Synthesis of aminoglycoside-3'-conjugates of 2'-O-methyl oligoribonucleotides and their invasion to a 19F labeled HIV-1 TAR model

The potential of aminoglycosides to induce RNA-invasion has been demonstrated. For this purpose, aminoglycoside-3'-conjugates of 2'-O-methyl oligoribonucleotides have been synthesized entirely on a solid phase. The synthesis includes an automated oligonucleotide chain elongation to solid-supported neomycin, ribostamycin, and methyl neobiosamine, and a two-step deprotection/release of the solid-supported conjugate, which allows exploitation of a simple protecting group scheme. Conjugates have been targeted to a (19)F labeled HIV-1 TAR RNA model (Trans Activation Response element of HIV), which allows monitoring of the invasion by (19)F NMR spectroscopy. A remarkably enhanced invasion, compared to that resulting from the corresponding unmodified 2'-O-methyl oligoribonucleotide (5'-CAGGCUCA-3'), has been obtained by the neomycin conjugate. The increased affinity results from a cooperative binding of the neomycin moiety and hybridization, though the invasion may also follow a mechanism, in which the first molar equivalent of the conjugate induces hybridization of the second.     

Local Knowledge and Conservation of Seagrasses in the Tamil Nadu State of India

Local knowledge systems are not considered in the conservation of fragile seagrass marine ecosystems. In fact, little is known about the utility of seagrasses in local coastal communities. This is intriguing given that some local communities rely on seagrasses to sustain their livelihoods and have relocated their villages to areas with a rich diversity and abundance of seagrasses. The purpose of this study is to assist in conservation efforts regarding seagrasses through identifying Traditional Ecological Knowledge (TEK) from local knowledge systems of seagrasses from 40 coastal communities along the eastern coast of India. We explore the assemblage of scientific and local traditional knowledge concerning the 1. classification of seagrasses (comparing scientific and traditional classification systems), 2. utility of seagrasses, 3. Traditional Ecological Knowledge (TEK) of seagrasses, and 4. current conservation efforts for seagrass ecosystems. Our results indicate that local knowledge systems consist of a complex classification of seagrass diversity that considers the role of seagrasses in the marine ecosystem. This fine-scaled ethno-classification gives rise to five times the number of taxa (10 species = 50 local ethnotaxa), each with a unique role in the ecosystem and utility within coastal communities, including the use of seagrasses for medicine (e.g., treatment of heart conditions, seasickness, etc.), food (nutritious seeds), fertilizer (nutrient rich biomass) and livestock feed (goats and sheep). Local communities are concerned about the loss of seagrass diversity and have considerable local knowledge that is valuable for conservation and restoration plans. This study serves as a case study example of the depth and breadth of local knowledge systems for a particular ecosystem that is in peril.     

Organic enrichment of sediments reduces arbuscular mycorrhizal fungi in oligotrophic lake plants

1. Arbuscular mycorrhizal fungi (AMF) commonly colonise isoetid species inhabiting oxygenated sediments in oligotrophic lakes but are usually absent in other submerged plants. We hypothesised that organic enrichment of oligotrophic lake sediments reduces AMF colonisation and hyphal growth because of sediment O₂ depletion and low carbon supply from stressed host plants. 2. We added organic matter to sediments inhabited by isoetids and measured pore‐water chemistry (dissolved O₂, inorganic carbon, Fe²⁺ and ), colonisation intensity of roots and hyphal density after 135 days of exposure. 3. Addition of organic matter reduced AMF colonisation of roots of both Lobelia dortmanna and Littorella uniflora, and high additions stressed the plants. Even small additions of organic matter almost stopped AMF colonisation of initially un‐colonised L. uniflora, though without reducing plant growth. Mean hyphal density in sediments was high (6 and 15 m cm^?3) and comparable with that in terrestrial soils (2–40 m cm^?3). Hyphal density was low in the upper 1 cm of isoetid sediments, high in the main root zone between 1 and 8 cm and positively related to root density. Hyphal surface area exceeded root surface area by 1.7–3.2 times. 4. We conclude that AMF efficiently colonise isoetids in oligotrophic sediments and form extensive hyphal networks. Small additions of organic matter to sediments induce sediment anoxia and reduce AMF colonisation of roots but cause no apparent plant stress. High organic addition induces night‐time anoxia in both the sediment and the plant tissue. Tissue anoxia reduces root growth and AMF colonisation, probably because of restricted translocation of nutrient ions and organic solutes between roots and leaves. Isoetids should rely on AMF for P uptake on nutrient‐poor mineral sediments but are capable of growing without AMF on organic sediments.     

Induction of TK mutations in human lymphoblastoid TK6 cells by the rat carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX)

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water, is carcinogenic in rats and genotoxic in mammalian cells in vitro. In the current study, the mechanism of genotoxicity of MX in human lymphoblastoid TK6 cells was investigated by use of the Comet assay, the micronucleus test, and the thymidine kinase (TK) gene-mutation assay. MX induced a concentration-dependent increase in micronuclei and TK mutations. The lowest effective concentrations in the MN test and the TK gene-mutation assay were 37.5μM and 25μM, respectively. In the Comet assay, a slight although not statistically significant increase was observed in the level of DNA damage induced by MX in the concentration range of 25-62.5μM. Molecular analysis of the TK mutants revealed that MX induced primarily point mutations or other small intragenic mutations (61%), while most of the remaining TK mutants (32%) were large deletions at the TK locus, leading to the hemizygous-type loss-of-heterozygosity (LOH) mutations. These findings show that aside from inducing point mutations, MX also generates LOH at the TK locus in human cells and may thus cause the inactivation of tumour-suppressor genes by LOH.     

Forest tree growth is linked to mycorrhizal fungal composition and function across Europe

Most trees form symbioses with ectomycorrhizal fungi (EMF) which influence access to growth-limiting soil resources. Mesocosm experiments repeatedly show that EMF species differentially affect plant development, yet whether these effects ripple up to influence the growth of entire forests remains unknown. Here we tested the effects of EMF composition and functional genes relative to variation in well-known drivers of tree growth by combining paired molecular EMF surveys with high-resolution forest inventory data across 15 European countries. We show that EMF composition was linked to a three-fold difference in tree growth rate even when controlling for the primary abiotic drivers of tree growth. Fast tree growth was associated with EMF communities harboring high inorganic but low organic nitrogen acquisition gene proportions and EMF which form contact versus medium-distance fringe exploration types. These findings suggest that EMF composition is a strong bio-indicator of underlying drivers of tree growth and/or that variation of forest EMF communities causes differences in tree growth. While it may be too early to assign causality or directionality, our study is one of the first to link fine-scale variation within a key component of the forest microbiome to ecosystem functioning at a continental scale.Subject terms: Microbial ecology, Forest ecology, Fungal ecology, Biogeochemistry     

Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance

Prostate cancer (PCa) is the most frequently diagnosed cancer in men worldwide and is likely to be caused by a number of genes with different modes of inheritance, population frequencies and penetrance. The objective of this study was to assess the familial aggregation of PCa in a sample of 1,546 nuclear families ascertained through an affected father and diagnosed during 1988–1993, from the unique, founder population-based resource of the Finnish Cancer Registry. Segregation analysis was performed for two cohorts of 557 early-onset and 989 late-onset families evaluating residual paternal effects and assuming that age at diagnosis followed a logistic distribution after log-transformation. The results did not support an autosomal dominant inheritance as has been reported in many of the hospital-based prostatectomy series. Instead, it confirmed the existence of hereditary PCa in the Finnish population under a complex model that included a major susceptibility locus with Mendelian recessive inheritance and a significant paternal regressive coefficient that is indicative of a polygenic/multifactorial component. The strengths of our study are the homogenous Finnish population, large epidemiological population-based data, histologically confirmed cancer diagnosis done before the PSA-era in Finland and registry based approach. Our results support the evidence that the inheritance of PCa is controlled by major genes and are in line with the previous linkage studies. Moreover, this is the first time a recessive inheritance is suggested to fit PCa in all data even when divided to early and late-onset cohorts. Sanna Pakkanen and Agnes B Baffoe-Bonnie equally contributed to this work.     

Impairment of proprioception after whiplash injury

Whiplash injury usually occurs in traffic accidents. Persons experienced this injury might have an impairment of proprioception clinically expressed as inability to determine the exact position of their heads. The aim of this study was to examine the loss of proprioception in people who had a whiplash injury. The study included 60 subjects with cervical spine injury, aged 20 to 50 years and 60 healthy volunteers matched by sex and age. The instrument used for cervical spine mobility assessment was the Cervical Measurement System (CMS), which determines the ability of subjects to return their head in the exact position as it was before they turned it 30 degrees left or right. Patients with cervical spine injury showed significant impairment of proprioception in comparison with healthy subjects (P < 0.001). The results support the hypothesis that subject with recent cervical spine injury have incorrect perception of their head position. Therefore, their rehabilitation should include the correction of proprioception and head coordination.     

Haloarchaeal communities in the crystallizers of two adriatic solar salterns

Solar salterns operate only for short dry periods of the year in the north shore of the Adriatic Sea because of its relatively humid and cold Mediterranean climate. In a previous paper, we showed that the NaCl precipitation ponds (crystallizers) of Northern Adriatic Secovlje salterns have different haloarchaeal populations from those typically found in dry and hot climates such as Southern Spain. To check whether there is a common pattern of haloarchaeal diversity in these less extreme conditions, diversity in crystallizers of other Adriatic solar salterns in Ston, Croatia was ascertained by molecular and culture methods. In addition, the cultivation approach was used to further describe haloarchaeal diversity in both salterns. Over the period of two solar salt collection seasons, isolates related to species of the genera Haloferax, Haloarcula, and Haloterrigena were recovered from both salterns. Within the same sampling effort, relatives of the genus Halorubrum and a Natrinema-like isolate were cultivated from Slovenian Secovlje salterns while Halobacterium related isolates were obtained from the Croatian Ston salterns. Concurrent with our previous findings, a library of Croatian saltern crystallizer PCR-amplified 16S rRNA genes was dominated by sequences related to the genus Halorubrum. The microbial community structure was similar in both salterns but diversity indices showed greater values in Slovenian salterns when compared with Croatian salterns.     

6-Shogaol,an active constituent of ginger,attenuates neuroinflammation and cognitive deficits in animal models of dementia

Recently, increased attention has been directed towards medicinal extracts as potential new drug candidates for dementia. Ginger has long been used as an important ingredient in cooking and traditional herbal medicine. In particular, ginger has been known to have disease-modifying effects in Alzheimer's disease (AD). However, there is no evidence of which constituents of ginger exhibit therapeutic effects against AD. A growing number of experimental studies suggest that 6-shogaol, a bioactive component of ginger, may play an important role as a memory-enhancing and anti-oxidant agent against neurological diseases. 6-Shogaol has also recently been shown to have anti-neuroinflammatory effects in lipopolysaccharide (LPS)-treated astrocytes and animal models of Parkinson’s disease, LPS-induced inflammation and transient global ischemia. However, it is still unknown whether 6-shogaol has anti-inflammatory effects against oligomeric forms of the Aβ (AβO) in animal brains. Furthermore, the effects of 6-shogaol against memory impairment in dementia models are also yet to be investigated. In this study, we found that administration of 6-shogaol significantly reduced microgliosis and astrogliosis in intrahippocampal AβO-injected mice, ameliorated AβO and scopolamine-induced memory impairment, and elevated NGF levels and pre- and post-synaptic marker in the hippocampus. All these results suggest that 6-shogaol may play a role in inhibiting glial cell activation and reducing memory impairment in animal models of dementia.