The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers. However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain

Outcomes of surgically treated sialoceles in 21 cats: A multi‐institutional retrospective study (2010–2021)

To report the outcomes of cats that underwent surgical correction for sialoceles. Multi-institutional retrospective cohort study. Twenty-one client-owned cats. Medical records were examined of cats diagnosed with sialocele, which underwent surgical intervention over an 11-year period at one of 10 referral hospitals. The data collected included signalment, clinical signs, diagnostic imaging, histopathology, surgical procedures performed, and postoperative complications. The most common presenting complaints for cats with sialocele included dysphagia and ptyalism. Only two cats had a recent history of trauma, and one was diagnosed with a concurrent sialolith. Most displayed visible tissue swelling, with ranulae being most common. Surgical treatment consisted of sialoadenectomy and/or marsupialization. Intraoperative complications occurred in three cats, and postoperative complications in five cats. No recurrence or development of contralateral sialoceles were reported during the follow-up period (30-968 days). The majority of cats did not have a clear underlying cause for developing a sialocele. The sublingual and mandibular salivary glands were presumed to be the most commonly affected. Mandibular and sublingual sialoadenectomy and/or marsupialization provided resolution of clinical signs to the 21 cats that underwent these procedures. Sialocele, although rare, should remain a differential diagnosis when managing cats with relevant clinical signs. Surgical intervention appears to offer resolution of signs with apparently low overall risk of complication or short-term recurrence. In cats it is necessary to evaluate whether sialoadenectomy is necessary, or whether marsupialization alone should be attempted as a less invasive first-line surgical intervention

Review on Superconducting Materials

Short review of the topical comprehension of the superconductor materials classes Cuprate High-Temperature Superconductors, other oxide superconductors, Iron-based Superconductors, Heavy-Fermion Superconductors, Nitride Superconductors, Organic and other Carbon-based Superconductors and Boride and Borocarbide Superconductors, featuring their present theoretical understanding and their aspects with respect to technical applications.Comment: A previous version of this article has been published in \" Applied Superconductivity: Handbook on Devices and Applications \", Wiley-VCH ISBN: 978-3-527-41209-9. The new extended and updated version will be published in \" Encyclopedia of Applied Physics \", Wiley-VC

There or not there? A multidisciplinary review and research agenda on the impact of transparent barriers on human perception, action, and social behavior

Contains fulltext : 145066.pdf (publisher's version ) (Open Access)Through advances in production and treatment technologies, transparent glass has become an increasingly versatile material and a global hallmark of modern architecture. In the shape of invisible barriers, it defines spaces while simultaneously shaping their lighting, noise, and climate conditions. Despite these unique architectural qualities, little is known regarding the human experience with glass barriers. Is a material that has been described as being simultaneously there and not there from an architectural perspective, actually there and/or not there from perceptual, behavioral, and social points of view? In this article, we review systematic observations and experimental studies that explore the impact of transparent barriers on human cognition and action. In doing so, the importance of empirical and multidisciplinary approaches to inform the use of glass in contemporary architecture is highlighted and key questions for future inquiry are identified.17 p

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

The Conformational Gymnastics of the Escherichia Coli SecA Molecular Machine and its Interactions with Signal Sequences

Protein secretion is a selective and regulated process that is essential in all organisms. In bacteria the preprotein translocase SecA, either free in the cytosol or associated with the SecYEG translocon, recognizes and binds most post-translational secretory proteins containing an N-terminal signal sequence. In Gram-negative bacteria, the molecular chaperone SecB binds many of the preproteins to keep them in a translocation-competent state. Subsequently, SecB delivers the preproteins to the translocon-associated SecA, which binds the signal sequence and also interacts with mature regions of the preprotein. After the preprotein/SecA/SecYEG complex has formed, the energy derived from ATP hydrolysis by SecA coupled with the proton motive force drives the insertion of the preprotein through the translocon pore. During the translocation reaction, the conformation of SecA dramatically changes from an inactive closed form (c-SecA) to one more active and open states. The various crystal structures of SecA have provided many structural details about c-SecA. The recent low resolution crystal structure of a fragment of SecA bound to SecYEG (Zimmer et al., 2008) has provided a starting point for structural analysis of the active and open conformation of SecA. Previous work in our laboratory demonstrated that an N-terminal proteolytic fragment of SecA, SecA64, is an activated form of SecA that with higher affinity signal peptides better than c-SecA (Triplett et al., 2001). To correlate the SecA64 results with full-length SecA, we determined that SecA in the presence of low concentrations of urea has an enhanced ATPase activity similar to translocation level, which is comparable to what was observed with SecA64. Analysis by CD and Trp fluorescence indicates the presence of an intermediate at 2.2 M urea at 22ºC (termed u-SecA). Using limited proteolysis, we determined that u-SecA is in an protease-sensitive conformation that mimics the translocation-active form of SecA. These structural rearrangements occur primarily in the C-terminal one-third of the protein. Next, we sought to understand the signal sequence interactions with c-SecA and translocation-active u-SecA. Using a photoactivatable cross-linking approach along with limited proteolysis, two-dimensional gels, and domain mapping with region-specific antibodies, the signal sequence-binding site was mapped to the interface of NBF II, PPXD, and HSD. The site is the same in both forms of SecA but in our data suggests u-SecA that the binding groove as expanded

NACA Technical Notes

Report presenting three modifications to the leading-edge region of the NACA 64A010 airfoil section, which were designed and tested two-dimensionally at both low and high subsonic speeds. The modifications increased the low-speed maximum lift coefficient of the symmetrical reference section, largely by increasing the angle of attack at which stall occurred