scholarly journals The cardiac nanoenvironment: form and function at the nanoscale

2021 ◽  
Author(s):  
Jashan P. Singh ◽  
Jennifer L. Young
Keyword(s):  
Large Scale ◽  
New Materials ◽  
Length Scales ◽  
Form And Function ◽  
Molecular Features ◽  
Wide Range ◽  
Physiological Homeostasis ◽  
Organ Level ◽  
And Function

AbstractMechanical forces in the cardiovascular system occur over a wide range of length scales. At the whole organ level, large scale forces drive the beating heart as a synergistic unit. On the microscale, individual cells and their surrounding extracellular matrix (ECM) exhibit dynamic reciprocity, with mechanical feedback moving bidirectionally. Finally, in the nanometer regime, molecular features of cells and the ECM show remarkable sensitivity to mechanical cues. While small, these nanoscale properties are in many cases directly responsible for the mechanosensitive signaling processes that elicit cellular outcomes. Given the inherent challenges in observing, quantifying, and reconstituting this nanoscale environment, it is not surprising that this landscape has been understudied compared to larger length scales. Here, we aim to shine light upon the cardiac nanoenvironment, which plays a crucial role in maintaining physiological homeostasis while also underlying pathological processes. Thus, we will highlight strategies aimed at (1) elucidating the nanoscale components of the cardiac matrix, and (2) designing new materials and biosystems capable of mimicking these features in vitro.

scholarly journals TOWARDS FUNCTIONAL ARCHITECTURAL DECOMPOSITION OF CONSTRAINED LAYER INFLATABLE SYSTEMS

2021 ◽  
Vol 1 ◽  
pp. 3219-3228
Author(s):  
Koray Benli ◽  
Jonathan Luntz ◽  
Diann Brei ◽  
Wonhee Kim ◽  
Paul Alexander ◽  
...  
Keyword(s):  
Conceptual Design ◽  
Form And Function ◽  
New Concepts ◽  
Wide Range ◽  
Systematic Understanding ◽  
And Function

AbstractPneumatically activated systems enable myriad types of highly functional inflatables employing a wide range of architectural approaches affecting their form and function, making systematic conceptual design difficult. A new architectural class of pneumatically activated systems, constrained layer inflatable systems, consists of hierarchically architected flat layers of thin airtight bladders that are internally and/or externally constrained to generate a variety of functionalities. The highly hierarchical architectural structure of constrained layer inflatable systems coincides with the hierarchy of produced functions, providing an opportunity for the development of a functional architectural decomposition, capturing the inherent relationship between architectural and functional hierarchies. The basis of the approach is conveyed through the design of an example constrained layer inflatable system. This approach empowers the systematic understanding of the interrelated architectural and functional breakdown of constrained layer inflatable systems, enabling designers to iteratively analyze, synthesize, and re-synthesize the components of the system improving existing designs and exploring new concepts.

scholarly journals A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Tao Yue ◽  
Da Zhao ◽  
Duc T. T. Phan ◽  
Xiaolin Wang ◽  
Joshua Jonghyun Park ◽  
...  
Keyword(s):  
Large Scale ◽  
Circulatory System ◽  
Vertical Direction ◽  
Microfluidic System ◽  
Vital Role ◽  
Microvascular Networks ◽  
Biological Studies ◽  
Wide Range ◽  
High Flexibility

AbstractThe vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening.

A widespread pathway for substitution of adenine by diaminopurine in phage genomes

Science ◽  
2021 ◽  
Vol 372 (6541) ◽  
pp. 512-516
Author(s):  
Yan Zhou ◽  
Xuexia Xu ◽  
Yifeng Wei ◽  
Yu Cheng ◽  
Yu Guo ◽  
...  
Keyword(s):  
Large Scale ◽  
Restriction Enzymes ◽  
Diverse Range ◽  
Host Restriction ◽  
Form And Function ◽  
Multienzyme System ◽  
Dna Modifications ◽  
Dna Production ◽  
And Function

DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importance of Z genomes remain unexplored. Here, we report a multienzyme system that supports Z-genome synthesis. We identified dozens of globally widespread phages harboring such enzymes, and we further verified the Z genome in one of these phages, Acinetobacter phage SH-Ab 15497, by using liquid chromatography with ultraviolet and mass spectrometry. The Z genome endows phages with evolutionary advantages for evading the attack of host restriction enzymes, and the characterization of its biosynthetic pathway enables Z-DNA production on a large scale for a diverse range of applications.

Emphatic Sentences: A Comparative-Translational Study of Formal-Functional Relations in English and Romanian

Transilvania ◽  
2021 ◽  
pp. 75-84
Author(s):  
Mona Arhire
Keyword(s):  
Target Language ◽  
Original Text ◽  
John Fowles ◽  
Translational Study ◽  
Form And Function ◽  
Functional Relations ◽  
Wide Range ◽  
Research Questions ◽  
And Function ◽  
Stylistic Device

Emphasis, a well-acknowledged stylistic device, is a carrier of a considerable load of emotional content in the fictional dialogue. Its manifestation can take sundry forms and can be attached to a wide range of feelings and can take different degrees of intensity, all of which determines the creation of the atmosphere and impacts the reception by the readership. This paper reports on the investigation of the occurrence of emphasis embedded in the dialogic utterances of John Fowles’ novel Mantissa. The focus lies on the relation between the formal construction of emphatic sentences and the functional values deriving therefrom. The study entails a comparative analysis of emphatic utterances depicted from the English original text and its translation into Romanian. The three research questions refer to the comparative-contrastive realization of emphatic sentences in the two languages, to the extent to which the functional component succeeds in being transferred to the target language and to possible means of compensation when structural differences pose translational problems. The analysis is structured along a typology of sentences adapted to the nature of the text under scrutiny and to the aims of this study. The findings and conclusions ultimately indicate the importance of establishing a relation between form and function in matter of emphasis in the literary dialogue as an act of communication depending on linguistic devices for its effectiveness.

scholarly journals Persistent Interactions with Bacterial Symbionts Direct Mature-Host Cell Morphology and Gene Expression in the Squid-Vibrio Symbiosis

mSystems ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Natacha Kremer ◽  
Eric J. Koch ◽  
Adil El Filali ◽  
Lawrence Zhou ◽  
Elizabeth A. C. Heath-Heckman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vibrio Fischeri ◽  
Microscopic Analysis ◽  
Daily Rhythm ◽  
Host Animal ◽  
Experimental Conditions ◽  
Content Type ◽  
Form And Function ◽  
Molecular Features ◽  
And Function

ABSTRACTIn horizontally transmitted symbioses, structural, biochemical, and molecular features both facilitate host colonization by specific symbionts and mediate their persistent carriage. In the association between the squidEuprymna scolopesand its luminous bacterial partnerVibrio fischeri, the symbionts interact with two epithelial fields; they interact (i) transiently with the superficial ciliated field that potentiates colonization and regresses within days of colonization and (ii) persistently with the cells that line the internal crypts, whose ultrastructure changes in response to the symbionts. Development of the association creates conditions that promote the symbiotic partner over the lifetime of the host. To determine whether light organ maturation requires continuous interactions withV. fischerior only the signaling that occurs during its initiation, we compared 4-week-old squid that were uncolonized with those colonized either persistently by wild-typeV. fischerior transiently by aV. fischerimutant that triggers early events in morphogenesis but does not persist. Microscopic analysis of the light organs showed that, while morphogenesis of the superficial ciliated field is greatly accelerated byV. fischericolonization, its eventual outcome is largely independent of colonization state. In contrast, the symbiont-induced changes in crypt cell shape require persistent host-symbiont interaction, reflected in the similarity between uncolonized and transiently colonized animals. Transcriptomic analyses reflected the microscopy results; host gene expression at 4 weeks was due primarily to the persistent interactions of host and symbiont cells. Further, the transcriptomic signature of specific pathways reflected the daily rhythm of symbiont release and regrowth and required the presence of the symbionts.IMPORTANCEA long-term relationship between symbiotic partners is often characterized by development and maturation of host structures that harbor the symbiont cells over the host’s lifetime. To understand the mechanisms involved in symbiosis maintenance more fully, we studied the mature bobtail squid, whose light-emitting organ, under experimental conditions, can be transiently or persistently colonized byVibrio fischerior remain uncolonized. Superficial anatomical changes in the organ were largely independent of symbiosis. However, both the microanatomy of cells with which symbionts interact and the patterns of gene expression in the mature animal were due principally to the persistent interactions of host and symbiont cells rather than to a response to early colonization events. Further, the characteristic pronounced daily rhythm on the host transcriptome required persistentV. fischericolonization of the organ. This experimental study provides a window into how persistent symbiotic colonization influences the form and function of host animal tissues.

scholarly journals hPSC-Derived Enteric Ganglioids Model Human ENS Development and Function

2022 ◽  
Author(s):  
Homa Majd ◽  
Ryan M Samuel ◽  
Jonathan T Ramirez ◽  
Ali Kalantari ◽  
Kevin Barber ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Xenograft Model ◽  
Developmental Relationships ◽  
Drug Candidates ◽  
Effective Strategies ◽  
Wide Range ◽  
Functional Features ◽  
And Function

The enteric nervous system (ENS) plays a central role in gut physiology and mediating the crosstalk between the gastrointestinal (GI) tract and other organs. The human ENS has remained elusive, highlighting the need for an in vitro modeling and mapping blueprint. Here we map out the developmental and functional features of the human ENS, by establishing robust and scalable 2D ENS cultures and 3D enteric ganglioids from human pluripotent stem cells (hPSCs). These models recapitulate the remarkable neuronal and glial diversity found in primary tissue and enable comprehensive molecular analyses that uncover functional and developmental relationships within these lineages. As a salient example of the power of this system, we performed in-depth characterization of enteric nitrergic neurons (NO neurons) which are implicated in a wide range of GI motility disorders. We conducted an unbiased screen and identified drug candidates that modulate the activity of NO neurons and demonstrated their potential in promoting motility in mouse colonic tissue ex vivo. We established a high-throughput strategy to define the developmental programs involved in NO neuron specification and discovered that PDGFR inhibition boosts the induction of NO neurons in enteric ganglioids. Transplantation of these ganglioids in the colon of NO neuron-deficient mice results in extensive tissue engraftment, providing a xenograft model for the study of human ENS in vivo and the development of cell-based therapies for neurodegenerative GI disorders. These studies provide a framework for deciphering fundamental features of the human ENS and designing effective strategies to treat enteric neuropathies.  

scholarly journals The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander GJ Skorput ◽  
Stephanie M Lee ◽  
Pamela WL Yeh ◽  
Hermes H Yeh
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Fetal Alcohol Spectrum Disorders ◽  
Behavioral Flexibility ◽  
Ethanol Exposure ◽  
Embryonic Mouse ◽  
Form And Function ◽  
Tangential Migration ◽  
And Function

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.

scholarly journals OncoThreads: Visualization of Large Scale Longitudinal Cancer Molecular Data

2021 ◽  
Author(s):  
Theresa A Harbig ◽  
Sabrina Nusrat ◽  
Tali Mazor ◽  
Qianwen Wang ◽  
Alexander Thomson ◽  
...  
Keyword(s):  
Longitudinal Data ◽  
Large Scale ◽  
Cancer Genomics ◽  
Temporal Patterns ◽  
Molecular Data ◽  
Liquid Biopsies ◽  
Sequencing Technologies ◽  
Molecular Features ◽  
Wide Range ◽  
The Impact

Molecular profiling of patient tumors and liquid biopsies over time with next-generation sequencing technologies and new immuno-profile assays are becoming part of standard research and clinical practice. With the wealth of new longitudinal data, there is a critical need for visualizations for cancer researchers to explore and interpret temporal patterns not just in a single patient but across cohorts. To address this need we developed OncoThreads, a tool for the visualization of longitudinal clinical and cancer genomics and other molecular data in patient cohorts. The tool visualizes patient cohorts as temporal heatmaps and Sankey diagrams that support the interactive exploration and ranking of a wide range of clinical and molecular features. This allows analysts to discover temporal patterns in longitudinal data, such as the impact of mutations on response to a treatment, e.g. emergence of resistant clones. We demonstrate the functionality of OncoThreads using a cohort of 23 glioma patients sampled at 2-4 timepoints. OncoThreads is freely available at http://oncothreads.gehlenborglab.org and implemented in Javascript using the cBioPortal web API as a backend.

scholarly journals Weighing trees with lasers: advances, challenges and opportunities

2018 ◽  
Vol 8 (2) ◽  
pp. 20170048 ◽  
Author(s):  
M. I. Disney ◽  
M. Boni Vicari ◽  
A. Burt ◽  
K. Calders ◽  
S. L. Lewis ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Large Scale ◽  
Three Dimensional ◽  
Point Clouds ◽  
3D Models ◽  
Tree Form ◽  
Form And Function ◽  
Challenges And Opportunities ◽  
And Function ◽  
Non Destructive

Terrestrial laser scanning (TLS) is providing exciting new ways to quantify tree and forest structure, particularly above-ground biomass (AGB). We show how TLS can address some of the key uncertainties and limitations of current approaches to estimating AGB based on empirical allometric scaling equations (ASEs) that underpin all large-scale estimates of AGB. TLS provides extremely detailed non-destructive measurements of tree form independent of tree size and shape. We show examples of three-dimensional (3D) TLS measurements from various tropical and temperate forests and describe how the resulting TLS point clouds can be used to produce quantitative 3D models of branch and trunk size, shape and distribution. These models can drastically improve estimates of AGB, provide new, improved large-scale ASEs, and deliver insights into a range of fundamental tree properties related to structure. Large quantities of detailed measurements of individual 3D tree structure also have the potential to open new and exciting avenues of research in areas where difficulties of measurement have until now prevented statistical approaches to detecting and understanding underlying patterns of scaling, form and function. We discuss these opportunities and some of the challenges that remain to be overcome to enable wider adoption of TLS methods.

Introduction—Minoan Built Environment: Past Studies, Recent Perspectives, and Future Challenges

2017 ◽  
Author(s):  
Quentin Letesson ◽  
Carl Knappett
Keyword(s):  
Twentieth Century ◽  
Built Environment ◽  
Large Scale ◽  
Monumental Architecture ◽  
Form And Function ◽  
Architectural Patterns ◽  
Future Challenges ◽  
Residential Quarters ◽  
And Function ◽  
Intensive Work

Architecture and urbanism have been of constant interest to Minoan archaeologists since the beginning of the twentieth century. While there is some scholarly bias to this, with the field deeply affected by Sir Arthur Evans’s focus on the monumental architecture of Knossos, Minoan Crete continues to yield abundant evidence for a substantial built environment. Focusing on urban and architectural remains creates a strong bias in favour of one block of time, the Neopalatial period, which produced the largest amount of wellpreserved settlements and buildings. Yet, in general, the evidence we now have on the Minoan built environment is an undeniable resource, one that continues to grow thanks to ongoing studies of pre-existing remains as well as new excavation and survey projects. As is clear in Evans’s magnum opus, The Palace of Minos at Knossos, the large-scale excavations typical of the dawn of the last century were heavily directed towards the urban cores of the largest Minoan sites (e.g. Boyd Hawes et al. 1908; Hutchinson 1950). The bulk of what we know about the Minoan built environment comes from the first half of the twentieth century, initially through the intensive work of the foreign schools at Malia, Phaistos, Palaikastro, Gournia, Mochlos, and Pseira, later joined by countless excavations by Greek archaeologists. Yet, synthetic treatments really only began with the work of James Walter Graham, in the form of numerous papers published in the American Journal of Archaeology (see Letesson 2009 for a detailed review), and especially his Palaces of Crete (Graham 1962). Nonetheless, his comparative analyses, which also dealt with non-palatial buildings, were largely focused on polite architecture. With a particular interest in form and function, he built on Evans’s insights to be the first to identify, across a large sample of buildings, recurring architectural patterns in the Minoan built environment (e.g. Piano Nobile, residential quarters, banquet halls). His studies also included an innovative quantitative component, emphasizing the existence of a unit of length that builders would have used to lay out the palaces and some of the so-called ‘villas’.

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