Antoni van Leeuwenhoek and measuring the invisible: The context of 16th and 17th century micrometry

This article explores the impact of 16th and 17th-century developments in micrometry on the methods Antoni van Leeuwenhoek employed to measure the microscopic creatures he discovered in various samples collected from his acquaintances and from local water sources. While other publications have presented Leeuwenhoek's measurement methods, an examination of the context of his techniques is missing. These previous measurement methods, driven by the need to improve navigation, surveying, astronomy, and ballistics, may have had an impact on Leeuwenhoek's methods. Leeuwenhoek was educated principally in the mercantile guild system in Amsterdam and Delft. He rose to positions of responsibility within Delft municipal government. These were the years that led up to his first investigations using the single-lens microscopes he became expert at creating, and that led to his first letter to the Royal Society in 1673. He also took measures to train in surveying and liquid assaying practices existing in his time, disciplines that were influenced by Pedro Nunes, Pierre Vernier, Rene Descartes, and others. While we may never know what inspired Leeuwenhoek's methods, the argument is presented that there were sufficient influences in his life to shape his approach to measuring the invisible.     

Structural basis for AMP binding to mammalian AMP-activated protein kinase

AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound.     

Genome-wide mapping with biallelic markers in Arabidopsis thaliana.

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.     

The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome

We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.     

Three new species,a synonymy and taxonomic notes on southern African members of the dung beetle genera Scarabaeus s. str. Linnaeus, 1758 and Escarabaeus Zídek & Pokorný, 2011 (Scarabaeidae: Scarabaeinae)

Three new species are described in the dung beetle genera Scarabaeus s. str. L., 1758, and Escarabaeus Zídek & Pokorný, 2011. Two comprise, Scarabaeus karae sp. nov. and Escarabaeus remii sp. nov. and are novelties. The third comprises Scarabaeus geminogalenus sp. nov., which describes a new species previously misidentified by Péringuey in 1901 and involved in a false synonymy by Janssens (1940). Notes are provided on the type specimen of Scarabaeus galenus. A close relative, Scarabaeus vicinus is recorded for the first time. Scarabaeus natalensis is synonymized with Scarabaeus basuto. Relationships and validity of a further five species are discussed: Scarabaeus convexus with S. spretus and S. rusticus; S. ebenus with S. interstitialis. The type specimen of Scarabaeus rixosus is also discussed. Distribution maps are provided for the new species and those in the S. galenus species complex.

http://zoobank.org/urn:lsid:zoobank.org:pub:CEC29F9E-2B2B-4568-8AE2-4CC65F79EC96     

High rates of photosynthesis in the desert shrub Chrysothamnus nauseosus ssp. albicaulis

  Basic aspects of photosynthesis were investigated in white rubber rabbitbrush ( Chrysothamnus nauseosus (Pallas) Britt. ssp. albicaulis ), a common C 3 deciduous shrub native to arid regions of the western U.S. Under favorable field conditions, net photosynthesis (P n ) ranged from 36 to 73 mgCO 2 · dm – 2 · hr – 1 , which is relatively high for a woody species. The leaves from the actively growing flowering shoots exhibited higher P n than those on the vegetative shoots. P n also varied according to the age of the leaves and the location of the plants. P n did not light saturate even at quantum flux densities (QFD) equivalent to full sunlight. The light compensation point was relatively high (ca 100 μ mol · m – 2 · S – 1 ), perhaps due to the presence of a tomentose vestiture on the leaf surface. At high QFD's, the stomatal conductance was high (ca 520 mmol · m – 2 · s – 1 ) for a woody species. RUBP - carboxylase content of the leaves ranged from 20 to 22 mg per gram F.W., which is similar to that found in most C 3 crop species. These results suggest that rabbitbrush is able to maintain high rates of P n , at least under nonstressed conditions.           

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.     

Mesodermal fate decisions of a stem cell: the Wnt switch

Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis.