scholarly journals Structure, Activity and Function of a Singing CPG Interneuron Controlling Cricket Species-Specific Acoustic Signaling

2018 ◽  
Vol 39 (1) ◽  
pp. 96-111 ◽  
Author(s):  
Pedro F. Jacob ◽  
Berthold Hedwig
Keyword(s):  
Acoustic Signaling ◽  
Structure Activity ◽  
Species Specific ◽  
And Function

scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Inflammatory Responses ◽  
Molecular Data ◽  
Model Organisms ◽  
Sequencing Data ◽  
Phenotypic Analysis ◽  
Age Related ◽  
Analogous Data ◽  
Species Specific ◽  
And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

scholarly journals Codon harmonization reduces amino acid misincorporation in bacterially expressed P. falciparum proteins and improves their immunogenicity

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Neeraja Punde ◽  
Jennifer Kooken ◽  
Dagmar Leary ◽  
Patricia M. Legler ◽  
Evelina Angov
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Codon Usage ◽  
Dna Sequences ◽  
Structural Integrity ◽  
Host Cells ◽  
Loss Of Function ◽  
Species Specific ◽  
And Function ◽  
The Impact

Abstract Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage. “Codon harmonization” more closely aligns native codon usage frequencies with those of the expression host particularly within putative inter-domain segments where slower rates of translation may play a role in protein folding. Heterologous expression of Plasmodium falciparum genes in Escherichia coli has been a challenge due to their AT-rich codon bias and the highly repetitive DNA sequences. Here, codon harmonization was applied to the malarial antigen, CelTOS (Cell-traversal protein for ookinetes and sporozoites). CelTOS is a highly conserved P. falciparum protein involved in cellular traversal through mosquito and vertebrate host cells. It reversibly refolds after thermal denaturation making it a desirable malarial vaccine candidate. Protein expressed in E. coli from a codon harmonized sequence of P. falciparum CelTOS (CH-PfCelTOS) was compared with protein expressed from the native codon sequence (N-PfCelTOS) to assess the impact of codon usage on protein expression levels, solubility, yield, stability, structural integrity, recognition with CelTOS-specific mAbs and immunogenicity in mice. While the translated proteins were expected to be identical, the translated products produced from the codon-harmonized sequence differed in helical content and showed a smaller distribution of polypeptides in mass spectra indicating lower heterogeneity of the codon harmonized version and fewer amino acid misincorporations. Substitutions of hydrophobic-to-hydrophobic amino acid were observed more commonly than any other. CH-PfCelTOS induced significantly higher antibody levels compared with N-PfCelTOS; however, no significant differences in either IFN-γ or IL-4 cellular responses were detected between the two antigens.

scholarly journals Discovery of a novel RORγ antagonist with skin-restricted exposure for topical treatment of mild to moderate psoriasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suxing Liu ◽  
Dong Liu ◽  
Ru Shen ◽  
Di Li ◽  
Qiyue Hu ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Clinical Success ◽  
Systemic Exposure ◽  
Skin Inflammation ◽  
Targeted Therapeutics ◽  
High Exposure ◽  
Structure Activity ◽  
Potential Safety ◽  
Systematic Structure ◽  
And Function

AbstractClinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest. Systematic structure activity relationship study and multi-parameter optimization led to the discovery of a novel RORγ antagonist (SHR168442) with desired properties for a topical drug. It suppressed the transcription of IL-17 gene, leading to reduction of IL-17 cytokine secretion. It showed high exposure in skin, but low in plasma. Topical application of SHR168442 in Vaseline exhibited excellent efficacy in the imiquimod-induced and IL-23-induced psoriasis-like skin inflammation mouse models and correlated with the reduction of Th17 pathway cytokines, IL-6, TNFα and IL-17A. This work demonstrated restricted skin exposure of RORγ antagonist may provide a new topical treatment option as targeted therapeutics for mild to moderate psoriasis patients and may be suitable for the treatment of any other inflammatory disorders that are accessible locally.

Plant K+ channels: structure, activity and function

1996 ◽  
Vol 24 (4) ◽  
pp. 964-971 ◽  
Author(s):  
I. Chérel ◽  
P. Daram ◽  
F. Gaymard ◽  
C. Horeau ◽  
J.-B. Thibaud ◽  
...  
Keyword(s):  
K Channels ◽  
Structure Activity ◽  
And Function

scholarly journals Equine Drug Transporters: A Mini-Review and Veterinary Perspective

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1064
Author(s):  
Brielle Rosa
Keyword(s):  
Drug Transport ◽  
Drug Disposition ◽  
Drug Transporters ◽  
Transport Proteins ◽  
Pharmacokinetic Parameters ◽  
Transporter Protein ◽  
Drug Pharmacokinetic ◽  
Species Specific ◽  
And Function

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

scholarly journals Structure and function of minor pilins of type IV pili

2019 ◽  
Vol 209 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Theis Jacobsen ◽  
Benjamin Bardiaux ◽  
Olivera Francetic ◽  
Nadia Izadi-Pruneyre ◽  
Michael Nilges
Keyword(s):  
Pathogenic Bacteria ◽  
Type Iv Pili ◽  
Host Cells ◽  
Type Ii Secretion ◽  
Type Iv Pilus ◽  
Type Iv ◽  
Flexible Fibers ◽  
Multiple Copies ◽  
Species Specific ◽  
And Function

AbstractType IV pili are versatile and highly flexible fibers formed on the surface of many Gram-negative and Gram-positive bacteria. Virulence and infection rate of several pathogenic bacteria, such as Neisseria meningitidis and Pseudomonas aeruginosa, are strongly dependent on the presence of pili as they facilitate the adhesion of the bacteria to the host cell. Disruption of the interactions between the pili and the host cells by targeting proteins involved in this interaction could, therefore, be a treatment strategy. A type IV pilus is primarily composed of multiple copies of protein subunits called major pilins. Additional proteins, called minor pilins, are present in lower abundance, but are essential for the assembly of the pilus or for its specific functions. One class of minor pilins is required to initiate the formation of pili, and may form a complex similar to that identified in the related type II secretion system. Other, species-specific minor pilins in the type IV pilus system have been shown to promote additional functions such as DNA binding, aggregation and adherence. Here, we will review the structure and the function of the minor pilins from type IV pili.

Validity of a patient-derived system of tissue-specific human endothelial cells: interleukin-6 as a surrogate marker in the coronary system

2007 ◽  
Vol 293 (3) ◽  
pp. H1721-H1728 ◽  
Author(s):  
Karla Lehle ◽  
Leoni A. Kunz-Schughart ◽  
Peter Kuhn ◽  
Stephan Schreml ◽  
Dietrich E. Birnbaum ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Umbilical Vein ◽  
Surrogate Marker ◽  
Tissue Specific ◽  
Monocyte Chemoattractant Protein 1 ◽  
Species Specific ◽  
And Function

The aim of our study was to evaluate the relevance of tissue- and species-specific endothelial cells (EC) to study EC-dependent mechanisms in inflammatory-mediated tissue injury. We established an isolation protocol for highly purified EC (pEC) preparations of different origin and compared EC-specific inflammatory responses. Fluorescence-activated cell separation was used to obtain pEC cultures from different human arterial (coronary artery, internal thoracic artery) and venous (umbilical vein, saphenous vein) vessels. All pEC were analyzed for growth kinetics, morphology, release of cytokines/chemokines, and expression of E-selectin. For all different EC cultures, purities of ≥99% were reproducibly achieved. The EC isolation did not affect EC growth, morphology, and function. However, characterization of pEC from different vessel materials revealed an intrinsic, tissue-specific functional heterogeneity of EC cultures. Despite an arterial and venous difference in the secretion of IL-8 and monocyte chemoattractant protein-1, especially EC from coronary arteries produced significantly more IL-6 compared with other EC types, independent of age, gender, and disease of the cell donors. In contrast, the expression of E-selectin was not affected. We conclude that the proposed isolation protocol allows the generation of a pEC bank, enabling us to study tissue-specific aspects at the level of the endothelium.

scholarly journals Long non-coding RNAs in wild wheat progenitors

2018 ◽  
Author(s):  
Alice Pieri ◽  
Mario Enrico Pè ◽  
Edoardo Bertolini
Keyword(s):  
Aegilops Tauschii ◽  
Noncoding Rnas ◽  
Reproductive Organs ◽  
Long Noncoding Rnas ◽  
D Genome ◽  
Specific Expression ◽  
Wild Wheat ◽  
Organ Specific ◽  
Species Specific ◽  
And Function

AbstractTriticum urartu and Aegilops tauschii are the diploid progenitors of the hexaploid Triticum aestivum (AuAuBBDD), donors of the Au and D genome respectively. In this work we investigate the long noncoding RNAs (lncRNAs) component of the genomes of these two wild wheat relatives. Sixty-eight RNA-seq libraries generated from several organs and conditions were retrieved from public databases. We annotated and characterized 14,515 T. urartu and 20,908 Ae. tauschii bona-fide lncRNA transcripts that show features similar to those of other plant and animal counterparts. Thousands of lncRNAs were found significantly modulated in different organs and exhibited organ specific expression, with a predominant accumulation in the spike, fostering the hypothesis of their crucial role in reproductive organs. Most of the organ-specific lncRNAs were found associated with transposable elements (TEs), indicating the possible role of TEs in lncRNA origin, differentiation and function. The majority of T. urartu and Ae. tauschii lncRNAs appear to be species-specific; nevertheless, we found some lncRNAs conserved between the two wheat progenitors, highlighting the presence and conservation of exonic splicing enhancers sites in multi-exon conserved lncRNAs. In addition, we found cases of lncRNA conservation and their cis regulatory regions spanning the wheat pre-domestication and post-domestication period. Altogether, these results represent the first comprehensive genome-wide encyclopedia of lncRNAs in wild wheat relatives, and they provide clues as to the hidden regulatory pathway mediated by long noncoding RNAs in these largely unexplored wheat progenitors.

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