bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Ellagic Acid on Paraoxanase - 1 Activity and DNA Damage in Acute Exercise
Authors: Kara Ersan , Çoban Funda Karabağ , Akıl Mustafa , Liman Recep , Ciğerci İbrahim Hakkı
Published: September 2019

The purpose of this study was to evaluate the correlation between exhaustive and intensive exercise with changes in paraoxonase-1 enzyme activity, oxidative DNA damage and the role of ellagic acid against possible damage.

The study was carried out on 32 male and adult Spraque - Dawley rats at the Experimental Animal Research and Research Center of Afyon Kocatepe University. The experimental animals were equally divided into four groups. Swimming exercises were performed as acute exercises for once and experimental animals are made to swim in groups including two rats following the completion of the study and before the decapitation.

At the end of the experiment, obtained blood samples; Paraoxonase-1 (PON-1), Malondialdehyde (MDA) and 8-HydroxyGuanine (8-OhdG) levels were measured to determine DNA damage and DNA damage was assessed by Comet Assay method.

As a result, PON-1 levels in rats with intense swimming training were found to be significantly lower (p <0.05) than the control group. MDA and (8-OhdG) levels were significantly higher in the swimming group than in the control group (p <0.05). As to the DNA damage determination by COMET analysis, DNA damage was observed in the swimming groups according to the control groups. When the ellagic acid groups were compared with the swimming groups, there was a significant increase in PON-1 levels, and the levels of MDA and (8-OhdG) were significantly lower than the swimming groups. The DNA damage was also found to be low in these groups.
miR‐122‐5p modulates the radiosensitivity of cervical cancer cells by regulating cell division cycle 25A (CDC25A)
Authors: Ding Feng‐Na , Gao Bao‐Hong , Wu Xia , Gong Chun‐Wu , Wang Wei‐Qing , Zhang Shu‐Mao
Published: September 2019

Cervical cancer is one of the most common gynecological malignancies globally, Unfortunately, radiotherapy and chemotherapy are not effective at treating some cases of this disease, and the 5‐year survival rate is only 40–50%. Cell division cycle 25A (CDC25A) has been shown to induce radioresistance in a variety of tumor cells, but the role of CDC25A in the radioresistance of cervical cancer has not been fully elucidated. Here, we report that CDC25A is highly expressed and miR‐122‐5p lowly expressed in cervical cancer tissues and cells. The TargetScan database was used to predict CDC25A as a target of miR‐122‐5p, and the interactions between miR‐122‐5p and CDC25A were further confirmed by western blot, real‐time PCR and dual‐luciferase reporter assay. Under X‐ray irradiation, up‐regulation of CDC25A can promote the radiation resistance of cervical cancer cells, whereas overexpression of miR‐122‐5p or knockdown of CDC25A inhibits the survival and induces apoptosis of cervical cancer colonies. In conclusion, our data suggest that miR‐122‐5p enhances the radiosensitivity of cervical cancer cells by targeting CDC25A.
Biophysical characterization and modulation of Transthyretin Ala97Ser
Authors: Liu Yo‐Tsen , Yen Yueh‐Jung , Ricardo Frans , Chang Yu , Wu Pei‐Hao , Huang Shing‐Jong , Lin Kon‐Ping , Yu Tsyr‐Yan
Published: September 2019

Objective

Ala97Ser (A97S) is the major transthyretin (TTR) mutation in Taiwanese patients of familial amyloid polyneuropathy (FAP), characterized by a late‐onset but rapidly deteriorated neuropathy. Tafamidis can restore the stability of some mutant TTR tetramers and slow down the progression of TTR‐FAP. However, there is little understanding of the biophysical features of A97S‐TTR mutant and the pharmacological modulation effect of tafamidis on it. This study aims to delineate the biophysical characteristics of A97S‐TTR and the pharmacological modulation effect of tafamidis on this mutant.

Method

The stability of TTR tetramers was assessed by urea denaturation and differential scanning calorimetry. Isothermal titration calorimetry (ITC) was used to measure the binding constant of tafamidis to TTR. Nuclear magnetic resonance spectroscopy (NMR) titration experiment was used to map out the tafamidis binding site.

Results

Chemical and thermal denaturation confirmed the destabilization effect of A97S. Consistent with other the amyloidogenic mutant, A97S‐TTR has slightly lower conformational stability. NMR revealed the binding site of A97S‐TTR with tafamidis is at the thyroxine binding pocket. The ITC experiments documented the high affinity of the binding which can effectively stabilize the A97S‐TTR tetramer.

Interpretation

This study confirmed the structural modulation effect of tafamidis on A97S‐TTR and implied the potential therapeutic benefit of tafamidis for A97S TTR‐FAP. This approach can be applied to investigate the modulation effect of tafamidis on other rare TTR variants and help to make individualized choices of available treatments for FAP patients.
Tilted Chiral Liquid Crystal Gratings for Efficient Large‐Angle Diffraction
Authors: Nys Inge , Stebryte Migle , Ussembayev Yera Ye. , Beeckman Jeroen , Neyts Kristiaan
Published: September 2019

Deflecting light with high efficiency over large angles with thin optical elements is challenging but offers tremendous potential for applications, such as wearable displays and optical communication systems. Compared to the complex production of metasurfaces, the self‐organization of liquid crystal (LC) superstructures provides an elegant and flexible way to produce high‐quality thin optical components. The periodically varying dielectric tensor in short‐pitch chiral LC gives rise to a photonic bandgap, which can be exploited to realize efficient diffractive mirrors in the visible wavelength range. However, large‐angle diffractive devices require a small in‐plane period, leading to complex self‐assembly behavior in the bulk. This work demonstrates that by patterning photoalignment layers at the surfaces with a period comparable to the chiral pitch, the LC self‐assembles into a tilted, defect‐free helical structure. The director configuration is calculated by finite element simulations and it is experimentally demonstrated that a single photoaligned substrate is sufficient to template the tilted chiral structure in the bulk. This structure effectively (88%) diffracts light over large angles (≈46°) and enables novel micrometer‐thin (≈3 µm) optical components that can be produced with an elegant manufacturing process. Due to flexibility of photoalignment, this process could easily be implemented in emerging photonic applications.
“Always on the go”: A qualitative study of the perceptions of cardiovascular disease risk among Latino cab drivers
Authors: Orleans Rachel , Boutin‐Foster Carla , Scott Ebony , Ramos Rosio , Faussett Zenobia , Lata Armijos Jorge D.
Published: September 2019

Background

The taxicab industry is a burgeoning occupation that predominantly employs immigrant males from low socioeconomic backgrounds. Factors such as sedentary nature, environmental factors, high stress coupled with socioeconomic factors may increase cardiovascular disease risk among taxicab drivers. Latinos, a growing immigrant population make up approximately 20% of this industry. However, few studies focus on their experiences as cab drivers or on the factors that may increase their cardiovascular risks.

Methods

This was an ethnographic qualitative study. Data was collected via individual interviews combined with Go‐Alongs. The Go‐Along is an observational qualitative method whereby researchers accompany participants during routine activities and make observations. Interviews and observations were transcribed and coded to identify emerging themes.

Results

Thirty‐two Latino male cab drivers participated; their mean age was 45 + 12 years; 47% did not finish high school; and 63% earned $30 000 or less. Time and stress emerged as dominant themes. Time constraints posed a barrier to healthy eating and physical activity. Drivers reported stress from constantly worrying about their finances and personal safety. Drivers also described stress from the physical toll of driving on the body. Go‐Alongs supported these themes and identified social interactions and environmental factors that could be leveraged for health promotion.

Conclusions

This study provided an opportunity for cab drivers to describe their perspectives on reasons why their occupation was associated with a high risk for cardiovascular disease. The Go‐Alongs contributed to the understanding of the social and environmental context that characterized cardiovascular risks in this occupation.
Tuning of Sensitivity in Thermochromic Luminescence by Regulating Molecular Rotation Based on Triphenylamine‐Substituted o‐Carboranes
Authors: Nishino Kenta , Tanaka Kazuo , Chujo Yoshiki
Published: September 2019

This study shows tuning of sensitivity in thermochromic luminescence from triphenylamine‐substituted o‐carboranes by regulating rotation barriers with a substituent effect. A series of o‐carborane dyads with various numbers of methyl substituents were prepared, and their optical properties were compared. Initially, significant dual‐emission properties consistent of the locally excited (LE) state and the induced charge transfer (ICT) state were observed from the solid samples of all dyads. In particular, diverse responses were obtained by cooling from the dyads. The pristine and mono‐substituted dyads presented thermally independent emission during temperature changes, whereas the detected thermochromic luminescence with drastic color change from red to blue originated from the alteration of intensity ratios between LE and CT emission bands. From mechanistic studies (experimental and theoretical), it was clearly shown that the difference in the rotation barrier of the o‐carborane unit caused by the substituent effect should play a key role in variable sensitivity in luminescent chromic behaviors in temperature change.
Kupfer‐katalysierte Triborierung terminaler Alkine mit B2pin2: Effiziente Synthese von 1,1,2‐Triborylalkenen
Authors: Liu Xiaocui , Ming Wenbo , Friedrich Alexandra , Kerner Florian , Marder Todd B.
Published: September 2019

Wir berichten über die katalytische Triborierung terminaler Alkine mit B2pin2 (Bis‐(pinakolato)‐dibor) unter Verwendung von einfach zugänglichem Cu(OAc)2 und PnBu3. Verschiedene 1,1,2‐Triborylalkene, eine Verbindungsklasse mit potentieller Funktion als Matrix‐Metallo‐Proteinase(MMP‐2)‐Inhibitor, werden direkt in mäßigen bis guten Ausbeuten erhalten. Das Verfahren zeichnet sich durch milde Reaktionsbedingungen, ein breites Substratspektrum und eine gute Verträglichkeit gegenüber funktionellen Gruppen aus. Diese Cu‐katalysierte Reaktion kann im Gramm‐Maßstab durchgeführt werden und liefert die entsprechenden 1,1,2‐Triborylalkene in mäßigen Ausbeuten. Die Verwendung solcher Verbindungen wird anhand weiterer Transformationen der C−B‐Bindungen zur Darstellung eines geminalen Dihalogenborylalkens (F, Cl, Br), eines Monohalogendiborylalkens (Cl, Br) und eines trans‐Diaryldiborylalkens demonstriert, welche bedeutende Synthesebausteine darstellen und bisher nur schwer zugänglich waren.
Copper‐Catalyzed Triboration of Terminal Alkynes Using B2pin2: Efficient Synthesis of 1,1,2‐Triborylalkenes
Authors: Liu Xiaocui , Ming Wenbo , Friedrich Alexandra , Kerner Florian , Marder Todd B.
Published: September 2019

We report herein the catalytic triboration of terminal alkynes with B2pin2 (bis(pinacolato)diboron) using readily available Cu(OAc)2 and PnBu3. Various 1,1,2‐triborylalkenes, a class of compounds that have been demonstrated to be potential matrix metalloproteinase (MMP‐2) inhibitors, were obtained directly in moderate to good yields. The process features mild reaction conditions, a broad substrate scope, and good functional group tolerance. This copper‐catalyzed reaction can be conducted on a gram scale to produce the corresponding 1,1,2‐triborylalkenes in modest yields. The utility of these products was demonstrated by further transformations of the C−B bonds to prepare gem‐dihaloborylalkenes (F, Cl, Br), monohaloborylalkenes (Cl, Br), and trans‐diaryldiborylalkenes, which serve as important synthons and have previously been challenging to prepare.
Immobilization of polyvinyl alcohol‐siloxane on the oxygen plasma‐modified polyurethane‐carbon nanotube composite matrix
Authors: Aidun Amir , Zamanian Ali , Ghorbani Farnaz
Published: September 2019

Polyurethane‐based scaffolds have been considered as a promising strategy for tissue regeneration. Herein, the polyurethane and carbon nanotubes electrospun scaffolds were modified by polyvinyl alcohol‐3‐glycidoxypropyl‐trimethoxysilane after oxygen plasma treatment to improve physicochemical and in vitro properties for efficient bone reconstruction. Finally, the morphology of scaffolds, chemical characterization, surface roughness, bioactivity, hydrophilicity, cell attachment, cell viability, and alkaline phosphatase activity were investigated. According to microscopy results, bead free and smooth fibers were obtained using electrospinning while the degree of uniformity was reduced after the surface modification process. However, the modification process induced higher hydrophilicity and bioactivity to prepared scaffolds. In addition, the attachment and viability of the cells were improved as a function of surface modification. The expression of alkaline phosphatase especially in modified fibers confirmed the initial potential of scaffolds for bone tissue engineering applications and further studies. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48477.
Protein‐facilitated gold nanoparticle formation as indicators of ionizing radiation
Authors: Thaker Amar , Pushpavanam Karthik , Bista Tomasz , Sapareto Stephen , Rege Kaushal , Nannenga Brent L.
Published: September 2019

The use of X‐ray radiation in radiotherapy is a common treatment for many cancers. Despite several scientific advances, determination of radiation delivered to the patient remains a challenge due to the inherent limitations of existing dosimeters including fabrication and operation. Here, we describe a colorimetric nanosensor that exhibits unique changes in color as a function of therapeutically relevant radiation dose (3–15 Gy). The nanosensor is formulated using a gold salt and maltose‐binding protein as a templating agent, which upon exposure to ionizing radiation is converted to gold nanoparticles. The formation of gold nanoparticles from colorless precursor salts renders a change in color that can be observed visually. The dose‐dependent multicolored response was quantified through a simple ultraviolet–visible spectrophotometer and the peak shift associated with the different colored dispersions was used as a quantitative indicator of therapeutically relevant radiation doses. The ease of fabrication, visual color changes upon exposure to ionizing radiation, and quantitative read‐out demonstrates the potential of protein‐facilitated biomineralization approaches to promote the development of next‐generation detectors for ionizing radiation.
Efficacy and safety of generic imatinib after switching from original imatinib in patients treated for chronic myeloid leukemia in the United States
Authors: Abou Dalle Iman , Kantarjian Hagop , Burger Jan , Estrov Zeev , Ohanian Maro , Verstovsek Srdan , Ravandi Farhad , Borthakur Gautam , Garcia‐Manero Guillermo , Jabbour Elias , Cortes Jorge
Published: September 2019

Introduction

Imatinib is standard therapy for patients with chronic myeloid leukemia (CML). In February 2016, a generic formulation entered the US market. Physicians and patients are frequently concerned about whether switching from original to generic drugs may affect the efficacy and/or safety.

Materials and methods

This is an observational retrospective study using medical charts of patients diagnosed with CML in the chronic phase who were treated with original imatinib from the year 2000 to 2017 and who were subsequently switched to generic imatinib.

Results

In this study, 38 patients have switched to generic imatinib. Before the switch, responses were assessed on all patients, all of them were in CCyR and 36 (95%) were in MMR, including 28 (74%) with MR4.5. Patients have received generic imatinib for a median of 19.4 (range, 3.4‐46.3) months. Molecular responses after switching were stable in 89%, improved in 8%, and worsened in 3% of patients. After switching, 15 (39%) patients reported new or worsening adverse events, including 5 (13%) patients with edema, 8 (21%) muscle cramps, 7 (18%) nausea, 6 (16%) diarrhea, and 5 (13%) fatigue.

Discussion

Bioequivalence studies demonstrated the same rate and extent of absorption of generic imatinib compared to the original form, which led to the FDA approval. In our observational series, most of the patients maintained their responses and none lost MMR. Adverse events noted were mild and well tolerated.

Conclusion

A change from original to generic imatinib appears to maintain efficacy and be generally safe. More patients and longer follow‐up are required to confirm these observations.
Identifying and understanding gaps in services for adults experiencing homelessness
Authors: Barile John P. , Pruitt Anna S. , Parker Josie L.
Published: September 2019

Gaps between service needs and availability often prevent individuals with a history of homelessness from accessing services and reestablishing permanent housing. This paper examines self‐identified service utilization and service needs based on data collected from an urban sample (N = 577) of adults experiencing homelessness. This study found that individuals differ in their use and continued need of services depending on the reasons they identified as contributing to their homelessness. The majority reported that they learned of services through word of mouth, had difficulty accessing services due to limited transportation options, and were most likely to use services that were in convenient locations that fulfilled their needs and where they were treated with respect. These findings have implications for developing coordinated intakes and the development and dissemination of services aimed at assisting individuals experiencing homelessness.
Did court order school to reinstate suspended cheerleader?
Authors: Gelpi Aileen
Published: September 2019

Immediately after the plaintiff's daughter was selected for a high school cheerleading squad in 2018, she attended an evening orientation at which all of the new members received new cheerleading shirts that showed the name of the high school. At that meeting, the cheerleading coach told the new members to refrain from posting anything on social media that gloated about making the squad.
Synthesis and Antioxidant Activity of Carane and Pinane Based Sulfenimines and Sulfinimines
Authors: Sudarikov Denis V. , Krymskaya Yulia V. , Shevchenko Oksana G. , Slepukhin Pavel A. , Rubtsova Svetlana A. , Kutchin Aleksandr V.
Published: September 2019

The synthesis of sulfenimines and sulfinimines has been carried out with 10‐hydroxyisocamphylthiol. The configuration of the compounds has been deduced by methods of NMR, DFT calculations and X‐ray diffraction analysis. The cytotoxic, antioxidant and membrane‐protective activity of the synthesized compounds as well as of the previously obtained sulfenimines and sulfinimines based on 4‐caranethiol have been determined.
Mechanistic Insights on the Functionalization of CO2 with Amines and Hydrosilanes Catalyzed by a Zwitterionic Iridium Carboxylate‐Functionalized Bis‐NHC Catalyst
Authors: Ojeda‐Amador Ana I. , Munarriz Julen , Alamán‐Valtierra Pablo , Polo Víctor , Puerta‐Oteo Raquel , Jiménez M. Victoria , Fernández‐Alvarez Francisco J. , Pérez‐Torrente Jesús J.
Published: September 2019

The zwitterionic complex [Cp*IrCl{(MeIm)2CHCOO}] (1) efficiently catalyzes the selective hydrosilylation of CO2 to afford the corresponding silylformate. The best reaction performance has been achieved in acetonitrile at 348 K using HSiMe2Ph. The 1‐catalyzed reaction of pyrrolidine with CO2 and HSiMe2Ph strongly depends on the CO2 pressure. At low concentration of CO2 (1 bar) formation of the corresponding silylcarbamate, by insertion of CO2 into the Si−N bond of the in situ generated silylamine was observed, while at higher pressure (3 bar) the formamide derivative was obtained as major reaction product. The unexpected formation of pyrrolidin‐1‐ium formate as intermediate of the reaction the 1‐catalyzed of CO2 with pyrrolidine and HSiMe2Ph has been observed, and its role in the formation of 1‐formylpyrrolidine rationalized. Moreover, a mechanism for the reaction of CO2 with hydrosilanes, in the presence and in the absence of amines, based on theoretical calculations has been proposed.
Type and case volume of health care facility influences survival and surgery selection in cases with early‐stage non–small cell lung cancer
Authors: Wang Shidan , Lai Sunny , von Itzstein Mitchell S. , Yang Lin , Yang Donghan M. , Zhan Xiaowei , Xiao Guanghua , Halm Ethan A. , Gerber David E. , Xie Yang
Published: September 2019

Background

With the expansion of non–small cell lung cancer (NSCLC) screening methods, the percentage of cases with early‐stage NSCLC is anticipated to increase. Yet it remains unclear how the type and case volume of the health care facility at which treatment occurs may affect surgery selection and overall survival for cases with early‐stage NSCLC.

Methods

A total of 332,175 cases with the American Joint Committee on Cancer (AJCC) TNM stage I and stage II NSCLC who were reported to the National Cancer Data Base (NCDB) by 1302 facilities were studied. Facility type was characterized in the NCDB as community cancer program (CCP), comprehensive community cancer program (CCCP), academic/research program (ARP), or integrated network cancer program (INCP). Each facility type was dichotomized further into high‐volume or low‐volume groups based on the case volume. Multivariate Cox proportional hazard models, the logistic regression model, and propensity score matching were used to evaluate differences in survival and surgery selection among facilities according to type and volume.

Results

Cases from ARPs were found to have the longest survival (median, 16.4 months) and highest surgery rate (74.8%), whereas those from CCPs had the shortest survival (median, 9.7 months) and the lowest surgery rate (60.8%). The difference persisted when adjusted by potential confounders. For cases treated at CCPs, CCCPs, and ARPs, high‐volume facilities had better survival outcomes than low‐volume facilities. In facilities with better survival outcomes, surgery was performed for a greater percentage of cases compared with facilities with worse outcomes.

Conclusions

For cases with early‐stage NSCLC, both facility type and case volume influence surgery selection and clinical outcome. Higher surgery rates are observed in facilities with better survival outcomes.
Proton‐beam therapy after radical prostatectomy: Continued DVH idolatry?
Authors: Lee W. Robert
Published: September 2019

Proton‐beam therapy results in lower doses to the bladder and rectum compared with intensity‐modulated radiation therapy. Despite these dosimetric differences, genitourinary and gastrointestinal toxicity is similar.
Development and sensory experience dependent regulation of microglia in barrel cortex
Authors: Kalambogias John , Chen Chia‐Chien , Khan Safraz , Son Titus , Wercberger Racheli , Headlam Carolyn , Lin Cindy , Brumberg Joshua C.
Published: September 2019

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals’ first postnatal month. Using immunohistochemistry to label microglia, we performed morphological reconstructions as well as densitometry analyses as a function of developmental age and sensory experience. Findings suggest that both developmental age and sensory experience has profound impact on microglia morphology. Following chronic sensory deprivation, microglia undergo a morphological transition from a monitoring or resting state to an altered morphological state, by exhibiting expanded cell body size and retracted processes. Sensory restoration via whisker regrowth returns these morphological alterations back to age‐matched control values. Our results indicate that microglia may be recruited to participate in the modulation of neuronal structural remodeling during developmental critical periods and in response to alteration in sensory input.
Development Times and Approval Success Rates for Drugs to Treat Infectious Diseases
Authors: DiMasi Joseph A. , Florez Maria I. , Stergiopoulos Stella , Peña Yaritza , Smith Zachary , Wilkinson Michael , Getz Kenneth A.
Published: September 2019

We gathered data from three pipeline databases and other public sources on development stage and clinical trial metrics for 1,914 investigational drugs, biologics, and vaccines and 2,769 clinical trials intended to treat a wide variety of infectious diseases. We included new molecular entities (NMEs), new formulations, and new combinations. Clinical trial times decreased from 2000–2008 to 2009–2017, varied by disease class, and were longer for trials with more subjects or more sites. Clinical approval success rates were higher for this set of diseases than those in the published literature for drugs across all therapeutic categories. NMEs to treat HIV had a success rate (16.0%) that was similar to those for drugs in general, whereas NME success rates for influenza and pneumonia were much higher (48.1% and 50.5%, respectively).
Acute stress impairs children's sustained attention with increased vulnerability for children of mothers reporting higher parenting stress
Authors: Roos Leslie E. , Giuliano Ryan J. , Beauchamp Kathryn G. , Berkman Elliot T. , Knight Erik L. , Fisher Philip A.
Published: September 2019

Despite evidence that acute stress impairs attention in adults, there has been minimal research in children. Here, the effects of acute stress on Go/No‐go performance were examined in young children (M age = 5.41 years). Given the critical role of the parent–child relationship to children's self‐regulatory development, the extent to which parenting stress predicts children's cognitive vulnerability to acute stress and autonomic reactivity was also investigated. A between‐groups design (n = 58 stress, n = 26 control) was used with oversampling of the stressor‐exposed children to examine individual differences. The Parenting Stress Index and subscales were employed as a measure of parenting stress. Acute stress impaired children's sustained attention, but not inhibitory control. Higher parenting stress was associated with vulnerability to attentional impairment. Parenting distress was also positively associated with sympathetic reactivity to acute stress, but neither sympathetic nor parasympathetic reactivity was associated with attentional impairment. A conceptual model of pathways through which repetitive acute stress may contribute to self‐regulatory difficulties is presented, including the potential buffering role of caregivers.
Weighing homoplasy against alternative scenarios with the help of macroevolutionary modeling: A case study on limb bones of fossorial sciuromorph rodents
Authors: Wölfer Jan , Nyakatura John A.
Published: September 2019

Homoplasy is a strong indicator of a phenotypic trait's adaptive significance when it can be linked to a similar function. We assessed homoplasy in functionally relevant scapular and femoral traits of Marmotini and Xerini, two sciuromorph rodent clades that independently acquired a fossorial lifestyle from an arboreal ancestor. We studied 125 species in the scapular dataset and 123 species in the femoral dataset. Pairwise evolutionary model comparison was used to evaluate whether homoplasy of trait optima is more likely than other plausible scenarios. The most likely trend of trait evolution among all traits was assessed via likelihood scoring of all considered models. The homoplasy hypothesis could never be confirmed as the single most likely model. Regarding likelihood scoring, scapular traits most frequently did not differ among Marmotini, Xerini, and arboreal species. For the majority of femoral traits, results indicate that Marmotini, but not Xerini, evolved away from the ancestral arboreal condition. We conclude on the basis of the scapular results that the forelimbs of fossorial and arboreal sciuromorphs share mostly similar functional demands, whereas the results on the femur indicate that the hind limb morphology is less constrained, perhaps depending on the specific fossorial habitat.
Silver spoon effects are constrained under extreme adult environmental conditions
Authors: Pigeon Gabriel , Loe Leif Egil , Bischof Richard , Bonenfant Christophe , Forchhammer Mads , Irvine R. Justin , Ropstad Erik , Stien Audun , Veiberg Vebjørn , Albon Steve
Published: September 2019

Early‐life environmental conditions may generate cohort differences in individual fitness, subsequently affecting population growth rates. Three, nonmutually exclusive hypotheses predict the nature of these fitness differences: (1) silver spoon effects, where individuals born in good conditions perform better across the range of adult environments; (2) the “environmental saturation” hypothesis, where fitness differences only occur in intermediate adult environmental conditions; and (3) the “environmental matching” or “predictive adaptive response” (PAR) hypothesis, where fitness is highest when adult environmental conditions match those experienced in early life. We quantified the context‐dependent effect of early‐life environment on subsequent reproductive success, survival, and population growth rate (λ) of Svalbard reindeer, and explored how well it was explained by the three hypotheses. We found that good early‐life conditions increased reproductive success compared to poor early‐life conditions, but only when experiencing intermediate adult environmental conditions. This is the first example of what appears to be both “beneficial” and “detrimental environmental saturation” in a natural system. Despite weak early‐life effects on survival, cohorts experiencing good early‐life conditions contributed to higher population growth rates, when simulating realistic variation in adult environmental conditions. Our results show how the combination of a highly variable environment and biological constraints on fitness components can suppress silver spoon effects at both extremes of the adult environmental gradient.
Biotransformation of Polycyclic Aromatic Hydrocarbons by Trout Liver S9 Fractions: Evaluation of Competitive Inhibition Using a Substrate Depletion Approach
Authors: Nichols John W. , Ladd Melanie A. , Hoffman Alex D. , Fitzsimmons Patrick N.
Published: September 2019

Environmental contaminants frequently occur as part of a chemical mixture, potentially resulting in competitive inhibition among multiple substrates metabolized by the same enzyme. Trout liver S9 fractions were used to evaluate the biotransformation of 3 polycyclic aromatic hydrocarbons (PAHs): phenanthrene, pyrene, and benzo[a]pyrene, tested as binary mixtures. Initial rates of biotransformation were determined using a substrate-depletion approach. The resulting data were then fitted by simultaneous nonlinear regression to a competitive inhibition model. In each case, the PAH possessing the lower Michaelis-Menten affinity constant (KM) competitively inhibited biotransformation of the other compound. Inhibition constants determined for the lower-KM compound were generally close to previously determined KM values, consistent with the suggestion that phase I biotransformation of PAHs is largely catalyzed by one or a small number of cytochrome P450 enzymes. The use of a substrate-depletion approach to perform enzyme-inhibition studies imposes practical limitations on experimental design and complicates the interpretation of derived kinetic constants. Nevertheless, the resulting information may have utility for chemical hazard assessments as well as the design and interpretation of controlled laboratory studies. Depletion experiments informed by measured chemical concentrations in tissues may also provide a means of determining whether enzyme inhibition occurs under relevant environmental conditions. Environ Toxicol Chem 2019;38:2729–2739. Published 2019 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America
Piperine as a neuroprotective functional component in rats with cerebral ischemic injury
Authors: Hua Shiyao , Liu Jiayue , Zhang Yiwei , Li Juan , Zhang Xinhui , Dong Lin , Zhao Yunsheng , Fu Xueyan
Published: September 2019

Long pepper (Piper longum L.) and black pepper (Piper nigrum L.) plants are commonly used as spices around the world and have also been postulated to have medicinal effects. Piperine, as the major alkaloid of P. nigrum and P. longum, has gained wide attention of the medical community and culinary enthusiasts. This study seeks to determine the effects of piperine on neuronal apoptosis in peri‐infarcted cerebral cortices of rats with permanent middle cerebral artery occlusion (pMCAO) injury. Evaluation of the different behavioral components was conducted after pMCAO. 2, 3, 5‐Triphenyltetrazolium chloride (TTC) was used to evaluate the area of cortical ischemia. Gross histopathological changes, as well as microscopic neuronal changes, were observed in brain tissue samples. The protein expression of Caspase‐3, Caspase‐9, Bax, Bcl‐2, and Cytochrome C (Cyt‐c) was analyzed using western blotting. The findings reveal that rats that received piperine treatment show markedly decreased neurological deficit, less ischemia‐induced cellular damage, as well as smaller areas of cerebral infarction, with less severe macro and microcellular cerebral structural changes. Western blotting analysis reveals that piperine administration inhibits Bax, while enhancing Bcl‐2 expression. The protein expression of Caspase‐3, Caspase‐9, and Cyt‐c was also found to be significantly inhibited. We conclude that piperine may provide several beneficial neuroprotective effects that warrant further investigation.
Genome‐wide association study of circulating folate one‐carbon metabolites
Authors: Wang Jun , Asante Isaac , Baron John A. , Figueiredo Jane C. , Haile Robert , Joan Levine A. , Newcomb Polly A. , Templeton Allyson S. , Schumacher Fredrick R. , Louie Stan G. , Casey Graham , Conti David V.
Published: September 2019

Experimental, observational, and clinical trials support a critical role of folate one‐carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome‐wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry. Twelve metabolites, including 5‐methyltetrahydrofolate, vitamin B2 (flavin mononucleotide and riboflavin), vitamin B6 (4‐pyridoxic acid, pyridoxal, and pyridoxamine), total homocysteine, methionine, S‐adenosylmethionine, S‐adenosylhomocysteine, cystathionine, and creatinine were measured from plasma using liquid chromatography‐mass spectrometry (LC‐MS) or LC‐MS/MS. For each individual biomarker, we estimated genotype array‐specific associations followed by a fixed‐effect meta‐analysis. We identified the variant rs35976024 (at 2p11.2 and intronic of ATOH8) associated with total homocysteine (p = 4.9 × 10−8). We found a group of six highly correlated variants on chromosome 15q14 associated with cystathionine (all p < 5 × 10−8), with the most significant variant rs28391580 (p = 2.8 × 10−8). Two variants (rs139435405 and rs149119426) on chromosome 14q13 showed significant (p < 5 × 10−8) associations with S‐adenosylhomocysteine. These three biomarkers with significant associations are closely involved in homocysteine metabolism. Furthermore, when assessing the principal components (PCs) derived from seven individual biomarkers, we identified the variant rs12665366 (at 6p25.3 and intronic of EXOC2) associated with the first PC (p = 2.3 × 10−8). Our data suggest that common genetic variants may play an important role in FOCM, particularly in homocysteine metabolism.
Gene‐based association analysis of survival traits via functional regression‐based mixed effect cox models for related samples
Authors: Chiu Chi‐yang , Zhang Bingsong , Wang Shuqi , Shao Jingyi , Lakhal‐Chaieb M'Hamed Lajmi , Cook Richard J. , Wilson Alexander F. , Bailey‐Wilson Joan E. , Xiong Momiao , Fan Ruzong
Published: September 2019

The importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests. In this paper, we extend this approach to analyze censored traits for family data or related samples using FR based mixed effect Cox models (FamCoxME). The FamCoxME model effect of major gene as fixed mean via functional data analysis techniques, the local gene or polygene variations or both as random, and the correlation of pedigree members by kinship coefficients or genetic relationship matrix or both. The association between the censored trait and the major gene is tested by likelihood ratio tests (FamCoxME FR LRT). Simulation results indicate that the LRT control the type I error rates accurately/conservatively and have good power levels when both local gene or polygene variations are modeled. The proposed methods were applied to analyze a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). The FamCoxME provides a new tool for gene‐based analysis of family‐based studies or related samples.
Determination of legal responsibility in shared airway management between anesthesiology and otolaryngology
Authors: Ideker Henry C. , Julakanti Jatin S. , Momin Nishat A. , Chaaban Mohamad R.
Published: September 2019

Background

Malpractice litigation remains an important point of contention in the United States. Airway management often sees multidisciplinary teams of anesthesiologists and otolaryngologists. This report analyzes lawsuits affecting both teams in airway management.

Methods

The Westlaw legal database (West Publishing Co., St. Paul, MN) was used to search for malpractice cases involving failed airway management, where both anesthesiology and otolaryngology were involved.

Results

Among the 28 cases analyzed, otolaryngology and anesthesiology were most commonly sued together (46.4%). When sued together, defendants were less likely to win and average award amounts ($4, 558 716) were higher. These cases most commonly occurred in the operating room (78.6%), involved a difficult/improper intubation (39.3%), alleged a failure to follow standard of care (57%), and resulted in death (60.7%).

Conclusion

These cases primarily cited failure to follow standard of care and communication failures. Efforts should be directed toward multidisciplinary airway management protocols and effective communication.
Hepatocyte Stress Increases Expression of Yes‐Associated Protein and Transcriptional Coactivator With PDZ‐Binding Motif in Hepatocytes to Promote Parenchymal Inflammation and Fibrosis
Authors: Mooring Meghan , Fowl Brendan H. , Lum Shelly Z.C. , Liu Ye , Yao Kangning , Softic Samir , Kirchner Rory , Bernstein Aaron , Singhi Aatur D. , Jay Daniel G. , Kahn C. Ronald , Camargo Fernando D. , Yimlamai Dean
Published: September 2019

Background and Aims

Activated hepatocytes are hypothesized to be a major source of signals that drive cirrhosis, but the biochemical pathways that convert hepatocytes into such a state are unclear. We examined the role of the Hippo pathway transcriptional coactivators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) in hepatocytes to facilitate cell–cell interactions that stimulate liver inflammation and fibrosis.

Approach and Results

Using a variety of genetic, metabolic, and liver injury models in mice, we manipulated Hippo signaling in hepatocytes and examined its effects in nonparenchymal cells to promote liver inflammation and fibrosis. YAP‐expressing hepatocytes rapidly and potently activate the expression of proteins that promote fibrosis (collagen type I alpha 1 chain, tissue inhibitor of metalloproteinase 1, platelet‐derived growth factor c, transforming growth factor β2) and inflammation (tumor necrosis factor, interleukin 1β). They stimulate expansion of myofibroblasts and immune cells, followed by aggressive liver fibrosis. In contrast, hepatocyte‐specific YAP and YAP/TAZ knockouts exhibit limited myofibroblast expansion, less inflammation, and decreased fibrosis after CCl4 injury despite a similar degree of necrosis as controls. We identified cellular communication network factor 1 (CYR61) as a chemokine that is up‐regulated by hepatocytes during liver injury but is expressed at significantly lower levels in mice with hepatocyte‐specific deletion of YAP or TAZ. Gain‐of‐function and loss‐of‐function experiments with CYR61 in vivo point to it being a key chemokine controlling liver fibrosis and inflammation in the context of YAP/TAZ. There is a direct correlation between levels of YAP/TAZ and CYR61 in liver tissues of patients with high‐grade nonalcoholic steatohepatitis.

Conclusions

Liver injury in mice and humans increases levels of YAP/TAZ/CYR61 in hepatocytes, thus attracting macrophages to the liver to promote inflammation and fibrosis.
SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters
Authors: Lyu Tianjiao , Jiang Yahui , Jia Nan , Che Xiaoxia , Li Qin , Yu Yinhua , Hua Keqin , Bast Robert C. , Feng Weiwei
Published: September 2019

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI‐121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3‐deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6‐ and/or ITGAM‐deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin‐mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3‐H3K4me3‐integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.
Transition‐Metal‐Catalyzed 1,2‐Carboboration of Alkenes: Strategies, Mechanisms, and Stereocontrol
Authors: Liu Zhen , Gao Yang , Zeng Tian , Engle Keary M.
Published: September 2019

During the past decade, many research groups have described catalytic methods for 1,2‐carboboration, allowing access to structurally complex organoboronates from alkenes. Various transition metals, especially copper, palladium, and nickel, have been widely used in these reactions. This review summarizes advances in this field, with a special focus on the catalytic cycles involved in different metal‐catalyzed carboboration reactions, as well as the regio‐ and stereochemical consequences of the underlying mechanisms. 1,2‐Carboboration of other unsaturated systems, such as alkynes and allenes, is outside of the scope of this review.
Sterilized chitosan‐based composite hydrogels: Physicochemical characterization and in vitro cytotoxicity
Authors: Rodríguez‐Rodríguez Rogelio , Velasquillo‐Martínez Cristina , Knauth Peter , López Zaira , Moreno‐Valtierra Maira , Bravo‐Madrigal Jorge , Jiménez‐Palomar Inés , Luna‐Bárcenas Gabriel , Espinosa‐Andrews Hugo , García‐Carvajal Zaira Y.
Published: September 2019

Gelatin/chitosan/polyvinyl alcohol hydrogels were fabricated at different polymer ratios using the freeze‐drying and sterilized by steam sterilization. The thermal stability, chemical structure, morphology, surface area, mechanical properties, and biocompatibility of hydrogels were evaluated by simultaneous thermal analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, confocal microscopy, adsorption/desorption of nitrogen, rheometry, and 3‐4,[5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide cell viability assay (MTT assay), respectively. The samples showed a decomposition onset temperature below 253.3 ± 4.8°C, a semicrystalline nature, and a highly porous structure. Hydrogels reached the maximum water uptake in phosphate‐buffered saline after 80 min, showing values from nine to twelve times their dry mass. Also, hydrogels exhibiting a solid‐like behavior ranging from 2,567 ± 467 to 48,705 ± 2,453 Pa at 0.1 rad/s (low frequency). The sterilized hydrogels showed low cytotoxicity (cell viability > 70%) to the HT29‐MTX‐E12 cell line. Sterilized hydrogels by steam sterilization can be good candidates as scaffolds for tissue engineering applications.