The novel leishmanial Copper P-type ATPase plays a vital role in intracellular parasite survival

2021 ◽  
Author(s):  
Rupam Paul ◽  
Sourav Banerjee ◽  
Samarpita Sen ◽  
Pratiksha Dubey ◽  
Anand K Bachhawat ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Life Forms ◽  
Vital Role ◽  
Copper Stress ◽  
The Novel ◽  
Free Living ◽  
Parasite Survival ◽  
Cellular Copper ◽  
P Type ◽  
Golgi Network

AbstractCopper is essential for all life forms; however in excess it is extremely toxic. Toxic properties of copper are utilized by hosts against various pathogenic invasions. Leishmania, in its both free-living and intracellular forms was found to exhibit appreciable tolerance towards copper-stress. To determine the mechanism of copper-stress evasion employed by Leishmania we identified and characterized the hitherto unknown Copper-ATPase in Leishmania major and determined its role in parasite’s survival in host macrophage cells. L. major Cu-ATPase, LmATP7, exhibits high homology with its orthologues at multiple conserved motifs. In promastigotes, LmATP7 localized to the plasma membrane with a fraction in intracellular puncta. Upon copper treatment, LmATP7 expression increases few folds. LmATP7 is capable of complementing copper transport in Cu-ATPase-Δ yeast strain. Promastigotes overexpressing LmATP7 exhibits higher survival upon copper stress indicating efficacious copper export compared to wild type parasites. We explored macrophage-Leishmanial interaction with respect to copper stress subjected by the host upon parasite and the parasite’s reciprocating response thereon to evade the stress. The Copper-P-type-ATPases ATP7A/7B serves as major copper exporter in eukaryotes that maintain cellular copper levels. We found that Leishmania infection, triggers ATP7A upregulation in macrophages. Additionally, as part of host response, ATP7A traffics from trans-Golgi network and transports copper to the endosomal and endolysosomal compartments harbouring the Leishmania amastigotes. Finally, we show LmATP7 overexpression in this parasite, increased amastigote survivability within infected macrophages, establishing its role in combating host-induced copper stress.

The Novel Dopant Profile Inspection Methodology by FIB

2010 ◽  
Author(s):  
Po Fu Chou ◽  
Li Ming Lu
Keyword(s):  
High Resolution ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
Real Sample ◽  
Physical Analysis ◽  
The Novel ◽  
High Contrast ◽  
Dopant Profile ◽  
P Type

Abstract Dopant profile inspection is one of the focused ion beam (FIB) physical analysis applications. This paper presents a technique for characterizing P-V dopant regions in silicon by using a FIB methodology. This technique builds on published work for backside FIB navigation, in which n-well contrast is observed. The paper demonstrates that the technique can distinguish both n- and p-type dopant regions. The capability for imaging real sample dopant regions on current fabricated devices is also demonstrated. SEM DC and FIB DC are complementary methodologies for the inspection of dopants. The advantage of the SEM DC method is high resolution and the advantage of FIB DC methodology is high contrast, especially evident in a deep N-well region.

Biomimicry: An Overview of Structures, Designs and Materials Inspired from Nature

2020 ◽  
Vol 13 (1) ◽  
pp. 3-15
Author(s):  
Arunachalam Vasanthanathan ◽  
Uthirakumar Siddharth ◽  
Manivannan Vignesh ◽  
Radhakrishnan Pravin
Keyword(s):  
Life Forms ◽  
Vital Role ◽  
X Ray ◽  
X Ray Imaging ◽  
Technological Growth ◽  
Evolution Of Life ◽  
Large Scope ◽  
Product Effectiveness ◽  
Water Turbines ◽  
Principle Objective

Background: Nature has always played a vital role in the evolution of life forms. The design of products in accordance with nature’s design, popularly known as biomimicry, had played a vital role in pushing the technology and product effectiveness to the next level. Humans have long sought to mimic not just the design, but also the methodology adopted by certain animals. For example, the walking technique of vertebrates has been effectively mimicked for a quadruped robot to make a system more efficient by consuming less power. Thus indirectly, nature acts as a driving factor in pushing technological growth. Methods: The principle objective of this paper is to provide an overview of popular bio mimicked products inspired by nature. This paper emphasizes a wide variety of products developed in the field of materials inspired by nature. Results: Wall-climbing robots, Sonar, X-ray imaging, Sandwich and Honeycomb structures are some of the popular products and designs inspired by nature. They have resulted in better designs, better products with improved efficiency and thus have proven to be better alternatives. Some products and designs such as Samara drone, Riblet surfaces, DSSCs, Biomimetic Drills and Water turbines have plenty of scopes to replace conventional products and designs. Conclusion: While plenty of products, structures and designs have successfully replaced older alternatives, there is still a large scope for biomimicry where it could potentially replace conventional products and designs to offer better efficiency.

scholarly journals A Mathematical Model of Contact Tracing during the 2014–2016 West African Ebola Outbreak

Mathematics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 608
Author(s):  
Danielle Burton ◽  
Suzanne Lenhart ◽  
Christina J. Edholm ◽  
Benjamin Levy ◽  
Michael L. Washington ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Disease Management ◽  
Ebola Virus ◽  
Virus Disease ◽  
Infected Individual ◽  
Vital Role ◽  
West African ◽  
Contact Tracing ◽  
The Novel ◽  
Using Data

The 2014–2016 West African outbreak of Ebola Virus Disease (EVD) was the largest and most deadly to date. Contact tracing, following up those who may have been infected through contact with an infected individual to prevent secondary spread, plays a vital role in controlling such outbreaks. Our aim in this work was to mechanistically represent the contact tracing process to illustrate potential areas of improvement in managing contact tracing efforts. We also explored the role contact tracing played in eventually ending the outbreak. We present a system of ordinary differential equations to model contact tracing in Sierra Leonne during the outbreak. Using data on cumulative cases and deaths, we estimate most of the parameters in our model. We include the novel features of counting the total number of people being traced and tying this directly to the number of tracers doing this work. Our work highlights the importance of incorporating changing behavior into one’s model as needed when indicated by the data and reported trends. Our results show that a larger contact tracing program would have reduced the death toll of the outbreak. Counting the total number of people being traced and including changes in behavior in our model led to better understanding of disease management.

scholarly journals Cofilin recruits F-actin to SPCA1 and promotes Ca2+-mediated secretory cargo sorting

2014 ◽  
Vol 206 (5) ◽  
pp. 635-654 ◽  
Author(s):  
Christine Kienzle ◽  
Nirakar Basnet ◽  
Alvaro H. Crevenna ◽  
Gisela Beck ◽  
Bianca Habermann ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Nitrilotriacetic Acid ◽  
Calcium Atpase ◽  
Secretory Proteins ◽  
Dependent Manner ◽  
Agarose Beads ◽  
P Type ◽  
Golgi Network ◽  
Phosphorylation Domain ◽  
Cargo Sorting

The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132–amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1–dependent manner. This domain, coupled to nickel nitrilotriacetic acid (Ni-NTA) agarose beads, specifically recruited F-actin in the presence of CFL-1 and, when expressed in HeLa cells, inhibited Ca2+ entry into the TGN and secretory cargo sorting. Mutagenesis of four amino acids in SPCA1 that represent the CFL-1 binding site also affected Ca2+ import into the TGN and secretory cargo sorting. Altogether, our findings reveal the mechanism of CFL-1–dependent recruitment of actin to SPCA1 and the significance of this interaction for Ca2+ influx and secretory cargo sorting.

LIGHT-INDUCED EXCESS CONDUCTIVITY AND THE ROLE OF ARGON IN THE DEPOSITION OF DOPING-MODULATED AMORPHOUS SILICON SUPERLATTICES.

1985 ◽  
Vol 56 ◽  
Author(s):  
F.-C. Su ◽  
S. Levine ◽  
P. E. Vanier ◽  
F. J. Kampas
Keyword(s):  
Amorphous Silicon ◽  
Amorphous Semiconductor ◽  
Excess Conductivity ◽  
The Novel ◽  
Semiconductor Superlattice ◽  
Deposition Parameters ◽  
Superlattice Structures ◽  
Argon Dilution ◽  
P Type

AbstractAmorphous semiconductor superlattice structures consisting of alternating n-type and p-type doped layers of hydrogenated amorphous silicon (a-Si:H) have been made by silane glow discharge in a single chamber system. These multilayered films show the novel phenomenon of light-induced excess conductivity (LEC) associated with a metastable state having a lifetime of order of days. This report shows that the LEC effect is quite dependent on the specific details of the deposition parameters, namely dilution of the silane with inert gas, substrate temperature and layer thickness. In order to investigate the origin of the LEC effect, argon dilution was used for specific regions of the structure. This experiment shows that the slow states are distributed throughout the layers, and are not concentrated at the interfaces.

A novel role for the peritrophic matrix in protecting Leishmania from the hydrolytic activities of the sand fly midgut

Parasitology ◽  
1997 ◽  
Vol 115 (4) ◽  
pp. 359-369 ◽  
Author(s):  
P. F. P. PIMENTA ◽  
G. B. MODI ◽  
S. T. PEREIRA ◽  
M. SHAHABUDDIN ◽  
D. L. SACKS
Keyword(s):  
Digestive Enzymes ◽  
Leishmania Major ◽  
Specific Inhibitor ◽  
Sand Fly ◽  
Peritrophic Matrix ◽  
Phlebotomus Papatasi ◽  
Hydrolytic Activities ◽  
Natural Vector ◽  
Parasite Survival

The role of the peritrophic matrix (PM) in the development of Leishmania major infections in a natural vector, Phlebotomus papatasi, was investigated by addition of exogenous chitinase to the bloodmeal, which completely blocked PM formation. Surprisingly, the absence of the PM was associated with the loss of midgut infections. The chitinase was not directly toxic to the parasite, nor were midgut infections lost due to premature expulsion of the bloodmeal. Most parasites were killed in chitinase-treated flies within the first 4 h after feeding. Substantial early killing was also observed in control flies, suggesting that the lack of PM exacerbates lethal conditions which normally exist in the blood-fed midgut. Early parasite mortality was reversed by soybean trypsin inhibitor. Allosamadin, a specific inhibitor of chitinase, led to a thickening of the PM, and also prevented the early parasite mortality seen in infected flies. Susceptibility to gut proteases was extremely high in transitional-stage parasites, while amastigotes and fully transformed promastigotes were relatively resistant. A novel role for the PM in promoting parasite survival is suggested, in which the PM creates a barrier to the rapid diffusion of digestive enzymes, and limits the exposure of parasites to these enzymes during the time when they are especially vulnerable to proteolytic damage.

scholarly journals Progress on the Synthesis and Application of CuSCN Inorganic Hole Transport Material in Perovskite Solar Cells

Materials ◽  
2018 ◽  
Vol 11 (12) ◽  
pp. 2592 ◽  
Author(s):  
Funeka Matebese ◽  
Raymond Taziwa ◽  
Dorcas Mutukwa
Keyword(s):  
Solar Cells ◽  
Energy Levels ◽  
Perovskite Solar Cells ◽  
Hole Mobility ◽  
Cost Effective ◽  
Vital Role ◽  
Hole Transport ◽  
Recombination Processes ◽  
Short Synthesis ◽  
P Type

P-type wide bandgap semiconductor materials such as CuI, NiO, Cu2O and CuSCN are currently undergoing intense research as viable alternative hole transport materials (HTMs) to the spiro-OMeTAD in perovskite solar cells (PSCs). Despite 23.3% efficiency of PSCs, there are still a number of issues in addition to the toxicology of Pb such as instability and high-cost of the current HTM that needs to be urgently addressed. To that end, copper thiocyanate (CuSCN) HTMs in addition to robustness have high stability, high hole mobility, and suitable energy levels as compared to spiro-OMeTAD HTM. CuSCN HTM layer use affordable materials, require short synthesis routes, require simple synthetic techniques such as spin-coating and doctor-blading, thus offer a viable way of developing cost-effective PSCs. HTMs play a vital role in PSCs as they can enhance the performance of a device by reducing charge recombination processes. In this review paper, we report on the current progress of CuSCN HTMs that have been reported to date in PSCs. CuSCN HTMs have shown enhanced stability when exposed to weather elements as the solar devices retained their initial efficiency by a greater percentage. The efficiency reported to date is greater than 20% and has a potential of increasing, as well as maintaining thermal stability.

Chromanones with Leishmanicidal Activity from Calea uniflora

2007 ◽  
Vol 62 (5-6) ◽  
pp. 353-356 ◽  
Author(s):  
Andréa Mendes do Nascimento ◽  
Fernanda Cristina Costa ◽  
Otavio Henrique Thiemann ◽  
Dionéia Camilo Rodrigues de Oliveira
Keyword(s):  
Biological Activity ◽  
Growth Inhibition ◽  
Leishmania Major ◽  
Spectroscopic Methods ◽  
The Novel ◽  
Leishmanicidal Activity ◽  
Significant Growth ◽  
Significant Growth Inhibition

The dichloromethane extract of Calea uniflora afforded a mixture of two novel chromanones, uniflorol-A (1) and uniflorol-B (2), and one known chromanone, 2,2-dimethyl-6- (1-hydroxyethyl)-chroman-4-one (3). The structures of these compounds were determined by spectroscopic methods. Biological activity of the compounds against Leishmania major promastigotes was evaluated. Mixture of the novel chromanones 1 and 2 showed significant growth inhibition of the parasite in the micrograms per milliliter range.

scholarly journals The Novel Genes emmABC Are Associated with Exopolysaccharide Production, Motility, Stress Adaptation, and Symbiosis in Sinorhizobium meliloti

2009 ◽  
Vol 191 (19) ◽  
pp. 5890-5900 ◽  
Author(s):  
Jennifer Morris ◽  
Juan E. González
Keyword(s):  
Sinorhizobium Meliloti ◽  
Genetic Factors ◽  
Leguminous Plant ◽  
The Novel ◽  
Two Component System ◽  
Cell Component ◽  
Plant Host ◽  
Free Living ◽  
Novel Genes ◽  
Exopolysaccharide Production

ABSTRACT The nitrogen-fixing symbiont Sinorhizobium meliloti senses and responds to constantly changing environmental conditions as it makes its way through the soil in search of its leguminous plant host, Medicago sativa (alfalfa). As a result, this bacterium regulates various aspects of its physiology in order to respond appropriately to stress, starvation, and competition. For example, exopolysaccharide production, which has been shown to play an important role in the ability of S. meliloti to successfully invade its host, also helps the bacterium withstand osmotic changes and other environmental stresses. In an effort to further elucidate the intricate regulation of this important cell component, we set out to identify genetic factors that may affect its production. Here we characterize novel genes that encode a small protein (EmmA) and a putative two-component system (EmmB-EmmC). A mutation in any of these genes leads to increased production of the symbiotically important exopolysaccharide succinoglycan. In addition, emm mutants display membrane-associated defects, are nonmotile, and are unable to form an optimal symbiosis with alfalfa, suggesting that these novel genes may play a greater role in the overall fitness of S. meliloti both during the free-living stage and in its association with its host.

scholarly journals Genomic Insights Into the Lifestyles of Thaumarchaeota Inside Sponges

2021 ◽  
Vol 11 ◽  
Author(s):  
Markus Haber ◽  
Ilia Burgsdorf ◽  
Kim M. Handley ◽  
Maxim Rubin-Blum ◽  
Laura Steindler
Keyword(s):  
The Novel ◽  
Glycine Cleavage System ◽  
Free Living ◽  
High Affinity ◽  
Branched Chain Amino Acid ◽  
Glycine Cleavage ◽  
Microbial Symbionts ◽  
Host Sponge ◽  
Branched Chain ◽  
Sponge Symbionts

Sponges are among the oldest metazoans and their success is partly due to their abundant and diverse microbial symbionts. They are one of the few animals that have Thaumarchaeota symbionts. Here we compare genomes of 11 Thaumarchaeota sponge symbionts, including three new genomes, to free-living ones. Like their free-living counterparts, sponge-associated Thaumarchaeota can oxidize ammonia, fix carbon, and produce several vitamins. Adaptions to life inside the sponge host include enrichment in transposases, toxin-antitoxin systems and restriction modifications systems, enrichments previously reported also from bacterial sponge symbionts. Most thaumarchaeal sponge symbionts lost the ability to synthesize rhamnose, which likely alters their cell surface and allows them to evade digestion by the host. All but one archaeal sponge symbiont encoded a high-affinity, branched-chain amino acid transporter system that was absent from the analyzed free-living thaumarchaeota suggesting a mixotrophic lifestyle for the sponge symbionts. Most of the other unique features found in sponge-associated Thaumarchaeota, were limited to only a few specific symbionts. These features included the presence of exopolyphosphatases and a glycine cleavage system found in the novel genomes. Thaumarchaeota have thus likely highly specific interactions with their sponge host, which is supported by the limited number of host sponge species to which each of these symbionts is restricted.

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