Nyasol and 1,3(5)-diphenyl-1-pentene related glycosides from Hypoxis angustifolia

From the rhizomes of Hypoxis angustifolia, nyasol, (Z)-1-(4′-hydroxyphenyl)-3-(4′-hydroxyphenyl)-l,4-pentadiene, has been isolated and identified, together with hypoxoside, nyasoside, nyaside and mononyasine A and B.     

Industrial wastewaters harbor a unique diversity of bacterial communities revealed by high-throughput amplicon analysis

Industrial wastewater effluents present a major source of water pollution, and can potentially alter the microbial ecological landscape. While there are numerous reports on the microbial quality of domestic municipal effluents and their perceived environmental effects, there are limited reports devoted to the study of bacterial diversity of effluents from individual industries before they are mixed up with other sources. This study analyzed both the physicochemical parameters and bacterial community structures of different industrial wastewaters using Illumina high-throughput sequencing platform. Industrial wastewater with temperature ranging from 18.9 to 21.5 °C, and total dissolved solid (TDS) levels at up to 4611 mg/L, appeared to be predominated by Proteobacteria (44.44–75.86%) with the exception of the Capegate sample where Actinobacteria (39.66%) were the highest. Sulfur levels were significantly higher (p?<?0.05) in Dixon wastewater constituting higher populations of sulfur reducing bacteria (SRB) compared to the other sites. Diversity index (Shannon-H index) and richness estimator (Chao1 index) ranged from 974 (Capegate) to 4552 (Dixon) and 6.04 (Dixon) to 4.15 (CWI), respectively. Multivariate analysis results highlighted that the bacterial communities were strongly shaped by physicochemical variables. The top 10 operational taxonomic units (OTUs) of each industrial sample had the potential to play important roles in the bioremediation and biodegradation of pollutants. Dominant OTUs belonging to the phyla Planctomyces from the Chemreem sample could not be classified to any genera and are likely to represent novel species.     

Synthetic extreme environments: overlooked sources of potential biotechnologically relevant microorganisms

Synthetic extreme environments like carwash effluent tanks and drains are potential sources of biotechnologically important microorganisms and molecules which have, however, remained unexplored. Using culture‐ and molecular‐based methods, a total of 17 bacterial isolates belonging to the genera Shewanella, Proteus, Paenibacillus, Enterobacter and Citrobacter, Aeromonas, Pseudomonas and Pantoea were identified. Hydrocarbon utilization and enzyme production screening assays showed that Aeromonas sp. CAC11, Paenibacillus sp. CAC12 and Paenibacillus sp. CAC13 and Citrobacter sp. PCW7 were able to degrade benzanthracene, naphthalene and diesel oil, Paenibacillus sp. CAC12 and Paenibacillus sp. CAC13 could produce cellulase enzyme, while Proteus sp. BPS2, Pseudomonas sp. SAS8 and Proteus sp. CAL3 could produce lipase. GC‐MS analysis of bacterial secondary metabolites resulted in identification of 107 different compounds produced by Proteus sp. BPS2, Paenibacillus sp. CAC12, Pseudomonas sp. SAS8, Proteus sp. CAL3 and Paenibacillus sp. CAC13. Most of the compounds identified by both GC‐MS and LC‐MS have previously been determined to have antibacterial, antifungal and/or anticancer properties. Further, microbial metabolites which have previously been known to be produced only by plants or microorganisms found in natural extreme environments were also identified in this study. This research has revealed the immense bioresource potential of microorganisms inhabiting synthetic extreme environments.     

Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities

Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.     

18th Sir Hans Krebs lecture. Knowledge-based protein modelling and design

A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ab initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek-key motifs.     

Reproductive change in Zimbabwe and Kenya: the role of the proximate determinants in recent fertility trends

This study examines trends in proximate determinants of fertility in Zimbabwe and Kenya. Findings from the four Demographic and Health Surveys conducted in these countries show that the dramatic fall in fertility in these countries is consistent with the underlying trends in the most important proximate determinants of fertility. In Zimbabwe, contraceptive use far exceeds other proximate determinants in influencing fertility levels and trends. The results show that the fertility inhibiting effects of contraception are more important than the effects of postpartum infecundability, marriage patterns, or sterility. The results also show that contraceptive use has its greatest suppressing effects in the middle and younger age groups. However, in Kenya, the dominant fertility inhibiting effect is postpartum infecundability, with contraception coming in second.     

Crystal structure of an Xrcc4-DNA ligase IV complex.

A complex of two proteins, Xrcc4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination. Here we report the crystal structure of human Xrcc4 bound to a polypeptide that corresponds to the DNA ligase IV sequence linking its two BRCA1 C-terminal (BRCT) domains. In the complex, a single ligase chain binds asymmetrically to an Xrcc4 dimer. The helical tails of Xrcc4 undergo a substantial conformational change relative to the uncomplexed protein, forming a coiled coil that unwinds upon ligase binding, leading to a flat interaction surface. A buried network of charged hydrogen bonds surrounded by extensive hydrophobic contacts explains the observed tightness of the interaction. The strong conservation of residues at the interface between the two proteins provides evidence that the observed mode of interaction has been maintained in NHEJ throughout evolution.     

Revision rates after primary hip and knee replacement in England between 2003 and 2006

Background

Hip and knee replacement are some of the most frequently performed surgical procedures in the world. Resurfacing of the hip and unicondylar knee replacement are increasingly being used. There is relatively little evidence on their performance. To study performance of joint replacement in England, we investigated revision rates in the first 3 y after hip or knee replacement according to prosthesis type.

Methods and Findings

We linked records of the National Joint Registry for England and Wales and the Hospital Episode Statistics for patients with a primary hip or knee replacement in the National Health Service in England between April 2003 and September 2006. Hospital Episode Statistics records of succeeding admissions were used to identify revisions for any reason. 76,576 patients with a primary hip replacement and 80,697 with a primary knee replacement were included (51% of all primary hip and knee replacements done in the English National Health Service). In hip patients, 3-y revision rates were 0.9% (95% confidence interval [CI] 0.8%–1.1%) with cemented, 2.0% (1.7%–2.3%) with cementless, 1.5% (1.1%–2.0% CI) with “hybrid” prostheses, and 2.6% (2.1%–3.1%) with hip resurfacing (p < 0.0001). Revision rates after hip resurfacing were increased especially in women. In knee patients, 3-y revision rates were 1.4% (1.2%–1.5% CI) with cemented, 1.5% (1.1%–2.1% CI) with cementless, and 2.8% (1.8%–4.5% CI) with unicondylar prostheses (p < 0.0001). Revision rates after knee replacement strongly decreased with age.

Interpretation

Overall, about one in 75 patients needed a revision of their prosthesis within 3 y. On the basis of our data, consideration should be given to using hip resurfacing only in male patients and unicondylar knee replacement only in elderly patients.     

Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ

The recently characterised 299-residue human XLF/Cernunnos protein plays a crucial role in DNA repair by non-homologous end joining (NHEJ) and interacts with the XRCC4-DNA Ligase IV complex. Here, we report the crystal structure of the XLF (1-233) homodimer at 2.3 A resolution, confirming the predicted structural similarity to XRCC4. The XLF coiled-coil, however, is shorter than that of XRCC4 and undergoes an unexpected reverse in direction giving rise to a short distorted four helical bundle and a C-terminal helical structure wedged between the coiled-coil and head domain. The existence of a dimer as the major species is confirmed by size-exclusion chromatography, analytical ultracentrifugation, small-angle X-ray scattering and other biophysical methods. We show that the XLF structure is not easily compatible with a proposed XRCC4:XLF heterodimer. However, we demonstrate interactions between dimers of XLF and XRCC4 by surface plasmon resonance and analyse these in terms of surface properties, amino-acid conservation and mutations in immunodeficient patients. Our data are most consistent with head-to-head interactions in a 2:2:1 XRCC4:XLF:Ligase IV complex.