Organization Of Constituents Research Articles

Evaluation of diffusion coefficient of P-glycoprotein molecules labeled with green fluorescent protein in living cell membrane.

The movement of individual molecules inside living cells has recently been resolved by single particles tracking (SPT) method which is a powerful tool for probing the organization and dynamics of the plasma membrane constituents. Effective treatment of metastatic cancers requires the toxic chemotherapy, however this therapy leads to the multidrug resistance phenomenon of the cancer cells, in which the cancer cells resist simultaneously to different drugs with different targets and chemical structures. P-glycoprotein molecules which are responsible for multidrug resistance of many cancer cells have been studied by cancer biologists during past haft of century. Recently, advances in laser and detector technologies have enabled single fluorophores to be visualized in aqueous solution. The development of the total internal reflection fluorescent microscope (TIRFM) provided means to monitor dynamic molecular localization in living cells. In this paper, P-glycoproteins (PGP) were labeled with green fluorescent protein (GFP) in living cell membrane of Madin-Darby canine kidney (MDCK) and the TIRFM method was used to characterize the dynamics of individual protein molecules on the surface of living cells. An evanescent field was produced by a totally internally reflected and a laser beam was illuminated the glass-water interface. GFP-PGP proteins that entered the evanescent field appeared as individual spots of light which were slighter than background fluorescence. We obtained high-resolution images and diffusion maps of membrane proteins on cell surface and showed the local diffusion properties of specific proteins on single cells. We also determined the diffusion coefficient, the mean square displacement and the average velocity of the tracked particles, as well as the heterogeneity of the cell environment. This study enabled us to understand single-molecule features in living cell and measure the diffusion kinetics of membrane-bound molecules.

Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer.

ObjectiveGastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. Insulin-like growth-factor-binding proteins (IGFBPs) were initially identified as passive inhibitors that combined with insulin-like growth factors (IGFs) in serum. However, more recent data have shown that they have different expression patterns and a variety of functions in the development and occurrence of cancers. Thus, their various roles in cancer still need to be elucidated. This study aimed to explore the IGFBPs and their prognostic value as markers in gastric cancer.MethodsOncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier Plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential expression, prognostic value, genetic alteration, and association with immune cell infiltration of IGFPBs in gastric cancer.ResultsExpression levels of IGFBP3, IGFBP4, and IGFBP7 were significantly elevated in gastric cancer tissues, whereas those of IGFBP1 were reduced in normal tissues. IGFBP1/5/7 expression was significantly associated with overall survival whereas IGFBP6/7 expression was significantly correlated with disease-free survival in gastric cancer patients. IGFBP3/5/6/7 were associated with clinical cancer stage. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that IGFBP3/5/7 were mainly enriched in focal adhesion, extracellular matrix structural constituent, cell-substratist junction, extracellular structure, and matrix organization. Stomach adenocarcinoma (STAD) and gastric cancer had more IGFBP1–7 mutations than other tumor types. Hub gene analysis showed that TP53 and IGF2 expression was significantly elevated in STAD patients; PLG, PAPPA, AFP, and CYR61 were associated with overall survival rate; and IGFALS, PLG, IGF1, AHSG, and FN1 were associated with disease-free survival. Finally, IGFBP3–7 were all associated with cancer-associated fibroblast infiltration in STAD, colon adenocarcinoma, and rectal adenocarcinoma.ConclusionOur study provides a comprehensive analysis and selection of IGFBPs as prognostic biomarkers in STAD. This was the first bioinformatic analysis study to describe the involvement of IGFBPs, especially IGFBP7, in gastric cancer development through the extracellular matrix.

Differential Polarization Imaging of Plant Cells. Mapping the Anisotropy of Cell Walls and Chloroplasts.

Modern light microscopy imaging techniques have substantially advanced our knowledge about the ultrastructure of plant cells and their organelles. Laser-scanning microscopy and digital light microscopy imaging techniques, in general—in addition to their high sensitivity, fast data acquisition, and great versatility of 2D–4D image analyses—also opened the technical possibilities to combine microscopy imaging with spectroscopic measurements. In this review, we focus our attention on differential polarization (DP) imaging techniques and on their applications on plant cell walls and chloroplasts, and show how these techniques provided unique and quantitative information on the anisotropic molecular organization of plant cell constituents: (i) We briefly describe how laser-scanning microscopes (LSMs) and the enhanced-resolution Re-scan Confocal Microscope (RCM of Confocal.nl Ltd. Amsterdam, Netherlands) can be equipped with DP attachments—making them capable of measuring different polarization spectroscopy parameters, parallel with the ‘conventional’ intensity imaging. (ii) We show examples of different faces of the strong anisotropic molecular organization of chloroplast thylakoid membranes. (iii) We illustrate the use of DP imaging of cell walls from a variety of wood samples and demonstrate the use of quantitative analysis. (iv) Finally, we outline the perspectives of further technical developments of micro-spectropolarimetry imaging and its use in plant cell studies.

Four Islands EcoHealth Network: an Australasian initiative building synergies between the restoration of ecosystems and human health

Reversing the spiraling trajectory of ecological degradation requires a profound paradigm shift that more explicitly links human and ecosystem health. Human health, as used here, includes well‐being and livelihoods, which are largely determined by socio‐cultural, economic, and environmental drivers. Ecological restoration and related restorative activities can contribute substantially to human health. However, restoration projects differ widely and health impacts can be difficult to quantify. Interdisciplinary restoration networks are important for investigating the complex socio‐cultural, economic, and environmental dynamics that characterize restoration practice and related health outcomes. We present the Four Islands EcoHealth Network (FIEN) as an exemplar for establishing interdisciplinary project connectivity to clarify intersections between ecosystem restoration and human health. FIEN is a cooperative regional restoration network within Australia and Aotearoa New Zealand which aims to research and devise strategies for restoration to simultaneously improve human health and repair native ecosystems. FIEN will operate collaboratively at local and regional scales to expand interdisciplinary research and outreach by linking research with experience‐based and Traditional Ecological Knowledge‐based restoration activities. The group's primary focus is value‐adding to the efforts of its constituent organizations by sharing expertise and methodologies to enable large‐scale analysis and comparison across adjacent regions, ultimately disseminating collective results through impactful science communication. We consider explicitly linking human and ecosystem health the best way forward to reverse the current downward trajectory of ecological degradation and declining human health, and propose FIEN as an approach which other restoration‐minded groups and coalitions might follow.

News, Programs, Publications, and Awards

News, Programs, Publications, and Awards

When convenience trumps quality of care: A population-based survey on direct to consumer orthodontics

Since the introduction of direct to consumer orthodontic (DTCO) products in the last decade, these products have been increasing in popularity among orthodontic patients. The purpose of the current article was to assess the populations' perception of DTCOs and to examine various factors that may influence their decision in choosing treatment with DTCO products. A cross-sectional population-based survey was conducted in the United States. The 35-question survey was disseminated through Amazon Mechanical Turk (Amazon.com, Inc, Seattle, Wash), and participants were asked questions about their demographics, their perceptions of DTCOs, orthodontists, and factors that may influence their decision should they decide to pursue orthodontic treatment. Pearson's correlations were conducted to assess the association between various factors and the participants' likelihood to choose DTCO products. A total of 1441 subjects participated in the study. More than 83% of the participants have considered pursuing orthodontic treatment to some extent. Twenty-three percent reported that they would highly likely choose DTCO products. The majority of participants reported convenience to be the greatest benefit of DTCOs, followed by cost. The majority of responses seemed to favor DTCOs. Forty-seven percent reported that the coronavirus disease 2019 pandemic did not affect their preference, whereas 26.6% reported to be more likely to pursue DTCOs because of the pandemic. The majority of participants seemed to perceive DTCOs as a viable alternative for seeking orthodontic care. Although participants had concerns about the coronavirus disease 2019 pandemic, results showed that the pandemic might not significantly affect the preferences. Orthodontists and their constituent organizations may consider more robust awareness and advocacy campaigns to educate the population about orthodontic treatment and the benefits of pursuing treatment with a trained orthodontist.

Intrinsic properties of osteomalacia bone evaluated by nanoindentation and FTIRM analysis

Osteomalacia is a pathological bone condition consisting in a deficient primary mineralization of the matrix, leading to an accumulation of osteoid tissue and reduced bone mechanical strength. The amounts, properties and organization of bone constituents at tissue level, are known to influence its mechanical properties. It is then important to investigate the relationship between mechanical behavior and tissue composition at this scale in order to provide a better understanding of bone fragility mechanisms associates with this pathology.Our purpose was to analyze the links between ultra-structural properties and the mechanical behavior of this pathological bone tissue (osteomalacia) at tissue level (mineral and osteoid separately, or global). Four bone biopsies were taken from patients with osteomalacia, and subsequently embedded, sectioned, and polished. Then nanoindentation tests were performed to determine local elastic modulus E, contact hardness Hc and true hardness H for both mineralized and organic bone phases and for the global bone. The creep of the bone was also studied using a special indentation procedure in order to assess visco-elasto-plastic (creep) bone behavior. This allowed a detailed study of the rheological models adapted to the bone and to calculate the parameters associated to a Burgers model. Ultra-structural parameters were measured by Fourier Transform InfraRed Microspectroscopy (FTIRM) on the same position as the indents.The use of rheological models confirmed a significant contribution from the organic phase on the viscous character of bone tissue. The elastic E and the elasto-plastic Hc deformation were correlated to both collagen maturity and Mineral/Matrix. The pure plastic deformation H was only correlated to the mineral phase. Our data show that mineral phase greatly affects mechanical variables (moduli and viscosities) and that organic phase (as illustrated in osteoid tissue) may play an important role in the creep behavior of bone. In conclusion, this study brings mechanical and physicochemical values for osteoid and mineral phases.

Physical traits of cancer

Cancer The biological and physical properties of tumors contribute to their growth and to treatment outcome. Although intense research efforts have helped to delineate cancer biology, the physics of cancer has only emerged in relatively recent times as a key area of research. Nia et al. reviewed the physical features that are common to tumors and that limit successful treatment: solid stresses, interstitial fluid pressure, stiffness (rigidity), and architecture and organization of tumor constituents. The authors provide a conceptual framework and discuss the origins of these distinct physical traits of cancer and how they enable and synergize with aberrant cancer biology to fuel cancer initiation, progression, immune evasion, and treatment resistance. Science , this issue p. [eaaz0868][1] [1]: /lookup/doi/10.1126/science.aaz0868

Physical traits of cancer

The role of the physical microenvironment in tumor development, progression, metastasis, and treatment is gaining appreciation. The emerging multidisciplinary field of the physical sciences of cancer is now embraced by engineers, physicists, cell biologists, developmental biologists, tumor biologists, and oncologists attempting to understand how physical parameters and processes affect cancer progression and treatment. Discoveries in this field are starting to be translated into new therapeutic strategies for cancer. In this Review, we propose four physical traits of tumors that contribute to tumor progression and treatment resistance: (i) elevated solid stresses (compression and tension), (ii) elevated interstitial fluid pressure, (iii) altered material properties (for example, increased tissue stiffness, which historically has been used to detect cancer by palpation), and (iv) altered physical microarchitecture. After defining these physical traits, we discuss their causes, consequences, and how they complement the biological hallmarks of cancer.

Immanence in «Being and time»

The purpose of this article is to lay out an attempt to analyze the concept of immanence in the famous work of Martin Heidegger «Being and time». Undoubtedly, as we will remind throughout the entire work, the very concept of immanence, taken in the strictest sense of the word, cannot be applied to the philosophical calculations of Heideggerian philosophy without, in one way or another, changing the very essential foundations of his philosophy. However, our analysis is aimed, without touching on these grounds, to trace a possible way to clarify those conceptual premises that could reveal, albeit not in an explicit form, the inner structure of Heidegger's philosophical project, or, to be more precise, the way by which within the textual structure itself (and, accordingly, the conceptual and terminological structure), the process of the internal genesis of the immanent space takes place, expressed in the correlative organization of essential constituents, which have the decisive importance both for Heidegger and for our project — being and entity.

The structural and ultrastructural organization of the cellular constituents of the trunk kidney of grass carp (Ctenopharyngodon idella).

The trunk kidney of grass carp mainly consisted of renal tubules with a few interstitial hematopoietic tissues. The component structure of fish nephron markedly varies between different species of fish. The nephron of grass carp consisted of morphologically distinct segments; renal corpuscles, neck segment, proximal, intermediate, distal, and collecting tubules. The glomerulus of renal corpuscles mainly composed of mesangial cells and well-developed podocytes that extended their processes to the endothelium of glomerular capillaries forming the filtration barrier. The podocytes expressed both α-SMA and the transforming growth factor gene, TGF-β. The proximal convoluted tubules (PCTs) expressed α-SMA iNOS2, and TGF-β. The cytoplasm of PCT was rich in mitochondria and rER, in addition to the presence of well-developed basolateral tubular system and apical brush borders. Collecting tubules distributed throughout the kidney and lined by principal and flask cells. The interstitial hemopoietic tissues contained iNOS2 -positive polymorphic granulocytes, CD3-positive T lymphocytes, rodlet cells, dendritic cells, macrophages, melanomacrophage centers, and telocytes. This study described for the first time the cellular components of the nephron and its associated hemopoietic tissues that can act as a basis for studying the structural changes that may occur in the kidney of grass carp during water salinitiy, environmental, or experimental conditions.

FEMA GRAS assessment of natural flavor complexes: Lavender, Guaiac Coriander-derived and related flavoring ingredients

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, fifth in the series, evaluates the safety of NFCs containing linalool and/or other characteristic mono- and sesquiterpenoid tertiary alcohols and esters using the safety evaluation procedure published by the FEMA Expert Panel in 2005 and updated in 2018. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of the chemical constituents of each NFC into well-defined congeneric groups. The safety of each NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of both the constituent congeneric groups and the NFCs. Sixteen NFCs, derived from the Lavandula, Aniba, Elettaria, Daucus, Salvia, Coriandrum, Ribes, Guaiacum/Bulnesia, Citrus, Pogostemon, Melaleuca and Michelia genera, were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.

The World Federation of Hemophilia Annual Global Survey 1999-2018.

The World Federation of Hemophilia (WFH) strives to achieve care for all patients with inherited bleeding disorders through research, advocacy, capacity building and education. The WFH developed and implemented the Annual Global Survey (AGS), through which comprehensive demographic and treatment data on bleeding disorders are collected each year from its constituent non-governmental national organizations. To describe the development, methodology and achievements of the WFH AGS over the past 20years. The AGS is a yearly cross-sectional survey. Data are collected using a standardized form (available online and on paper), quality checked and reviewed, and published in English, French and Spanish. Over time, the AGS has been modified in response to changes in treatment landscape or emerging new issues. Over the past 20years, the AGS has reported an increase in the number of countries participating in the survey, a tripling in the number of people identified with rare bleeding disorders and an increase in the amount of factor used to treat people with haemophilia. Yet, a large treatment inequity gap still exists across the globe. In response to this gap, the WFH has analysed the AGS reports which has stimulated further development in quality of care indicators, estimates of the global prevalence of haemophilia, patient-level data collection efforts like the World Bleeding Disorders Registry and the Gene Therapy Registry. The AGS has provided evidence to support research, programme planning and development activities of the WFH.

Submicroscopic changes of periodont in simulation of chronic opioid influence during ten weeks and medicamental correction

Prolonged opioid abuse provokes lesions of the tooth-jaw system, making it difficult to carry out differential diagnosis and treatment of pathology of organs and tissues, of the oral cavity.The purpose of the work — to find out the peculiarities of ultrastructural organization of periodontal tissues with the medication corrective action of pentoxifylline and ceftriaxone against the background of a ten-week opioid exposure.Material and methods. The studies were performed on white adult male rats (22), who were administered intramuscularly opioid analgesic nalbuphine for 70 days, gradually increasing the dose every 2 weeks (from 0.212 to 0.283 mg/kg). Pentoxifylline (2.857 mg/kg) for 4 weeks and ceftriaxone (2.86 mg/kg) for 11 days were used to correct pathological changes in the periodontium. For electron microscopic examination, we used fragments of periodontal tissues in the gum region, and ultrathin sections were made according to conventional methods.Results. Submicroscopically, in the epithelial cells of the mucous membrane of the rats revealed shallow invasions of carioma, swelling of mitochondria, indistinctly structured intercellular contacts, available nuclei and euchromatin in the karyoplasm. In the periodontal lesions of collagen fibril ordering are present, leukocyte infiltration, tissue basophils and macrophages are degranulated. There is a certain improvement in the structural organization of the components of the microcirculatory bed, erythrocytes are predominantly present in the lumens of the blood capillaries, and no sludge effect has been detected.Conclusions. The use of the combined action of drugs pentoxifylline and ceftriaxone causes a protective effect, favorably affecting the microcirculation, which indicates a slight positive dynamics of the ultrastructural organization of constituents of periodontal components against the background of long-acting opioids.

Thinking- Skins

Thinking- Skins

FEMA GRAS assessment of natural flavor complexes: Cinnamomum and Myroxylon-derived flavoring ingredients

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, third in the series, considers NFCs composed primarily of constituents with the 3-phenyl-2-propenyl or a cinnamyl functional group, using the procedure outlined in 2005 and updated in 2018 to evaluate the safety of naturally-occurring mixtures for their intended use as flavor ingredients. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. Six NFCs from the Myroxylon and Cinnamomum genera, Balsam Oil, Peru (FEMA 2117), Tolu Balsam Extract (FEMA 3069), Cassia Bark Extract (FEMA 2257), Cassia Bark Oil (FEMA 2258), Cinnamon Bark Extract (FEMA 2290) and Cinnamon Bark Oil (FEMA 2291) were evaluated and affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients.

Ukrainian World Tribune

The article refers to the World Congress of Free Ukrainians (WCFU), founded in New York in November 1967. The WCFU united 150 Ukrainian public, political and faith-based organizations. The elected Presidium of the Congress established special committees, which began to work on the coordination of Ukrainian organizations in the West regarding the provision of assistance to Ukrainian refugees and communities in the Americas, Western Europe and Australia, protection of human rights and of political prisoners of Ukrainian descent in the USSR, development of Ukrainian education and culture in the expatriate environment, etc. The WCFU opened its information office at the UN, which brought to the attention of diplomats from different countries the facts about the struggle of the Congress for an independent Ukraine, information about Ukrainian political prisoners, the russification process in Ukraine and Holodomor of 1932–1933. Owing to this effective influence, Canada, with its powerful and numerous Ukrainian community, was the first in the Western world to recognize the independence of Ukraine. In 1991, the WCFU organized a mass demonstration in front of the White House in Washington for the recognition of the young Ukrainian state. In December of the same year, the Congress, together with the Ukrainian World Foundation, announced the creation of the Ukrainian Reconstruction Fund. Since then, this organization has gradually become one of the consistent lobbyists of Ukraine’s national interests in the world. Having changed its name to the Ukrainian World Congress (UWC), it is constantly engaged in the establishment of a positive international image of Ukraine, promotion of its rich historical heritage as well as compelling changes in its society. At the same time, in the circles of this international association there is a certain disappointment with the social and economic situation in Ukraine and lack of real results in the fight against corruption. However, the UWC seeks to contribute to the further development of the historical homeland. Today UWC has an extensive network of constituent organizations and maintains relations with Ukrainian communities in 61 countries. Keywords: WCFU, Ukrainian World Congress, New York, Canada, historical homeland.

To Pay or Not to Pay Community Preceptors? That Is a Question …

Phenomenon: Pairing medical students with community-based preceptors has provided unique medical education advantages. However, due to an increase in the number of M.D.-granting medical schools and medical school class sizes, academic medical institutions have struggled to recruit community preceptors to teach their students. This task has been made more difficult due to rising pressures upon institutions and clinicians—for example, increased productivity demands, greater volume and oversight of electronic health record documentation, and competition for community preceptors from both D.O. and non-U.S.-based medical schools. Although academic institutions have historically relied largely on altruistic motives and intrinsic rewards to actively engage and retain community-based preceptors, alternative models have arisen, chiefly those in which community-based preceptors are explicitly compensated for teaching. Approach: To study this phenomenon, representatives of the Alliance for Clinical Education developed and deployed a 31-item survey accompanied with a subset of free text questions to the collective membership of its 8-member constituent organizations. Survey questions explored if community preceptors were compensated indirectly or directly and what types of compensation were provided, if any. There were 188 surveys analyzed, with an estimated response rate of 18.2%. Findings: Twenty-six percent of respondents indicated they compensate community preceptors directly and/or indirectly. Respondents discussed their motivations for payment (or nonpayment), mechanisms for paying, aspirations to pay, and expectations of the recipient. No statistically significant association was found when comparing responses of paid versus not paid by region. Free text responses provided additional insight regarding payment considerations, institutional competition, recruitment/retention, recognition, and education issues. Insights: Increasingly, medical schools are finding it necessary to provide funding for community preceptors in order to retain them. New creative forms of compensation to community preceptors may prove important in the future for this vital aspect of medical student education.

FEMA GRAS assessment of natural flavor complexes: Citrus-derived flavoring ingredients

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA) initiated a re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavoring ingredients. This publication is the first in a series and summarizes the evaluation of 54 Citrus-derived NFCs using the procedure outlined in Smith et al. (2005) and updated in Cohen et al. (2018) to evaluate the safety of naturally-occurring mixtures for their intended use as flavoring ingredients. The procedure relies on a complete chemical characterization of each NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. As a result of the application of the procedure, 54 natural flavor complexes derived from botanicals of the Citrus genus were affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.

Large-Scale Cortical Networks for Hierarchical Prediction and Prediction Error in the Primate Brain

According to predictive-coding theory, cortical areas continuously generate and update predictions of sensory inputs at different hierarchical levels and emit prediction errors when the predicted and actual inputs differ. However, predictions and prediction errors are simultaneous and interdependent processes, making it difficult to disentangle their constituent neural network organization. Here, we test the theory by using high-density electrocorticography (ECoG) in monkeys during an auditory "local-global" paradigm in which the temporal regularities of the stimuli were controlled at two hierarchical levels. We decomposed the broadband data and identified lower- and higher-level prediction-error signals in early auditory cortex and anterior temporal cortex, respectively, and a prediction-update signal sent from prefrontal cortex back to temporal cortex. The prediction-error and prediction-update signals were transmitted via γ (>40Hz) and α/β (<30Hz) oscillations, respectively. Our findings provide strong support for hierarchical predictive coding and outline how it is dynamically implemented using distinct cortical areas and frequencies.