates for clinical applications.     

The structure and mechanism of methanol dehydrogenase

This is a review of recent work on methanol dehydrogenase (MDH), a pyrroloquinoline quinone (PQQ)-containing enzyme catalysing the oxidation of methanol to formaldehyde in methylotrophic bacteria. Although it is the most extensively studied of this class of dehydrogenases, it is only recently that there has been any consensus about its mechanism. This is partly due to recent structural studies on normal and mutant enzymes and partly due to more definitive work on the mechanism of related alcohol and glucose dehydrogenases. This work has also led to conclusions about the subsequent path of electrons and protons during the reoxidation of the reduced quinol form of the prosthetic group.