scholarly journals Sequence-dependent mechanics of collagen reflect its structural and functional organization

2020 ◽  
Author(s):  
Alaa Al-Shaer ◽  
Aaron Lyons ◽  
Yoshihiro Ishikawa ◽  
Billy G. Hudson ◽  
Sergei P. Boudko ◽  
...  
Keyword(s):  
Network Formation ◽  
Environmental Changes ◽  
Functional Organization ◽  
Collagen Iv ◽  
Chloride Ions ◽  
Basement Membranes ◽  
Collagen Iii ◽  
High Flexibility ◽  
The Impact ◽  
Collagenous Domain

AbstractExtracellular matrix mechanics influence diverse cellular functions, yet surprisingly little is known about the mechanical properties of their constituent collagens. In particular, network-forming collagen IV, an integral component of basement membranes, has been far less studied than fibril-forming collagens. A key feature differentiating collagen IV is the presence of interruptions in the triple-helix-defining (Gly-X-Y) sequence along its collagenous domain. Here, we used atomic force microscopy (AFM) to determine the impact of these interruptions on the flexibility of collagen. Our extracted flexibility profile reveals that collagen IV possesses highly heterogeneous mechanics, ranging from semi-flexible regions as found for fibril-forming collagens to a lengthy region of high flexibility towards its N terminus. A simple model in which flexibility is dictated only by the presence of interruptions fit the extracted profile reasonably well, providing insight into the alignment of chains and supporting the role of interruptions in instilling flexibility. However, limitations of this model were illuminated by our determination of variable flexibility along continuously triple-helical collagen III, which we found to possess a high-flexibility region around its matrix-metalloprotease (MMP) binding site. Surprisingly, proline content did not correlate with local flexibility in either collagen type. We also found that physiologically relevant changes in pH and chloride concentration did not alter the flexibility of collagen IV, indicating such environmental changes are not used to control its compaction during secretion. Although extracellular chloride ions play a role in triggering collagen IV network formation, they do not appear to modulate the structure of its collagenous domain.

Endothelial k-RasV12 Expression Induces Capillary Deficiency Attributable to Marked Tube Network Expansion Coupled to Reduced Pericytes and Basement Membranes

2021 ◽  
Author(s):  
Zheying Sun ◽  
Scott S. Kemp ◽  
Prisca K. Lin ◽  
Kalia N. Aguera ◽  
George E. Davis
Keyword(s):  
Protein Kinase ◽  
Basement Membrane ◽  
Arteriovenous Malformations ◽  
Network Formation ◽  
Tube Formation ◽  
Small Gtpase ◽  
Basement Membranes ◽  
Formation Mechanisms ◽  
Lumen Formation ◽  
The Impact

Objective: We sought to determine how endothelial cell (EC) expression of the activating k-Ras mutation, k-RasV12, affects their ability to form lumens and tubes and interact with pericytes during capillary assembly Approach and Results: Using defined bioassays where human ECs undergo observable tubulogenesis, sprouting behavior, pericyte recruitment to EC-lined tubes, and pericyte-induced EC basement membrane deposition, we assessed the impact of EC k-RasV12 expression on these critical processes that are necessary for proper capillary network formation. This mutation, which is frequently seen in human ECs within brain arteriovenous malformations, was found to markedly accentuate EC lumen formation mechanisms, with strongly accelerated intracellular vacuole formation, vacuole fusion, and lumen expansion and with reduced sprouting behavior, leading to excessively widened tube networks compared with control ECs. These abnormal tubes demonstrate strong reductions in pericyte recruitment and pericyte-induced EC basement membranes compared with controls, with deficiencies in fibronectin, collagen type IV, and perlecan deposition. Analyses of signaling during tube formation from these k-RasV12 ECs reveals strong enhancement of Src, Pak2 (P21 [RAC1 (Rac family small GTPase 1)] activated kinase 2), b-Raf (v-raf murine sarcoma viral oncogene homolog B1), Erk (extracellular signal–related kinase), and Akt activation and increased expression of PKCε (protein kinase C epsilon), MT1-MMP (membrane-type 1 matrix metalloproteinase), acetylated tubulin and CDCP1 (CUB domain-containing protein 1; most are known EC lumen regulators). Pharmacological blockade of MT1-MMP, Src, Pak, Raf, Mek (mitogen-activated protein kinase) kinases, Cdc42 (cell division cycle 42)/Rac1, and Notch markedly interferes with lumen and tube formation from these ECs. Conclusions: Overall, this novel work demonstrates that EC expression of k-RasV12 disrupts capillary assembly due to markedly excessive lumen formation coupled with strongly reduced pericyte recruitment and basement membrane deposition, which are critical pathogenic features predisposing the vasculature to develop arteriovenous malformations.

scholarly journals A chloride ring is an ancient evolutionary innovation mediating the assembly of the collagen IV scaffold of basement membranes

2019 ◽  
Vol 294 (20) ◽  
pp. 7968-7981 ◽  
Author(s):  
Vadim Pedchenko ◽  
Ryan Bauer ◽  
Elena N. Pokidysheva ◽  
Alaa Al-Shaer ◽  
Nancy R. Forde ◽  
...  
Keyword(s):  
Principal Component ◽  
Chloride Ion ◽  
Collagen Iv ◽  
Chloride Ions ◽  
Basement Membranes ◽  
Critical Event ◽  
Single Chain ◽  
Evolutionary Innovation ◽  
Evolution And Development ◽  
Evolutionarily Conserved

Collagen IV scaffold is a principal component of the basement membrane (BM), a specialized extracellular matrix that is essential for animal multicellularity and tissue evolution. Scaffold assembly begins with the trimerization of α-chains into protomers inside the cell, which then are secreted and undergo oligomerization outside the cell. For the ubiquitous scaffold composed of α1- and α2-chains, both intracellular and extracellular stages are mediated by the noncollagenous domain (NC1). The association of protomers is chloride-dependent, whereby chloride ions induce interactions of the protomers' trimeric NC1 domains leading to NC1 hexamer formation. Here, we investigated the mechanisms, kinetics, and functionality of the chloride ion-mediated protomer assembly by using a single-chain technology to produce a stable NC1 trimer comprising α1, α2, and α1 NC1 monomers. We observed that in the presence of chloride, the single-chain NC1-trimer self-assembles into a hexamer, for which the crystal structure was determined. We discovered that a chloride ring, comprising 12 ions, induces the assembly of and stabilizes the NC1 hexamer. Furthermore, we found that the chloride ring is evolutionarily conserved across all animals, first appearing in cnidarians. These findings reveal a fundamental role for the chloride ring in the assembly of collagen IV scaffolds of BMs, a critical event enabling tissue evolution and development. Moreover, the single-chain technology is foundational for generating trimeric NC1 domains of other α-chain compositions to investigate the α121, α345, and α565 collagen IV scaffolds and to develop therapies for managing Alport syndrome, Goodpasture's disease, and cancerous tumor growth.

Designing a CRM Framework for online & offline sports footwear retailers

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Rodrigo Cueva ◽  
Guillem Rufian ◽  
Maria Gabriela Valdes
Keyword(s):  
Environmental Changes ◽  
Customer Relationship ◽  
Business Strategies ◽  
Economic Sectors ◽  
Running Shoes ◽  
Brick And Mortar ◽  
Key Factor ◽  
On Line ◽  
The Impact

The use of Customer Relationship Managers to foster customers loyalty has become one of the most common business strategies in the past years.  However, CRM solutions do not fill the abundance of happily ever-after relationships that business needs, and each client’s perception is different in the buying process.  Therefore, the experience must be precise, in order to extend the loyalty period of a customer as much as possible. One of the economic sectors in which CRM’s have improved this experience is retailing, where the personalized attention to the customer is a key factor.  However, brick and mortar experiences are not enough to be aware in how environmental changes could affect the industry trends in the long term.  A base unified theoretical framework must be taken into consideration, in order to develop an adaptable model for constructing or implementing CRMs into companies. Thanks to this approximation, the information is complemented, and the outcome will increment the quality in any Marketing/Sales initiative. The goal of this article is to explore the different factors grouped by three main domains within the impact of service quality, from a consumer’s perspective, in both on-line and off-line retailing sector.  Secondly, we plan to go a step further and extract base guidelines about previous analysis for designing CRM’s solutions focused on the loyalty of the customers for a specific retailing sector and its product: Sports Running Shoes.

scholarly journals Quit Experiences among Primary Care Patients Enrolled in a Smoking Cessation Pilot RCT Early in the COVID-19 Pandemic

2021 ◽  
Vol 18 (3) ◽  
pp. 1011
Author(s):  
Andrea A. Joyce ◽  
Grace M. Styklunas ◽  
Nancy A. Rigotti ◽  
Jordan M. Neil ◽  
Elyse R. Park ◽  
...  
Keyword(s):  
Primary Care ◽  
Text Messaging ◽  
Risk Perceptions ◽  
Environmental Changes ◽  
Age Groups ◽  
Text Messages ◽  
Increased Risk ◽  
Primary Care Patients ◽  
The Impact ◽  
At Home

The impact of the COVID-19 pandemic on US adults’ smoking and quitting behaviors is unclear. We explored the impact of COVID-19 on smoking behaviors, risk perceptions, and reactions to text messages during a statewide stay-at-home advisory among primary care patients who were trying to quit. From May–June 2020, we interviewed smokers enrolled in a 12-week, pilot cessation trial providing text messaging and mailed nicotine replacement medication (NCT04020718). Twenty-two individuals (82% white, mean age 55 years), representing 88% of trial participants during the stay-at-home advisory, completed exit interviews; four (18%) of them reported abstinence. Interviews were thematically analyzed by two coders. COVID-19-induced environmental changes had mixed effects, facilitating quitting for some and impeding quitting for others. While stress increased for many, those who quit found ways to cope with stress. Generally, participants felt at risk for COVID-19 complications but not at increased risk of becoming infected. Reactions to COVID-19 and quitting behaviors differed across age groups, older participants reported difficulties coping with isolation (e.g., feeling disappointed when a text message came from the study and not a live person). Findings suggest that cessation interventions addressing stress and boredom are needed during COVID-19, while smokers experiencing isolation may benefit from live-person supports.

scholarly journals The intensity of slope and fluvial processes after a catastrophic windthrow event in small catchments in the Tatra Mountains

2021 ◽  
Vol 18 (6) ◽  
pp. 1405-1423
Author(s):  
Dariusz Strzyżowski ◽  
Elżbieta Gorczyca ◽  
Kazimierz Krzemień ◽  
Mirosław Żelazny
Keyword(s):  
Environmental Changes ◽  
Bedload Transport ◽  
Strong Wind ◽  
Tatra Mountains ◽  
Salvage Logging ◽  
Fluvial Processes ◽  
Wind Events ◽  
And Control ◽  
The Tatra Mountains ◽  
The Impact

AbstractStrong wind events frequently result in creating large areas of windthrow, which causes abrupt environmental changes. Bare soil surfaces within pits and root plates potentially expose soil to erosion. Absence of forest may alter the dynamics of water circulation. In this study we attempt to answer the question of whether extensive windthrows influence the magnitude of geomorphic processes in 6 small second- to third-order catchments with area ranging from 0.09 km2 to 0.8 km2. Three of the catchments were significantly affected by a windthrow which occurred in December 2013 in the Polish part of the Tatra Mountains, and the other three catchments were mostly forested and served as control catchments. We mapped the pits created by the windthrow and the linear scars created by salvage logging operations in search of any signs of erosion within them. We also mapped all post-windthrow landslides created in the windthrow-affected catchments. The impact of the windthrow on the fluvial system was investigated by measuring a set of channel characteristics and determining bedload transport intensity using painted tracers in all the windthrow-affected and control catchments. Both pits and linear scars created by harvesting tend to become overgrown by vegetation in the first several years after the windthrow. The only signs of erosion were observed in 10% of the pits located on convergent slopes. During the period from the windthrow event in 2013 until 2019, 5 very small (total area <100 m2) shallow landslides were created. The mean distance of bedload transport was similar (t-test, p=0.05) in most of the windthrow-affected and control catchments. The mapping of channels revealed many cases of root plates fallen into a channel and pits created near a channel. A significant amount of woody debris delivered into the channels influenced the activity of fluvial processes by creating alternating zones of erosion and accumulation.

scholarly journals Environmental Changes and Cultural Transitions in SW Iberia during the Early-Mid Holocene

2021 ◽  
Vol 11 (8) ◽  
pp. 3580
Author(s):  
Cristina Val-Peón ◽  
Juan I. Santisteban ◽  
José A. López-Sáez ◽  
Gerd-Christian Weniger ◽  
Klaus Reicherter
Keyword(s):  
Dietary Habits ◽  
Environmental Changes ◽  
Source Area ◽  
Direct Access ◽  
Special Focus ◽  
Early Neolithic ◽  
Archaeological Data ◽  
Local Resources ◽  
Climate Events ◽  
The Impact

The SW coast of the Iberian Peninsula experiences a lack of palaeoenvironmental and archaeological data. With the aim to fill this gap, we contribute with a new palynological and geochemical dataset obtained from a sediment core drilled in the continental shelf of the Algarve coast. Archaeological data have been correlated with our multi-proxy dataset to understand how human groups adapted to environmental changes during the Early-Mid Holocene, with special focus on the Mesolithic to Neolithic transition. Vegetation trends indicate warm conditions at the onset of the Holocene followed by increased moisture and forest development ca. 10–7 ka BP, after which woodlands are progressively replaced by heaths. Peaks of aridity were identified at 8.2 and 7. 5 ka BP. Compositional, textural, redox state, and weathering of source area geochemical proxies indicates abrupt palaeoceanographic modifications and gradual terrestrial changes at 8.2 ka BP, while the 7.5 ka BP event mirrors a decrease in land moisture availability. Mesolithic sites are mainly composed of seasonal camps with direct access to the coast for the exploitation of local resources. This pattern extends into the Early Neolithic, when these sites coexist with seasonal and permanent occupations located in inland areas near rivers. Changes in settlement patterns and dietary habits may be influenced by changes in coastal environments caused by the sea-level rise and the impact of the 8.2 and 7.5 ka BP climate events.

scholarly journals Social Evaluation of Public Open Space Services and Their Impact on Well-Being: A Micro-Scale Assessment from a Coastal University

2021 ◽  
Vol 13 (8) ◽  
pp. 4372
Author(s):  
Abdullah Addas ◽  
Ahmad Maghrabi
Keyword(s):  
Open Space ◽  
Environmental Changes ◽  
Positive Impact ◽  
Well Being ◽  
Social Evaluation ◽  
Open Spaces ◽  
Rapid Urbanization ◽  
Public Open Space ◽  
The Impact ◽  
Public Open Spaces

Public open spaces services have been shown to be profoundly affected by rapid urbanization and environmental changes, and in turn, they have influenced socio-cultural relationships and human well-being. However, the impact of these changes on public open space services (POSS) remains unexplored, particularly in the Saudi Arabian context. This study examines the socio-cultural influence of POSS on the King Abdulaziz University campus, Jeddah, Saudi Arabia and the impact of these services on well-being. A field survey and questionnaire were used to collect data. Non-parametric tests (Kruskal–Wallis and Mann–Whitney tests) were used to find significant differences in the importance of POSS as perceived by stakeholders based on socio-demographic attributes. Factor analysis was performed for 14 POSS to identify those that are most important. The study showed that (i) university stakeholders are closely linked to services provided by public open spaces (POS) and dependent on POSS, (ii) there were significant differences in the perceived importance of POSS according to gender, age, and social groups, and (iii) 70 to 90% of stakeholders reported POSS as having a positive impact on well-being. Thus, the findings will help design and plan POSS to meet the needs of society and promote well-being.

scholarly journals Impact of the municipal merger on watershed management: a study of Lake Kasumigaura, Japan

2021 ◽  
Author(s):  
Takeshi Mizunoya ◽  
Noriko Nozaki ◽  
Rajeev Kumar Singh
Keyword(s):  
Watershed Management ◽  
Large Scale ◽  
Environmental Changes ◽  
Water Environment ◽  
Reduction Rate ◽  
Oxygen Demand ◽  
Policy Implications ◽  
Pollution Reduction ◽  
Lake Kasumigaura ◽  
The Impact

AbstractIn the early 2000s, Japan instituted the Great Heisei Consolidation, a national strategy to promote large-scale municipal mergers. This study analyzes the impact that this strategy could have on watershed management. We select the Lake Kasumigaura Basin, the second largest lake in Japan, for the case study and construct a dynamic expanded input–output model to simulate the ecological system around the Lake, the socio-environmental changes over the period, and their mutual dependency for the period 2012–2020. In the model, we regulate and control the following water pollutants: total nitrogen, total phosphorus, and chemical oxygen demand. The results show that a trade-off between economic activity and the environment can be avoided within a specific range of pollution reduction, given that the prefectural government implements optimal water environment policies, assuming that other factors constraining economic growth exist. Additionally, municipal mergers are found to significantly reduce the budget required to improve the water environment, but merger budget efficiency varies nonlinearly with the reduction rate. Furthermore, despite the increase in financial efficiency from the merger, the efficiency of installing domestic wastewater treatment systems decreases drastically beyond a certain pollution reduction level and eventually reaches a limit. Further reductions require direct regulatory instruments in addition to economic policies, along with limiting the output of each industry. Most studies on municipal mergers apply a political, administrative, or financial perspective; few evaluate the quantitative impact of municipal mergers on the environment and environmental policy implications. This study addresses these gaps.

scholarly journals The Impact of Climate Change on the Resistance of Rice Near-Isogenic Lines with Resistance Genes Against Brown Planthopper

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yun-Hung Kuang ◽  
Yu-Fu Fang ◽  
Shau-Ching Lin ◽  
Shin-Fu Tsai ◽  
Zhi-Wei Yang ◽  
...  
Keyword(s):  
Climate Change ◽  
Resistance Genes ◽  
Environmental Changes ◽  
Gene Pyramiding ◽  
Brown Planthopper ◽  
Inhibitory Effect ◽  
Near Isogenic Lines ◽  
Impact Of Climate Change ◽  
Isogenic Lines ◽  
The Impact

Abstract Background The impact of climate change on insect resistance genes is elusive. Hence, we investigated the responses of rice near-isogenic lines (NILs) that carry resistance genes against brown planthopper (BPH) under different environmental conditions. Results We tested these NILs under three environmental settings (the atmospheric temperature with corresponding carbon dioxide at the ambient, year 2050 and year 2100) based on the Intergovernmental Panel on Climate Change prediction. Comparing between different environments, two of nine NILs that carried a single BPH-resistant gene maintained their resistance under the environmental changes, whereas two of three NILs showed gene pyramiding with two maintained BPH resistance genes despite the environmental changes. In addition, two NILs (NIL-BPH17 and NIL-BPH20) were examined in their antibiosis and antixenosis effects under these environmental changes. BPH showed different responses to these two NILs, where the inhibitory effect of NIL-BPH17 on the BPH growth and development was unaffected, while NIL-BPH20 may have lost its resistance during the environmental changes. Conclusion Our results indicate that BPH resistance genes could be affected by climate change. NIL-BPH17 has a strong inhibitory effect on BPH feeding on phloem and would be unaffected by environmental changes, while NIL-BPH20 would lose its ability during the environmental changes.

scholarly journals Virus-Like Particles Produced Using the Brome Mosaic Virus Recombinant Capsid Protein Expressed in a Bacterial System

2021 ◽  
Vol 22 (6) ◽  
pp. 3098
Author(s):  
Aleksander Strugała ◽  
Jakub Jagielski ◽  
Karol Kamel ◽  
Grzegorz Nowaczyk ◽  
Marcin Radom ◽  
...  
Keyword(s):  
Ionic Strength ◽  
Mosaic Virus ◽  
Capsid Protein ◽  
Self Assembly ◽  
Environmental Changes ◽  
Expression System ◽  
Brome Mosaic Virus ◽  
Virus Like Particles ◽  
Assembly Principles ◽  
The Impact

Virus-like particles (VLPs), due to their nanoscale dimensions, presence of interior cavities, self-organization abilities and responsiveness to environmental changes, are of interest in the field of nanotechnology. Nevertheless, comprehensive knowledge of VLP self-assembly principles is incomplete. VLP formation is governed by two types of interactions: protein–cargo and protein–protein. These interactions can be modulated by the physicochemical properties of the surroundings. Here, we used brome mosaic virus (BMV) capsid protein produced in an E. coli expression system to study the impact of ionic strength, pH and encapsulated cargo on the assembly of VLPs and their features. We showed that empty VLP assembly strongly depends on pH whereas ionic strength of the buffer plays secondary but significant role. Comparison of VLPs containing tRNA and polystyrene sulfonic acid (PSS) revealed that the structured tRNA profoundly increases VLPs stability. We also designed and produced mutated BMV capsid proteins that formed VLPs showing altered diameters and stability compared to VLPs composed of unmodified proteins. We also observed that VLPs containing unstructured polyelectrolyte (PSS) adopt compact but not necessarily more stable structures. Thus, our methodology of VLP production allows for obtaining different VLP variants and their adjustment to the incorporated cargo.

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