A long-distance avian migrant compensates for longitudinal displacement during spring migration

In order to perform true bicoordinate navigation, migratory birds need to be able to determine geographic latitude and longitude. The determination of latitude is relatively easy from either stellar or magnetic cues [1-3], but the determination of longitude seems challenging [4, 5]. It has therefore been suggested that migrating birds are unable to perform bicoordinate navigation and that they probably only determine latitude during their return migration [5]. However, proper testing of this hypothesis requires displacement experiments with night-migratory songbirds in spring that have not been performed. We therefore displaced migrating Eurasian reed warblers (Acrocephalus scirpaceus) during spring migration about 1000 km toward the east and found that they were correcting for displacements by shifting their orientation from the northeast at the capture site to the northwest after the displacement. This new direction would lead them to their expected breeding areas. Our results suggest that Eurasian reed warblers are able to determine longitude and perform bicoordinate navigation. This finding is surprising and presents a new intellectual challenge to bird migration researchers, namely, which cues enable birds to determine their east-west position.     

The In ovo CAM-assay as a Xenograft Model for Sarcoma

Sarcoma is a very rare disease that is heterogeneous in nature, all hampering the development of new therapies. Sarcoma patients are ideal candidates for personalized medicine after stratification, explaining the current interest in developing a reproducible and low-cost xenotransplant model for this disease. The chick chorioallantoic membrane is a natural immunodeficient host capable of sustaining grafted tissues and cells without species-specific restrictions. In addition, it is easily accessed, manipulated and imaged using optical and fluorescence stereomicroscopy. Histology further allows detailed analysis of heterotypic cellular interactions.This protocol describes in detail the in ovo grafting of the chorioallantoic membrane with fresh sarcoma-derived tumor tissues, their single cell suspensions, and permanent and transient fluorescently labeled established sarcoma cell lines (Saos-2 and SW1353). The chick survival rates are up to 75%. The model is used to study graft- (viability, Ki67 proliferation index, necrosis, infiltration) and host (fibroblast infiltration, vascular ingrowth) behavior. For localized grafting of single cell suspensions, ECM gel provides significant advantages over inert containment materials. The Ki67 proliferation index is related to the distance of the cells from the surface of the CAM and the duration of application on the CAM, the latter determining a time frame for the addition of therapeutic products.     

Bis-phosphonium salts of pyridoxine: The relationship between structure and antibacterial activity

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr > Et > Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6-bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c]pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5 times (MICs = 1–1.25 μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1 μg/ml) and lower cytotoxicity on HEK-293 cells (CC₅₀ = 200 μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin.     

Activity patterns in the Sahara Desert: an interpretation based on cross-sectional geometric properties

The Garamantian civilization flourished in modern Fezzan, Libya, between 900 BC and 500 AD, during which the aridification of the Sahara was well established. Study of the archaeological remains suggests a population successful at coping with a harsh environment of high and fluctuating temperatures and reduced water and food resources. This study explores the activity patterns of the Garamantes by means of cross-sectional geometric properties. Long bone diaphyseal shape and rigidity are compared between the Garamantes and populations from Egypt and Sudan, namely from the sites of Kerma, el-Badari, and Jebel Moya, to determine whether the Garamantian daily activities were more strenuous than those of other North African populations. Moreover, sexual dimorphism and bilateral asymmetry are assessed at an intra- and inter-population level. The inter-population comparisons showed the Garamantes not to be more robust than the comparative populations, suggesting that the daily Garamantian activities necessary for survival in the Sahara Desert did not generally impose greater loads than those of other North African populations. Sexual dimorphism and bilateral asymmetry in almost all geometric properties of the long limbs were comparatively low among the Garamantes. Only the lower limbs were significantly stronger among males than females, possibly due to higher levels of mobility associated with herding. The lack of systematic bilateral asymmetry in cross-sectional geometric properties may relate to the involvement of the population in bilaterally intensive activities or the lack of regular repetition of unilateral activities.     

The VEGFR2 receptor tyrosine kinase undergoes constitutive endosome-to-plasma membrane recycling

The VEGFR2 receptor tyrosine kinase regulates vascular physiology and animal development. The mechanism underlying VEGFR2 membrane trafficking is not well understood. Herein, we show that VEGFR2 undergoes membrane recycling in both vascular and non-vascular cells. In primary human endothelial cells, VEGFR2 normally distributes between the plasma membrane and early endosomes undergoing endocytosis and recycling. This pathway is independent of VEGFR tyrosine kinase activity and occurs constitutively, similar to other integral membrane proteins such as the transferrin receptor and β1 integrin. Expression of a VEGFR2-EGFP hybrid protein in non-vascular cells revealed plasma membrane and endosome distribution. The VEGF-A ligand stimulated phosphorylation of residue Y1175 on VEGFR2-EGFP which is a key hallmark of receptor activation. Live cell imaging and quantitative analysis showed that activated VEGFR2-EGFP displayed reduced mobility linked to endocytosis and recycling between the plasma membrane and endosomes. Total internal reflection microscopy and kinetics indicates that VEGFR2 undergoes recycling between the plasma membrane and peripheral endosomes proximal to the membrane bilayer. We thus provide evidence that the VEGFR2 receptor tyrosine kinase undertakes a constitutive recycling pathway between the peripheral endosomes and cell surface and this exists in both vascular and non-vascular cells.     

Exome Sequence Reveals Mutations in CoA Synthase as a Cause of Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA.     

The use of generalized linear models and generalized estimating equations in bioarchaeological studies

The current article explores whether the application of generalized linear models (GLM) and generalized estimating equations (GEE) can be used in place of conventional statistical analyses in the study of ordinal data that code an underlying continuous variable, like entheseal changes. The analysis of artificial data and ordinal data expressing entheseal changes in archaeological North African populations gave the following results. Parametric and nonparametric tests give convergent results particularly for P values <0.1, irrespective of whether the underlying variable is normally distributed or not under the condition that the samples involved in the tests exhibit approximately equal sizes. If this prerequisite is valid and provided that the samples are of equal variances, analysis of covariance may be adopted. GLM are not subject to constraints and give results that converge to those obtained from all nonparametric tests. Therefore, they can be used instead of traditional tests as they give the same amount of information as them, but with the advantage of allowing the study of the simultaneous impact of multiple predictors and their interactions and the modeling of the experimental data. However, GLM should be replaced by GEE for the study of bilateral asymmetry and in general when paired samples are tested, because GEE are appropriate for correlated data. Am J Phys Anthropol 153:473–483, 2014. © 2013 Wiley Periodicals, Inc.     

The “deduction” approach: A non-invasive method for estimating secondary production of earthworm communities

Secondary production is an important parameter for the study of population dynamics and energy flow through animal communities. Secondary production of earthworm communities has been determined with the size-frequency and instantaneous growth rate methods, whereby earthworm populations are repeatedly sampled at regular intervals and the change in biomass of cohorts or individuals between sampling dates is determined. The major disadvantage of repeated sampling is that it disturbs the soil and permanently removes earthworms from the study area. The “deduction” approach is a theoretical model that partitions individuals into defined pools and makes assumptions about the growth, recruitment and mortality of each pool. In 2004 and 2005, earthworms were added to undisturbed field enclosures and the “deduction” approach was used to estimate secondary production of the indigenous and added earthworm populations during the crop growing period (17–18 weeks) in each year. Secondary production estimates made by the “deduction” approach were similar to estimates from direct earthworm sampling in temperate agroecosystems. The “deduction” approach is an indirect method that estimates population dynamics and secondary production, and is appropriate for manipulation experiments where removal of organisms and physical disturbance of the habitat by repeated sampling could bias results.     

Regulation of ion transport proteins by membrane phosphoinositides

Over the past decade, there has been an explosion in the number of membrane transport proteins that have been shown to be sensitive to the abundance of phosphoinositides in the plasma membrane. These proteins include voltage-gated potassium and calcium channels, ion channels that mediate sensory and nociceptive responses, epithelial transport proteins and ionic exchangers. Each of the regulatory lipids is also under multifaceted regulatory control. Phosphoinositide modulation of membrane proteins in neurons often has a dramatic effect on neuronal excitability and synaptic transmitter release. The repertoire of lipid signalling mechanisms that regulate membrane proteins is intriguingly complex and provides a rich array of topics for neuroscience research.