Annual Cycle and Migration Strategies of a Trans-Saharan Migratory Songbird: A Geolocator Study in the Great Reed Warbler

Recent technological advancements now allow us to obtain geographical position data for a wide range of animal movements. Here we used light-level geolocators to study the annual migration cycle in great reed warblers (Acrocephalus arundinaceus), a passerine bird breeding in Eurasia and wintering in sub-Saharan Africa. We were specifically interested in seasonal strategies in routes and schedules of migration. We found that the great reed warblers (all males, no females were included) migrated from the Swedish breeding site in early August. After spending up to three weeks at scattered stopover sites in central to south-eastern Europe, they resumed migration and crossed the Mediterranean Sea and Sahara Desert without lengthy stopovers. They then spread out over a large overwintering area and each bird utilised two (or even three) main wintering sites that were spatially separated by a distinct mid-winter movement. Spring migration initiation date differed widely between individuals (1-27 April). Several males took a more westerly route over the Sahara in spring than in autumn, and in general there were fewer long-distance travels and more frequent shorter stopovers, including one in northern Africa, in spring. The shorter stopovers made spring migration on average faster than autumn migration. There was a strong correlation between the spring departure dates from wintering sites and the arrival dates at the breeding ground. All males had a high migration speed in spring despite large variation in departure dates, indicating a time-minimization strategy to achieve an early arrival at the breeding site; the latter being decisive for high reproductive success in great reed warblers. Our results have important implications for the understanding of long-distance migrants’ ability to predict conditions at distant breeding sites and adapt to rapid environmental change.     

Biology of the TAM Receptors

The TAM receptors—Tyro3, Axl, and Mer—comprise a unique family of receptor tyrosine kinases, in that as a group they play no essential role in embryonic development. Instead, they function as homeostatic regulators in adult tissues and organ systems that are subject to continuous challenge and renewal throughout life. Their regulatory roles are prominent in the mature immune, reproductive, hematopoietic, vascular, and nervous systems. The TAMs and their ligands—Gas6 and Protein S—are essential for the efficient phagocytosis of apoptotic cells and membranes in these tissues; and in the immune system, they act as pleiotropic inhibitors of the innate inflammatory response to pathogens. Deficiencies in TAM signaling are thought to contribute to chronic inflammatory and autoimmune disease in humans, and aberrantly elevated TAM signaling is strongly associated with cancer progression, metastasis, and resistance to targeted therapies.The name of the TAM family is derived from the first letter of its three constituents—Tyro3, Axl, and Mer (Prasad et al. 2006). As detailed in Figure 1, members of this receptor tyrosine kinase (RTK) family were independently identified by several different groups and appear in the early literature under multiple alternative names. However, Tyro3, Axl, and Mer (officially c-Mer or MerTK for the protein, Mertk for the gene) have now been adopted as the NCBI designations. The TAMs were first grouped into a distinct RTK family (the Tyro3/7/12 cluster) in 1991, through PCR cloning of their kinase domains (Lai and Lemke 1991). The isolation of full-length cDNAs for Axl (O''Bryan et al. 1991), Mer (Graham et al. 1994), and Tyro3 (Lai et al. 1994) confirmed their segregation into a structurally distinctive family of orphan RTKs (Manning et al. 2002b). The two ligands that bind and activate the TAMs—Gas6 and Protein S (Pros1)—were identified shortly thereafter (Ohashi et al. 1995; Stitt et al. 1995; Mark et al. 1996; Nagata et al. 1996).Open in a separate windowFigure 1.TAM receptors and ligands. The TAM receptors (red) are Tyro3 (Lai and Lemke 1991; Lai et al. 1994)—also designated Brt (Fujimoto and Yamamoto 1994), Dtk (Crosier et al. 1994), Rse (Mark et al. 1994), Sky (Ohashi et al. 1994), and Tif (Dai et al. 1994); Axl (O''Bryan et al. 1991)—also designated Ark (Rescigno et al. 1991), Tyro7 (Lai and Lemke 1991), and Ufo (Janssen et al. 1991); and Mer (Graham et al. 1994)—also designated Eyk (Jia and Hanafusa 1994), Nyk (Ling and Kung 1995), and Tyro12 (Lai and Lemke 1991). The TAMs are widely expressed by cells of the mature immune, nervous, vascular, and reproductive systems. The TAM ligands (blue) are Gas6 and Protein S (Pros1). The carboxy-terminal SHBG domains of the ligands bind to the immunoglobulin (Ig) domains of the receptors, induce dimerization, and activate the TAM tyrosine kinases. When γ-carboxylated in a vitamin-K-dependent reaction, the amino-terminal Gla domains of the dimeric ligands bind to the phospholipid phosphatidylserine expressed on the surface on an apposed apoptotic cell or enveloped virus. See text for details. (From Lemke and Burstyn-Cohen 2010; adapted, with permission, from the authors.)Subsequent progress on elucidating the biological roles of the TAM receptors was considerably slower and ultimately required the derivation of mouse loss-of-function mutants (Camenisch et al. 1999; Lu et al. 1999). The fact that Tyro3^−/−, Axl^−/−, and Mer^−/− mice are all viable and fertile permitted the generation of a complete TAM mutant series that included all possible double mutants and even triple mutants that lack all three receptors (Lu et al. 1999). Remarkably, these Tyro3^−/−Axl^−/−Mer^−/− triple knockouts (TAM TKOs) are viable, and for the first 2–3 wk after birth, superficially indistinguishable from their wild-type counterparts (Lu et al. 1999). Because many RTKs play essential roles in embryonic development, even single loss-of-function mutations in RTK genes often result in an embryonic-lethal phenotype (Gassmann et al. 1995; Lee et al. 1995; Soriano 1997; Arman et al. 1998). The postnatal viability of mice in which an entire RTK family is ablated completely—the TAM TKOs can survive for more than a year (Lu et al. 1999)—is therefore highly unusual. Their viability notwithstanding, the TAM mutants go on to develop a plethora of phenotypes, some of them debilitating (Camenisch et al. 1999; Lu et al. 1999; Lu and Lemke 2001; Scott et al. 2001; Duncan et al. 2003; Prasad et al. 2006). Almost without exception, these phenotypes are degenerative in nature and reflect the loss of TAM signaling activities in adult tissues that are subject to regular challenge, renewal, and remodeling. These activities are the subject of this review.     

Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines

To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super‐resolution microscopy approach to determine the absolute stoichiometry of the human nuclear pore complex (NPC), possibly the largest eukaryotic protein complex. We show that the human NPC has a previously unanticipated stoichiometry that varies across cancer cell types, tissues and in disease. Using large‐scale proteomics, we provide evidence that more than one third of the known, well‐defined nuclear protein complexes display a similar cell type‐specific variation of their subunit stoichiometry. Our data point to compositional rearrangement as a widespread mechanism for adapting the functions of molecular machines toward cell type‐specific constraints and context‐dependent needs, and highlight the need of deeper investigation of such structural variants.     

Melanin in <Emphasis Type="Italic">Fonsecaea pedrosoi</Emphasis>: a trap for oxidative radicals

Background  

The pathogenic fungus Fonsecaea pedrosoi constitutively produces the pigment melanin, an important virulence factor in fungi. Melanin is incorporated in the cell wall structure and provides chemical and physical protection for the fungus.     

Sciatic neuropathy following endovascular treatment of a limb vascular malformation

Background and aim

Allow for protection of briefly ischemic tissues against the harmful effects of subsequent prolonged ischemia is a phenomennon called as Ischemic Preconditioning (IP). IP has not been studied in ischemia-reperfusion (I/R) model of peripheral nerve before. We aimed to study the effects of acute IP on I/R injury of peripheral nerve in rats.

Method

70 adult male rats were randomly divided into 5 groups in part 1 experimentation and 3 groups in part 2 experimentation. A rat model of severe nerve ischemia which was produced by tying iliac arteries and all idenfiable anastomotic vessels with a silk suture (6-0) was used to study the effects of I/R and IP on nerve biochemistry. The suture technique used was a slip-knot technique for rapid release at time of reperfusion in the study. Cytoplasmic vacuolar degeneration was also histopathologically evaluated by light microscopic examination in sciatic nerves of rats at 7th day in part 2 study.

Results

3 hours of Reperfusion resulted in an increase in nerve malondialdehyde levels when compared with ischemia and non-ischemia groups (p < 0.001 and p < 0.0001 respectively). IP had significantly lower nerve MDA levels than 3 h reperfusion group (p < 0.001). The differences between ischemic, IP and non-ischemic control groups were not significant (p > 0.05). There was also a significant decrease in vacoular degeneration of sciatic nerves in IP group than I/R group (p < 0.05).

Conclusion

IP reduces the severity of I/R injury in peripheral nerve as shown by reduced tissue MDA levels at 3 th hour of reperfusion and axonal vacoulization at 7 th postischemic day.     

Advanced monitoring and control of pharmaceutical production processes with Pichia pastoris by using Raman spectroscopy and multivariate calibration methods

This contribution includes an investigation of the applicability of Raman spectroscopy as a PAT analyzer in cyclic production processes of a potential Malaria vaccine with Pichia pastoris. In a feasibility study, Partial Least Squares Regression (PLSR) models were created off‐line for cell density and concentrations of glycerol, methanol, ammonia and total secreted protein. Relative cross validation errors RMSE_cvrel range from 2.87% (glycerol) to 11.0% (ammonia). In the following, on‐line bioprocess monitoring was tested for cell density and glycerol concentration. By using the nonlinear Support Vector Regression (SVR) method instead of PLSR, the error RMSE_Prel for cell density was reduced from 5.01 to 2.94%. The high potential of Raman spectroscopy in combination with multivariate calibration methods was demonstrated by the implementation of a closed loop control for glycerol concentration using PLSR. The strong nonlinear behavior of exponentially increasing control disturbances was met with a feed‐forward control and adaptive correction of control parameters. In general the control procedure works very well for low cell densities. Unfortunately, PLSR models for glycerol concentration are strongly influenced by a correlation with the cell density. This leads to a failure in substrate prediction, which in turn prevents substrate control at cell densities above 16 g/L.     

Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67

The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.