PathBeat. Number 14 (Winter 2013) University of Iowa Department of Pathology.

University of Iowa Department of Pathology newsletter.

PathBeat. Number 13 (Winter 2012) University of Iowa Department of Pathology.

University of Iowa Department of Pathology newsletter.

Experimentally increased group diversity improves disease resistance in an ant species.

A leading hypothesis linking parasites to social evolution is that more genetically diverse social groups better resist parasites. Moreover, group diversity can encompass factors other than genetic variation that may also influence disease resistance. Here, we tested whether group diversity improved disease resistance in an ant species with natural variation in colony queen number. We formed experimental groups of workers and challenged them with the fungal parasite Metarhizium anisopliae. Workers originating from monogynous colonies (headed by a single queen and with low genetic diversity) had higher survival than workers originating from polygynous ones, both in uninfected groups and in groups challenged with M. anisopliae. However, an experimental increase of group diversity by mixing workers originating from monogynous colonies strongly increased the survival of workers challenged with M. anisopliae, whereas it tended to decrease their survival in absence of infection. This experiment suggests that group diversity, be it genetic or environmental, improves the mean resistance of group members to the fungal infection, probably through the sharing of physiological or behavioural defences.

Case studies and mathematical models of ecological speciation. 1. Cichlids in a crater lake.

A recent study of a pair of sympatric species of cichlids in Lake Apoyo in Nicaragua is viewed as providing probably one of the most convincing examples of sympatric speciation to date. Here, we describe and study a stochastic, individual-based, explicit genetic model tailored for this cichlid system. Our results show that relatively rapid (<20,000 generations) colonization of a new ecological niche and (sympatric or parapatric) speciation via local adaptation and divergence in habitat and mating preferences are theoretically plausible if: (i) the number of loci underlying the traits controlling local adaptation, and habitat and mating preferences is small; (ii) the strength of selection for local adaptation is intermediate; (iii) the carrying capacity of the population is intermediate; and (iv) the effects of the loci influencing nonrandom mating are strong. We discuss patterns and timescales of ecological speciation identified by our model, and we highlight important parameters and features that need to be studied empirically to provide information that can be used to improve the biological realism and power of mathematical models of ecological speciation.

Copy number variation of KIR genes influences HIV-1 control.

A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection.

Does the physical disector method provide an accurate estimation of sensory neuron number in rat dorsal root ganglia?

The physical disector is a method of choice for estimating unbiased neuron numbers; nevertheless, calibration is needed to evaluate each counting method. The validity of this method can be assessed by comparing the estimated cell number with the true number determined by a direct counting method in serial sections. We reconstructed a 1/5 of rat lumbar dorsal root ganglia taken from two experimental conditions. From each ganglion, images of 200 adjacent semi-thin sections were used to reconstruct a volumetric dataset (stack of voxels). On these stacks the number of sensory neurons was estimated and counted respectively by physical disector and direct counting methods. Also, using the coordinates of nuclei from the direct counting, we simulate, by a Matlab program, disector pairs separated by increasing distances in a ganglion model. The comparison between the results of these approaches clearly demonstrates that the physical disector method provides a valid and reliable estimate of the number of sensory neurons only when the distance between the consecutive disector pairs is 60 microm or smaller. In these conditions the size of error between the results of physical disector and direct counting does not exceed 6%. In contrast when the distance between two pairs is larger than 60 microm (70-200 microm) the size of error increases rapidly to 27%. We conclude that the physical dissector method provides a reliable estimate of the number of rat sensory neurons only when the separating distance between the consecutive dissector pairs is no larger than 60 microm.

Three-stranded DNA structure; is this the secret of DNA homologous recognition?

A novel type of triple-stranded DNA structure was proposed by several groups to play a crucial role in homologous recognition between single- and double-stranded DNA molecules. In this still putative structure a duplex DNA was proposed to co-ordinate a homologous single strand in its major groove side. In contrast to the well-characterized pyrimidine-purine-pyrimidine triplexes in which the two like strands are antiparallel and which are restricted to poly-pyrimidine-containing stretches, the homology-specific triplexes would have like strands in parallel orientation and would not be restricted to any particular sequence provided that there is a homology between interacting DNA molecules. For many years the stereo-chemical possibility of forming homology-dependent three- or four-stranded DNA structures during the pairing stage of recombination reactions was seriously considered in published papers. However, only recently has there been a marked increase in the number of papers that have directly tested the formation of triple-stranded DNA structures during the actual pairing stage of the recombination reaction. Unfortunately the results of these tests are not totally clear cut; while some laboratories presented experimental evidence consistent with the formation of triplexes, others studying the same or very similar systems offered alternative explanations. The aim of this review is to present the current state of the central question in the mechanism of homologous recombination, namely, what kind of DNA structure is responsible for DNA homologous recognition. Is it a novel triplex structure or just a classical duplex?

Sedimentation and electrophoretic migration of DNA knots and catenanes.

Various site-specific recombination enzymes produce different types of knots or catenanes while acting on circular DNA in vitro and in vivo. By analysing the types of knots or links produced, it is possible to reconstruct the order of events during the reaction and to deduce the molecular "architecture" of the complexes that different enzymes form with DNA. Until recently it was necessary to use laborious electron microscopy methods to identify the types of knots or catenanes that migrate in different bands on the agarose gels used to analyse the products of the reaction. We reported recently that electrophoretic migration of different knots and catenanes formed on the same size DNA molecules is simply related to the average crossing number of the ideal representations of the corresponding knots and catenanes. Here we explain this relation by demonstrating that the expected sedimentation coefficient of randomly fluctuating knotted or catenated DNA molecules in solution shows approximately linear correlation with the average crossing number of ideal configurations of the corresponding knots or catenanes.

Executive Order Number Eighty-Four February, 2014

In this order the governor declares that volunteerism is an integral part of Iowa's future and well-being and creates the Governor's Council on National Service in Iowa.

Origin and evolution of homologous repeated sequences in the mitochondrial DNA control region of shrews.

The complete mitochondrial DNA (mtDNA) control region was amplified and directly sequenced in two species of shrew, Crocidura russula and Sorex araneus (Insectivora, Mammalia). The general organization is similar to that found in other mammals: a central conserved region surrounded by two more variable domains. However, we have found in shrews the simultaneous presence of arrays of tandem repeats in potential locations where repeats tend to occur separately in other mammalian species. These locations correspond to regions which are associated with a possible interruption of the replication processes, either at the end of the three-stranded D-loop structure or toward the end of the heavy-strand replication. In the left domain the repeated sequences (R1 repeats) are 78 bp long, whereas in the right domain the repeats are 12 bp long in C. russula and 14 bp long in S. araneus (R2 repeats). Variation in the copy number of these repeated sequences results in mtDNA control region length differences. Southern blot analysis indicates that level of heteroplasmy (more than one mtDNA form within an individual) differs between species. A comparative study of the R2 repeats in 12 additional species representing three shrew subfamilies provides useful indications for the understanding of the origin and the evolution of these homologous tandemly repeated sequences. An asymmetry in the distribution of variants within the arrays, as well as the constant occurrence of shorter repeated sequences flanking only one side of the R2 arrays, could be related to asymmetry in the replication of each strand of the mtDNA molecule. The pattern of sequence and length variation within and between species, together with the capability of the arrays to form stable secondary structures, suggests that the dominant mechanism involved in the evolution of these arrays in unidirectional replication slippage.

Evolutionary history of the greater white-toothed shrew (Crocidura russula) inferred from analysis of mtDNA, Y, and X chromosome markers.

We investigate the evolutionary history of the greater white-toothed shrew across its distribution in northern Africa and mainland Europe using sex-specific (mtDNA and Y chromosome) and biparental (X chromosome) markers. All three loci confirm a large divergence between eastern (Tunisia and Sardinia) and western (Morocco and mainland Europe) lineages, and application of a molecular clock to mtDNA divergence estimates indicates a more ancient separation (2.25 M yr ago) than described by some previous studies, supporting claims for taxonomic revision. Moroccan ancestry for the mainland European population is inconclusive from phylogenetic trees, but is supported by greater nucleotide diversity and a more ancient population expansion in Morocco than in Europe. Signatures of rapid population expansion in mtDNA, combined with low X and Y chromosome diversity, suggest a single colonization of mainland Europe by a small number of Moroccan shrews >38 K yr ago. This study illustrates that multilocus genetic analyses can facilitate the interpretation of species' evolutionary history but that phylogeographic inference using X and Y chromosomes is restricted by low levels of observed polymorphism.

Swiss EMBnet node web server.

EMBnet is a consortium of collaborating bioinformatics groups located mainly within Europe (http://www.embnet.org). Each member country is represented by a 'node', a group responsible for the maintenance of local services for their users (e.g. education, training, software, database distribution, technical support, helpdesk). Among these services a web portal with links and access to locally developed and maintained software is essential and different for each node. Our web portal targets biomedical scientists in Switzerland and elsewhere, offering them access to a collection of important sequence analysis tools mirrored from other sites or developed locally. We describe here the Swiss EMBnet node web site (http://www.ch.embnet.org), which presents a number of original services not available anywhere else.

Prise en charge du carcinome hépatocettulaire en 2010 [Management of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide and its incidence has increased over the last years in most developed countries. The majority of HCCs occur in the context of liver cirrhosis. Therefore, patients with cirrhosis and those with hepatitis B virus infection should enter a surveillance program. Detection of a focal liver lesion by ultrasound should be followed by further investigations to confirm the diagnosis and to permit staging. A number of curative and palliative treatment options are available today. The choice of treatment will depend on the tumor stage, liver function and the presence of portal hypertension as well as the general condition of the patient. A multidisciplinary approach is mandatory to offer to each patient the best treatment.

ISBN (international standard book number) -an international perspective

Esitelmä Suomen ISBN-keskus 30 vuotta -juhlassa Helsingin yliopistossa 7.11.2002