MS 150 Guide to the Richard S. Ruiz, MD Papers (1925-2007)

The Richard S. Ruiz, MD, papers, MS 150, includes materials from 1925 through 2007 related to the Hermann Eye Center and Memorial Hermann Hospital. Dr. Ruiz was the Chief of Ophthalmology at Hermann Hospital who built up and improved the teaching faculty at Hermann Hospital and the one with the vision for the Hermann Eye Center and made it possible. This collection encompasses this period of time in Dr. Ruiz\u27s career. See more at MS 150

Zannichellia contorta

This species is native to southern, central and eastern Spain, with an old record from the Atlas Mountains in northern Morocco requiring confirmation. The species is very sensitive to eutrophication and deterioration of water quality. The Area of Occupancy (AOO) has been estimated to be less than 500 km2 based on confirmed records and knowledge that its habitat is in continuous decline and at least 40% of the known localities have disappeared, especially in southern Spain. Moreover, an ongoing continuing decline in AOO, habitat quality and number of subpopulations of this species due to the increase in nutrients concentration from waters of the streams where it lives, which stops its growth, has been observed. The same process of habitat deterioration is happening in central and eastern Spain. The population of this species is severely fragmented with more than half of its subpopulations being isolated with no exchange possibilities and suspected to have reached no viable levels. It therefore qualifies to be listed in the category Endangered (EN B2ab(ii,iii,iv)) in the Mediterranean region. Resource and habitat protection and site management are needed. Other recommended conservation measures are ex situ conservation, population and distribution research, and habitat and population monitoring

A precise characterisation of the top quark electro-weak vertices at the ILC

Top quark production in the process $e^+e^- \to t\bar{t}$ at a future linear electron positron collider with polarised beams is a powerful tool to determine indirectly the scale of new physics. The presented study, based on a detailed simulation of the ILD detector concept, assumes a centre-of-mass energy of $\sqrt{s}=500\,$GeV and a luminosity of $\mathcal{L}=500\,{\rm fb}^{-1}$ equally shared between the incoming beam polarisations of $\mathcal{P}_{e^-}, \mathcal{P}_{e^+} =\pm0.8,\mp0.3$. Events are selected in which the top pair decays semi-leptonically and the cross sections and the forward-backward asymmetries are determined. Based on these results, the vector, axial vector and tensorial $CP$ conserving couplings are extracted separately for the photon and the $Z^0$ component. With the expected precision, a large number of models in which the top quark acts as a messenger to new physics can be distinguished with many standard deviations. This will dramatically improve expectations from e.g. the LHC for electro-weak couplings of the top quark.Comment: This work is an update of arXiv:1307.8102, minor changes w.r.t. v1 (typos, wrong grammar, incomplete sentences etc.

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent

Vpu Antagonizes BST-2–Mediated Restriction of HIV-1 Release via β-TrCP and Endo-Lysosomal Trafficking

The interferon-induced transmembrane protein BST-2/CD317 (tetherin) restricts the release of diverse enveloped viruses from infected cells. The HIV-1 accessory protein Vpu antagonizes this restriction by an unknown mechanism that likely involves the down-regulation of BST-2 from the cell surface. Here, we show that the optimal removal of BST-2 from the plasma membrane by Vpu requires the cellular protein β-TrCP, a substrate adaptor for a multi-subunit SCF E3 ubiquitin ligase complex and a known Vpu-interacting protein. β-TrCP is also required for the optimal enhancement of virion-release by Vpu. Mutations in the DSGxxS β-TrCP binding-motif of Vpu impair both the down-regulation of BST-2 and the enhancement of virion-release. Such mutations also confer dominant-negative activity, consistent with a model in which Vpu links BST-2 to β-TrCP. Optimal down-regulation of BST-2 from the cell surface by Vpu also requires the endocytic clathrin adaptor AP-2, although the rate of endocytosis is not increased; these data suggest that Vpu induces post-endocytic membrane trafficking events whose net effect is the removal of BST-2 from the cell surface. In addition to its marked effect on cell-surface levels, Vpu modestly decreases the total cellular levels of BST-2. The decreases in cell-surface and intracellular BST-2 are inhibited by bafilomycin A1, an inhibitor of endosomal acidification; these data suggest that Vpu induces late endosomal targeting and partial degradation of BST-2 in lysosomes. The Vpu-mediated decrease in surface expression is associated with reduced co-localization of BST-2 and the virion protein Gag along the plasma membrane. Together, the data support a model in which Vpu co-opts the β-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor

Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers

The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5high centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67+ AID+ CXCR4+ centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites iden tified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor

Mapping the cellular landscape of Atlantic salmon head kidney by single cell and single nucleus transcriptomics

Single-cell transcriptomics is the current gold standard for global gene expression profiling, not only in mammals and model species, but also in non-model fish species. This is a rapidly expanding field, creating a deeper understanding of tissue heterogeneity and the distinct functions of individual cells, making it possible to explore the complexities of immunology and gene expression on a highly resolved level. In this study, we compared two single cell transcriptomic approaches to investigate cellular heterogeneity within the head kidney of healthy farmed Atlantic salmon (Salmo salar). We compared 14,149 cell transcriptomes assayed by single cell RNA-seq (scRNA-seq) with 18,067 nuclei transcriptomes captured by single nucleus RNA-Seq (snRNA-seq). Both approaches detected eight major cell populations in common: granulocytes, heamatopoietic stem cells, erythrocytes, mononuclear phagocytes, thrombocytes, B cells, NK-like cells, and T cells. Four additional cell types, endothelial, epithelial, interrenal, and mesenchymal cells, were detected in the snRNA-seq dataset, but appeared to be lost during preparation of the single cell suspension submitted for scRNA-seq library generation. We identified additional heterogeneity and subpopulations within the B cells, T cells, and endothelial cells, and revealed developmental trajectories of heamatopoietic stem cells into differentiated granulocyte and mononuclear phagocyte populations. Gene expression profiles of B cell subtypes revealed distinct IgM and IgT-skewed resting B cell lineages and provided insights into the regulation of B cell lymphopoiesis. The analysis revealed eleven T cell sub-populations, displaying a level of T cell heterogeneity in salmon head kidney comparable to that observed in mammals, including distinct subsets of cd4/cd8-negative T cells, such as tcrγ positive, progenitor-like, and cytotoxic cells. Although snRNA-seq and scRNA-seq were both useful to resolve cell type-specific expression in the Atlantic salmon head kidney, the snRNA-seq pipeline was overall more robust in identifying several cell types and subpopulations. While scRNA-seq displayed higher levels of ribosomal and mitochondrial genes, snRNA-seq captured more transcription factor genes. However, only scRNA-seq-generated data was useful for cell trajectory inference within the myeloid lineage. In conclusion, this study systematically outlines the relative merits of scRNA-seq and snRNA-seq in Atlantic salmon, enhances understanding of teleost immune cell lineages, and provides a comprehensive list of markers for identifying major cell populations in the head kidney with significant immune relevance.</p

Mapping the cellular landscape of Atlantic salmon head kidney by single cell and single nucleus transcriptomics

The study was funded by grants from the Research Council Norway (ID:302191), the University of Edinburgh's Data Driven Innovation Initiative (Scottish Funding Council Beacon ‘Building Back Better’ Call), and the Biotechnology and Biological Sciences Research Council, including the institutional strategic programme grants BBS/E/D/10002071, BBS/E/RL/230001C, BBS/E/D/20002174, BBS/E/RL/230002B, and the responsive mode grants BB/W005859/1 and BB/W008564/1. NH is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (ref. 219542/Z/19/Z). UG is supported by the Research Council of Norway (ID:274635).Peer reviewe

Flotation Immunoassay: Masking the Signal from Free Reporters in Sandwich Immunoassays

In this work, we demonstrate that signal-masking reagents together with appropriate capture antibody carriers can eliminate the washing steps in sandwich immunoassays. A flotation immunoassay (FI) platform was developed with horseradish peroxidase chemiluminescence as the reporter system, the dye Brilliant Blue FCF as the signal-masking reagent, and buoyant silica micro-bubbles as the capture antibody carriers. Only reporters captured on micro-bubbles float above the dye and become visible in an analyte-dependent manner. These FIs are capable of detecting proteins down to attomole levels and as few as 106 virus particles. This signal-masking strategy represents a novel approach to simple, sensitive and quantitative immunoassays in both laboratory and point-of-care settings

On the possibility of magneto-structural correlations: detailed studies of di-nickel carboxylate complexes

A series of water-bridged dinickel complexes of the general formula [Ni&lt;sub&gt;2&lt;/sub&gt;(μ&lt;sub&gt;2&lt;/sub&gt;-OH&lt;sub&gt;2&lt;/sub&gt;)(μ2- O&lt;sub&gt;2&lt;/sub&gt;C&lt;sup&gt;t&lt;/sup&gt;Bu)&lt;sub&gt;2&lt;/sub&gt;(O&lt;sub&gt;2&lt;/sub&gt;C&lt;sup&gt;t&lt;/sup&gt;Bu)2(L)(L0)] (L = HO&lt;sub&gt;2&lt;/sub&gt;C&lt;sup&gt;t&lt;/sup&gt;Bu, L0 = HO&lt;sub&gt;2&lt;/sub&gt;C&lt;sup&gt;t&lt;/sup&gt;Bu (1), pyridine (2), 3-methylpyridine (4); L = L0 = pyridine (3), 3-methylpyridine (5)) has been synthesized and structurally characterized by X-ray crystallography. The magnetic properties have been probed by magnetometry and EPR spectroscopy, and detailed measurements show that the axial zero-field splitting, D, of the nickel(ii) ions is on the same order as the isotropic exchange interaction, J, between the nickel sites. The isotropic exchange interaction can be related to the angle between the nickel centers and the bridging water molecule, while the magnitude of D can be related to the coordination sphere at the nickel sites