David S. Thaler

University of Basel | UNIBAS · Biozentrum - Center for Molecular Life Sciences

Choosing whether to represent data in an abstract or concrete manner through sonification is generally dependent on the applicability of the dataset and personal preference of the designer. For supporting a visualization with a high level of abstraction, a sonification can purposefully act as a complement by giving concrete contextual cues to the d...

As biological sequence databases continue growing, so do the insight that they promise to shed on the shape of the genetic diversity of life. However, to fulfil this promise the software must remain usable, be able to accommodate a large amount of data and allow use of modern high performance computing infrastructure. In this study we present a rei...

Objectives To develop a biological diary (CoronaCal) that allows anyone in the community to collect and store serial saliva samples and chart symptoms on ordinary printer paper. Methods Diaries were analyzed for the presence of SARS-CoV-2 RNA using established polymerase chain reaction (PCR) procedures. CoronaCal diaries were distributed to volunt...

Background The testing of saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has become a useful and common method to diagnose coronavirus disease 2019 (Covid-19). However, there are limited examples of serial testing with correlated clinical metadata, especially in the outpatient setting. Method We developed a met...

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly c...

This commentary encourages the regular archiving of nucleic-acid-stabilized serial samples of wastewaters and/or sewage. Stabilized samples would facilitate retrospective reconstitution of built environments’ biological fluids. Biological time capsules would allow retrospective searches for nucleic acids from viruses such as SARS-CoV-2. Current res...

Animal and plant biodiversity is decreasing. In contrast, the global direction and the pace of change in microbial, including viral, biodiversity is unknown. Important niches for microbial diversity occur in highly specific associations with plants and animals, and these niches are lost as hosts become extinct. The taxonomic diversity of human gut...

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of molecular mechanisms underlying phage-host interactions is mostly confi...

COVID-19: sample for future analysis Resources for COVID-19 testing in many parts of the world are still limited. We suggest that future value could be realized if samples were to be widely taken now and saved for analysis as more resources become available. Besides diagnostic screening, this sample analysis alone — or in combination with mobile an...

Antimicrobial resistance continues to outpace the development of new chemotherapeutics. Novel pathogens continue to evolve and emerge. Public health innovation has the potential to open a new front in the war of “our wits against their genes” (Joshua Lederberg). Dense sampling coupled to next generation sequencing can increase the spatial and tempo...

Background Excess water in all its forms (moisture, dampness, hidden water) in buildings negatively impacts occupant health but is hard to reliably detect and quantify. Recent advances in through-wall imaging recommend microwaves as a tool with a high potential to noninvasively detect and quantify water throughout buildings. Methods Microwaves in...

Session, established a new work stream on "digital sequence information" (DSI) on genetic resources for food and agriculture (GRFA). It requested the preparation of an exploratory fact-finding scoping study on DSI on GRFA with information on, inter alia, terminology used in this area, actors involved with DSI on GRFA, the types and extent of uses o...

DNA Barcodes: Controversies, Mechanisms and Future Applications Invitation to submit manuscripts Oct 2018 - July 2019 Frontiers in Ecology and Evolution > Research Topics Editors: David S. Thaler and Rodney L. Honeycutt https://www.frontiersin.org/research-topics/8789/dna-barcodes-controversies-mechanisms-and-future-applications#overview

More than a decade of DNA barcoding encompassing about five million specimens covering 100,000 animal species supports the generalization that mitochondrial DNA clusters largely overlap with species as defined by domain experts. Most barcode clustering reflects synonymous substitutions. What evolutionary mechanisms account for synonymous clusters b...

More than a decade of DNA barcoding encompassing about five million specimens covering 100,000 animal species supports the generalization that mitochondrial DNA clusters largely overlap with species as defined by domain experts. Most barcode clustering reflects synonymous substitutions. What evolutionary mechanisms account for synonymous clusters b...

DNA barcodes for species identification and the analysis of human mitochondrial variation have developed as independent fields even though both are based on sequences from animal mitochondria. This study finds questions within each field that can be addressed by reference to the other. DNA barcodes are based on a 648-bp segment of the mitochondrial...

The Neolithic revolution—the transition of our species from hunter and gatherer to cultivator—began approximately 14,000 years ago and is essentially complete for macroscopic food. Humans remain largely pre-Neolithic in our relationship with microbes but starting with the gut we continue our hundred-year project of approaching the ability to assess...

Background: DNA barcode differences within animal species are usually much less than differences among species, making it generally straightforward to match unknowns to a reference library. Here we aim to better understand the evolutionary mechanisms underlying this usual "barcode gap" pattern. We employ avian barcode libraries to test a central p...

Unlabelled: Specialized transduction has proven to be useful for generating deletion mutants in most mycobacteria, including virulent Mycobacterium tuberculosis. We have improved this system by developing (i) a single-step strategy for the construction of allelic exchange substrates (AES), (ii) a temperature-sensitive shuttle phasmid with a greate...

The difficulty of diagnosing active tuberculosis (TB) and lack of rapid drug susceptibility testing (DST) at the point of care remain critical obstacles to TB control. This report describes a high-intensity mycobacterium-specific-fluorophage (ϕ2GFP10) that for the first time allows direct visualization of Mycobacterium tuberculosis in clinical sput...

The rapid and accurate diagnosis of active tuberculosis (TB) and its drug susceptibility remain a challenge. Phenotypic assays allow determination of antibiotic susceptibilities even if sequence data are not available or informative. We review 2 emerging diagnostic approaches, reporter phage and breath tests, both of which assay mycobacterial metab...

A new apparatus enhances the biosafety of containment (biosafety level 3 [BSL-3]) and provides experimental reproducibility for aerosol infection experiments with MDR and XDR Mycobacterium tuberculosis. The methods are generally applicable to the study of airborne pathogens.

The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectio...

PCR in principle can detect a single target molecule in a reaction mixture. Contaminating bacterial DNA in reagents creates a practical limit on the use of PCR to detect dilute bacterial DNA in environmental or public health samples. The most pernicious source of contamination is microbial DNA in DNA polymerase preparations. Importantly, all commer...

The algebra of target theory for damage by radiation was laid out by Atwood and Norman in 1949. Their equations provide a widely embraced framework for distinguishing single-hit and multi-hit mechanisms of damage. The present work asks whether in vitro damage to DNA duplexes by different agents affects amplification by the polymerase chain reaction...

Fundamental questions in evolution concern deep divisions in the living world and vertical versus horizontal information transfer. Two contrasting views are: (i) three superkingdoms Archaea, Eubacteria, and Eukarya based on vertical inheritance of genes encoding ribosomes; versus (ii) a prokaryotic/eukaryotic dichotomy with unconstrained horizontal...

A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702–705) offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an indiv...

Primer sets used to document quorum sensing genes Vp 4552 (0.05 MB DOC)

Bioluminescence/Growth relationship of Vibrio harveyi changes with growth medium. The bioluminescence-growth relationships of wild type Vh upon diluting Difco Marine Broth (MB) with artificial seawater (ASW). (A) Strain BB120, MB:ASW = 1:2 (Growth Rate Open Squares, Filled Squares Bioluminescence. Relative Light Units (RLU) expressed as counts per...

The light-emitting Vibrios provide excellent material for studying the interaction of cellular communication with growth rate because bioluminescence is a convenient marker for quorum sensing. However, the use of bioluminescence as a marker is complicated because bioluminescence itself may affect growth rate, e.g. by diverting energy. The marker ef...

The purpose of this article is fourfold: (1) To frame the intellectual context of “adaptive”, “directed”, or “Cairnsian” mutation. This area of research is—and will likely remain—controversial. (2) To review the points to be considered when critically reading in the field; (3) to consider the question of how mechanisms for an “intelligent” generati...

Chromosomal rearrangements are key events in cancer and evolution. These chromosomal rearrangements are dependent upon either legitimate, i.e. homologous, or illegitimate recombination of DNA. Recombination – legitimate or illegitimate – is often limited by the number of double-strand breaks (DSBs) in DNA. The number of DSBs in several biological s...

In a variant of the standard PCR reaction termed bridging, or jumping, PCR the primer-bound sequences are originally on separate template molecules. Bridging can occur if, and only if, the templates contain a region of sequence similarity. A 3' end of synthesis in one round of synthesis that terminates in this region of similarity can prime on the...

Vaillancourt and Newell (Neurobiol. of Aging 2001) show that although many aging systems decrease in complexity as anticipated by Lipsitz and Goldberger (JAMA 1992), other aging systems increase in complexity. Vaillancourt and Newell explain the discrepancy by proposing that systems with a point attractor decrease in complexity with age, whereas th...

Screening phage-displayed peptide libraries (biopanning) is an important technique for acquiring peptide ligands and for mapping peptide epitopes recognized by antibodies (Ab). In biological samples, other materials, not only contaminants but also natural constituents, often interfere with biopanning. Capture methods use anchoring Abs that reduce t...

Two peptide motifs that bind to C1q have been identified from phage displayed libraries. A first panning cycle recovered phage that displayed a [N/S]PFxL motif. A synthetic peptide with that motif blocked those phage from binding to C1q. A second panning cycle was conducted with the [N/S]PFxL motif peptide present, leading to recovery of phage disp...

Biopanning has been used extensively in conjunction with purified components, but there are also examples in which mixtures of targets have been investigated. This study introduces a methodological innovation, termed iterative panning and blocking (IPAB), to extend the range of specific interactions that can be probed in mixtures. Here this procedu...

Evolution and development are both lineage processes but are often conceptualized as occurring by different and mutually exclusive mechanisms. It is conventionally asserted that evolution occurs via the random generation of diversity and the subsequent survival of those that pass selection. On the other hand, development is too often presented as p...

Two monoclonal IgM Abs have been produced from lymphocytes isolated from two human umbilical cord bloods. These mAbs recognize a conformational epitope present in a CNBr digestion fraction of lactoferrin. Linear epitopes recognized by each mAb were selected from several phage display peptide libraries. In each case, phages displaying a peptide with...

The T4 head protein, gp2, promotes head-tail joining during phage morphogenesis and is also incorporated into the phage head. It protects the injected DNA from degradation by exonuclease V during the subsequent infection. In this study, we show that recombinant gp2, a very basic protein, rapidly kills the cells in which it is expressed. To further...

Handwerger and colleagues demonstrated that a particular clinical isolate of Enterococcus faecium, designated GUC, and here redesignated as GUCR, can conjugatively transfer vancomycin resistance. The vancomycin resistance is encoded by a chromosomally born linked set of genes in the donor, designated the vanA cluster, to the chromosome of an E. fae...

Algorithms for computing with DNA currently require the construction of pools of molecules in which each distinct molecule represents a different starting point for the calculation. We have begun building such pools using the technique of parallel overlap assembly that is already used for the generation of diversity in biologically useful combinato...

The neo-darwinian synthesis resulted from the realization that mendelian inheritance changed the darwinian model of biological evolution. Darwin assumed that parents' genes blend into each other in their offspring. This was problematical because a fitter variant's genes would blend upon mating, and become diluted into the gene pool. Mendelism solve...

There is an apparent paradox between the reported requirements for λ DNA packaging in vivo and in vitro. In vivo, DNA concatemers are required for packaging. On the other hand, in vitro, packaging extracts can encapsidate either linear or circular monomeric λ DNA. Perhaps cellular nucleases restrict the in vivo ability of monomers to package by deg...

In biological evolution, the rate of mutations is “encoded” by enzymes which can be mutated like any other gene. Inspired by this feature, we present a simple Brownian motion model, in which the temperature itself is a dynamical variable. Intrawell and interwell relaxations occur at different “temperatures” and have different dynamics, and the Kram...

DNA and RNA are the polynucleotides known to carry genetic information in life. Chemical variants of DNA and RNA backbones have been used in structure-function and biosynthesis studies in vitro, and in antisense pharmacology, where their properties of nuclease resistance and enhanced cellular uptake are important. This study addressed the question...

Chimeras of RNA and DNA have distinctive physical and biological properties. Chimeric oligonucleotides that contained one, two or three ribonucleotides whose phosphodiester backbone was covalently continuous with DNA were synthesized. Site-directed mutagenesis was used to assess genetic information transfer from the ribonucleotide positions. Transf...

Sex and recombination generate variation via processes that depend on an underlying complementarity between participants. Sex between DNA segments depends on their sequences having enough in common. Viewed in this way, sex does not depend on genes that originate in separate cells. Sex in the single genome uses many of the same mechanisms as interge...

Homologous recombination can provide a basis for the construction of an ordered set of overlapping clones. The principle is to make two libraries, each in a vector that has a different selectable marker flanking the insert site. Recombination between the flanking markers, leading to a selectable phenotype, can only occur as the consequence of cross...

Bacillus subtilis can exist in a diploid state in which two genetically distinct chromosomes co-exist in the same cell and yet only one of them is expressed, thereby determining the phenotype. Such cells are called non-complementing diploids (Ncds). In this study, two types of experiments are reported which indicate that a previously known pleiotro...

The requirement for DNA sequence homology in generalized genetic recombination is greatly relaxed in bacterial mutL, mutS and mutH mutants deficient in mismatch repair. In such mutants, intergeneric recombination occurs efficiently between Escherichia coli and Salmonella typhimurium, which are approximately 20% divergent in DNA sequence. This findi...

Wild-type Escherichia coli are resistant to genetic transformation by purified linear DNA, probably in part because of exonuclease activity. We demonstrate that E. coli containing a recD mutation could be easily transformed by linearized plasmids containing a selectable marker. The marker was transferred to the chromosome by homologous recombinatio...

RecBCD enzyme is centrally important in homologous recombination in Escherichia coli and is the source of ExoV activity. Null alleles of either the recB or the recC genes, which encode the B and C subunits, respectively, manifest no recombination and none of the nuclease functions characteristic of the holoenzyme. Loss of the D subunit, by a recD m...

Recombination mediated by the Red pathway of bacteriophage lambda is focused towards sites of double-chain cuts. Double-chain ends created either by type II restriction enzymes acting at unmodified recognition sites or by lambda's packaging enzyme, terminase, acting at cos are utilized in a manner similar to the double-chain break repair pathway of...

The double-strand-break repair (DSBR) model was formulated to account for various aspects of yeast mitotic and meiotic recombination. In this study three features of the DSBR model are tested for Red-mediated recombination between phage lambda and lambda dv, a plasmid that is perfectly homologous to about 10% of lambda. The results support the appl...

The double-strand-break repair (DSBR) model was formulated to account for various aspects of yeast mitotic and meiotic recombination. In this study three features of the DSBR model are tested for Red-mediated recombination between phage X and Xdv, a plasmid that is perfectly homologous to about 10% of X. The results support the applicability of the...

The Red recombination pathway of phage lambda is shown to target recombination to double-chain ends of DNA. A double-chain cut, delivered in vivo to only one of two parents participating in a lambda lytic cross by a type II restriction endonuclease, increases the proportion of crossing over in the interval containing the cut compared with other int...

We examined linkage relationships for RecBC-mediated recombination in lytic cycle crosses of lambda phages bearing two cohesive end sites (cos) oriented in the same direction. The relationships obtained imply that a given recombinant tends to be packaged from the cos site that is the nearer one to the right of the exchange. In view of the previousl...

Typescript. Thesis (Ph. D.)--University of Oregon, 1986. Includes vita and abstract. Includes bibliographical references (leaves 110-121).