Mapping human genetic ancestry

The human genome is a mosaic with respect to its evolutionary history. Based on a phylogenetic analysis of 23,210 DNA sequence alignments from human, chimpanzee, gorilla, orangutan, and rhesus, we present a map of human genetic ancestry. For about 23% of our genome, we share no immediate genetic ancestry with our closest living relative, the chimpanzee. This encompasses genes and exons to the same extent as intergenic regions. We conclude that about 1/3 of our genes started to evolve as human-specific lineages before the differentiation of human, chimps, and gorillas took place. This explains recurrent findings of very old human-specific morphological traits in the fossils record, which predate the recent emergence of the human species about 5-6 MYA. Furthermore, the sorting of such ancestral phenotypic polymorphisms in subsequent speciation events provides a parsimonious explanation why evolutionary derived characteristics are shared among species that are not each other's closest relatives.     

Impact categories for life cycle assessment research of seafood production systems: Review and prospectus

Goal, Scope and Background In face of continued declines in global fisheries landings and concurrent rapid aquaculture development, the sustainability of seafood production is of increasing concern. Life Cycle Assessment (LCA) offers a convenient means of quantifying the impacts associated with many of the energetic and material inputs and outputs in these industries. However, the relevant but limited suite of impact categories currently used in most LCA research fails to capture a number of important environmental and social burdens unique to fisheries and aquaculture. This article reviews the impact categories used in published LCA research of seafood production to date, reports on a number of methodological innovations, and discusses the challenges to and opportunities for further impact category developments. Main Features The range of environmental and socio-economic impacts associated with fisheries and aquaculture production are introduced, and both the commonly used and innovative impact categories employed in published LCA research of seafood production are discussed. Methodological innovations reported in agricultural LCAs are also reviewed for possible applications to seafood LCA research. Challenges and options for including additional environmental and socioeconomic impact categories are explored. Results A review of published LCA research in fisheries and aquaculture indicates the frequent use of traditional environmental impact categories as well as a number of interesting departures from the standard suite of categories employed in LCA studies in other sectors. Notable examples include the modeling of benthic impacts, by-catch, emissions from anti-fouling paints, and the use of Net Primary Productivity appropriation to characterize biotic resource use. Socio-economic impacts have not been quantified, nor does a generally accepted methodology for their consideration exist. However, a number of potential frameworks for the integration of such impacts into LCA have been proposed. Discussion LCA analyses of fisheries and aquaculture call attention to an important range of environmental interactions that are usually not considered in discussions of sustainability in the seafood sector. These include energy use, biotic resource use, and the toxicity of anti-fouling paints. However, certain important impacts are also currently overlooked in such research. While prospects clearly exist for improving and expanding on recent additions to environmental impact categories, the nature of the LCA framework may preclude treatment of some of these impacts. Socio-economic impact categories have only been described in a qualitative manner. Despite a number of challenges, significant opportunities exist to quantify several important socio-economic impacts. Conclusion The limited but increasing volume of LCA research of industrial fisheries and aquaculture indicates a growing interest in the use of LCA methodology to understand and improve the sustainability performance of seafood production systems. Recent impact category innovations, and the potential for further impact category developments that account for several of the unique interactions characteristic of fisheries and aquaculture will significantly improve the usefulness of LCA in this context, although quantitative analysis of certain types of impacts may remain beyond the scope of the LCA framework. The desirability of incorporating socio-economic impacts is clear, but such integration will require considerable methodological development. Recommendations and Perspectives While the quantity of published LCA research for seafood production systems is clearly increasing, the influence this research will have on the ground remains to be seen. In part, this will depend on the ability of LCA researchers to advance methodological innovations that enable consideration of a broader range of impacts specific to seafood production. It will also depend on the ability of researchers to communicate with a broader audience than the currently narrow LCA community.     

Assessment of Land Use Impacts on the Natural Environment. Part 1: An Analytical Framework for Pure Land Occupation and Land Use Change (8 pp)

- Part 1: An analytical framework for pure land occupation and land use change Part 2: Generic characterization factors for local species diversity in Central Europe - Preamble. This series of two papers is based on a PhD thesis (Koellner 2003) and develops a method on how to assess land use impacts on biodiversity in the framework of LCA. Part 1 further expands the analytical framework of the thesis for pure land occupation and land use change. Part 2 rests on a much richer database compared to the thesis in order to quantify generic characterization factors for local species' richness. - Abstract Goal, Scope and Background. In the framework of LCA, land use is broadly accepted as an impact category. However, the methodology for the assessment of damages on the natural environment was and still is the subject of discussion. The main objective of this paper is to contribute to that discussion by providing a consistent methodological framework for the assessment of land occupation and transformation. Methods We clarify the context of LCA relevant land use decisions. Based on that, we develop a formal model with damage functions and generic characterization factors for quantifying damages on ecosystems from land occupation and land transformation. The characterization factor for land occupation and land use change is labeled Ecosystem Damage Potential (EDP). We analytically address the substitutability of area and time occupied in order to produce a constant output. Results Based on the proposed method, it is possible to calculate the damages from complex series of land transformation, land occupation, and land restoration. A main feature of the method is that land transformation is assessed based on a factual or virtual, restoration time. This means that the damage of land transformation is largest for land use types which are difficult to restore and need extremely long to develop (e.g. thousand of years and more for primary forest and peatbog). In addition, we could show that area and time of occupation are not substitutable. The more severe the damage potential of a specific land use type is, the better it is to minimize the area and maximize the duration of occupation. Discussion An approach for the assessment of pure land occupation and land use change was developed in this paper, which is not geographically referenced. Developing geographically-referenced land use inventories and impact assessment methods can increase their accuracy. The information cost to provide geographically referenced data on land use for practical LCA applications, however, would increase enormously. Conclusions An impact assessment method for land use with generic characterization factors improves the basis for decision-making in industry and other organizations. It can best be applied to marginal land use decisions; that is, to decisions in which the consequences are so small that the quality or quantity of environmental parameters of a region is not noticeably altered. Recommendations and Perspective . One main problem to address is the development of reliable generic characterization factors, which express the ecosystem damage potential of specific land use types. The characterization factors should be developed on an empirical basis, which allow decision makers to get access to knowledge from environmental sciences in a very condensed form. In order to support decisions on distinct land use projects, methods should be developed, which allow accomplishing a generic assessment with site-dependent assessments.     

AMPA receptor biogenesis and trafficking

AMPA-type glutamate receptors mediate the majority of fast excitatory transmission in the central nervous system. The trafficking of AMPA receptors to and from synapses alters synaptic strength and has been recognized as a central mechanism underlying various forms of synaptic plasticity. Both secretory and endocytic trafficking events seem to be driven by the subunit composition of AMPA receptor tetramers. Moreover, recent work suggests that synapses employ different tetramer combinations in response to altered synaptic input, suggesting the existence of signalling pathways that mediate remodelling of AMPA receptors. These latest developments and recent progress in elucidating the mechanisms that underlie channel assembly and trafficking are the subject of this review.     

5-Alkynyl-2'-deoxyuridines: chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells

Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231.     

Metal requirements and phosphodiesterase activity of tRNase Z enzymes

The endonuclease tRNase Z from A. thaliana (AthTRZ1) was originally isolated for its tRNA 3' processing activity. Here we show that AthTRZ1 also hydrolyzes the phosphodiester bond in bis(p-nitrophenyl) phosphate (bpNPP) with a kcat of 7.4 s-1 and a KM of 8.5 mM. We analyzed 22 variants of AthTRZ1 with respect to their ability to hydrolyze bpNPP. This mutational mapping identified fourteen variants that lost the ability to hydrolyze bpNPP and seven variants with reduced activity. Surprisingly, a single amino acid change (R252G) resulted in a ten times higher activity compared to the wild type enzyme. tRNase Z enzymes exist in long and short forms. We show here that in contrast to the short tRNase Z enzyme AthTRZ1, the long tRNase Z enzymes do not have bpNPP hydrolysis activity pointing to fundamental differences in substrate cleavage between the two enzyme forms. Furthermore, we determined the metal content of AthTRZ1 and analyzed the metal requirement for bpNPP hydrolysis. AthTRZ1 shows a high affinity for Zn2+ ions; even upon incubation with metal chelators, 0.76 Zn2+ ions are retained per dimer. In contrast to bpNPP hydrolysis, pre-tRNA processing requires additional metal ions, Mn2+ or Mg2+, as Zn2+ ions alone are insufficient.     

A spectroscopic study of the temperature induced modifications on ferredoxin folding and iron-sulfur moieties

Thermal perturbation of the dicluster ferredoxin from Acidianus ambivalens was investigated employing a toolbox of spectroscopic methods. FTIR and visible CD were used for assessing changes of the secondary structure and coarse alterations of the [3Fe4S] and [4Fe4S] cluster moieties, respectively. Fine details of the disassembly of the metal centers were revealed by paramagnetic NMR and resonance Raman spectroscopy. Overall, thermally induced unfolding of AaFd is initiated with the loss of -helical content at relatively low temperatures (T(app)(m) approximately 44 degrees C), followed by the disruption of both iron-sulfur clusters (T(app)(m) approximately 53-60 degrees C). The degradation of the metal centers triggers major structural changes on the protein matrix, including the loss of tertiary contacts (T(app)(m) approximately 58 degrees C) and a change, rather than a significant net loss, of secondary structure (T(app)(m) approximately 60 degrees C). This latter process triggers a secondary structure reorganization that is consistent with the formation of a molten globule state. The combined spectroscopic approach here reported illustrates how changes in the metalloprotein organization are intertwined with disassembly of the iron-sulfur centers, denoting the conformational interplay of the protein backbone with cofactors.     

Steps towards a miniaturized, robust and autonomous measurement device for the long-term monitoring of patient activity: ActiBelt.

We describe the first steps in the development of a wearable measurement device for measuring a subject's three-dimensional acceleration. The ultimate aim is a standard measurement instrument integrated in a belt buckle that allows objective evaluation of treatment and rehabilitation measures in patients, in particular for disabling chronic diseases such as multiple sclerosis. In a first step we combined standard hardware elements to record test data from healthy volunteers. We then developed algorithms to automatically distinguish between different stages of activity, such as jogging, walking, lying, standing and sitting, and to detect and count steps. Distinction between standing and sitting is the most difficult to accomplish. As a first validation, we calculated the distance traveled from data of 17 experiments and a total of 4.5 h, for which one proband was walking and running for a known distance, and compared the results with two commercially available pedometers. We could show that the relative error for the ActiBelt is only half of that for the two pedometers. Apart from developing much smaller, robust and integrated hardware, we describe ideas on how to develop algorithms that allow extraction of a "baseline step pattern" in analogy to baseline ECG to define and detect clinically relevant deviations.     

Sexual harassment in live-bearing fishes (Poeciliidae): comparing courting and noncourting species

Sexual harassment by males has been reported from several live-bearingfishes (Poeciliidae) and has been shown to inflict costs onfemales. For example, poeciliid females have reduced feedingopportunities when accompanied by a male because females dedicateattention to avoiding male copulation attempts. Poeciliid speciesdiffer considerably in male mating behavior, such as the presenceor absence of courtship. Courting males display in front ofthe females, but males attempting to sneak-copulate approachfemales from behind, that is, in the blind portion of theirvisual field, and force copulations, which can be viewed asa male persistence trait. We predicted that poeciliid femalesneed to be more vigilant in the presence of noncourting males,and costs of harassment by noncourting males might be stronger.In a comparative approach we examined the costs of male sexualharassment for females as reduced feeding time in 9 speciesof live-bearing fishes, including courting (Poecilia latipinna,Poecilia reticulata, Xiphophorus cortezi, Xiphophorus variatus)and noncourting species (Poecilia mexicana [surface- and cave-dwellingform], Poecilia orri, Gambusia affinis, Gambusia geiseri, Heterandriaformosa). In all species examined except for the cave form ofP. mexicana, focal females spent significantly less time feedingin the presence of a male than when together with another female.The time females spent feeding was found to significantly declinewith increasing male mating activity (sum of all sexual behaviors),but there was no support for the idea that females would spendmore time feeding in the presence of courting males comparedwith noncourting ones.