Acquired bleeding disorders

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities. This review addresses (a) acquired hemophilia A, an autoimmune disorder characterized by inhibitory autoantibodies against coagulation factor VIII; (b) acquired von Willebrand syndrome in patients with cardiovascular disorders, where shear stress abnormalities result in destruction of von Willebrand factor; and (c) liver function disorders that comprise complex changes in pro- and anti-hemostatic factors, whose clinical implications are often difficult to predict. The article provides an overview on the pathophysiology, diagnostic tests and state-of-the-art treatment strategies

HES and Mox genes are expressed during early mesoderm formation in a mollusk with putative ancestral features

The mesoderm is considered the youngest of the three germ layers. Although its morphogenesis has been studied in some metazoans, the molecular components underlying this process remain obscure for numerous phyla including the highly diverse Mollusca. Here, expression of Hairy and enhancer of split (HES), Mox, and myosin heavy chain (MHC) was investigated in Acanthochitona fascicularis, a representative of Polyplacophora with putative ancestral molluscan features. While AfaMHC is expressed throughout myogenesis, AfaMox1 is only expressed during early stages of mesodermal band formation and in the ventrolateral muscle, an autapomorphy of the polyplacophoran trochophore. Comparing our findings to previously published data across Metazoa reveals Mox expression in the mesoderm in numerous bilaterians including gastropods, polychaetes, and brachiopods. It is also involved in myogenesis in molluscs, annelids, tunicates, and craniates, suggesting a dual role of Mox in mesoderm and muscle formation in the last common bilaterian ancestor. AfaHESC2 is expressed in the ectoderm of the polyplacophoran gastrula and later in the mesodermal bands and in putative neural tissue, whereas AfaHESC7 is expressed in the trochoblasts of the gastrula and during foregut formation. This confirms the high developmental variability of HES gene expression and demonstrates that Mox and HES genes are pleiotropic

Midbody-Localized Aquaporin Mediates Intercellular Lumen Expansion During Early Cleavage of an Invasive Freshwater Bivalve

Intercellular lumen formation is a crucial aspect of animal development and physiology that involves a complex interplay between the molecular and physical properties of the constituent cells. Embryos of the invasive freshwater mussel Dreissena rostriformis are ideal models for studying this process due to the large intercellular cavities that readily form during blastomere cleavage. Using this system, we show that recruitment of the transmembrane water channel protein aquaporin exclusively to the midbody of intercellular cytokinetic bridges is critical for lumenogenesis. The positioning of aquaporin-positive midbodies thereby influences the direction of cleavage cavity expansion. Notably, disrupting cytokinetic bridge microtubules impairs not only lumenogenesis but also cellular osmoregulation. Our findings reveal a simple mechanism that provides tight spatial and temporal control over the formation of luminal structures and likely plays an important role in water homeostasis during early cleavage stages of a freshwater invertebrate species

A mosaic of conserved and novel modes of gene expression and morphogenesis in mesoderm and muscle formation of a larval bivalve

The mesoderm gives rise to several key morphological features of bilaterian animals including endoskeletal elements and the musculature. A number of regulatory genes involved in mesoderm and/or muscle formation (e.g., Brachyury (Bra), even-skipped (eve), Mox, myosin II heavy chain (mhc)) have been identified chiefly from chordates and the ecdysozoans Drosophila and Caenorhabditis elegans, but data for non-model protostomes, especially those belonging to the ecdysozoan sister clade, Lophotrochozoa (e.g., flatworms, annelids, mollusks), are only beginning to emerge. Within the lophotrochozoans, Mollusca constitutes the most speciose and diverse phylum. Interestingly, however, information on the morphological and molecular underpinnings of key ontogenetic processes such as mesoderm formation and myogenesis remains scarce even for prominent molluscan sublineages such as the bivalves. Here, we investigated myogenesis and developmental expression of Bra, eve, Mox, and mhc in the quagga mussel Dreissena rostriformis, an invasive freshwater bivalve and an emerging model in invertebrate evodevo. We found that all four genes are expressed during mesoderm formation, but some show additional, individual sites of expression during ontogeny. While Mox and mhc are involved in early myogenesis, eve is also expressed in the embryonic shell field and Bra is additionally present in the foregut. Comparative analysis suggests that Mox has an ancestral role in mesoderm and possibly muscle formation in bilaterians, while Bra and eve are conserved regulators of mesoderm development of nephrozoans (protostomes and deuterostomes). The fully developed Dreissena veliger larva shows a highly complex muscular architecture, supporting a muscular ground pattern of autobranch bivalve larvae that includes at least a velum muscle ring, three or four pairs of velum retractors, one or two pairs of larval retractors, two pairs of foot retractors, a pedal plexus, possibly two pairs of mantle retractors, and the muscles of the pallial line, as well as an anterior and a posterior adductor. As is typical for their molluscan kin, remodelling and loss of prominent larval features such as the velum musculature and various retractor systems appear to be also common in bivalves

Translation of two-photon microscopy to the clinic: multimodal multiphoton CARS tomography of in vivo human skin

Two-photon microscopes have been successfully translated into clinical imaging tools to obtain high-resolution optical biopsies for in vivo histology. We report on clinical multiphoton coherent anti-Stokes Raman spectroscopy (CARS) tomography based on two tunable ultrashort near-infrared laser beams for label-free in vivo multimodal skin imaging. The multiphoton biopsies were obtained with the compact tomograph “MPTflex-CARS” using a photonic crystal fiber, an optomechanical articulated arm, and a four-detector-360 deg measurement head. The multiphoton tomograph has been employed to patients in a hospital with diseased skin. The clinical study involved 16 subjects, 8 patients with atopic dermatitis, 4 patients with psoriasis vulgaris, and 4 volunteers served as control. Two-photon cellular autofluorescence lifetime, second harmonic generation (SHG) of collagen, and CARS of intratissue lipids/proteins have been detected with single-photon sensitivity, submicron spatial resolution, and picosecond temporal resolution. The most important signal was the autofluorescence from nicotinamide adenine dinucleotide [NAD(P)H]. The SHG signal from collagen was mainly used to detect the epidermal–dermal junction and to calculate the ratio elastin/collagen. The CARS/Raman signal provided add-on information. Based on this view on the disease-affected skin on a subcellular level, skin areas affected by dermatitis and by psoriasis could be clearly identified. Multimodal multiphoton tomographs may become important label-free clinical high-resolution imaging tools for in vivo skin histology to realize rapid early diagnosis as well as treatment control

The quagga mussel genome and the evolution of freshwater tolerance

Freshwater dreissenid mussels evolved from marine ancestors during the Miocene ∼30 million years ago and today include some of the most successful and destructive invasive species of freshwater environments. Here, we sequenced the genome of the quagga mussel Dreissena rostriformis to identify adaptations involved in embryonic osmoregulation. We provide evidence that a lophotrochozoan-specific aquaporin water channel, a vacuolar ATPase subunit and a sodium/hydrogen exchanger are involved in osmoregulation throughout early cleavage, during which time large intercellular fluid-filled 'cleavage cavities' repeatedly form, coalesce and collapse, expelling excess water to the exterior. Independent expansions of aquaporins coinciding with at least five freshwater colonization events confirm their role in freshwater adaptation. Repeated aquaporin expansions and the evolution of membrane-bound fluid-filled osmoregulatory structures in diverse freshwater taxa point to a fundamental principle guiding the evolution of freshwater tolerance and provide a framework for future species control efforts

Adding chemically selective subtraction to multi-material 3D additive manufacturing

Existing photoresists for 3D laser lithography that can be removed after development in a subtractive manner typically suffer from harsh cleavage conditions. Here, we report chemoselectively cleavable photoresists for 3D laser lithography based on silane crosslinkers, allowing the targeted degradation of 3D printed microstructures under mild conditions. Three bifunctional silane crosslinkers carrying various substitutions on the silicon atom are synthesized. The photoresists are prepared by mixing these silane crosslinkers with pentaerythritol triacrylate and a two-photon photoinitiator. The presence of pentaerythritol triacrylate significantly enhances the direct laser written structures with regard to resolution, while the microstructures remain cleavable. For the targeted cleavage of the fabricated 3D microstructures, simply a methanol solution including inorganic salts is required, highlighting the mild cleavage conditions. Critically, the photoresists can be cleaved selectively, which enables the sequential degradation of direct laser written structures and allows for subtractive manufacturing at the micro- and nanoscale

New high-resolution age data from the Ediacaran-Cambrian boundary indicate rapid, ecologically driven onset of the Cambrian explosion

The replacement of the late Precambrian Ediacaran biota by morphologically disparate animals at the beginning of the Phanerozoic was a key event in the history of life on Earth, the mechanisms and the timescales of which are not entirely understood. A composite section in Namibia providing biostratigraphic and chemostratigraphic data bracketed by radiometric dating constrains the Ediacaran–Cambrian boundary to 538.6–538.8 Ma, more than 2 Ma younger than previously assumed. The U–Pb-CA-ID TIMS zircon ages demonstrate an ultrashort time frame for the LAD of the Ediacaran biota to the FAD of a complex, burrowing Phanerozoic biota represented by trace fossils to a 410 ka time window of 538.99±0.21 Ma to 538.58±0.19 Ma. The extremely short duration of the faunal transition from Ediacaran to Cambrian biota within less than 410 ka supports models of ecological cascades that followed the evolutionary breakthrough of increased mobility at the beginning of the Phanerozoic

Analyzing the Effects of Neutron Polarizabilities in Elastic Compton Scattering off 3{}^3He

Motivated by the fact that a polarized ${}^3$He nucleus behaves as an `effective' neutron target, we examine manifestations of neutron electromagnetic polarizabilities in elastic Compton scattering from the Helium-3 nucleus. We calculate both unpolarized and double-polarization observables using chiral perturbation theory to next-to-leading order (${\mathcal O}(e^2 Q)$) at energies, $\omega \leq m_{\pi}$, where $m_{\pi}$ is the pion mass. Our results show that the unpolarized differential cross section can be used to measure neutron electric and magnetic polarizabilities, while two double-polarization observables are sensitive to different linear combinations of the four neutron spin polarizabilities. [Note added in 2018] The qualitative conclusions and analytic formulae presented in this paper are correct, but several of the numerical results are wrong: see the erratum posted as arXiv:1804.01206 for further details. A full suite of corrected numerical results for cross sections and asymmetries can be found in Margaryan et al., arXiv:1804.00956. They can also be obtained as an interactive Mathematica notebook by emailing [email protected]: 40 pages, 16 figure