bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic modeling of interannual variation of hydrologic variables
Authors: Dralle David , Karst Nathaniel , Müller Marc , Vico Giulia , Thompson Sally E. 
Published: July 2017

AbstractQuantifying the interannual variability of hydrologic variables (such as annual flow volumes, and solute or sediment loads) is a central challenge in hydrologic modeling. Annual or seasonal hydrologic variables are themselves the integral of instantaneous variations and can be well approximated as an aggregate sum of the daily variable. Process‐based, probabilistic techniques are available to describe the stochastic structure of daily flow, yet estimating interannual variations in the corresponding aggregated variable requires consideration of the autocorrelation structure of the flow time series. Here we present a method based on a probabilistic streamflow description to obtain the interannual variability of flow‐derived variables. The results provide insight into the mechanistic genesis of interannual variability of hydrologic processes. Such clarification can assist in the characterization of ecosystem risk and uncertainty in water resources management. We demonstrate two applications, one quantifying seasonal flow variability and the other quantifying net suspended sediment export.
Lysogeny
Authors: Tan Jason A , Christie Gail E 
Published: July 2017

Abstract

Lysogeny is the harbouring of a dormant bacteriophage (phage) genome in a growing bacterial host. The well‐studied coliphage lambda system provided the paradigm for the role of regulatory proteins in determining the fate of the infected cell (lysis vs lysogeny) as well as the role of environmental signals that influence this decision. Studies of lambda also led to the classic models for site‐specific integration of phage DNA into the bacterial chromosome and for prophage induction during the SOS response by RecA‐mediated repressor cleavage. Beyond a common requirement for a phage‐encoded repressor to maintain lysogeny, phages other than lambda exhibit substantial diversity in the mechanisms underlying regulation of the lysis/lysogeny decision, integration, and prophage induction. Lysogeny has profound consequences on bacterial evolution, leading to acquisition of new traits, enhanced bacterial fitness, gene disruption and/or genomic rearrangements. Phages that are capable of lysogeny provide a reservoir of genetic diversity for their hosts.

Key Concepts

Lysogeny is widespread; prophages are present in ∼1/2 of all sequenced bacterial chromosomes, and many strains carry multiple prophages.

Regulation of the phage lysis/lysogeny decision is an example of a bistable gene expression circuit.

DNA looping occurs when protein molecules which bind to noncontiguous DNA sites also bind to each other, bringing together DNA sites that are normally some distance apart.

Some temperate phages can perpetuate their genomes without integration into the chromosome by plasmid formation, where phage genomes replicate autonomously to keep pace with cell division.

Prophage induction is the activation of a prophage to enter the lytic cycle, either spontaneously or by treating lysogenic cells with various agents.

Specialised recombination protein machineries are required to establish phage integration. These can be host or phage encoded and bind to dsDNA sequences to catalyse recombination.

Site‐specific recombination, which entails breakage and joining of DNA at specific sequences, is used by phages and plasmids and facilitates separation of daughter chromosomes in bacterial cell division.

In transposition, some DNA elements, including phage genomes, move from one site to another by action of transposases encoded by the element.

Temperate phages provide a mobile genetic reservoir that allows bacteria to adapt to new environments. Prophage‐encoded accessory genes provide new traits that can enhance bacterial fitness or virulence.

Lysogeny is transient, allowing bacteria plasticity in their responses to environmental challenges.
Molecular Genetics of Polygenic Hypertension
Authors: Deng Alan Y 
Published: July 2017

Abstract

Essential hypertension is one of the most damaging health risk factors; however, its underlying mechanisms of pathogeneses continue to be undeciphered. To assist this endeavour, investigations utilising human populations and rodent models have revealed numerous genetic building blocks known as quantitative trait loci (QTLs) for blood pressure (BP). Although BP is a quantitatively measured trait manifesting in a continuous variation in heterogeneous populations, each QTL governing it appears to functionally behave as an independent and ‘monogenic’ Mendelian determinant. Mechanistically, multiple QTLs are functionally modularised by epistasis that implies a common pathway or cascade among them, whereas others belong to parallel epistatic modules/pathways. These insights suggest that similar genetic mechanisms probably shepherd the genetic architectures in physiological functions for essential hypertension. Translations of gene discovery to therapeutic targets and diagnostic tools will require biology‐based function validations of specific genes constituting BP QTLs in appropriate animal models.

Key Concepts

There is a regulatory hierarchy in the genetic architecture governing the functional biology of BP determination.

When a master control is removed, modularity and epistatic hierarchy, not a cumulation of minuscule effects, determine the functionality of multiple QTLs on BP.

Mechanistically, separate epistatic modules integrating BP QTLs are best explained by independent pathways, each consisting of multiple components that act in sequential cascades in a pathway.

As there are fewer pathways than the components comprising them, a defective protein product
per se
encoded by a mutated QTL, either qualitatively or quantitatively, can lead to a deficient BP‐regulating pathway of pathogenesis and does not have to directly act on BP as a physiological agent.
Treatment of HepatitisC
Authors: Mecci Ali Jibran , Cheung Michelle 
Published: July 2017

AbstractHepatitis C virus (HCV) infection is a prime example of the speed at which modern medical science has evolved. Within 30 years of its discovery, this virus now has highly effective treatments with response rates up to 100%. HCV infection affects 3% of the world's population and can lead to severe sequelae. Chronic infection may progress to cirrhosis, hepatocellular carcinoma and death. Successful clearance of HCV prevents and may reverse such complications.The discovery of specific drug targets for HCV has revolutionised treatment using direct‐acting antivirals (DAAs). DAAs are potent and safe, allowing individuals who were unable to tolerate interferon treatment, to be cured.The WHO has targeted elimination of HCV by 2030. HCV treatment is triumphant with remarkable new drug developments, but at the same time, still a work in progress.Key ConceptsHepatitis C treatment has evolved in many areas from imaging to treatment.DAAs have improved treatment for patients by increasing SVR and tolerability.Eradication of HCV is now feasible, though barriers remain.HCV is a blood borne virus.Breakthroughs in basic science have been translated into real advances in patient care.
Role of Intermediate Filaments in Cell Locomotion
Authors: Fujiwara Sachiko , Mizuno Kensaku 
Published: July 2017

Abstract

Cell locomotion is essential for diverse pathophysiological processes, including embryogenesis, immune responses, wound healing and cancer metastasis. Intermediate filaments (IFs) are resilient cytoskeleton components that provide structural support and mechanical protection. Accumulating evidence suggests that IFs are dynamic structures that function as a scaffold for signalling networks, which regulate cell locomotion, shape change and mechanical responses. The dynamics of IFs are regulated by posttranslational modifications, crosstalk with other cytoskeletons and association with cell adhesion complexes. IFs differentially regulate cell locomotion, depending on the particular IF protein, the cell type, the cellular context and the mode of cell migration. In general, vimentin filaments promote and keratin filaments inhibit cell locomotion. These cytoplasmic IFs regulate cell locomotion by modulating the localisation and activity of signalling molecules and influencing the stability of cell–cell and cell–substrate adhesion complexes. Nuclear lamin‐A represses cell locomotion by stiffening the nucleus.

Key Concepts

Intermediate filaments (IFs) constitute the resilient cytoskeleton that provides structural support and protects cells from external forces.

IFs function as a dynamic scaffold for signalling networks that regulate locomotion, shape change and mechanical responses.

Cytoplasmic IFs are linked to desmosomes and hemidesmosomes at cell adhesion sites and linker of nucleoskeleton and cytoskeleton (LINC) complexes on the nuclear membrane.

The reorganisation and dynamics of IFs are regulated by posttranslational modifications, crosstalk with other cytoskeletons and association with cell adhesion complexes.

IFs differentially regulate cell locomotion, depending on the particular IF protein, the cell type, the cellular context and the mode of cell migration.

Vimentin IFs generally promote cell locomotion by destabilising desmosomes, promoting focal adhesion maturation and affecting the activity of signalling molecules.

Keratin IFs generally repress cell locomotion by stabilising desmosomes and hemidesmosomes and affecting the localisation and activity of signalling molecules.

Nuclear lamin‐A represses cell locomotion by stiffening the nucleus.

Keratin IFs and Rho signalling are mutually regulated, providing a feedback mechanism during mechanical responses.
Marine Fungi
Authors: Walker Allison K , Vélez Patricia , González María C 
Published: July 2017

Abstract

Marine fungi are an ecological, not a taxonomic, grouping, known primarily as saprotrophs from intertidal zones where they represent an important food source for invertebrates. These osmotrophs also play important roles as mutualists and pathogens in marine systems, and provide a wealth of antimicrobial and bioactive compounds. Currently, our knowledge of marine fungal diversity, biology and ecology comes mainly from intertidal zones such as sand beaches, saltmarshes and mangroves. However, fungi are also present in the water column and at depth, where many discoveries await. With modern molecular techniques and many marine habitats unexplored for fungi, this growing field is poised to make important contributions to our knowledge of the ecological and biogeochemical functions of the oceans. Critical to this is identifying keystone fungal players, their ecological significance, and distribution patterns.

Key Concepts

Marine fungi are an ecological, not a taxonomic assemblage.

Although intertidal saprotrophs are the most studied, fungi exist and are understudied in many marine habitats, including the water column and deep sea.

Many novel compounds have been isolated from marine fungi.

Mycologists must participate in conservation planning to protect the future of marine fungal biodiversity.

Marine fungi are understudied and it is estimated many new species await discovery.
Evolutionary Biology and Mitochondrial Genomics: 50 000 Mitochondrial
DNA
Genomes and Counting
Authors: DeSalle Rob , Hadrys Heike 
Published: July 2017

Abstract

Mitochondrial deoxyribonucleic acid (mtDNA) is a small circular piece of deoxyribonucleic acid (DNA) that resides inside of mitochondria in the cytoplasm of most eukaryotic cells. It has been used by evolutionary biologists for nearly four decades as an analytical tool for everything from tracing human lineages and how people moved across the planet to studies about natural selection. More recently, mtDNA has become even more useful in evolutionary biology as a result of the ease with which the entire molecule can be sequenced. Large numbers of fully sequenced mitochondrial genomes have been generated as a result of next‐generation sequencing (NGS) and powerful bioinformatic approaches.

Key Concepts

Mitochondrial DNA has been used to study evolutionary biology for nearly four decades.

The capacity to sequence whole mitochondrial genomes has become an important part of the expansion of the role of this molecule in evolutionary biology.

MtDNA genome information has contributed to the study of human mtDNA haplogroup studies, animal phylogeography and phylogenetic studies, ancient DNA studies, studies of natural selection and studies of nuclear mitochondrial interactions.

As of 2017, over 500 ancient human mtDNA genomes have been sequenced.

As of 2017, over 100 ancient animal mtDNA genomes have been sequenced.

An important new area where mtDNA genomics will contribute in the future is in using DNA sequence analysis of natural history collection specimens.
Combining Sanford Arylations on Benzodiazepines with the Nuisance Effect
Authors: Khan Raysa , Boonseng Sarote , Kemmitt Paul D. , Felix Robert , Coles Simon J. , Tizzard Graham J. , Williams Gareth , Simmonds Olivia , Harvey Jessica‐Lily , Atack John , Cox Hazel , Spencer John 
Published: July 2017

Abstract5‐Phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐ones react under palladium‐ and visible light photoredox catalysis, in refluxing methanol, with aryldiazonium salts to afford the respective 5‐(2‐arylphenyl) analogues. With 2‐ or 4‐fluorobenzenediazonium derivatives, both fluoroaryl‐ and methoxyaryl‐ products were obtained, the latter resulting from a SNAr on the fluorobenzenediazonium salt (“nuisance effect”). A computational DFT analysis of the palladium‐catalysed and the palladium/ruthenium‐photocalysed mechanism for the functionalization of benzodiazepines indicated that, in the presence of the photocatalyst, the reaction proceeds via a low‐energy SET pathway avoiding the high‐energy oxidative addition step in the palladium‐only catalysed reaction pathway.magnified image
Phase Segregation Enhanced Ion Movement in Efficient Inorganic CsPbIBr2 Solar Cells
Authors: Li Wei , Rothmann Mathias Uller , Liu Amelia , Wang Ziyu , Zhang Yupeng , Pascoe Alexander R. , Lu Jianfeng , Jiang Liangcong , Chen Yu , Huang Fuzhi , Peng Yong , Bao Qiaoliang , Etheridge Joanne , Bach Udo , Cheng Yi‐Bing 
Published: July 2017

AbstractOrganic–inorganic hybrid perovskite solar cells with mixed cations and mixed halides have achieved impressive power conversion efficiency of up to 22.1%. Phase segregation due to the mixed compositions has attracted wide concerns, and their nature and origin are still unclear. Some very useful analytical techniques are controversial in microstructural and chemical analyses due to electron beam‐induced damage to the “soft” hybrid perovskite materials. In this study photoluminescence, cathodoluminescence, and transmission electron microscopy are used to study charge carrier recombination and retrieve crystallographic and compositional information for all‐inorganic CsPbIBr2 films on the nanoscale. It is found that under light and electron beam illumination, “iodide‐rich” CsPbI(1+x)Br(2−x) phases form at grain boundaries as well as segregate as clusters inside the film. Phase segregation generates a high density of mobile ions moving along grain boundaries as ion migration “highways.” Finally, these mobile ions can pile up at the perovskite/TiO2 interface resulting in formation of larger injection barriers, hampering electron extraction and leading to strong current density–voltage hysteresis in the polycrystalline perovskite solar cells. This explains why the planar CsPbIBr2 solar cells exhibit significant hysteresis in efficiency measurements, showing an efficiency of up to 8.02% in the reverse scan and a reduced efficiency of 4.02% in the forward scan, and giving a stabilized efficiency of 6.07%.
Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single‐Molecule Spectroscopy
Authors: Gilburt James A. H. , Sarkar Hajrah , Sheldrake Peter , Blagg Julian , Ying Liming , Dodson Charlotte A. 
Published: July 2017

AbstractThe conformation of the activation loop (T‐loop) of protein kinases underlies enzymatic activity and influences the binding of small‐molecule inhibitors. By using single‐molecule fluorescence spectroscopy, we have determined that phosphorylated Aurora A kinase is in dynamic equilibrium between a DFG‐in‐like active T‐loop conformation and a DFG‐out‐like inactive conformation, and have measured the rate constants of interconversion. Addition of the Aurora A activating protein TPX2 shifts the equilibrium towards an active T‐loop conformation whereas addition of the inhibitors MLN8054 and CD532 favors an inactive T‐loop. We show that Aurora A binds TPX2 and MLN8054 simultaneously and provide a new model for kinase conformational behavior. Our approach will enable conformation‐specific effects to be integrated into inhibitor discovery across the kinome, and we outline some immediate consequences for structure‐based drug discovery.
Gold‐Triggered Uncaging Chemistry in Living Systems
Authors: Pérez‐López Ana M. , Rubio‐Ruiz Belén , Sebastián Víctor , Hamilton Lloyd , Adam Catherine , Bray Thomas L. , Irusta Silvia , Brennan Paul M. , Lloyd‐Jones Guy C. , Sieger Dirk , Santamaría Jesús , Unciti‐Broceta Asier 
Published: July 2017

AbstractRecent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate the fate of molecules in complex biological systems. A bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous gold catalysis and facilitates the activation of a structurally diverse range of therapeutics in cancer cell culture. Furthermore, this solid‐supported catalytic system enabled locally controlled release of a fluorescent dye into the brain of a zebrafish for the first time, offering a novel way to modulate the activity of bioorthogonal reagents in the most fragile and complex organs.
Diastereo‐ and Enantioselective Synthesis of β‐Aminoboronate Esters by Copper(I)‐Catalyzed 1,2‐Addition of 1,1‐Bis[(pinacolato)boryl]alkanes to Imines
Authors: Kim Jeongho , Ko Kwangwook , Cho Seung Hwan 
Published: July 2017

AbstractReported herein is an efficient copper(I)‐catalytic system for the diastereo‐ and enantioselective 1,2‐addition of 1,1‐bis[(pinacolato)boryl]alkanes to protected imines to afford synthetically valuable enantioenriched β‐aminoboron compounds bearing contiguous stereogenic centers. The reaction exhibits a broad scope with respect to protected imines and 1,1‐bis[(pinacolato)boryl]alkanes, thus providing β‐aminoboronate esters with excellent diastereo‐ and enantioselectivity. The synthetic utility of the obtained β‐aminoboronate ester was also demonstrated.
Organic Dye Adsorption by Amphiphilic Tris‐Urea Supramolecular Hydrogel
Authors: Takeshita Juri , Hasegawa Yuki , Yanai Kazushige , Yamamoto Ayumu , Ishii Ayumi , Hasegawa Miki , Yamanaka Masamichi 
Published: July 2017

AbstractThe development of an effective adsorbent for cleansing polluted water is required for environmental purification. In this respect, a supramolecular hydrogel constructed by the self‐assembly of small molecules could be a strong candidate. Adsorption experiments of organic dyes were performed using supramolecular hydrogels of amphiphilic tris‐urea 1. Cationic organic dyes were adsorbed efficiently; indeed, the adsorption of methylene blue was as high as 4.19 mol equivalents relative to 1. Two luminescence peaks were observed in the rhodamine 6G‐adsorbed supramolecular hydrogels, and their ratios varied with the amount of dye adsorbed. Fluorescence microscopy images of the supramolecular hydrogel at lower dye levels exhibited fibrous fluorescence consistent with the fibrous aggregates of 1. According to these results, adsorption may proceed gradually, that is, occurring initially on the fibers and later in the aqueous spaces of the supramolecular hydrogel.
Zero and second‐derivative synchronous fluorescence spectroscopy for the quantification of two non‐classical β‐lactams in pharmaceutical vials: Application to stability studies
Authors: Elzanfaly Eman S. , Youssif Rania M. , Salama Nahla N. , Fayed Ahmed S. , Hendawy Hassan A.M. , Salem Maissa Y. 
Published: July 2017

AbstractThe formation of metal chelates with various ligands may lead to the production of fluorescent chelates or enhance the fluorescence of the chelating agent. This paper describes two sensitive, selective and computer‐solved methods, namely, zero order (SF) and second‐derivative synchronous spectrofluorimetry (SDSFS) for nano‐quantitation of two carbapenems; meropenem (MP) and ertapenem (EP). The methods are based on the chelation of MP with Tb3+ and EP with Zr4+ in buffered organic medium at pH 4.0 to produce fluorescent chelates. In the zero order method, the relative synchronous fluorescence intensity is measured at 327.0 nm at Δλ = 70.0 and 100.0 nm for MP and EP, respectively. The second method utilizes a second‐derivative technique to enhance the method selectivity and emphasize a stability‐indicating approach. The peak amplitudes (2D) of the second‐derivative synchronous spectra were estimated to be 333.06 and 330.06 nm for MP and EP, respectively. The proposed synchronous spectrofluorimetric methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied successfully for the analysis of MP and EP in pure forms, pharmaceutical vials and in synthetic mixtures with different degradants of both drugs. Under optimum conditions, the mole‐ratio method was applied and the co‐ordination ratios of MP–Tb3+ and EP–Zr4+chelates were found to be 1:1 and 1:3. The formation constants for the chelation complexes were evaluated using the Benesi–Hildebrand's equation; the free energy change (ΔG) was also calculated. The results indicated that EP–Zr4+ was more stable than the MP–Tb3+ chelate. Moreover, the developed methods were found to be selective and inexpensive for quantitative determination of both drugs in quality control laboratories at nano‐levels.
Runx3 inhibits melanoma cell migration through regulation of cell shape change
Authors: Zhang Xin , Wang Linghui , Zeng Xianlu , Fujita Takashi , Liu Wenguang 
Published: July 2017

AbstractThe transcription factor Runx3 is a known tumor suppressor gene, and its expression is frequently lost in melanoma. However, the potential contribution of the loss of Runx3 expression to melanoma development and progression remains unclear. In this in vitro study, we demonstrated that ectopic Runx3 re‐expression in B16‐F10 melanoma cells changed the cell shape from elongated and branched to spread and unbranched, which enhanced stress fiber formation, increased the number of mature and fibrillar focal adhesions, and up‐regulated fibronectin expression. In association with the cell shape change, the Runx3 re‐expression in B16‐F10 melanoma cells inhibited cell migration. Moreover, the phenotype of the Runx3 induced cell shape change was partially resembled when the melanoma cells were cultured on a fibronectin‐coated coverslip, suggesting that fibronectin may mediate the Runx3 induced cell shape change of the melanoma cells. Taken together, our findings suggest that Runx3 may regulate cell shape to inhibit melanoma cell migration partly through enhancing stress fiber formation and ECM protein production. Our present study provides further evidence for the idea that cell shape change is potentially correlated with melanoma development and progression.