The ability of land plants to synthesize glucuronoxylans predates the evolution of tracheophytes

Glucuronoxylans with a backbone of 1,4-linked β-D-xylosyl residues are ubiquitous in the secondary walls of gymnosperms and angiosperms. Xylans have been reported to be present in hornwort cell walls, but their structures have not been determined. In contrast, the presence of xylans in the cell walls of mosses and liverworts remains a subject of debate. Here we present data that unequivocally establishes that the cell walls of leafy tissue and axillary hair cells of the moss Physcomitrella patens contain a glucuronoxylan that is structurally similar to glucuronoxylans in the secondary cell walls of vascular plants. Some of the 1,4-linked β-D-xylopyranosyl residues in the backbone of this glucuronoxylan bear an α-D-glucosyluronic acid (GlcpA) sidechain at O-2. In contrast, the lycopodiophyte Selaginella kraussiana synthesizes a glucuronoxylan substituted with 4-O-Me-α-D-GlcpA sidechains, as do many hardwood species. The monilophyte Equisetum hyemale produces a glucuronoxylan with both 4-O-Me-α-D-GlcpA and α-D-GlcpA sidechains, as does Arabidopsis. The seedless plant glucuronoxylans contain no discernible amounts of the reducing-end sequence that is characteristic of gymnosperm and eudicot xylans. Phylogenetic studies showed that the P. patens genome contains genes with high sequence similarity to Arabidopsis CAZy family GT8, GT43 and GT47 glycosyltransferases that are likely involved in xylan synthesis. We conclude that mosses synthesize glucuronoxylan that is structurally similar to the glucuronoxylans present in the secondary cell walls of lycopodiophytes, monilophytes, and many seed-bearing plants, and that several of the glycosyltransferases required for glucuronoxylan synthesis evolved before the evolution of tracheophytes.     

Use of the Oncotype DX 21-gene assay to guide adjuvant decision making in early-stage breast cancer

The decision to use adjuvant chemotherapy in patients with early stage breast cancer involves the consideration of many factors that traditionally rely heavily on tumor size and lymph node involvement and a limited set of biologic characteristics such as estrogen receptor and HER2 expression. Overtreatment with cytotoxic chemotherapy is a significant concern among patients and physicians. Using the currently accepted guidelines it has been estimated that a large percentage of patients receiving chemotherapy for low-risk breast cancers may be overtreated. Gene expression profiling is a new technology being developed to help improve risk stratification of patients and to predict outcomes. The Oncotype DXtrade mark assay is one example of a gene expression profile validated in women with lymph node-negative, estrogen receptor-expressing breast cancer. This assay and others aim to help improve risk classification and recurrence prediction and, therefore, optimize selection of patients for adjuvant chemotherapy.     

Heterocyst patterns without patterning proteins in cyanobacterial filaments

We have quantitatively modeled heterocyst differentiation after fixed nitrogen step-down in the filamentous cyanobacterium Anabaena sp. PCC 7120 without lateral inhibition due to the patterning proteins PatS or HetN. We use cell growth and division together with fixed-nitrogen dynamics and allow heterocysts to differentiate upon the local exhaustion of available fixed nitrogen. Slow transport of fixed nitrogen along a shared periplasmic space allows for fast growing cells to differentiate ahead of their neighbors. Cell-to-cell variability in growth rate determines the initial heterocyst pattern. Early release of fixed nitrogen from committed heterocysts allows a significant fraction of vegetative cells to be retained at later times. We recover the experimental heterocyst spacing distributions and cluster size distributions of Khudyakov and Golden [Khudyakov, I.Y., Golden, J.W., 2004. Different functions of HetR, a master regulator of heterocyst differentiation in Anabaena sp PCC 7120, can be separated by mutation. Proc. Natl. Acad. Sci. U. S. A. 101, 16040-16045].     

Variation in the benefits of multiple mating on female fertility in wild stalk‐eyed flies

Polyandry, female mating with multiple males, is widespread across many taxa and almost ubiquitous in insects. This conflicts with the traditional idea that females are constrained by their comparatively large investment in each offspring, and so should only need to mate once or a few times. Females may need to mate multiply to gain sufficient sperm supplies to maintain their fertility, especially in species in which male promiscuity results in division of their ejaculate among many females. Here, we take a novel approach, utilizing wild‐caught individuals to explore how natural variation among females and males influences fertility gains for females. We studied this in the Malaysian stalk‐eyed fly species Teleopsis dalmanni. After an additional mating, females benefit from greatly increased fertility (proportion fertile eggs). Gains from multiple mating are not uniform across females; they are greatest when females have high fecundity or low fertility. Fertility gains also vary spatially, as we find an additional strong effect of the stream from which females were collected. Responses were unaffected by male mating history (males kept with females or in male‐only groups). Recent male mating may be of lesser importance because males in many species, including T. dalmanni, partition their ejaculate to maintain their fertility over many matings. This study highlights the importance of complementing laboratory studies with data on wild‐caught populations, where there is considerable heterogeneity between individuals. Future research should focus on environmental, demographic and genetic factors that are likely to significantly influence variation in individual female fecundity and fertility.     

Impact of Schistosoma mansoni on Malaria Transmission in Sub-Saharan Africa

Background

Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children.

Methodology

We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities.

Principal Findings

Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities.

Conclusions/Significance

Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden.     

The role of mutation accumulation in HIV progression

The onset of AIDS is characterized by the collapse of the immune system after a prolonged asymptomatic period. The mechanistic basis of this disease progression has remained obscure, hindering the development of effective therapies. Here I present a mechanism that underlies the deterioration of the immune system during HIV infection. The elevated turnover of lymphocytes throughout the asymptomatic period is postulated to result in the accumulation of deleterious mutations, which impairs immunological function, replicative ability and viability of lymphocytes. This mutational meltdown is proposed to occur throughout the hierarchy of lymphocyte progenitors, resulting in the deterioration of lymphocyte regeneration and an ensuing rise in viral loads. A mathematical model is used to illustrate this mechanism of progressive immunological deterioration. Mutation accumulation may explain not only the decline in CD4+T cells, but also the functional deterioration of CD4+T cells, CD8+T cells and B cells, and the exhaustion of lymphocyte regeneration.     

Coral recruitment patterns in the Florida Keys

This study examines scleractinian zooxanthellate coral recruitment patterns in the Florida Keys to determine if differences in density or community composition exist between regions. From July to September 2002, nine patch reefs, three in each of the upper, middle and lower Keys, were surveyed for coral recruits (colonies <5 cm in diameter) using randomly placed quadrats and transects. Coral recruits were enumerated, measured, and identified to genus. Fourteen genera of corals were observed across all sites and ranged from five to 13 per site. Densities ranged from 6.29 +/- 1.92 (mean +/- SE) to 39.08 +/- 4.53 recruits m(-2), and there were significant site and regional differences in recruit densities. The density of recruits in the upper Keys was significantly lower than in the middle and lower Keys. In addition, the upper Keys were less diverse and had a different recruit size-frequency distribution. The majority of recruits were non-massive scleractinian species that contribute relatively little to overall reef-building processes, a finding that is similar to previous studies. Fewer recruits of massive species were found in the upper Keys compared to the middle and lower Keys. The recruitment patterns of the reefs in the upper Keys could potentially hinder their ability to recover from stress and disturbances.     

Influence of surface shape on DNA binding of bimetallo helicates

In order to probe the DNA-helicate interactions responsible for the DNA binding and remarkable changes of the DNA secondary structure induced by a tetracationic bi-metallo helicate [Fe(2)(L(1))(3)](4+) (L(1)=C(25)H(20)N(4)), we have designed and synthesised derivatives with hydrophobic methyl groups at different positions on the ligand backbone. Two dimetallo helicates [Fe(2)(L(i))(3)](4+) were prepared using ligands L(3) and L(5) with the methyl substituent on, respectively, the 3 and 5 positions of the pyridyl ring thus producing a wider or slightly longer tetracationic DNA binder. UV/visible absorbance, circular and linear dichroism spectroscopies have been used to characterize the interactions of the cylinders with DNA with the aim of investigating any sequence preference or selectivity upon binding. Competitive binding studies using fluorescent dyes Hoechst 33258 (a minor groove binder), ethidium bromide (an intercalator) and a major groove binding cation (cobalt (III) hexammine) which induces the B-->Z transition have been employed to determine the binding geometries of the enantiomers of two methylated helicates (L(3) and L(5)) to DNA and compare with the data obtained previously for the unmethylated analogue (L(1)). The results demonstrate that the racemic mixtures and the resolved enantiomers of all helicates bind to DNA inducing structural changes. The overall conclusion from the effect of adding these groups to the surface of the parent helicate is that increasing the width (L(3)) reduces the DNA binding strength, the bending and coiling effect and the groove selectivity of the enantiomers compared with the parent compound. There is limited evidence to suggest a slight GC sequence preference. Lengthening the helicate (L(5)) results in DNA interactions similar to those of the parent compounds, with an increased preference of the P enantiomer for the minor groove indicating an enhancement of mode selectivity.