At the crossroads from Asia to Europe: spring migration of raptors and black storks in Dadia National Park (Greece)

Migrating raptors and black storks (Ciconia nigra) were studied in Dadia National Park, Greece, during spring 2003–2005. Vantage points and transects were used to evaluate magnitude, phenology, local variation and direction. We observed 23 species and 2030 individuals, including 715 common buzzards (Buteo buteo), 547 black storks and 136 short-toed eagles (Circaetus gallicus). Species-specific migration peaks were detected, starting in the second half of March, e.g. common buzzard, short-toed eagle, black stork, and ending early May, e.g. Levant sparrowhawk (Accipiter brevipes), red-footed falcon (Falco vespertinus), honey buzzard (Pernis apivorus). Most raptors were observed in the Evros valley, which may function as a migration corridor. The average direction of passing raptors was north. Species’ proportions and phenology in the study area were similar to those in neighbouring Bosphorus and Marmara Flyways. Further migration monitoring should be established in the area, which will provide important information not least to inform wind farm development location.     

Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2

We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.     

Mechanism of variations in environmental magnetic proxies of lake sediments from Nam Co, Tibet during the Holocene

High-resolution environmental records from the Tibetan Plateau are essential to understand past global climatic and environmental changes. Magnetic minerals in lake sediments are important proxies to reconstruct environmental and climatic changes. Nam Co (lake) is a typical great lake in the transitional region of southwest monsoon in the Tibetan Plateau. Previous studies have extensively focused on geochemistry, microfossils, sedimentology and biochemistry analysis of Nam Co, which provides sound interpretation of paleoclimatic and paleoenvironmental changes. However, up to now, no systematic environmental magnetic studies have been carried out. Therefore, high-resolution and systematic magnetic studies combined with geochemical parameters were carried on lake sediments of core NC 08/01 from Nam Co for the Holocene period (11.3 cal ka BP) in order to explore how magnetic properties of the sediments respond to climatic changes. Based on variations of magnetic proxies, the sequence can be separated into 3 units. Unit 1 (236-199 cm, 11.3-7.8 cal ka BP) contains dominantly coarse-grained magnetite with homogeneous grain size. A positive correlation between magnetite and Ti strongly suggests that these coarse-grained detrital magnetites reflect detrital input signals due to insignificant effects of postdepositional dissolution processes on these coarse-grained magnetite particles. For Unit 2 (198-102 cm, 7.8-2.1 cal ka BP), magnetic grain size is finer and the corresponding concentration of magnetite is also reduced. This is mainly due to significant dissolution of these fine-grained detrital magnetite particles, which were transported under reduced water flow conditions during this period. For Unit 3 (101-0 cm, 2.1-0 cal ka BP), the bulk magnetic properties are dominated by a mixture of single domain biogenic magnetite and detrital magnetite. The concentration of magnetic minerals is not correlated with the Ti content. In conclusion, the preservation of magnetic minerals in the lake sediment and thus the corresponding magnetic properties are related to the initial grain size. Combination of magnetic properties (including variation of grain size and concentration) and other proxies of detrital inputs (e.g. Ti) can be used to infer the variation of redox conditions in Nam Co. These results provide a viable framework for reconstructing the paleoenvironmental changes of this lake.     

Improving solver performance through redundancy

It is well known that hierarchies of mathematical programming formulations with different numbers of variables and constraints have a considerable impact regarding the quality of solutions obtained once these formulations are fed to a commercial solver. In addition, even if dimensions are kept the same, changes in formulations may largely influence solvability and quality of results. This becomes evident especially if redundant constraints are used. We propose a related framework for information collection based on these constraints. We exemplify by means of a well-known combinatorial optimization problem from the knapsack problem family, i.e., the multidimensional multiple-choice knapsack problem (MMKP). This incorporates a relationship of the MMKP to some generalized set partitioning problems. Moreover, we investigate an application in maritime shipping and logistics by means of the dynamic berth allocation problem (DBAP), where optimal solutions are reached from the root node within the solver.     

Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis

Endolysosomal cysteine cathepsins functionally cooperate. Cathepsin B (Ctsb) and L (Ctsl) double-knockout mice die 4 weeks after birth accompanied by (autophago-) lysosomal accumulations within neurons. Such accumulations are also observed in mouse embryonic fibroblasts (MEFs) deficient for Ctsb and Ctsl. Previous studies showed a strong impact of Ctsl on the MEF secretome. Here we show that Ctsb alone has only a mild influence on extracellular proteome composition. Protease cleavage sites dependent on Ctsb were identified by terminal amine isotopic labeling of substrates (TAILS), revealing a prominent yet mostly indirect impact on the extracellular proteolytic cleavages. To investigate the cooperation of Ctsb and Ctsl, we performed a quantitative secretome comparison of wild-type MEFs and Ctsb ^?/? Ctsl ^?/? MEFs. Deletion of both cathepsins led to drastic alterations in secretome composition, highlighting cooperative functionality. While many protein levels were decreased, immunodetection corroborated increased levels of matrix metalloproteinase (MMP)-2. Re-expression of Ctsl rescues MMP-2 abundance. Ctsl and to a much lesser extent Ctsb are able to degrade MMP-2 at acidic and neutral pH. Addition of active MMP-2 to the MEF secretome degrades proteins whose levels were also decreased by Ctsb and Ctsl double deficiency. These results suggest a degradative Ctsl—MMP-2 axis, resulting in increased MMP-2 levels upon cathepsin deficiency with subsequent degradation of secreted proteins such as collagen α-1 (I).     

New imaging probes to track cell fate: reporter genes in stem cell research

Cell fate is a concept used to describe the differentiation and development of a cell in its organismal context over time. It is important in the field of regenerative medicine, where stem cell therapy holds much promise but is limited by our ability to assess its efficacy, which is mainly due to the inability to monitor what happens to the cells upon engraftment to the damaged tissue. Currently, several imaging modalities can be used to track cells in the clinical setting; however, they do not satisfy many of the criteria necessary to accurately assess several aspects of cell fate. In recent years, reporter genes have become a popular option for tracking transplanted cells, via various imaging modalities in small mammalian animal models. This review article examines the reporter gene strategies used in imaging modalities such as MRI, SPECT/PET, Optoacoustic and Bioluminescence Imaging. Strengths and limitations of the use of reporter genes in each modality are discussed.     

Role of the ubiquitin-like protein Hub1 in splice-site usage and alternative splicing

Alternative splicing of pre-messenger RNAs diversifies gene products in eukaryotes and is guided by factors that enable spliceosomes to recognize particular splice sites. Here we report that alternative splicing of Saccharomyces cerevisiae SRC1 pre-mRNA is promoted by the conserved ubiquitin-like protein Hub1. Structural and biochemical data show that Hub1 binds non-covalently to a conserved element termed HIND, which is present in the spliceosomal protein Snu66 in yeast and mammals, and Prp38 in plants. Hub1 binding mildly alters spliceosomal protein interactions and barely affects general splicing in S. cerevisiae. However, spliceosomes that lack Hub1, or are defective in Hub1-HIND interaction, cannot use certain non-canonical 5' splice sites and are defective in alternative SRC1 splicing. Hub1 confers alternative splicing not only when bound to HIND, but also when experimentally fused to Snu66, Prp38, or even the core splicing factor Prp8. Our study indicates a novel mechanism for splice site utilization that is guided by non-covalent modification of the spliceosome by an unconventional ubiquitin-like modifier.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold

The fidelity and specificity of information flow within a cell is controlled by scaffolding proteins that assemble and link enzymes into signalling circuits. These circuits can be inhibited by bacterial effector proteins that post-translationally modify individual pathway components. However, there is emerging evidence that pathogens directly organize higher-order signalling networks through enzyme scaffolding, and the identity of the effectors and their mechanisms of action are poorly understood. Here we identify the enterohaemorrhagic Escherichia coli O157:H7 type III effector EspG as a regulator of endomembrane trafficking using a functional screen, and report ADP-ribosylation factor (ARF) GTPases and p21-activated kinases (PAKs) as its relevant host substrates. The 2.5?? crystal structure of EspG in complex with ARF6 shows how EspG blocks GTPase-activating-protein-assisted GTP hydrolysis, revealing a potent mechanism of GTPase signalling inhibition at organelle membranes. In addition, the 2.8?? crystal structure of EspG in complex with the autoinhibitory Iα3-helix of PAK2 defines a previously unknown catalytic site in EspG and provides an allosteric mechanism of kinase activation by a bacterial effector. Unexpectedly, ARF and PAKs are organized on adjacent surfaces of EspG, indicating its role as a 'catalytic scaffold' that effectively reprograms cellular events through the functional assembly of GTPase-kinase signalling complex.