Incorporating biotic factors in species distribution modeling: are interactions with soil microbes important?

It is increasingly recognized that species distributions are driven by both abiotic factors and biotic interactions. Despite much recent work incorporating competition, predation, and mutualism into species distribution models (SDMs), the focus has been confined to aboveground macroscopic interactions. Biotic interactions between plants and soil microbial communities are understudied as potentially important drivers of plant distributions. Some soil bacteria promote plant growth by cycling nutrients, while others are pathogenic; thus they have a high potential for influencing plant occurrence. We investigated the influence of soil bacterial clades on the distributions of bryophytes and 12 vascular plant species in a high elevation talus‐field ecosystem in the Rocky Mountain Front Range, Colorado, USA. We used an information‐theoretic criterion (AICc) modeling approach to compare SDMs with the following different sets of predictors: abiotic variables, abiotic variables and other plant abundances, abiotic variables and soil bacteria clade relative abundances, and a full model with abiotic factors, plant abundances, and bacteria relative abundances. We predicted that bacteria would influence plant distributions both positively and negatively, and that these interactions would improve prediction of plant species distributions. We found that inclusion of either plant or bacteria biotic predictors generally improved the fit, deviance explained, and predictive power of the SDMs, and for the majority of the species, adding information on both other plants and bacteria yielded the best model. Interactions between the modeled species and biotic predictors were both positive and negative, suggesting the presence of competition, parasitism, and facilitation. While our results indicate that plant–plant co‐occurrences are a stronger driver of plant distributions than plant–bacteria co‐occurrences, they also show that bacteria can explain parts of plant distributions that remain unexplained by abiotic and plant predictors. Our results provide further support for including biotic factors in SDMs, and suggest that belowground factors be considered as well.     

Linkage of congenital recessive deafness (gene DFNB10) to chromosome 21q22.3.

Deafness is a heterogeneous trait affecting approximately 1/1,000 newborns. Genetic linkage studies have already implicated more than a dozen distinct loci causing deafness. We conducted a genome search for linkage in a large Palestinian family segregating an autosomal recessive form of nonsyndromic deafness. Our results indicate that in this family the defective gene, DFNB10, is located in a 12-cM region near the telomere of chromosome 21. This genetic distance corresponds to <2.4 Mbp. Five marker loci typed from this region gave maximum LOD scores > or = to 3. Homozygosity of marker alleles was evident for only the most telomeric marker, D21S1259, suggesting that DFNB10 is closest to this locus. To our knowledge, this is the first evidence, at this location, for a gene that is involved in the development or maintenance of hearing. As candidate genes at these and other deafness loci are isolated and characterized, their roles in hearing will be revealed and may lead to development of mechanisms to prevent deafness.     

DNA methyltransferase homologue TRDMT1 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA

In eukaryotes, cytosine methylation regulates diverse biological processes such as gene expression, development and maintenance of genomic integrity. However, cytosine methylation and its functions in pathogenic apicomplexan protozoans remain enigmatic. To address this, here we investigated the presence of cytosine methylation in the nucleic acids of the protozoan Plasmodium falciparum. Interestingly, P. falciparum has TRDMT1, a conserved homologue of DNA methyltransferase DNMT2. However, we found that TRDMT1 did not methylate DNA, in vitro. We demonstrate that TRDMT1 methylates cytosine in the endogenous aspartic acid tRNA of P. falciparum. Through RNA bisulfite sequencing, we mapped the position of 5-methyl cytosine in aspartic acid tRNA and found methylation only at C38 position. P. falciparum proteome has significantly higher aspartic acid content and a higher proportion of proteins with poly aspartic acid repeats than other apicomplexan pathogenic protozoans. Proteins with such repeats are functionally important, with significant roles in host-pathogen interactions. Therefore, TRDMT1 mediated C38 methylation of aspartic acid tRNA might play a critical role by translational regulation of important proteins and modulate the pathogenicity of the malarial parasite.     

Comparative nuclear and mitochondrial genome diversity in humans and chimpanzees

Restriction mapping and sequencing have shown that humans have substantially lower levels of mitochondrial genome diversity (d) than chimpanzees. In contrast, humans have substantially higher levels of heterozygosity (H) at protein-coding loci, suggesting a higher level of diversity in the nuclear genome. To investigate the discrepancy further, we sequenced a segment of the mitochondrial genome control region (CR) from 49 chimpanzees. The majority of these were from the Pan troglodytes versus subspecies, which was underrepresented in previous studies. We also estimated the average heterozygosity at 60 short tandem repeat (STR) loci in both species. For a total sample of 115 chimpanzees, d = 0.075 +/0 0.037, compared to 0.020 +/- 0.011 for a sample of 1,554 humans. The heterozygosity of human STR loci is significantly higher than that of chimpanzees. Thus, the higher level of nuclear genome diversity relative to mitochondrial genome diversity in humans is not restricted to protein-coding loci. It seems that humans, not chimpanzees, have an unusual d/H ratio, since the ratio in chimpanzees is similar to that in other catarrhines. This discrepancy in the relative levels of nuclear and mitochondrial genome diversity in the two species cannot be explained by differences in mutation rate. However, it may result from a combination of factors such as a difference in the extent of sex ratio disparity, the greater effect of population subdivision on mitochondrial than on nuclear genome diversity, a difference in the relative levels of male and female migration among subpopulations, diversifying selection acting to increase variation in the nuclear genome, and/or directional selection acting to reduce variation in the mitochondrial genome.      

Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome?

Down syndrome (DS; trisomy 21) is associated with a wide range of variable clinical features, one of the most common being congenital heart defects (CHD). We used molecular genetic techniques to study the inheritance of genes on chromosome 21 in children with DS and CHD. Polymorphic markers on the long arm of chromosome 21 were analysed in 99 families who had a child with DS. Of these, 60 children had a CHD and 39 children had no CHD. Heterotrisomy describes the inheritance of an allele from each of three different grandparents. In some cases heterotrisomy will involve the inheritance of three different alleles. Heterotrisomic regions were defined as those showing retention of non-disjoining parental heterozygosity at polymorphic loci in the non-disjoined chromosomes of children with DS. Using polymorphic non-coding markers, we identified a consistent 9.6-cM minimum region (D21S167-HMG14) of heterotrisomy in children with DS and ventricular septal defect (VSD). Comparing individuals with DS and VSD to all others with DS (those either with no CHD or with any other CHD combined) shows the individuals with DS and VSD to have significantly more non-reduction or heterotrisomy in this region (P=0.006, Fisher's exact test, two-tailed). We postulate that heterotrisomy for a gene or genes in this region is a contributing factor to the pathogenesis of VSD in trisomy 21 either through the presence of three different specific alleles or through the presence of specific combinations of alleles.     

C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes.     

Studies on proinsulin and proglucagon biosynthesis and conversion at the subcellular level: I. Fractionation procedure and characterization of the subcellular fractions

Anglerfish islets were homogenized in 0.25 M sucrose and separated into seven separate subcellular fractions by differential and discontinuous density gradient centrifugation. The objective was to isolate microsomes and secretory granules in a highly purified state. The fractions were characterized by electron microscopy and chemical analyses. Each fraction was assayed for its content of protein, RNA, DNA, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG). Ultrastructural examination showed that two of the seven subcellular fractions contain primarily mitochondria, and that two others consist almost exclusively of secretory granules. A fifth fraction contains rough and smooth microsomal vesicles. The remaining two fractions are the cell supernate and the nuclei and cell debris. The content of DNA and RNA in all fractions is consistent with the observed ultrastructure. More than 82 percent of the total cellular IRI and 89(percent) of the total cellular IRG are found in the fractions of secretory granules. The combined fractions of secretory granules and microsomes consistently yield >93 percent of the total IRG. These results indicate that the fractionation procedure employed yields fractions of microsomes and secretory granules that contain nearly all the immunoassayable insulin and glucagons found in whole islet tissue. These fractions are thus considered suitable for study of proinsulin and proglucagon biosynthesis and their metabolic conversion at the subcellular level.