The small SLC43 family: facilitator system l amino acid transporters and the orphan EEG1

The SLC43 family is composed of only three genes coding for the plasma membrane facilitator system l amino acid transporters LAT3 (SLC43A1; TC 2.A.1.44.1) and LAT4 (SLC43A2; TC 2.A.1.44.2), and the orphan protein EEG1 (SLC43A3; TC 2.A.1.44.3). Besides the known mechanism of transport of LAT3 and LAT4, their physiological roles still remain quite obscure. Morphants suggested a role of LAT3 in renal podocyte development in zebrafish. Expression in liver and skeletal muscle, and up-regulation by starvation suggest a role of LAT3 in the flux of branched-chain amino acids (BCAAs) from liver and skeletal muscle to the bloodstream. Finally, LAT3 is up-regulated in androgen-dependent cancers, suggesting a role in mTORC1 signaling in this type of tumors. In addition, LAT4 might contribute to the transfer of BCAAs from mother to fetus. Unfortunately, the EEG1 mouse model (EEG1(Y221∗)) described here has not yet offered a clue to the physiological role of this orphan protein.

Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses.

Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings.

Assessing and mapping LD and SLM to directly support the planning and scaling up of SLM interventions to combat desertification

Global investment in Sustainable Land Management (SLM) has been substantial, but knowledge gaps remain. Overviews of where land degradation (LD) is taking place and how land users are addressing the problem using SLM are still lacking for most individual countries and regions. Relevant maps focus more on LD than SLM, and they have been compiled using different methods. This makes it impossible to compare the benefits of SLM interventions and prevents informed decision-making on how best to invest in land. To fill this knowledge gap, a standardised mapping method has been collaboratively developed by the World Overview of Conservation Approaches and Technologies (WOCAT), FAO’s Land Degradation Assessment in Drylands (LADA) project, and the EU’s Mitigating Desertification and Remediating Degraded Land (DESIRE) project. The method generates information on the distribution and characteristics of LD and SLM activities and can be applied at the village, national, or regional level. It is based on participatory expert assessment, documents, and surveys. These data sources are spatially displayed across a land-use systems base map. By enabling mapping of the DPSIR framework (Driving Forces-Pressures-State-Impacts-Responses) for degradation and conservation, the method provides key information for decision-making. It may also be used to monitor LD and conservation following project implementation. This contribution explains the mapping method, highlighting findings made at different levels (national and local) in South Africa and the Mediterranean region. Keywords: Mapping, Decision Support, Land Degradation, Sustainable Land Management, Ecosystem Services, Participatory Expert Assessment

Impact of dams, dam removal and dam-related river engineering structures on sediment connectivity and channel morphology of the Fugnitz and the Kaja Rivers

In terms of changing flow and sediment regimes of rivers, dams are often regarded as the most dominant form of human impact on fluvial systems. Dams can decrease the flux of water and sediments leading to channel changes such as upstream aggradation and downstream degradation. The opposite effects occur when dams are removed. Channel degradation often requires further intervention in terms of river bed and bank protection works. The situation evolves more complex in river systems that are impacted by a series of dams due to feedback processes between the different system compartments. A number of studies have recently investigated geomorphic systems using connectivity approaches to improve the understanding of geomorphic system response to change. This paper presents a case study investigating the impact of dam construction, dam removal and dam-related river bed and bank protection measures on the sediment connectivity and channel morphology of the Fugnitz and the Kaja Rivers using a combination of DEM analyses, field surveys and landscape evolution modelling. For both river systems the results revealed low sediment connectivity accompanied by a fine river bed sediment facies in river sections upstream of active dams and of removed dams with protection measures. Contrarily, high sediment connectivity which was accompanied by a coarse river bed sediment facies was observed in river sections either located downstream of active dams or of removed dams with upstream protection. In terms of channel changes, significant channel degradation was examined at locations downstream of active dams and of removed dams. Channel bed and bank protection measures prevent erosion and channel slope recovery after dam removal. Landscape evolution modeling revealed a complex geomorphic response to dam construction and dam removal as sediment output rates and therefore geomorphic processes have been shown to act in a non-linear manner. These insights are deemed to have major implications for river management and conservation, as quality and state of riverine habitats are determined by channel morphology and river bed sediment composition.

Genes to blood pressure: The effects of variation in genes of the renin-angiotensin system on the hormonal and renal control of blood pressure

Objective. Essential hypertension affects 25% of the US adult population and is a leading contributor to morbidity and mortality. Because BP is a multifactorial phenotype that resists simple genetic analysis, intermediate phenotypes within the complex network of BP regulatory systems may be more accessible to genetic dissection. The Renin-Angiotensin System (RAS) is known to influence intermediate and long-term blood pressure regulation through alterations in vascular tone and renal sodium and fluid resorption. This dissertation examines associations between renin (REN), angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) gene variation and interindividual differences in plasma hormone levels, renal hemodynamics, and BP homeostasis.^ Methods. A total of 150 unrelated men and 150 unrelated women, between 20.0 and 49.9 years of age and free of acute or chronic illness except for a history of hypertension (11 men and 7 women, all off medications), were studied after one week on a controlled sodium diet. RAS plasma hormone levels, renal hemodynamics and BP were determined prior to and during angiotensin II (Ang II) infusion. Individuals were genotyped by PCR for a variable number tandem repeat (VNTR) polymorphism in REN, and for the following restriction fragment length polymorphisms (RFLP): AGT M235T, ACE I/D, and AT1 A1166C. Associations between clinical measurements and allelic variation were examined using multiple linear regression statistical models.^ Results. Women homozygous for the AT1 1166C allele demonstrated higher intracellular levels of sodium (p = 0.044). Men homozygous for the AGT T235 allele demonstrated a blunted decrement in renal plasma flow in response to Ang II infusion (p = 0.0002). There were no significant associations between RAS gene variation and interindividual variation in RAS plasma hormone levels or BP.^ Conclusions. Rather than identifying new BP controlling genes or alleles, the study paradigm employed in this thesis (i.e., measured genes, controlled environments and interventions) may provide mechanistic insight into how candidate genes affect BP homeostasis. ^

CHROMOSOMAL MAPPING, LINKAGE RELATIONSHIPS, AND EVOLUTIONARY STUDIES OF THE HUMAN ANONYMOUS DNA CLONE D1S1 (IN SITU HYBRIDIZATION, PRIMATES, GENE MAPPING, AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA, GENE DUPLICATION)

D1S1, an anonymous human DNA clone originally called (lamda)Ch4-H3 or (lamda)H3, was the first single copy mapped to a human chromosome (1p36) by in situ hybridization. The chromosomal assignment has been confirmed in other laboratories by repeating the in situ hybridization but not by another method. In the present study, hybridization to a panel of hamster-human somatic cell hybrids revealed copies of D1S1 on both chromosomes 1 and 3. Subcloning D1S1 showed that the D1S1 clone itself is from chromosome 3, and the sequence detected by in situ hybridization is at least two copies of part of the chromosome 3 copy. This finding demonstrates the importance of verifying gene mapping with two methods and questions the accuracy of in situ hybridization mapping.^ Non-human mammals have only one copy of D1S1, and the non-human primate D1S1 map closely resembles the human chromosome 3 copy. Thus, the human chromosome 1 copies appear to be part of a very recent duplication that occurred after the divergence between humans and the other great apes.^ A moderately informative HindIII D1S1 RFLP was mapped to chromosome 3. This marker and 12 protein markers were applied to a linkage study of autosomal dominant retinitis pigmentosa (ADRP). None of the markers proved linkage, but adding the three families examined to previously published data raises the ADRP:Rh lod score to 1.92 at (THETA) = 0.30. ^

The Protection and Promotion of Cultural Diversity in a Digital Networked Environment : Mapping Possible Advances to Coherence

The present paper is the result of a four-year-long project examining the concept and the policies of cultural diversity and the impact of digital media upon the regulatory environment where the goal of cultural diversity is to be achieved. The focus of the project was primarily on the international level and in particular on the World Trade Organization (WTO) and the United Nations Educational Scientific and Cultural Organization (UNESCO), which also epitomise the often framed as opposing pair of trade and culture. In the broad context of the project, we sought to pinpoint the essential elements of an international trade-and-culture conducive framework that can also overcome the existing fragmentation in the field of international law and move towards more coherent solutions. In a narrower context, we sketched some possible improvements to the WTO law that can make it more suitable to the digital networked environment and to the objective of diverse media that some states aspire. . Our key messages are: (1) Neither the WTO nor UNESCO currently offers appropriate solutions to the trade and culture predicament and allows for efficient protection and promotion of cultural diversity; (2) The trade and culture discourse is overly politicised and due to the related path dependencies, a number of feasible solutions appears presently blocked; (3) The digital networked environment has profoundly changed the ways cultural content is created, distributed, accessed and consumed, and may thus offer good reasons to reassess and readjust the present models of governance; (4) Access to information appears to be the most appropriate focus of the discussions with view to protecting and promoting cultural diversity in the new digital media setting, both in local and global contexts; (5) This new focal point demands also broadening and interconnecting the policy discussions, which should go beyond the narrow scope of audiovisual media services, but cautiously account for the developments at the network and applications levels, as well as in other domains, such as most notably intellectual property rights protection; (6) There are various ways in which the WTO can be made more conducive to cultural policy considerations and these include, among others, improved and updated services classifications; enhanced legal certainty with regard to digitally transferred goods and services; incorporation of rules on subsidies for services and on competition.

Thermal and Barometric Constraints on the Intrusive and Unroofing History of the Black Mountains: Implications for Timing, Initial Dip, and Kinematics of Detachment Faulting in the Death-Valley Region, California

Unroofing of the Black Mountains, Death Valley, California, has resulted in the exposure of 1.7 Ga crystalline basement, late Precambrian amphibolite facies metasedimentary rocks, and a Tertiary magmatic complex. The Ar-40/Ar-39 cooling ages, obtained from samples collected across the entire length of the range (>55 km), combined with geobarometric results from synextensional intrusions, provide time-depth constraints on the Miocene intrusive history and extensional unroofing of the Black Mountains. Data from the southeastern Black Mountains and adjacent Greenwater Range suggest unroofing from shallow depths between 9 and 10 Ma. To the northwest in the crystalline core of the range, biotite plateau ages from approximately 13 to 6.8 Ma from rocks making up the Death Valley turtlebacks indicate a midcrustal residence (with temperatures >300-degrees-C) prior to extensional unroofing. Biotite Ar-40/Ar-39 ages from both Precambrian basement and Tertiary plutons reveal a diachronous cooling pattern of decreasing ages toward the northwest, subparallel to the regional extension direction. Diachronous cooling was accompanied by dike intrusion which also decreases in age toward the northwest. The cooling age pattern and geobarometric constraints in crystalline rocks of the Black Mountains suggest denudation of 10-15 km along a northwest directed detachment system, consistent with regional reconstructions of Tertiary extension and with unroofing of a northwest deepening crustal section. Mica cooling ages that deviate from the northwest younging trend are consistent with northwestward transport of rocks initially at shallower crustal levels onto deeper levels along splays of the detachment. The well-known Amargosa chaos and perhaps the Badwater turtleback are examples of this "splaying" process. Considering the current distance of the structurally deepest samples away from moderately to steeply east tilted Tertiary strata in the southeastern Black Mountains, these data indicate an average initial dip of the detachment system of the order of 20-degrees, similar to that determined for detachment faults in west central Arizona and southeastern California. Beginning with an initially listric geometry, a pattern of footwall unroofing accompanied by dike intrusion progress northwestward. This pattern may be explained by a model where migration of footwall flexures occur below a scoop-shaped banging wall block. One consequence of this model is that gently dipping ductile fabrics developed in the middle crust steepen in the upper crust during unloading. This process resolves the low initial dips obtained here with mapping which suggests transport of the upper plate on moderately to steeply dipping surfaces in the middle and upper crust.