Developmental Bias in Cleavage-Stage Mouse Blastomeres

BACKGROUND: The cleavage-stage mouse embryo is composed of superficially equivalent blastomeres that will generate both the embryonic inner cell mass (ICM) and the supportive trophectoderm (TE). However, it remains unsettled whether the contribution of each blastomere to these two lineages can be accounted for by chance. Addressing the question of blastomere cell fate may be of practical importance, because preimplantation genetic diagnosis requires removal of blastomeres from the early human embryo. To determine whether blastomere allocation to the two earliest lineages is random, we developed and utilized a recombination-mediated, noninvasive combinatorial fluorescent labeling method for embryonic lineage tracing. RESULTS: When we induced recombination at cleavage stages, we observed a statistically significant bias in the contribution of the resulting labeled clones to the trophectoderm or the inner cell mass in a subset of embryos. Surprisingly, we did not find a correlation between localization of clones in the embryonic and abembryonic hemispheres of the late blastocyst and their allocation to the TE and ICM, suggesting that TE-ICM bias arises separately from embryonic-abembryonic bias. Rainbow lineage tracing also allowed us to demonstrate that the bias observed in the blastocyst persists into postimplantation stages and therefore has relevance for subsequent development. CONCLUSIONS: The Rainbow transgenic mice that we describe here have allowed us to detect lineage-dependent bias in early development. They should also enable assessment of the developmental equivalence of mammalian progenitor cells in a variety of tissues.Molecular and Cellular Biolog

UV absorblayıcı madde uygulamalarında ultrasonik enerjinin etkileri

Dünyayı çevreleyen ozon tabakasının gün geçtikçe incelmesi ve UV radyasyonunun insan sağlığını olumsuz etkilemesi nedeni ile insanların UV ışınlarından korunması gereklidir. UV radyasyonun belirli oranlardaki emilimi insan sağlığına yararlı iken, aşırı olanlar cilt kanseri, güneş yanığı ve katarakt gibi hastalıklara neden olmaktadır. Giysiler UV radyasyonuna karşı koruma sağlayabilirken, bu aşamada radyasyonun dozu da önem taşımaktadır. Bu nedenle tekstil materyallerine UV absorban maddeler, liflerin üretimi esnasında ya da bitim işlemlerinde uygulanmaktadır. UV absorban maddelerin kullanılmasıyla, tekstil ürünlerinde UV ışınlarının geçirgenliğinin yoğunluk derecesi azaltılır. UV absorbanları materyale gelen ışık tarafından meydana gelen olumsuz etkileri ergeller [1,3] Bu araştırmada UV absorbanların etkileri yöntemler açısından karşılaştırılmıştır. Bu yöntemler; klasik, ultrasonik prop ve ultrasonik banyo yöntemleridir. Araştırmada %100 pamuklu bezayağı, Dimi 2/1, Dimi 3/1, ve Rips 2/1 örgüsüne sahip dört farklı dokuma kumaşa ön terbiye işlemi uygulandıktan sonra, üç farklı yönteme göre, bu kumaşlara %0 ve % l UV absorban madde uygulanmıştır. Kumaşların 290-400 nm dalga boyu aralıklarında % transmitans değerleri ölçülmüştür. Bu değerler kullanılarak UFP değerleri hesaplanmış ve UV radyasyona karşı koruma kategorileri belirlenmiştir. Ayrıca kumaşların beyazlık derecesi ölçümleri yapılmış, ölçümler için UV absorban uygulanmamış ağartılmış materyal standart kabul edilmiştir. Klasik yöntem, ultrasonik prop ve ultrasonik banyo yöntemi bu yöntemle karşılaştırılmıştır

The Influence of L-Carnitine on Oxidative Modification of LDL In Vitro

Owing to their structure and function, low-density lipoproteins (LDLs) are particularly susceptible to the oxidative modifications. To prevent against oxidative modification of LDL, L-carnitine, with endogenous small water-soluble quaternary amine possessing antioxidative properties, was used. The aim of this paper was to prove the in vitro influence of L-carnitine on the degree of oxidative modification of the lipid part (estimated by conjugated dienes, lipid hydroperoxides, and malondialdehyde levels) and the protein part (estimated by dityrosine and tryptophan levels) of LDL native and oxidized by cooper ions. The level of lipophylic LDL antioxidant—α-tocopherol was also measured

Visualizing Escherichia coli Sub-Cellular Structure Using Sparse Deconvolution Spatial Light Interference Tomography

Studying the 3D sub-cellular structure of living cells is essential to our understanding of biological function. However, tomographic imaging of live cells is challenging mainly because they are transparent, i.e., weakly scattering structures. Therefore, this type of imaging has been implemented largely using fluorescence techniques. While confocal fluorescence imaging is a common approach to achieve sectioning, it requires fluorescence probes that are often harmful to the living specimen. On the other hand, by using the intrinsic contrast of the structures it is possible to study living cells in a non-invasive manner. One method that provides high-resolution quantitative information about nanoscale structures is a broadband interferometric technique known as Spatial Light Interference Microscopy (SLIM). In addition to rendering quantitative phase information, when combined with a high numerical aperture objective, SLIM also provides excellent depth sectioning capabilities. However, like in all linear optical systems, SLIM's resolution is limited by diffraction. Here we present a novel 3D field deconvolution algorithm that exploits the sparsity of phase images and renders images with resolution beyond the diffraction limit. We employ this label-free method, called deconvolution Spatial Light Interference Tomography (dSLIT), to visualize coiled sub-cellular structures in E. coli cells which are most likely the cytoskeletal MreB protein and the division site regulating MinCDE proteins. Previously these structures have only been observed using specialized strains and plasmids and fluorescence techniques. Our results indicate that dSLIT can be employed to study such structures in a practical and non-invasive manner

A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings

BackgroundCytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)–related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. We assessed the next-generation BTK inhibitor zanubrutinib in SARS-CoV-2–infected patients with respiratory distress.MethodCohort 1 had a prospective, randomized, double-blind, placebo-controlled design; cohort 2 had a single-arm design. Adults with SARS-CoV-2 requiring hospitalization (without mechanical ventilation) were randomized in cohort 1. Those on mechanical ventilation ≤24 hours were enrolled in cohort 2. Patients were randomized 1:1 to zanubrutinib 320 mg once daily or placebo (cohort 1), or received zanubrutinib 320 mg once daily (cohort 2). Co-primary endpoints were respiratory failure-free survival rate and time to return to breathing room air at 28 days. Corollary studies to assess zanubrutinib’s impact on immune response were performed.ResultsSixty-three patients in cohort 1 received zanubrutinib (n=30) or placebo (n=33), with median treatment duration of 8.5 and 7.0 days, respectively. The median treatment duration in cohort 2 (n=4) was 13 days; all discontinued treatment early. In cohort 1, respiratory failure-free survival and the estimated rates of not returning to breathing room air by day 28 were not significantly different between treatments. Importantly, serological response to coronavirus disease 2019 (COVID-19) was not impacted by zanubrutinib. Lower levels of granulocyte colony-stimulating factor, interleukin (IL)-10, monocyte chemoattractant protein-1, IL-4, and IL-13 were observed in zanubrutinib-treated patients. Moreover, single-cell transcriptome analysis showed significant downregulation of inflammatory mediators (IL-6, IL-8, macrophage colony-stimulating factor, macrophage inflammatory protein-1α, IL-1β) and signaling pathways (JAK1, STAT3, TYK2), and activation of gamma-delta T cells in zanubrutinib-treated patients.ConclusionsMarked reduction in inflammatory signaling with preserved SARS-CoV-2 serological response was observed in hospitalized patients with COVID-19 respiratory distress receiving zanubrutinib. Despite these immunological findings, zanubrutinib did not show improvement over placebo in clinical recovery from respiratory distress. Concurrent administration of steroids and antiviral therapy to most patients may have contributed to these results. Investigation of zanubrutinib may be warranted in other settings where cytokine release and immune cell exhaustion are important.Clinical Trial Registrationhttps://www.clinicaltrials.gov/study/NCT04382586, identifier NCT04382586

Income Distribution and Economic Crises

This paper analyzes the relationship between income distribution and the severity of economic crises, where the severity is measured by the length and the depth of the recessions. Using an extensive panel dataset on income distribution and employing an event study framework, we find significant evidence that there is a negative association between the prevailing degree of income inequality and the severity of the recessions. In the case of high income countries that have bad income distribution, however, recessions are observed to be longer than the average. This observation is likely to result from the combination of the strong status-quo bias of the financially powerful income groups and the available means to redistribute towards the poor so as to help mitigate the pressures for reforms to improve income distribution via creative destruction. The longer period of recessions observed in developed countries than in less developed countries in the aftermath of the Great Recession is in support of this argument. The findings also reveal that recessions tend to be longer during the decade of the 1990s than the rest of the period studied. The evidence regarding the corrective effect on the recessions of accommodative fiscal or monetary policy stance, measured by the size of the government and the inflation rate, is observed to be only barely significant on average. Wirh regard to the impact of recessions on income distribution, the evidence in the paper indicates that the post-crises income distribution worsens significantly with the length but improves with the depth of the preceding recession. We also note that, in addition to the persistence effect, the lack of monetary discipline worsens income distribution in the postcrises period significantly