Metabolism and Functions of Inositol Pyrophosphates: Insights Gained from the Application of Synthetic Analogues

Inositol pyrophosphates (PP-InsPs) comprise an important group of intracellular, diffusible cellular signals that a wide range of biological processes throughout the yeast, plant, and animal kingdoms. It has been difficult to gain a molecular-level mechanistic understanding of the actions of these molecules, due to their highly phosphorylated nature, their low levels, and their rapid metabolic turnover. More recently, these obstacles to success are being surmounted by the chemical synthesis of a number of insightful PP-InsP analogs. This review will describe these analogs and will indicate the important chemical and biological information gained by using them.

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GS-Preprocess: Containerized GUIDE-seq Data Analysis Tools with Diverse Sequencer Compatibility

10.1101/2020.01.26.914861 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tomás C. Rodríguez ◽

Henry E. Pratt ◽

PengPeng Liu ◽

Nadia Amrani ◽

Lihua Julie Zhu

Keyword(s):

Dna Cleavage ◽

Biological Processes ◽

Dna Breaks ◽

Genome Wide ◽

Wide Range ◽

Data Output ◽

Miseq Platform ◽

Low Levels ◽

Standard Output ◽

Adapter Trimming

AbstractRNA-guided nucleases (e.g. CRISPR-Cas) are used in a breadth of clinical and basic scientific subfields for the investigation or modification of biological processes. While these modern platforms for site-specific DNA cleavage are highly accurate, some applications (e.g. gene editing therapeutics) cannot tolerate DNA breaks at off-target sites, even at low levels. Thus, it is critically important to determine the genome-wide targeting profile of candidate RNA-guided nucleases prior to use. GUIDE-seq is a high-quality, easy-to-execute molecular method that detects and quantifies off-target cleavage. However, this method may remain costly or inaccessible to some researchers due to its library sequencing and analysis protocols, which require a MiSeq platform that must be preprogramed for non-standard output. Here, we present GS-Preprocess, an open-source containerized software that can use standard raw data output (BCL file format) from any Illumina sequencer to create input for the Bioconductor GUIDEseq off-target profiling package. Single-command GS-Preprocess performs FASTQ demultiplexing, adapter trimming, alignment, and UMI reference construction, improving the ease and accessibility of the GUIDE-seq method for a wide range of researchers.

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Production and Purification of Endogenously Modified tRNA-Derived Small RNAs

10.1101/2020.01.21.913749 ◽

2020 ◽

Author(s):

Aleksej Drino ◽

Vera Oberbauer ◽

Conor Troger ◽

Eva Janisiw ◽

Dorothea Anrather ◽

...

Keyword(s):

Small Rnas ◽

Molecular Level ◽

Molecular Function ◽

Biological Processes ◽

Biological Impact ◽

Rna Sequences ◽

Preparative Scale ◽

Transfer Rnas ◽

Wide Range ◽

Biological Sources

ABSTRACTDuring particular stress conditions, transfer RNAs (tRNAs) become substrates of stress-induced endonucleases, resulting in the production of distinct tRNA-derived small RNAs (tsRNAs). These small RNAs have been implicated in a wide range of biological processes, but how isoacceptor and even isodecoder-specific tsRNAs act at the molecular level is still poorly understood. Importantly, stress-induced tRNA cleavage affects only a few tRNAs of a given isoacceptor or isodecoder, raising the question as to how such limited molecule numbers could exert measurable biological impact. While the molecular function of individual tsRNAs is likely mediated through association with other molecules, addressing the interactome of specific tsRNAs has only been attempted by using synthetic RNA sequences. Since tRNAs carry post-transcriptional modifications, tsRNAs are likely modified but the extent of their modifications remains largely unknown. Here, we developed a biochemical framework for the production and purification of specific tsRNAs using human cells. Preparative scale purification of tsRNAs from biological sources should facilitate experimentally addressing as to how exactly these small RNAs mediate the multitude of reported molecular functions.

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Crystallographic Studies of Enzymes

Crystals ◽

10.3390/cryst10010006 ◽

2019 ◽

Vol 10 (1) ◽

pp. 6

Author(s):

T. Doohun Kim ◽

Kyeong Kyu Kim

Keyword(s):

Chemical Reactions ◽

Molecular Level ◽

Biological Processes ◽

Research Papers ◽

Functional Aspects ◽

Wide Range ◽

New Directions ◽

Living Organisms ◽

And Function ◽

Structural Aspects

Enzymes are biological catalysts, which work to accelerate chemical reactions at the molecular level in living organisms. They are major players in the control of biological processes such as replication, transcription, protein synthesis, metabolism, and signaling. Like inorganic catalysts, enzymes function by decreasing the activation energy of chemical reactions, thereby enhancing the rate of the reactions. Enzymes are widely used for chemical, food, pharmaceutical, medicinal, analytical, clinical, forensic, and environmental applications. Therefore, studies on their structure, mechanism, and function, using a wide range of experimental and computational methods, are necessary to understand better enzymes in biological processes. For this special issue, “Crystallographic Studies of Enzymes", we have collected research papers on enzymes with structural aspects and functional aspects; here we briefly discuss the contents of such research papers as follows, with the aim of suggesting new directions of investigation in the fields of enzyme research, protein engineering, and drug development.

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Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier

Current Pharmaceutical Design ◽

10.2174/1381612826666200417143800 ◽

2020 ◽

Vol 26 (27) ◽

pp. 3234-3250

Author(s):

Sushil K. Kashaw ◽

Prashant Sahu ◽

Vaibhav Rajoriya ◽

Pradeep Jana ◽

Varsha Kashaw ◽

...

Keyword(s):

Drug Delivery ◽

Biomedical Engineering ◽

Viral Infections ◽

Slow Release ◽

Molecular Level ◽

Release Kinetics ◽

Biologically Active ◽

Release Process ◽

Rapid Release ◽

Wide Range

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

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A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

Current Organic Chemistry ◽

10.2174/1385272824666200303115444 ◽

2020 ◽

Vol 24 (5) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Ligia S. da Silveira Pinto ◽

Thatyana R. Alves Vasconcelos ◽

Claudia Regina B. Gomes ◽

Marcus Vinícius N. de Souza

Keyword(s):

Side Effects ◽

Anticancer Agents ◽

Heterocyclic Compounds ◽

Biological Activities ◽

Present Review ◽

Pharmacological Properties ◽

Important Group ◽

Wide Range ◽

Anti Inflammatory

Azetidin-2-ones (β-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

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Enantioselective Catalytic C-H Amidations: An Highlight

Catalysts ◽

10.3390/catal11040471 ◽

2021 ◽

Vol 11 (4) ◽

pp. 471

Author(s):

Eleonora Tosi ◽

Renata Marcia de Figueiredo ◽

Jean-Marc Campagne

Keyword(s):

Biological Activity ◽

Chemical Synthesis ◽

Crucial Role ◽

Medicinal Chemistry ◽

Life Sciences ◽

Biological Processes ◽

Chiral Molecules ◽

Material Sciences ◽

Innovative Approaches

The crucial role played by compounds bearing amide functions, not only in biological processes but also in several fields of chemistry, life polymers and material sciences, has brought about many significant discoveries and innovative approaches for their chemical synthesis. Indeed, a plethora of strategies has been developed to reach such moieties. Amides within chiral molecules are often associated with biological activity especially in life sciences and medicinal chemistry. In most of these cases, their synthesis requires extensive rethinking methodologies. In the very last years (2019–2020), enantioselective C-H functionalization has appeared as a straightforward alternative to reach chiral amides. Therein, an overview on these transformations within this timeframe is going to be given.

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Energetics of mesoscale cell turbulence in two-dimensional monolayers

Communications Physics ◽

10.1038/s42005-021-00530-6 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Shao-Zhen Lin ◽

Wu-Yang Zhang ◽

Dapeng Bi ◽

Bo Li ◽

Xi-Qiao Feng

Keyword(s):

Kinetic Energy ◽

Tumor Metastasis ◽

Cell Types ◽

Boltzmann Distribution ◽

Scaling Exponent ◽

Biological Processes ◽

Two Dimensional ◽

Cell Monolayers ◽

Wide Range ◽

Epithelial Cell Monolayers

AbstractInvestigation of energy mechanisms at the collective cell scale is a challenge for understanding various biological processes, such as embryonic development and tumor metastasis. Here we investigate the energetics of self-sustained mesoscale turbulence in confluent two-dimensional (2D) cell monolayers. We find that the kinetic energy and enstrophy of collective cell flows in both epithelial and non-epithelial cell monolayers collapse to a family of probability density functions, which follow the q-Gaussian distribution rather than the Maxwell–Boltzmann distribution. The enstrophy scales linearly with the kinetic energy as the monolayer matures. The energy spectra exhibit a power-decaying law at large wavenumbers, with a scaling exponent markedly different from that in the classical 2D Kolmogorov–Kraichnan turbulence. These energetic features are demonstrated to be common for all cell types on various substrates with a wide range of stiffness. This study provides unique clues to understand active natures of cell population and tissues.

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An Insight into Saponins from Quinoa (Chenopodium quinoa Willd): A Review

Molecules ◽

10.3390/molecules25051059 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1059 ◽

Cited By ~ 7

Author(s):

Khadija El Hazzam ◽

Jawhar Hafsa ◽

Mansour Sobeh ◽

Manal Mhada ◽

Moha Taourirte ◽

...

Keyword(s):

Heat Treatment ◽

Bitter Taste ◽

Biological Activities ◽

Chenopodium Quinoa ◽

Toxic Effects ◽

Mechanical Abrasion ◽

Important Group ◽

The Past ◽

Wide Range ◽

Insight Into

Saponins are an important group found in Chenopodium quinoa. They represent an obstacle for the use of quinoa as food for humans and animal feeds because of their bitter taste and toxic effects, which necessitates their elimination. Several saponins elimination methods have been examined to leach the saponins from the quinoa seeds; the wet technique remains the most used at both laboratory and industrial levels. Dry methods (heat treatment, extrusion, roasting, or mechanical abrasion) and genetic methods have also been evaluated. The extraction of quinoa saponins can be carried out by several methods; conventional technologies such as maceration and Soxhlet are the most utilized methods. However, recent research has focused on technologies to improve the efficiency of extraction. At least 40 saponin structures from quinoa have been isolated in the past 30 years, the derived molecular entities essentially being phytolaccagenic, oleanolic and serjanic acids, hederagenin, 3β,23,30 trihydroxy olean-12-en-28-oic acid, 3β-hydroxy-27-oxo-olean-12en-28-oic acid, and 3β,23,30 trihydroxy olean-12-en-28-oic acid. These metabolites exhibit a wide range of biological activities, such as molluscicidal, antifungal, anti-inflammatory, hemolytic, and cytotoxic properties.

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Acceptance threshold theory can explain occurrence of homosexual behaviour

Biology Letters ◽

10.1098/rsbl.2014.0603 ◽

2015 ◽

Vol 11 (1) ◽

pp. 20140603 ◽

Cited By ~ 22

Author(s):

Katharina C. Engel ◽

Lisa Männer ◽

Manfred Ayasse ◽

Sandra Steiger

Keyword(s):

Animal Species ◽

Reproductive Potential ◽

Search Time ◽

Same Sex ◽

Burying Beetles ◽

Acceptance Threshold ◽

Threshold Theory ◽

Wide Range ◽

Low Levels ◽

Perceived Costs

Same-sex sexual behaviour (SSB) has been documented in a wide range of animals, but its evolutionary causes are not well understood. Here, we investigated SSB in the light of Reeve's acceptance threshold theory. When recognition is not error-proof, the acceptance threshold used by males to recognize potential mating partners should be flexibly adjusted to maximize the fitness pay-off between the costs of erroneously accepting males and the benefits of accepting females. By manipulating male burying beetles' search time for females and their reproductive potential, we influenced their perceived costs of making an acceptance or rejection error. As predicted, when the costs of rejecting females increased, males exhibited more permissive discrimination decisions and showed high levels of SSB; when the costs of accepting males increased, males were more restrictive and showed low levels of SSB. Our results support the idea that in animal species, in which the recognition cues of females and males overlap to a certain degree, SSB is a consequence of an adaptive discrimination strategy to avoid the costs of making rejection errors.

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Subinhibitory Antimicrobial Concentrations: A Review of In Vitro and In Vivo Data

Canadian Journal of Infectious Diseases ◽

10.1155/1992/793607 ◽

1992 ◽

Vol 3 (4) ◽

pp. 193-201 ◽

Cited By ~ 14

Author(s):

George G Zhanel ◽

Daryl J Hoban ◽

Godfrey KM Harding

Keyword(s):

Antimicrobial Activity ◽

Animal Studies ◽

Molecular Level ◽

Bacterial Virulence ◽

Antibacterial Effects ◽

Wide Range ◽

Immune Defences

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.

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