A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

Lake geochemistry reveals marked environmental change in Southwest China during the Mid Miocene Climatic Optimum

Science Bulletin - The Mid-Miocene Climatic Optimum (MMCO; ~15–17 Ma) was one of the short-term climatic warm events that punctuated the Cenozoic long-term cooling trend. Because...     

Alkyltransferase-like proteins: molecular switches between DNA repair pathways

Alkyltransferase-like proteins (ATLs) play a role in the protection of cells from the biological effects of DNA alkylation damage. Although ATLs share functional motifs with the DNA repair protein and cancer chemotherapy target O ⁶-alkylguanine-DNA alkyltransferase, they lack the reactive cysteine residue required for alkyltransferase activity, so its mechanism for cell protection was previously unknown. Here we review recent advances in unraveling the enigmatic cellular protection provided by ATLs against the deleterious effects of DNA alkylation damage. We discuss exciting new evidence that ATLs aid in the repair of DNA O ⁶-alkylguanine lesions through a novel repair cross-talk between DNA-alkylation base damage responses and the DNA nucleotide excision repair pathway.     

Genetic analysis of the rare species Salix arizonica (Salicacea) and associated willows in Arizona and Utah

Management decisions affecting the rare plant Arizona willow ( Salix arizonica ) will be aided by understanding genetic similarities among populations of this species. Random Amplified Polymorphic DNA (RAPD) analysis was conducted on 20 populations of S. arizonica , 12 populations of 5 congeners, and 2 samples of outgroup, Populus tremuloides . A phenogram based on DNA markers shows clear separation of populations of S. arizonica from those of co-occurring willow species, but similarity is low (～ 37%) between Utah and Arizona populations of S. arizonica . Evaluation of the relationship of habitat characteristics and geographic distance to genetic similarity reveals that environment and genetic similarity are poorly correlated. Considering Arizona versus Utah populations, we found a significant negative relationship between geographic distance and genetic similarity ( r = 0.936), but no significant relationship between interpopulation distance and genetic similarity within Arizona or Utah. The wide geographic disjunction of S. arizonica populations in Utah and Arizona appears to have existed for a long period during which genetic drift, random mutations, and selection for somewhat different habitats have pushed the 2 regional complexes along separate evolutionary trajectories. Preservation of genetic variation within S. arizonica will require protection of multiple populations in Arizona and Utah.     

Waterfowl distribution and abundance during spring migration in southern Oregon and northeastern California

We used aerial surveys to study abundance and distribution of waterfowl (ducks, geese, swans, and coots) during spring in southern Oregon and northeastern California (SONEC). Total waterfowl-use days in SONEC during the 119-day, 5 January–3 May, spring period was similar during 2002 (127,977,700) and 2003 (128,076,200) and averaged 1,075,900 birds per day (bpd); these estimates should be adjusted upward 4%–10% to account for areas not surveyed. Waterfowl abundance peaked in mid-March in both years: 2,095,700 in 2002 and 1,681,700 in 2003. Northern Pintail ( Anas acuta ) was the most abundant species in both years, accounting for 25.6% of the 2002 and 24.5% of the 2003 waterfowl-use days. Pintail abundance peaked during the 13 March survey at 689,300 in 2002 and 532,100 in 2003. All other dabbling ducks accounted for 27.6% and 28.6%, diving ducks for 13.5% and 9.2%, geese for 24.6% and 29.3%, swans for 2.8% and 1.9%, and coots for 5.8% and 6.4% of the spring waterfowl-use days in SONEC during 2002 and 2003, respectively. Although use days changed little for total waterfowl (+0.08%) and dabbling ducks (–0.1%), diving duck use was lower (–32%), and goose use days were greater (+19%) in 2003 than in 2002. Distribution was similar in both years, with the most waterfowl use in the Lower (66%) and Upper (14%) Klamath subregions; 2%–6% occurred in each of the other subregions. Although the Lower Klamath subregion received the greatest overall waterfowl use, distribution among subregions varied among species and surveys, and all subregions were important during some part of the spring for 1 or more species. Peak spring abundance in SONEC during 2002 and 2003 averaged 50.3% of the midwinter abundance in California (all survey regions) and southern Oregon (69-3 survey region) for all waterfowl, 46.1% for dabbling ducks, 62.4% for diving ducks, 68.8% for geese, 109.4% for swans, and 43.8% for coots. Each spring, 75% of all waterfowl use in SONEC occurred on federal, state, or Nature Conservancy lands (i.e., protected areas). On protected areas there was a higher percentage of dabbling ducks (80.5%), geese (70.5%), and coots (81.5%) than diving ducks (60.4%) and swans (49%). Waterfowl use of Klamath Basin National Wildlife Refuge (NWR) averaged 42% greater during spring 2002–2003 (568,500 bpd) than during 1998–2001 (Gilmer et al. 2004). Numerous factors likely impacted magnitude and distribution of waterfowl use of SONEC during spring, including weather, waterfowl populations, SONEC habitat, and species ecology. SONEC is a critical spring staging area for waterfowl that winter in the Central Valley of California and other Pacific Flyway regions and should be a major focus area for waterfowl-habitat conservation efforts.     

Case study research in the social sciences

In this paper, we offer an introduction to case study research in the social sciences. We begin with a discussion of the definition of case study research. Next, we point to various purposes that case study research may serve in the social sciences and then turn to outline the main philosophical issues raised by case study research. Finally, we briefly present the papers in this special issue.     

PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR

Loss of the promyelocytic leukaemia (PML) tumour suppressor has been observed in several human cancers. The tumour-suppressive function of PML has been attributed to its ability to induce growth arrest, cellular senescence and apoptosis. Here we identify PML as a critical inhibitor of neoangiogenesis (the formation of new blood vessels) in vivo, in both ischaemic and neoplastic conditions, through the control of protein translation. We demonstrate that in hypoxic conditions PML acts as a negative regulator of the synthesis rate of hypoxia-inducible factor 1alpha (HIF-1alpha) by repressing mammalian target of rapamycin (mTOR). PML physically interacts with mTOR and negatively regulates its association with the small GTPase Rheb by favouring mTOR nuclear accumulation. Notably, Pml-/- cells and tumours display higher sensitivity both in vitro and in vivo to growth inhibition by rapamycin, and lack of PML inversely correlates with phosphorylation of ribosomal protein S6 and tumour angiogenesis in mouse and human tumours. Thus, our findings identify PML as a novel suppressor of mTOR and neoangiogenesis.