bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Photoredox/Nickel‐Catalyzed Three‐Component Carbofunctionalization of Alkenes
Authors: García‐Domínguez Andrés , Mondal Rahul , Nevado Cristina
Published: June 2019

The potential of merging photoredox and nickel catalysis to perform multicomponent alkene difunctionalizations under visible‐light irradiation is demonstrated here. Secondary and tertiary alkyl groups, as well as sulfonyl moieties can be added to the terminal position of the double bond with simultaneous arylation of the internal carbon atom in a single step under mild reaction conditions. The process, devoid of stoichiometric additives, benefits from the use of bench‐stable and easy‐to‐handle reagents, is operationally simple, and tolerates a wide variety of functional groups.
Chemoenzymatic Platform for Synthesis of Chiral Organofluorines Based on Type II Aldolases
Authors: Fang Jason , Hait Diptarka , Head‐Gordon Martin , Chang Michelle C. Y.
Published: June 2019

Aldolases are C−C bond forming enzymes that have become prominent tools for sustainable synthesis of complex synthons. However, enzymatic methods of fluorine incorporation into such compounds are lacking due to the rarity of fluorine in nature. Recently, the use of fluoropyruvate as a non‐native aldolase substrate has arisen as a solution. Here, we report that the type II HpcH aldolases efficiently catalyze fluoropyruvate addition to diverse aldehydes, with exclusive (3S)‐selectivity at fluorine that is rationalized by DFT calculations on a mechanistic model. We also measure the kinetic parameters of aldol addition and demonstrate engineering of the hydroxyl group stereoselectivity. Our aldolase collection is then employed in the chemoenzymatic synthesis of novel fluoroacids and ester derivatives in high stereopurity (d.r. 80–98 %). The compounds made available by this method serve as precursors to fluorinated analogs of sugars, amino acids, and other valuable chiral building blocks.
Half‐sandwich Ir (III) and Rh (III) complexes as catalysts for water oxidation with double‐site
Authors: Li Peng , Liu Jin‐Bao , Han Sheng , Deng Wei , Yao Zi‐Jian
Published: June 2019

A series of neutral binuclear iridium and rhodium complexes were synthesized based on bis‐imine ligands under mild conditions. These half‐sandwich late transition metal complexes were isolated in good yields and characterized by elemental analysis, 1H NMR, 13C NMR, HR‐MS, and FT‐IR spectroscopies, and the solid state structure of complexes 1 and 2 were further confirmed by single‐crystal X‐ray diffraction. Cyclic voltammetry (CV) characterization indicated that the complex 1 has the best catalyst for water oxidation process with TOF of 0.8 s−1 at low overpotential of 0.325 V in methanol‐phosphate buffer. The proposed double‐site water oxidation mechanism had been also speculated.
Individuals in the prediabetes stage exhibit reduced hippocampal tail volume and executive dysfunction
Authors: Dong Sun , Dongwei Lu , Zhang Junjian , Liang Jinyu , Sun Zhenmeng , Fang Jian
Published: June 2019

Introduction

High glucose levels are associated with cognitive impairment and total hippocampal volume reductions. However, the effects of the blood glucose level on hippocampal subfield volumes remain unclear, especially in the prediabetes stage.

Methods

Sixty participants were enrolled in this cross‐sectional study and were divided into the nondiabetes, prediabetes, and diabetes groups according to their medical history and A1c level. A full battery of neuropsychological tests was used to assess the global cognition, executive function, attention, verbal fluency, working memory, immediate memory, and delayed memory. FreeSurfer 6.0 was used for the hippocampus parcellation. Hippocampal subfield volumes were adjusted by intracranial volume. Analyses of covariance, multiple linear regression, and partial correlation analysis were used to explore the relationship between A1c level, cognitive function, and hippocampal subfields volume, in which age, sex, education years, body mass index, history of hypertension, level of cholesterol, and the presence of ApoE4‐positive status were adjusted.

Results

Significant differences in the total left hippocampal volume (p = 0.046) and left hippocampal tail volume (p = 0.014) were noted among three groups. Significant correlation was identified between the A1c level and the volume of left hippocampal tail (r = −0.334, p = 0.009) after adjusting all the covariants. Increased A1c level was significantly associated with executive dysfunction, as assessed by trail making test B (R = 0.503, p = 0.0016) and Stroop test C (R = 0.506, p = 0.001).

Conclusions

Our results support that the left hippocampal tail volume may be served as an early marker of diabetes‐related brain damage, associated with executive dysfunction. Clinicians should pay closer attention to adults in the prediabetes stage to prevent later cognitive impairment.
Adsorption Kinetics of Cellulase and Xylanase Immobilized on Magnetic Mesoporous Silica
Authors: Jannah Sulaiman Nurul , Mansor Azmi Fadziyana , Rahman Roshanida A. , Illias Rosli M. , Shaarani Shalyda M.
Published: June 2019

The adsorption kinetics of cellulase and xylanase immobilized on magnetically separable, hierarchically ordered mesocellular mesoporous silica (M‐HMMS) was investigated. The adsorption of cellulase on M‐HMMS followed pseudo‐second‐order kinetics while the xylanase adsorption followed the Avrami model. Intraparticle and film diffusion also affected this process. These results enable in‐depth knowledge of the cellulase and xylanase adsorption mechanisms on M‐HMMS for better future applications by improving the stability of the immobilization.
An Azo Coupling Strategy for Protein 3‐Nitrotyrosine Derivatization
Authors: Liu Yuxin , Zhou Pengcheng , Da Honghong , Jia Huiyi , Bai Feifei , Hu Guodong , Zhang Baoxin , Fang Jianguo
Published: June 2019

Herein, a strategy for the selective derivatization of 3‐nitrotyrosine‐containing proteins using the classic azo coupling reaction as the key step is described. This novel approach featured multiple advantages and was successfully applied to detect picomole levels of protein tyrosine nitration in biological samples.
Heterojunction α‐Fe2O3/ZnO Films with Enhanced Photocatalytic Properties Grown by Aerosol‐Assisted Chemical Vapour Deposition
Authors: Jiamprasertboon Arreerat , Kafizas Andreas , Sachs Michael , Ling Min , Alotaibi Abdullah M. , Lu Yao , Siritanon Theeranun , Parkin Ivan P. , Carmalt Claire J.
Published: June 2019

Type I heterojunction films of α‐Fe2O3/ZnO are reported here as a non‐titania based photocatalyst, which shows remarkable enhancement in the photocatalytic properties towards stearic acid degradation under UVA‐light exposure (λ=365 nm), with a quantum efficiency of ξ=4.42±1.54×10−4 molecules degraded/photon, which was about 16 times greater than that of α‐Fe2O3, and 2.5 times greater than that of ZnO. Considering that the degradation of stearic acid requires 104 electron transfers for each molecule, this represents an overall quantum efficiency of 4.60 % for the α‐Fe2O3/ZnO heterojunction. Time‐resolved transient absorption spectroscopy (TAS) revealed the charge‐carrier behaviour responsible for this increase in activity. Photogenerated electrons, formed in the ZnO layer, were transferred into the α‐Fe2O3 layer on the pre‐μs timescale, which reduced electron–hole recombination. This increased the lifetime of photogenerated holes formed in ZnO, which oxidise stearic acid. The heterojunction α‐Fe2O3/ZnO films grown herein show potential environmental applications as coatings for self‐cleaning windows and surfaces.
Chirally Twisted Ultrathin Polydopamine Nanoribbons: Synthesis and Spontaneous Assembly of Silver Nanoparticles on Them
Authors: Awasthi Anand Kumar , Bhagat Somnath D. , Ramakrishnan Reshma , Srivastava Aasheesh
Published: June 2019

Polydopamine (PDA) is a synthetic polymeric material with immense potential in biomedical and surface functionalization applications. Herein, we have screened self‐assemblies formed by Phenylalanine‐based amphiphiles (Phe‐AMPs) as soft templates for preparing chiral PDA nanostructures. Our study revealed that the amphiphile2endowed with a primary amine residue afforded chirally‐twisted ultrathin nanoribbons of PDA under optimized conditions. The chirality at the Phe residue of2modulated the twist‐chirality of the PDA nanoribbons; thel‐2resulted in nanoribbons with right‐handed twist, whereas thed‐2induced a left‐handed twist to the ribbons. The racemic mixture of these two amphiphiles produced flat, achiral tapes. The PDA ribbon thickness was ≈5.86±0.40 nm, whereas its width and length were ≈133.5±3.2 nm and >5000 nm, respectively. Upon dialysis, hollow PDA nanotubes were obtained due to curling of the PDA nanoribbons. These PDA‐nanoarchitectures were employed to spontaneously form and assemble Ag‐nanoparticles along the edges of the PDA nanoribbons. In this work we are reporting chirality controlled synthesis of PDA nanostructures for the first time.
p16 immunocytochemistry on aspirate smears of neck masses: Another option for determining the HPV status in metastatic head and neck squamous cell carcinoma
Authors: Griffith Christopher C.
Published: June 2019

A recent study has demonstrated the potential for performing p16 immunocytochemistry on routinely collected aspirate smears of metastatic squamous cell carcinoma of the head and neck. In some cases, p16 immunocytochemistry on already collected aspirate smears may be the only available option, so this could be a valuable method that eliminates the need for repeat sampling before clinical staging and management decisions.
Stereochemistry, Stereodynamics, and Redox and Complexation Behaviors of 2,2′‐Diaryl‐1,1′‐Biazulenes
Authors: Tsuchiya Takahiro , Katsuoka Yuka , Yoza Kenji , Sato Hiroyasu , Mazaki Yasuhiro
Published: June 2019

2,2′‐Diaryl‐1,1′‐biazulenes were synthesized and electronic communication between the azulene subunits was suggested based on redox measurements. The linkage of azulene at the 1‐position also appeared to increase the HOMO levels. In addition, cyclic voltammetry measurements of 2‐arylazulenes showed a return peak associated with the oxidation, which was not observed for azulene. The stabilization of the single‐electron oxidant may be due to the SOMO‐HOMO energy inversion phenomenon. X‐ray crystallography of the azulene dimers revealed that this species possessed a syn‐type structure in which both aryl groups in the 2‐positions formed π‐stacks. The twisted structure was indicated to be in the (R)‐ or (S)‐configuration for all molecules in the unit cell. Spontaneous resolution was also shown. Furthermore, from the solid circular dichroism (CD) spectral measurements, the relationship between the absolute configuration of the molecules and the CD spectra was determined. A racemization rotational barrier of ca. 27 kcal mol−1 was calculated. Moreover, the pyridylazulene dimer cyclized upon reaction with PdCl2 to form a 3 : 3 complex, in which the biazulene units cyclized to give ratios between the (R)‐ and (S)‐forms of either 2 : 1 or 1 : 2.
Anti‐inflammatory and diuretic effects of the diterpene ent‐dihydrotucumanoic acid
Authors: Alonso‐Castro Angel Josabad , Arana‐Argáez Víctor E. , Deveze‐Alvarez Martha Alicia , Chan‐Zapata Ivan , Torres‐Romero Julio Cesar , Carranza‐Álvarez Candy , Luna‐Rubio Sarahí , González‐Chávez Marco M. , Zapata‐Morales Juan R. , Aragón‐Martínez Othoniel H. , Ramírez‐Morales Marco Antonio
Published: June 2019

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent‐dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti‐inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti‐inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ‐carrageenan‐induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 μg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500–1,000 μg/mL showed moderate genotoxicity. In LPS‐stimulated macrophages, DTA showed IC50 values of 74.85 μg/mL (TNF‐α) and 58.12 μg/mL (NO), whereas the maximum inhibition of IL‐6 (24%) and IL‐1β (36%) was recorded at 200 μg/mL. DTA induced in vivo anti‐inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti‐inflammatory activity of DTA seems to be associated with the decrease in the release of TNF‐α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L‐NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti‐inflammatory and diuretic effects, but lacked antioxidant effects.
Modeling genetic epilepsies in a dish
Authors: Niu Wei , Parent Jack M.
Published: June 2019

Human pluripotent stem cells (hPSCs), including embryonic and induced pluripotent stem cells, provide a powerful platform for mechanistic studies of disorders of neurodevelopment and neural networks. hPSC models of autism, epilepsy, and other neurological disorders are also advancing the path toward designing and testing precision therapies. The field is evolving rapidly with the addition of genome‐editing approaches, expanding protocols for the two‐dimensional (2D) differentiation of different neuronal subtypes, and three‐dimensional (3D) human brain organoid cultures. However, the application of these techniques to study complex neurological disorders, including the epilepsies, remains a challenge. Here, we review previous work using both 2D and 3D hPSC models of genetic epilepsies, as well as recent advances in the field. We also describe new strategies for applying these technologies to disease modeling of genetic epilepsies, and discuss current challenges and future directions.
Seed banks trigger ecological resilience in subalpine meadows abandoned after arable farming on the Tibetan Plateau
Authors: Ma Miaojun , Baskin Carol C. , Li Wenjin , Zhao Yunpeng , Zhao Yin , Zhao Liang , Chen Ning , Du Guozhen
Published: June 2019

Although long‐term agricultural activity frequently decreases biodiversity, it remains unclear whether such biodiversity losses are readily reversible. There is no doubt that the important ecological function of seed bank is ecological memory, but few researchers have explored the role of seed banks in grassland ecosystem resilience and threshold theory. We used a space‐for‐time subrogation method, i.e., a natural meadow (never farmed but used for moderate gazing) and meadows farmed for 30 yr and then abandoned for 1, 10, and 20 yr, to determine if the biodiversity/ecosystem of subalpine meadows could be reversed to the natural vegetation state and to investigate the role of soil seed banks in grassland ecosystem restoration and resilience. After 20 yr of natural regeneration, aboveground vegetation composition and properties had recovered to the natural meadow state, suggesting that critical thresholds were not crossed. Seed bank composition and structure exhibited almost no change after agricultural disturbance for decades. The persistent seed bank had the highest contribution to vegetation regeneration in the 1‐yr abandoned field, which had the highest seed density. Similarity between the seed bank and aboveground vegetation and seed density decreased with years since abandonment. Since the seed bank still reflected the desired state, the system had inherent resilience and had not have crossed the transition threshold. Thus, high‐diversity persistent seed banks are an important indicator of high resilience of this ecosystem. High similarity between the seed bank and vegetation in early‐abandoned fields may indicate that ecological resilience is triggered and be a warning signal that interventions are needed to avoid a state transition. In applying alternative stable state theory to ecological restoration, much attention should be given to the soil seed bank.
Managing farm ponds as breeding sites for amphibians: key trade‐offs in agricultural function and habitat conservation
Authors: Swartz Timothy M. , Miller James R.
Published: June 2019

Millions of farm ponds have been constructed in agricultural landscapes around the globe. These ponds are built to support a variety of functions, including erosion control, cattle grazing, and recreational fishing, but their role as breeding habitat for amphibians remains poorly understood. We addressed this knowledge gap by studying farm ponds in the eastern Great Plains of the United States, a pond‐dense region dominated by agriculture. We used field surveys and occupancy modeling to identify the important biophysical components of amphibian habitat and to assess the species‐specific effects of cattle and fish presence on breeding occupancy. We next used a chronosequence to determine whether pond renovation, which often occurs when ponds are about 40 yr old, threatens the development of amphibian habitat. Nine amphibian species bred in the farm ponds that we surveyed, and the relationship between breeding occupancy and habitat variables varied by species. We found that the pH conditions associated with amphibian breeding occupancy were significantly more likely to occur in older ponds (>50 yr old). Emergent vegetation cover was also associated with increased breeding probability and rarely reached high levels in newer ponds. Since the older ponds with suitable habitat are at an age where renovation is likely needed to restore their agricultural function, this habitat may be at risk. We suggest that conservation of amphibians in farm ponds in the United States will require adopting renovation and management practices that balance the multiple uses of these sites and maintain a mosaic of pond successional states.
Does the heritability of chronic low back pain depend on how the condition is assessed?
Authors: Carvalho‐E‐Silva Ana Paula M. C. , Harmer Alison R. , Pinheiro Marina B. , Madrid‐Valero Juan J. , Ferreira Manuela , Ordoñana Juan R. , H.Ferreira Paulo
Published: June 2019

Background

Although the influence of genetics on chronic low back pain (LBP) has been previously examined, few studies have investigated whether the impact of genetic factors on LBP depends on how the condition is assessed.

Methods

We investigated the contribution of genetics and environment on chronic LBP: lifetime prevalence, pain intensity (recent and worst) and activity limitation (anytime and recent) in a cross‐sectional study with 1,598 adult twins. All twins answered a self‐reported questionnaire about health‐related questions. We conducted classic twin analyses using structural equation models to estimate the genetic and environmental influences in LBP phenotypes.

Results

We found a heritability of 26% (95%CI: 0.09–0.42) for lifetime chronic LBP; 36% (95%CI: 0.18–0.52) and 25% (95%CI: 0.03–0.46) for activity limitation due to chronic LBP, related to lifetime and most recent episode, respectively; and heritability of 35% (95%CI: 0.11–0.55) for pain intensity associated with the most recent episode. Genetics showed no significant influence in pain intensity experienced during the worst LBP episode.

Conclusions

Genetic factors appear to significantly contribute to the variance in chronic LBP including lifetime chronic LBP, activity limitation and pain intensity associated with more recent episodes of LBP, but not for pain intensity associated with people's report of the worst pain episode. Heritability estimates was fairly similar across different LBP outcomes in a population‐based twin sample, and not dependent on how it is assessed or experienced. However, we could not detect any significant heritability for a report of intensity experienced during the worst LBP episode experienced.

Significance

Heritability estimates were similar for different low back pain definitions, and therefore not dependent on how chronic low back pain is experienced or assessed, in the same population‐based sample.
Distinct element modelling of the in‐plane cyclic response of URM walls subjected to shear‐compression
Authors: Malomo Daniele , DeJong Matthew J. , Penna Andrea
Published: June 2019

The in‐plane capacity of unreinforced masonry (URM) elements may vary considerably depending on several factors, including boundary conditions, aspect ratio, vertical overburden, and masonry texture. Since the overall system resistance mainly relies on the in‐plane lateral capacity of URM components when out‐of‐plane modes are adequately prevented, the structural assessment of URM structures could benefit from advanced numerical approaches able to account for these factors simultaneously. This paper aims at enhancing and optimising the employment of the distinct element method, currently confined to the analysis of local mechanisms of reduced‐scale dry‐joint blocky assemblies, with a view to simulate the experimentally observed responses of a series of URM full‐scale specimens with mortared joints subjected to quasi‐static in‐plane cyclic loading. To this end, a mesoscale modelling approach is proposed that employs a simplified microscale modelling approach to effectively capture macroscale behaviour. Dynamic relaxation schemes are employed, in combination with time, size, and mass‐scaling procedures, to decrease computational demand. A new methodology for numerically describing both unit, mortar and hybrid failure modes, also including masonry crushing due to high‐compression stresses, is proposed. Empirical and homogenisation formulae for inferring the elastic properties of interface between elements are also verified, enabling the proposed approach to be applied more broadly. Using this modelling strategy, the interaction between stiffness degradation and energy dissipation rate was accounted for numerically. Although the models marginally underestimate the energy dissipation in the case of slender piers, a good agreement was obtained in terms of lateral strength, hysteretic response, and crack pattern.
Imidacloprid Poisoning of Songbirds Following a Drench Application of Trees in a Residential Neighborhood in California, USA
Authors: Rogers Krysta H. , McMillin Stella , Olstad Katie J. , Poppenga Robert H.
Published: June 2019

In March 2017, 26 American goldfinches (Spinus tristis) were found dead following a drench application of imidacloprid in California (USA). Identical seed fragments were present in the digestive tracts. Imidacloprid was detected in 4 separate pooled samples from 18 birds, in crop/gizzard contents (4.8 ± 1.3 ppm; range 2.2–8.5 ppm) and liver tissues (3.9 ± 0.6 ppm; range 2.1–4.8 ppm). We suspect that fallen elm (Ulmus sp.) seeds were contaminated with imidacloprid during the drench application and subsequently ingested, resulting in acute toxicity and death. Environ Toxicol Chem 2019;38:1724–1727. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
PAMAM: Power analysis in multiancestry admixture mapping
Authors: Gautam Yadu , Ghandikota Sudhir , Chen Siqi , Mersha Tesfaye B.
Published: June 2019

Admixed populations arise when two or more previously isolated populations interbreed. Admixture mapping (AM) methods are used for tracing the ancestral origin of disease‐susceptibility genetic loci in the admixed population such as African American and Latinos. AM is different from genome‐wide association studies in that ancestry rather than genotypes are tracked in the association process. The power and sample size of AM primarily depend on proportion of admixture and differences in the risk allele frequencies among the ancestral populations. Ensuring sufficient power to detect the effect of ancestry on disease susceptibility is critical for interpretability and reliability of studies using AM approach. However, there is no power and sample size analysis tool existing for AM studies in admixed population. In this study, we developed power analysis of multiancestry AM (PAMAM) to estimate power and sample size for two‐way and three‐way population admixtures. PAMAM is the first web‐based bioinformatics tool developed to calculate power and sample size in admixed population under a variety of genetic and disease phenotype models. It is a valuable resource for investigators to design a cost‐efficient study and develop grant application to pursue AM studies. PAMAM is built on JavaScript back‐end with HTML front‐end. It is accessible through any modern web browser such as Firefox, Internet Explorer, and Google Chrome regardless of operating system. It is a user‐friendly tool containing links for support information including user manual and examples, and freely available at https://research.cchmc.org/mershalab/PAMAM/login.html.
THE GENERIC STATUS OF PERENNIAL SPECIES OF LINANTHUS (POLEMONIACEAE)
Authors: Patterson Robert
Published: June 2019

The perennial species of Linanthus have been regarded as members of a number of different genera in the Polemoniaceae, the most notable being Leptodactylon, Linanthus, and Linanthastrum. A reexamination of the characters used in taxonomic treatments of this species complex, plus a consideration of new or as yet little considered characters suggests that these species are best included in Linanthus. The genus Linanthastrum is rejected herein based on its original circumscription.
A NEW APPROACH TO THE EXPERIMENTAL PROPAGATION OF BRYOPHYTES
Authors: Shaw Jonathan
Published: June 2019

A new method for the experimental propagation of bryophytes involves drying the gametophytes, grinding them to a fine powder, and sowing the powder on native or other kinds of soil. The method is easy and rapid, and results in regeneration of normal morphology. The method can be applied to studies of systematic relationships among congeneric species, ecotypic differentiation, and competition.
TRANSFER OF EREMOTROPA SCIAPHILA TO MONOTROPASTRUM (ERICACEAE: MONOTROPOIDEAE)
Authors: Wallace Gary D.
Published: June 2019

Andres (1953) described Eremotropa sciaphila based on a single collection by Otto Schoch from Yunnan, China made in 1916. Andres's paper came to my attention during preparation of a monograph of the Monotropoideae (Wallace, 1975), and the specimen was finally located and examined. In this paper I shall the consider the description and identity of this most interesting plant.
miR‐330 suppresses EMT and induces apoptosis by downregulating HMGA2 in human colorectal cancer
Authors: Mansoori Behzad , Mohammadi Ali , Naghizadeh Sanaz , Gjerstorff Morten , Shanehbandi Dariush , Shirjang Solmaz , Najafi Souzan , Holmskov Uffe , Khaze Vahid , Duijf Pascal H.G. , Baradaran Behzad
Published: June 2019

MicroRNAs (miRNAs) are important molecular regulatorsof cellular signaling and behavior. They alter gene expression by targeting messenger RNAs, including those encoding transcriptional regulators, such as HMGA2. While HMGA2 is oncogenic in various tumors, miRNAs may be oncogenic or tumor suppressive. Here, we investigate the expression of HMGA2 and the miRNA miR‐330 in a patient with colorectal cancer (CRC) samples and their effects on oncogenic cellular phenotypes. We found that HMGA2 expression is increased and miR‐330 expression is decreased in CRCs and each predicts poor long‐term patient survival. Stably increased miR‐330 expression in human colorectal cancer cells (HCT116) and SW480 CRC cell lines downregulate the oncogenic expression of HMGA2, a predicted miR‐330 target. Additionally, this promotes apoptosis and decreases cell migration and viability. Consistently, it also decreases protein‐level expression of markers for epithelial‐to‐mesenchymal‐transition (Snail‐1, E‐cadherin, and Vascular endothelial growth factor receptors) and transforming growth factor β signaling (SMAD3), as well as phospho‐ Protein kinase B (AKT) and phospho‐STAT3 levels. We conclude that miR‐330 acts as a tumor suppressor miRNA in CRC by suppressing HMGA2 expression and reducing cell survival, proliferation, and migration. Thus, we identify miR‐330 as a promising candidate for miRNA replacement therapy for patients with CRC.
Expression of the double‐stranded RNA‐dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion
Authors: Piazzi Manuela , Bavelloni Alberto , Greco Sara , Focaccia Enrico , Orsini Arianna , Benini Stefania , Gambarotti Marco , Faenza Irene , Blalock William L.
Published: June 2019

Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress‐activated kinase double‐stranded RNA‐dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS‐2 osteosarcoma cell lines were stably transfected with wild‐type or dominant‐negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS‐2), enhanced cellular migration (U2OS), and invasive migration (SaOS‐2). In contrast, overexpression of DN‐PKR inhibited attachment‐independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.
SCD1 regulates the AMPK/SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle
Authors: Dziewulska Anna , Dobosz Aneta M. , Dobrzyn Agnieszka , Smolinska Agnieszka , Kolczynska Katarzyna , Ntambi James M. , Dobrzyn Pawel
Published: June 2019

Stearoyl‐CoA desaturase (SCD) is a rate‐limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids. It plays an important role in regulating skeletal muscle metabolism. Lack of the SCD1 gene increases the rate of fatty acid β‐oxidation through activation of the AMP‐activated protein kinase (AMPK) pathway and the upregulation of genes that are related to fatty acid oxidation. The mechanism of AMPK activation under conditions of SCD1 deficiency has been unclear. In the present study, we found that the ablation/inhibition of SCD1 led to AMPK activation in skeletal muscle through an increase in AMP levels whereas muscle‐specific SCD1 overexpression decreased both AMPK phosphorylation and the adenosine monophosphate/adenosine triphosphate (AMP/ATP) ratio. Changes in AMPK phosphorylation that were caused by SCD1 down‐ and upregulation affected NAD+ levels following changes in NAD+‐dependent deacetylase sirtuin‐1 (SIRT1) activity and histone 3 (H3K9) acetylation and methylation status. Moreover, mice with muscle‐targeted overexpression of SCD1 were more susceptible to high‐fat diet‐induced lipid accumulation and the development of insulin resistance compared with wild‐type mice. These data show that SCD1 is involved in nucleotide (ATP and NAD+) metabolism and suggest that the SCD1‐dependent regulation of muscle steatosis and insulin sensitivity are mediated by cooperation between AMPK‐ and SIRT1‐regulated pathways. Altogether, the present study reveals a novel mechanism that links SCD1 with the maintenance of metabolic homeostasis and insulin sensitivity in skeletal muscle.
When Consumers Prefer Bundles with Noncomplementary Items to Bundles with Complementary Items: The Role of Mindset Abstraction
Authors: Karataş Mustafa , Gürhan‐Canli Zeynep
Published: June 2019

Past research shows that consumers evaluate bundles with complementary items more favorably than they evaluate bundles with noncomplementary items. In a series of four experiments that involve evaluation, willingness to pay, and real choice, we show that this well‐established effect is moderated by the level of mindset abstraction. Complementarity (vs. noncomplementarity) among bundle items prompts relatively concrete (vs. abstract) thinking (study 1). Consequently, consumers evaluate complementary (vs. noncomplementary) bundles more favorably when they think in more concrete (vs. abstract) terms (study 2) or when the consumption context involves lower (vs. higher) spatial (study 3) or temporal (study 4) distance. These effects are mediated by consumers’ heightened sense of “feeling right” during decision making under construal fit (study 4). Finally, the level of complementarity among bundle items differentially influences mental abstraction because of consumers’ tendency to perceive bundles as a single inseparable unit. Therefore, the effect attenuates when consumers adopt a separating—rather than a connecting—mindset (study 3). Overall, this work significantly extends past research on product bundles and offers several managerial implications.
Clinical translation of gene medicine
Authors: Wang Fazhan , Qin Zhou , Lu Hansi , He Siyan , Luo Jing , Jin Chaohui , Song Xiangrong
Published: June 2019

Gene therapy has recently witnessed accelerated progress as a new therapeutic strategy with the potential to treat a range of inherited and acquired diseases. Billions of dollars have been invested in basic and clinical research on gene medicine, with ongoing clinical trials focused on cancer, monogenic diseases, cardiovascular diseases and other refractory diseases. Advances addressing the inherent challenges of gene therapy, particularly those related to retaining the delivery efficacy and minimizing unwanted immune responses, provide the basis for the widespread clinical application of gene medicine. Several types of genes delivered by viral or non‐viral delivery vectors have demonstrated encouraging results in both animals and humans. As augmented by clinical indications, gene medicine techniques have rapidly become a promising alternative to conventional therapeutic strategies because of their better clinical benefit and lower toxicities. Their application in the clinic has been extensive as a result of the approval of many gene therapy drugs in recent years. In this review, we provide a comprehensive overview of the clinical translation of gene medicine, focusing on the key events and latest progress made regarding clinical gene therapy products. We also discuss the gene types and non‐viral materials with respect to developing gene therapeutics in clinical trials.
Intravoxel Incoherent Motion Diffusion‐Weighted Imaging for Evaluation of the Cell Density and Angiogenesis of Cirrhosis‐Related Nodules in an Experimental Rat Model: Comparison and Correlation With Dynamic Contrast‐Enhanced MRI
Authors: Luo Jiawen , Zhou Kunpeng , Zhang Bin , Luo Ning , Bian Jie
Published: June 2019

Background

Intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) and dynamic contrast‐enhanced MRI (DCE‐MRI) are sensitive imaging modalities for detecting liver lesions, but their value in evaluating cirrhosis‐related nodules remains unclear.

Purpose

To investigate whether IVIM‐DWI and DCE‐MRI can differentiate different types of cirrhosis‐related nodules, and whether these modalities can monitor changes in cell density and angiogenesis during the malignant transformation of cirrhosis‐related nodules in a rat model

Study Type

Prospective.

Animal Model

Thirty‐five male Sprague–Dawley rats with 106 cirrhosis‐related nodules (19 regenerative nodules [RNs], 47 dysplastic nodules [DNs], and 40 hepatocellular carcinomas [HCCs]).

Field Strength/Sequence

IVIM‐DWI and DCE sequence at 3.0T MRI.

Assessment

IVIM‐DWI parameters (D, D*, f, and apparent diffusion coefficient [ADC]) and DCE‐MRI parameters (Ktrans, Kep, and Ve) were calculated by two radiologists using postprocessing software. The “cell density” and “unpaired arterial ratio” were analyzed with a microscope by two pathologists.

Statistical Tests

MRI parameters were compared among the different types of nodules by one‐way analysis of variance or the Kruskal–Wallis test. The Pearson correlation test was used to analyze the correlation of MRI parameters with the pathological types of nodules, cell density, and unpaired arterial ratio.

Results

The Ktrans, Kep, and Ve values of HCCs were significantly higher than those of DNs and RNs. D and ADC values were significantly lower in HCCs than in DNs and RNs. There were moderate positive correlations of Ktrans with the pathological types of nodules and the unpaired arterial ratio. Moderate negative correlations were observed among D, ADC, and the pathological types of nodules, between D and cell density, and between ADC and cell density.

Data Conclusion

IVIM‐DWI and DCE‐MRI are valuable in differentiating different types of cirrhotic‐related nodules. D and ADC are correlated with changes in cell density during the malignant transformation of cirrhosis‐related nodules, while Ktrans is correlated with increased angiogenesis.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2020;51:812–823.
On the limit Sobolev regularity for Dirichlet and Neumann problems on Lipschitz domains
Authors: Costabel Martin
Published: June 2019

We construct a bounded C1 domain Ω in for which the regularity for the Dirichlet and Neumann problems for the Laplacian cannot be improved, that is, there exists f in such that the solution of in Ω and either on or on is contained in but not in for any . An analogous result holds for Sobolev spaces with .
SPARE: Sparse‐view reconstruction challenge for 4D cone‐beam CT from a 1‐min scan
Authors: Shieh Chun‐Chien , Gonzalez Yesenia , Li Bin , Jia Xun , Rit Simon , Mory Cyril , Riblett Matthew , Hugo Geoffrey , Zhang Yawei , Jiang Zhuoran , Liu Xiaoning , Ren Lei , Keall Paul
Published: June 2019

Purpose

Currently, four‐dimensional (4D) cone‐beam computed tomography (CBCT) requires a 3–4 min full‐fan scan to ensure usable image quality. Recent advancements in sparse‐view 4D‐CBCT reconstruction have opened the possibility to reduce scan time and dose. The aim of this study is to provide a common framework for systematically evaluating algorithms for 4D‐CBCT reconstruction from a 1‐min scan. Using this framework, the AAPM‐sponsored SPARE Challenge was conducted in 2018 to identify and compare state‐of‐the‐art algorithms.

Methods

A clinically realistic CBCT dataset was simulated using patient CT volumes from the 4D‐Lung database. The selected patients had multiple 4D‐CT sessions, where the first 4D‐CT was used as the prior CT, and the rest were used as the ground truth volumes for simulating CBCT projections. A GPU‐based Monte Carlo tool was used to simulate the primary, scatter, and quantum noise signals. A total of 32 CBCT scans of nine patients were generated. Additional qualitative analysis was performed on a clinical Varian and clinical Elekta dataset to validate the simulation study. Participants were blinded from the ground truth, and were given 3 months to apply their reconstruction algorithms to the projection data. The submitted reconstructions were analyzed in terms of root‐mean‐squared‐error (RMSE) and structural similarity index (SSIM) with the ground truth within four different region‐of‐interests (ROI) — patient body, lungs, planning target volume (PTV), and bony anatomy. Geometric accuracy was quantified as the alignment error of the PTV.

Results

Twenty teams participated in the challenge, with five teams completing the challenge. Techniques involved in the five methods included iterative optimization, motion‐compensation, and deformation of the prior 4D‐CT. All five methods rendered significant reduction in noise and streaking artifacts when compared to the conventional Feldkamp–Davis–Kress (FDK) algorithm. The RMS of the three‐dimensional (3D) target registration error of the five methods ranged from 1.79 to 3.00 mm. Qualitative observations from the Varian and Elekta datasets mostly concur with those from the simulation dataset. Each of the methods was found to have its own strengths and weaknesses. Overall, the MA‐ROOSTER method, which utilizes a 4D‐CT motion model for temporal regularization, had the best and most consistent image quality and accuracy.

Conclusion

The SPARE Challenge represents the first framework for systematically evaluating state‐of‐the‐art algorithms for 4D‐CBCT reconstruction from a 1‐min scan. Results suggest the potential for reducing scan time and dose for 4D‐CBCT. The challenge dataset and analysis framework are publicly available for benchmarking future reconstruction algorithms.
Class I and II histone deacetylase expression is not altered in human amyotrophic lateral sclerosis: Neuropathological and positron emission tomography molecular neuroimaging evidence
Authors: Dios Amanda M. , Babu Suma , Granucci Eric J. , Mueller Kaly A. , Mills Alexandra N. , Alshikho Mohamad J. , Zürcher Nicole R. , Cernasov Paul , Gilbert Tonya M. , Glass Jonathan D. , Berry James D. , Atassi Nazem , Hooker Jacob M. , Sadri‐Vakili Ghazaleh
Published: June 2019

Introduction

There is an unmet need for mechanism‐based biomarkers and effective disease modifying treatments in amyotrophic lateral sclerosis (ALS). Previous findings have provided evidence that histone deacetylases (HDAC) are altered in ALS, providing a rationale for testing HDAC inhibitors as a therapeutic option.

Methods

We measured class I and II HDAC protein and transcript levels together with acetylation levels of downstream substrates by using Western blotting in postmortem tissue of ALS and controls. [11C]Martinostat, a novel HDAC positron emission tomography ligand, was also used to assess in vivo brain HDAC alterations in patients with ALS and healthy controls (HC).

Results

There was no significant difference in HDAC levels between patients with ALS and controls as measured by Western blotting and reverse‐transcription quantitative polymerase chain reaction. Similarly, no differences were detected in [11C]Martinostat–positron emission tomography uptake in ALS participants compared with HCs.

Discussion

These findings provide evidence that alterations in HDAC isoforms are not a dominant pathological feature at the bulk tissue level in ALS.
Coping, stress, and negative childhood experiences: The link to psychopathology, self‐harm, and suicidal behavior
Authors: McLafferty Margaret , Armour Cherie , Bunting Brendan , Ennis Edel , Lapsley Coral , Murray Elaine , O'Neill Siobhan
Published: June 2019

Early life experiences, such as childhood adversities or poor parenting practices, can impact on the ability to cope with stressors across the lifespan. Furthermore, poor coping skills can lead to the development of mental illnesses, self‐harm, and suicidal behavior. This study aimed to examine demographic differences in stress levels and to determine if those who had endured negative childhood experiences would be more likely to develop psychological problems and display suicidal behavior when current stress levels were accounted for. The study also explored the link between coping and mental health problems. Finally, it aimed to predict risk and protective factors related to good coping skills. The study utilized data obtained from the Ulster University Student Wellbeing Study, conducted across four university campuses in Northern Ireland in 2015 (n = 716) as part of the World Health Organization World Mental Health (WMH) International College Student Initiative. Mental health problems and early childhood experiences were examined using questions adapted from the WMH Composite International Diagnostic Interview, with self‐harm and suicidal behavior measured using the Self‐Injurious Thoughts and Behaviors Interview (SITBI). Females, non‐heterosexuals, and older students experienced more current stress. When current stress levels were high, childhood adversities and parental overcontrol and overindulgence were related to higher rates of mental health problems, self‐harm, and suicidal behavior. Poor coping skills were associated with negative mental health outcomes. Social support and good emotion‐regulation strategies were related to effective coping, while parental overcontrol and overindulgence, female gender, and younger age were related to poorer coping. The study highlights the importance of developing good coping skills to deal with life stressors, thereby minimizing the risk of psychological problems and suicidal behavior. The findings provide support for initiatives to help parents improve their parenting skills and other programs to help young people cope with stress, and to develop social networks and adaptive emotion‐regulation strategies.
Production of antimicrobial silver nanoparticles modified by alkanethiol self‐assembled monolayers by direct current atmospheric pressure glow discharge generated in contact with a flowing liquid anode
Authors: Dzimitrowicz Anna , Krychowiak‐Masnicka Marta , Pohl Pawel , Krolicka Aleksandra , Cyganowski Piotr , Jermakowicz‐Bartkowiak Dorota , Jamroz Piotr
Published: June 2019

Direct current atmospheric pressure glow discharge (dc‐APGD) generated in contact with a flowing liquid anode (FLA) is used for continuous synthesis of size‐defined silver nanoparticles (AgNPs) modified by a (11‐mercaptoundecyl)‐N,N,N‐trimethylammonium chloride (TMA) alkanethiol self‐assembled monolayer. The impact of the operating parameters (concentration of Ag(I) ions, solution flow rate, discharge current) on the size of TMA‐AgNPs is examined. Design of experiments along with response surface methodology reveals that it is possible to obtain size‐defined TMA‐AgNPs, the smallest being 1.21 ± 0.80 nm. Furthermore, the reactive species involved in formation of TMA‐AgNPs are identified using optical emission spectrometry. TMA‐AgNPs are characterized by several other experimental techniques, which confirm production of approximately spherical, well‐dispersed TMA‐AgNPs. Additionally, attenuated total reflection Fourier transform infrared spectroscopy and UV/Vis absorption spectrophotometry confirmed that the surface of Ag nanostructures is covered by TMA. TMA‐AgNPs display antimicrobial activity toward multiple human pathogens (Escherichia coli, Staphylococcus aureus, and Candida albicans) with minimal bactericidal concentrations or minimal fungicidal concentrations of 3.90 ± 0.15, 7.79 ± 0.30, and 3.90 ± 0.15 mg/L, respectively.