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William Holden Hutton (1860-1930) was a British historian and Dean of Winchester Cathedral. In this slim volume, Hutton writes of the long period of feudal anarchy following the death of King Henry I in 1135, during which Henry’s implacable daughter, Mathilda, battled the ineffectual King Stephen. Hutton then describes the turbulent reign of the great King Henry II, the reigns of Kings Richard, John, Henry III, and of the first two Edwards, rulers who whether weak or strong, rigid or resourceful, were grimly opposed by their powerful barons. – Summary by Pamela Nagami This title is avalable for free download at: www.librivox.org.

By Chien-Chun Liu, Chen-Hsien You, Po-Jung Wang, Jau-Song Yu, Guo-Jen Huang, Chien-Hsin Liu, Wen-Chin Hsieh, Chih-Chuan Lin In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom—freeze-dried neurotoxic antivenom (FNAV)—against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known.

Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two ‘true’ cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N.

Kaouthia and N. Siamensis venoms, but not O. Hannah venom. Popping Sound In Shoulder When Throwing. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. Kaouthia and N. Siamensis venoms.

The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites. Tratto da: www.plos.org. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license. By Wu-Jung Lee, Benjamin Falk, Chen Chiu, Anand Krishnan, Jessica H. Arbour, Cynthia F. Emulator Download For Iphone. Moss Animals enhance sensory acquisition from a specific direction by movements of head, ears or eyes.

As active sensing animals, echolocating bats also aim their directional sonar beam to selectively “illuminate” a confined volume of space, facilitating efficient information processing by reducing echo interference and clutter. Such sonar beam control is generally achieved by head movements or shape changes of the sound-emitting mouth or nose. However, lingual-echolocating Egyptian fruit bats, Rousettus aegyptiacus, which produce sound by clicking their tongue, can dramatically change beam direction at very short temporal intervals without visible morphological changes. The mechanism supporting this capability has remained a mystery. Here we measured signals from free-flying Egyptian fruit bats and discovered a systematic angular sweep of beam focus across increasing frequency. This unusual signal structure has not been observed in other animals, and cannot be explained by the conventional and widely used “piston model” that describes the emission pattern of other bat species.

Through modeling we show that the observed beam features can be captured by an array of tongue-driven sound sources located along the side of the mouth, and that the sonar beam direction can be steered parsimoniously by inducing changes to the pattern of phase differences through moving tongue location. The effects are broadly similar to those found in a phased array–an engineering design widely found in human-made sonar systems that enables beam direction changes without changes in the physical transducer assembly. Our study reveals an intriguing parallel between biology and human engineering in solving problems in fundamentally similar ways. Tratto da: www.plos.org. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.

Siller, Himanshu Sharma, Shuai Li, June Yang, Yong Zhang, Michael J. Holtzman, Wipawee Winuthayanon, Holly Colognato, Bernadette C. Holdener, Feng-Qian Li, Ken-Ichi Takemaru Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood.

Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown. In this study, we have generated a novel conditional mouse model that lacks CEP164 in multiciliated tissues and the testis.

These mice show a profound loss of airway, ependymal, and oviduct multicilia and develop hydrocephalus and male infertility. Using primary cultures of tracheal multiciliated cells as a model system, we found that CEP164 is critical for multiciliogenesis, at least in part, via its regulation of small vesicle recruitment, ciliary vesicle formation, and basal body docking. In addition, CEP164 is necessary for the proper recruitment of another distal appendage/transition fiber protein Chibby1 (Cby1) and its binding partners FAM92A and FAM92B to the ciliary base in multiciliated cells. In contrast to primary ciliogenesis, CEP164 is dispensable for the recruitment of intraflagellar transport (IFT) components to multicilia. Finally, we provide evidence that CEP164 differentially controls the ciliary targeting of membrane-associated proteins, including the small GTPases Rab8, Rab11, and Arl13b, in multiciliated cells. Altogether, our studies unravel unique requirements for CEP164 in primary versus multiciliogenesis and suggest that CEP164 modulates the selective transport of membrane vesicles and their cargoes into the ciliary compartment in multiciliated cells. Furthermore, our mouse model provides a useful tool to gain physiological insight into diseases associated with defective multicilia.

Tratto da: www.plos.org. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license. By Christoph Baldow, Sebastian Salentin, Michael Schroeder, Ingo Roeder, Ingmar Glauche Over the past decades, quantitative methods linking theory and observation became increasingly important in many areas of life science.

Subsequently, a large number of mathematical and computational models has been developed. The BioModels database alone lists more than 140,000 Systems Biology Markup Language (SBML) models. However, while the exchange within specific models classes has been supported by standardisation and database efforts, the generic application and especially the re-use of models is still limited by practical issues such as easy and straight forward model execution. MAGPIE, a Modeling and Analysis Generic Platform with Integrated Evaluation, closes this gap by providing a software platform for both, publishing and executing computational models without restrictions on the programming language, thereby combining a maximum on flexibility for programmers with easy handling for non-technical users.

MAGPIE goes beyond classical SBML platforms by including all models, independent of the underlying programming language, ranging from simple script models to complex data integration and computations. We demonstrate the versatility of MAGPIE using four prototypic example cases. We also outline the potential of MAGPIE to improve transparency and reproducibility of computational models in life sciences. A demo server is available at magpie.imb.medizin.tu-dresden.de.

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