Special issue: left-right asymmetry and cardiac morphogenesis

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Commensurate Growth of Magnetite Microinclusions in Olivine under Mantle Conditions

Magnetite-bearing multiphase solid inclusions hosted in metamorphic olivine have been interpreted as final products of the trapping of the aqueous fluid produced by the subduction-zone dehydration of former serpentinites. We provide here a careful analysis performed by microfocus single-crystal X-ray diffraction of inclusions found in harzburgites from the Almirez Complex (Bétic Cordillera, Spain) to determine the occurrence of preferential crystallographic orientation relationships between the olivine host and the magnetite inclusion. The results demonstrate that the magnetite–olivine interface selectively displays parallelism between crystallographic planes (111) and (100) and between crystallographic directions ⟨110⟩ and ⟨011⟩, respectively. This evidence points to a clear epitaxial growth of magnetite on olivine. The calculation of the geometrical misfit between the two lattices in contact as a function of their relative azimuthal orientation shows that, under the aforementioned reciprocal orientation, a perfect commensurism is achieved; i.e., all of the nodes of the magnetite lattice coincide with nodes of the olivine lattice. This particular relationship must be interpreted as a unique occurrence, playing a fundamental role in favoring the heterogeneous nucleation of magnetite on olivine

Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Label-free electrochemical immunosensor as a reliable point-of-care device for the detection of Interleukin-6 in serum samples from patients with psoriasis

interleukin-6 (IL-6) plays a crucial role in autoimmunity and chronic inflammation. this study aims to develop a low-cost, simple-to-manufacture, and user-friendly label-free electrochemical point-of-care device for the rapid detection of IL-6 in patients with psoriasis. precisely, a sandwich-based format immunosensor was developed using two primary antibodies (mAb-IL6 clone-5 and clone-7) and screen-printed electrodes modified with an inexpensive recycling electrochemical enhancing material, called biochar. mAb-IL6 clone-5 was used as a covalently immobilized capture bioreceptor on modified electrodes, and mAb-IL6 clone-7 was used to recognize the immunocomplex (Anti-IL6 clone-5 and IL-6) and form the sandwich. cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to conduct electrochemical characterization of the layer-by-layer assembly of the immunosensor, while square wave voltammetry (SWV) was used to perform the sensing. the developed immunosensor demonstrated robust analytical performance in buffer solution, with a wide linear range (LR) by varying from 2 to 250 pg/mL, a good limit of detection (LOD) of 0.78 pg/mL and reproducibility (RSD<7%). In addition, a spectrophotometric ELISA kit was employed to validate the results obtained with the label-free device by analyzing twenty-five serum samples from control and patients affected by psoriasis. a strong correlation in terms of pg/mL concentration of IL-6 was found comparing the two methods, with the advantage for our label-free biosensor of an ease use and a quicker detection time. based on IL-6 levels, the proposed immunosensor is a dependable, non-invasive screening device capable of predicting disease onset, progression, and treatment efficacy

Primary spinel + chlorite inclusions in mantle garnet formed at ultrahigh-pressure

Multiphase inclusions represent microenvironments where the interaction between fluid and host mineral is preserved during the rock geological path. Under its peculiar chemical-physical constraints, the entrapped solute-rich fluid might follow a crystallisation mechanism which is not predictable through simple equilibrium arguments. In this letter, by the modelling of solid-solution equilibrium and the application of principles of mass conservation, we demonstrate that cavities in mantle garnet filled with slab-derived fluids can re-equilibrate to a pyrope + spinel + chlorite assemblage at the same high P-T of their formation. The basis of this occurrence is a dissolution-reprecipitation mechanism, triggered by a dilute, non-equilibrated slab fluid

Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux

Lymph node metastases displaying lower Ki-67 immunostaining activity than the primary breast cancer

The aim of the study was to verify by Ki-67 immunostaining if any difference exists in the cell proliferating fraction between primary breast tumors (PTs) and matching positive axillary lymph nodes (ALNs). PATIENTS AND METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 160 node-positive breast carcinomas and in their respective lymph node metastases. RESULTS: An increase of Ki-67 immunoreactive cells in ALN compared with that of PTs was observed in 84% of cases (ALN: mean 17%, PTs: mean 8%; p < 0.001), whereas 16% of the cases showed Ki-67 value two to six times lower in the ALNs than in the corresponding PTs (ALN: mean 3.2%, PTs mean 12.5%; p < 0.005). The decrease of Ki-67 positive cells in the ALN was independent from the histotype and the histological grade of the tumor. CONCLUSION: A different cell proliferation fraction between PTs and matching positive ALNs was demonstrated and underlined that the existence of a group of patients with decreased number of Ki-67 immunoreactive cells in lymph node metastases compared with that of the primary tumors could be taken into account in the choice of therapeutic strategy

Unveiling the complexity of japanese metallic threads

In the framework of an extensive survey campaign on a collection of Japanese samurai armors, metallic threads from different parts of the traditional equipment were studied by several analytical techniques. The collection of armors belongs to Museo delle Culture (Lugano, Switzerland) and it is composed of ten elements, which date back from the 15th to 20th century. Metallic threads under study come from six of ten elements of the collection and represent a complex and unique multimaterial, which shows specific characteristics in Japanese tradition (kinran). The multianalytical approach based on ATR-FTIR spectroscopy and SEM-EDX analysis, together with a careful observation with optical and digital microscopy, permitted to obtain a complete characterization of materials, which have shown a great variability in metal foils and in organic adhesives (urushi, animal glue, starch). Gold and silver turned out to be not so largely used as scholars thought, while aluminum showed a great diffusion. Within the collection of analyzed armors, the obtained results allowed us for the first time to get a complete comprehension of materials and techniques used by Japanese craftsmen, and to observe differences in the quality of the materials and in manufacture technology over the centuries