bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Concern: Preventive effect of nerolidol on isoproterenol induced myocardial damage in Wistar rats: Evidences from biochemical and histopathological studies
Authors: Asaikumar Loordhurani , Vennila Lakshmanan , Akila Palaniyandi , Sivasangari Subramanian , Kanimozhi Kaliyamoorthi , Premalatha Vengatesan , Sindhu Ganapathi
Published: July 2019

The present study aimed at investigating the protective effects of nerolidol (NRD) against myocardial infarction (MI) induced by isoproterenol (ISO) in Wistar rats. The rats were randomly divided into five groups, each group consisting of six rats. Group I were treated as control rats, group II received NRD (200 mg/kg b.w.) by intragastric intubation for 21 days, group III received ISO (60 mg/kg b.w) subcutaneously (s.c) for two consecutive days on 22nd and 23rd day, group IV and V received NRD (100 and 200 mg/kg b.w) as in group II and additionally ISO was given for two consecutive days (22nd and 23rd). On 24th day all the rats were sacrificed by cervical dislocation and the blood and heart samples were collected. In the present study, ISO‐induced myocardial damage was indicated by the changes in body weight, heart weight and the cardiac and hepatic marker enzymes such as creatine kinase (CK), creatine kinase‐MB (CK‐MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and troponin T and I (cTnT, cTnI) in the serum. In addition, the levels of lipid peroxidation products such as thiobarbituric acid reactive substances (TBARS), conjugated dines (CD), and lipid hydroperoxides (LHPs) increased significantly in the plasma and heart tissue. Activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST) in erythrocytes and heart tissue and the levels of nonenzymatic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH) in plasma and heart tissue were decreased in ISO‐induced rats. Histopathological observations were also supported with the biochemical parameters. Pretreatment with NRD at different doses (100 and 200 mg/kg b.w) for 21 days prevented the above changes induced by ISO. The 200 mg/kg b.w of NRD was more pronounced than the other dose and brought back all the above parameters near to normalcy.
Evolution of the intermuscular bones in the Cyprinidae (Pisces) from a phylogenetic perspective
Authors: Yang Kunfeng , Jiang Wansheng , Wang Xiaoai , Zhang Yuanwei , Pan Xiaofu , Yang Junxing
Published: July 2019

Intermuscular bones (IBs) are widely present in morphologically generalized teleost fishes and are commonly found in the Cyprinidae. Intermuscular bones are small, hard spicules of bone that are formed by ossification in the myosepta between neighboring myomeres. Why fish have IBs, and whether there is any evolutionary pattern to their occurrence, has been poorly understood. However, the presence of IBs does substantially affect the meat quality and commercial values of many cyprinid fishes in aquaculture. In this study, we sampled 592 individuals of cyprinid fishes to systematically investigate the evolution of IBs from a phylogenetic point of view. We found that the total number of IBs in the Cyprinidae ranged from 73 to 169, and we clarified that only two categories of IBs (epineural and epipleural) were present in all examined cyprinids. Most of the IBs were distributed in the posterior region of the fish, which might be an optimal target for selecting fewer IB strains in aquaculture. There was a positive correlation between IBs and the number of vertebrae, thus making it possible to predict the approximate number of IBs by counting the number of vertebrae. Although the IBs displayed some correlation with phylogenetic relationships in some lineages and to ecological factors such as diet (especially carnivore), in an overall view the variations of IBs in cyprinids were extremely diverse. The number and patterns of IBs in these fishes may reflect their phylogenetic history, but have been shaped by multiple environment factors. In this study, we also confirmed that X‐ray photography remains an optimal and reliable method for the study of IBs.
Linking demographic and food‐web models to understand management trade‐offs
Authors: Kadin Martina , Frederiksen Morten , Niiranen Susa , Converse Sarah J.
Published: July 2019

Alternatives in ecosystem‐based management often differ with respect to trade‐offs between ecosystem values. Ecosystem or food‐web models and demographic models are typically employed to evaluate alternatives, but the approaches are rarely integrated to uncover conflicts between values. We applied multistate models to a capture–recapture dataset on common guillemots Uria aalge breeding in the Baltic Sea to identify factors influencing survival. The estimated relationships were employed together with Ecopath‐with‐Ecosim food‐web model simulations to project guillemot survival under six future scenarios incorporating climate change. The scenarios were based on management alternatives for eutrophication and cod fisheries, issues considered top priority for regional management, but without known direct effects on the guillemot population. Our demographic models identified prey quantity (abundance and biomass of sprat Sprattus sprattus) as the main factor influencing guillemot survival. Most scenarios resulted in projections of increased survival, in the near (2016–2040) and distant (2060–2085) future. However, in the scenario of reduced nutrient input and precautionary cod fishing, guillemot survival was projected to be lower in both future periods due to lower sprat stocks. Matrix population models suggested a substantial decline of the guillemot population in the near future, 24% per 10 years, and a smaller reduction, 1.1% per 10 years, in the distant future. To date, many stakeholders and Baltic Sea governments have supported reduced nutrient input and precautionary cod fishing and implementation is underway. Negative effects on nonfocal species have previously not been uncovered, but our results show that the scenario is likely to negatively impact the guillemot population. Linking model results allowed identifying trade‐offs associated with management alternatives. This information is critical to thorough evaluation by decision‐makers, but not easily obtained by food‐web models or demographic models in isolation. Appropriate datasets are often available, making it feasible to apply a linked approach for better‐informed decisions in ecosystem‐based management.
Soil texture and precipitation seasonality influence plant community structure in North American temperate shrub steppe
Authors: Renne Rachel R. , Bradford John B. , Burke Ingrid C. , Lauenroth William K.
Published: July 2019

In drylands, the coexistence of grasses and woody plants has been attributed to soil‐water resource partitioning. Soil texture and precipitation seasonality can influence the amount and distribution of water in the soil, and their interaction may play an important role in determining the relative importance of grasses and woody plants. We investigated the influence of this interaction on plant functional types across a broad range of precipitation regimes and soil textures in western North America by analyzing plant‐cover data collected at 2,084 plots that included the widespread shrub big sagebrush (Artemisia tridentata Nutt.). We characterized how the significance of the inverse‐texture effect varies across soil conditions by quantifying relationships between precipitation and foliar cover on finer‐ vs. coarser‐textured soils across a range of potential texture divisions represented by sand content. We found evidence of the inverse‐texture effect for every plant functional type (except for cheatgrass) that we examined with at least one component of precipitation (annual, warm, or cold season), and provide the first evidence for this effect in locations with cold‐season‐dominated precipitation regimes. The texture and precipitation combinations that exhibited the inverse‐texture effect varied with plant functional type, presumably because of effects of soil texture on water availability at different soil depths with season. Furthermore, we found an inverse‐texture effect that was remarkably similar for shrub cover with cold‐season precipitation and grass cover with warm‐season precipitation. These results provide new insight into how the inverse‐texture effect interacts with precipitation seasonality to influence plant functional type composition in drylands, and further suggest that quantifying the soil‐texture division at which the inverse‐texture effect is relevant under a given set of environmental conditions may provide support for the effect across dryland plant communities.
Catalytic Assessment of Copper(I) Complexes and a Polymer Analog towards the One‐Pot Synthesis of Imines and Quinoxalines
Authors: Sindhuja Dharmalingam , Vasanthakumar Punitharaj , Bhuvanesh Nattamai , Karvembu Ramasamy
Published: July 2019

Three copper(I) complexes, [CuCl(L)(PPh3)2] [L = FL (1), BL (2) or TL (3)] were prepared from [(PPh3)2Cu(µ‐Cl)2Cu(PPh3)] and N‐carbamothioylfuran‐2‐carboxamide (FL), N‐carbamothioylbenzamide (BL) or N‐carbamothioylthiophene‐2‐carboxamide (TL) ligands in benzene and four‐coordinated tetrahedral copper complexes were well characterized by various spectroscopic techniques (UV/Vis, FT‐IR, 1H NMR, 13C NMR and 31P NMR). The molecular structure of the ligands (FL and BL) and complexes was established from single‐crystal X‐ray diffraction studies. Copper complexes have been shown to catalyse the one‐pot synthesis of imines and quinoxalines. Heterogenized catalyst (4) was prepared by reacting more active complex 3 with polystyrene supported triphenylphosphane, and characterized by elemental analyses, and DRS‐UV, FT‐IR, ICP‐OES, and solid‐state NMR techniques. Catalytic activity of the complexes (3 and 4) was tested in the formation of imines from alcohols and amines, and quinoxalines from hydroxy ketones and diamines. Heterogeneity and reusability of catalyst 4 were evaluated, and the catalyst can be reused for four runs without any loss in activity.
Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise
Authors: Matsubara Takanori , Hayashi Koei , Wakatsuki Koji , Abe Masahiro , Ozaki Noriyuki , Yamanaka Akihiro , Mizumura Kazue , Taguchi Toru
Published: July 2019

Background

Delayed onset muscle soreness (DOMS) is characterized by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood.

Methods

We examined whether muscular myelinated Aδ‐fibres, in addition to unmyelinated C‐fibres, are involved in LC‐induced mechanical hypersensitivity, and whether acid‐sensing ion channel (ASIC)‐3 expressed in thin‐fibre afferents contributes to this type of pain using a rat model of DOMS. The peripheral contribution of ASIC3 was investigated using single‐fibre electrophysiological recordings in extensor digitorum longus muscle‐peroneal nerve preparations in vitro.

Results

Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2 μM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22 µM) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2 μM) in naïve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of Aδ‐ and C‐fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the Aδ‐ and C‐fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle.

Conclusions

These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin‐fibre receptors in delayed onset muscular mechanical hypersensitivity after LC.

Significance

Here, we show that not only C‐ but also Aδ‐fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid‐sensing ion channel (ASIC)‐3 expressed in the thin‐fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.
Nerve growth factor‐induced muscle hyperalgesia facilitates ischaemic contraction‐evoked pain
Authors: Sørensen Line Bay , Gazerani Parisa , Graven‐Nielsen Thomas
Published: July 2019

Background

Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo‐sensitive channels affecting muscle pain sensitivity. This double‐blinded crossover study in healthy humans assessed contraction‐evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic‐saline).

Methods

Twenty‐one subjects participated in two experimental phases, each including five sessions over 7 days, with a gap of 4 weeks in‐between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non‐ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3 hr, 1, 3, and 7 days post‐injection, and after the ischaemic‐contractions and post‐cuff deflation at Day0 and Day1.

Results

Increased Likert scores of pain were present for 7 days after NGF compared to control injections (p < .05). Higher NRS pain scores of ischaemic‐contractions were seen when contracting the muscle injected with NGF compared to baseline (p = .003) and control (p = .012). Pain during non‐ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3 hr, Day1 and Day3 post‐injection (p < .05) in both conditions. Compared with pre‐contractions, PPTs were increased following ischaemic contractions at Day0 (p < .05) and Day1 (p < .05) in both conditions.

Conclusion

This study showed that ischaemic contraction‐evoked pain was facilitated in an NGF‐sensitized muscle.

Significance

Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC3 and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)‐sensitized muscle compared with non‐ischaemic contractions and in the non‐sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre‐sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.
Elicitation: A biotechnological tool for enhanced production of secondary metabolites in hairy root cultures
Authors: Halder Mihir , Sarkar Sayantika , Jha Sumita
Published: July 2019

Elicitation is a possible aid to overcome various difficulties associated with the large‐scale production of most commercially important bioactive secondary metabolites from wild and cultivated plants, undifferentiated or differentiated cultures. Secondary metabolite accumulation in vitro or their efflux in culture medium has been elicited in the undifferentiated or differentiated tissue cultures of several plant species by the application of a low concentration of biotic and abiotic elicitors in the last three decades. Hairy root cultures are preferred for the application of elicitation due to their genetic and biosynthetic stability, high growth rate in growth regulator‐free media, and production consistence in response to elicitor treatment. Elicitors act as signal, recognized by elicitor‐specific receptors on the plant cell membrane and stimulate defense responses during elicitation resulting in increased synthesis and accumulation of secondary metabolites. Optimization of various parameters, such as elicitor type, concentration, duration of exposure, and treatment schedule is essential for the effectiveness of the elicitation strategies. Combined application of different elicitors, integration of precursor feeding, or replenishment of medium or in situ product recovery from the roots/liquid medium with the elicitor treatment have showed improved accumulation of secondary metabolites due to their synergistic effect. This is a comprehensive review about the progress in the elicitation approach to hairy root cultures from 2010 to 2019 and the information provided is valuable and will be of interest for scientists working in this area of plant biotechnology.
Role of fixing nitrogen in common bean growth under water deficit conditions
Authors: Fenta Berhanu Amsalu , Beebe Stephen E. , Kunert Karl J.
Published: July 2019

In common bean (Phaseolus vulgaris L), limited information is available if potential of nodulation and symbiotic nitrogen fixation is associated with the expression of traits that confer better adaptation to drought conditions. Adaptive traits were therefore measured in N‐fixing bean lines BAT 477, DOR 364, and PAN 185 and in nonnodulating lines BAT 477‐NN and DOR 364‐NN. Drought affected growth in all bean lines and decreased chlorophyll content but more in DOR 364‐NN and BAT 477‐NN, and also reduced nodule size with highest reduction in DOR 364 (21.6%). Loss of nitrogen fixation under drought conditions was further associated with lower water use efficiency, measured as carbon isotope ratio of 13C/12C, and lower %N in shoots when compared to capability to fix nitrogen. Loss of symbiotic nitrogen fixation in mutant bean lines DOR 364‐NN and BAT 477‐NN negatively affected root architectural traits under drought. Under drought conditions, line BAT 477‐NN had about 50% lower values for all root architectural traits, such as root angle, strongly emphasizing an association of capability to fix nitrogen with root development. An association between capability to fix nitrogen and maintaining a better harvest index and seed yield was also found in the study. Under well‐watered conditions, all N‐fixing lines had a higher harvest index and seed yield (2.6–2.8 t of seed yield/ha) in comparison with the two nonfixing bean lines (1.4 t/ha). Although the harvest index and seed yield declined due to drought in all tested lines, this decline was only significant for line DOR 364‐NN (harvest index) and lines DOR 364‐NN and BAT 477‐NN (seed yield). Our study has overall demonstrated an important association between the capability of maintaining atmospheric N‐fixation and expression of traits conferring better adaptation to drought conditions with any change in nitrogen fixation affecting these traits.
Temporomandibular disorder in head and neck cancer patients undergoing radiotherapy: Clinical findings and patient‐reported symptoms
Authors: Pauli Nina , Mejersjö Christina , Fagerberg‐Mohlin Bodil , Finizia Caterina
Published: July 2019

Background

The aim of this study was to investigate how common temporomandibular disorder (TMD) symptoms are among head and neck cancer (HNC) patients before and after oncological treatment.

Methods

Eighty‐nine patients with HNC receiving radiotherapy were enrolled in the study. Patients were examined before radiotherapy and at 6 and 12 months after radiotherapy to evaluate the function and tenderness of the temporomandibular jaw and the muscles of mastication as well as the patient‐reported symptoms.

Results

At 6 months after radiotherapy, there was a large increase in the number of patients reporting problems with opening their mouth, fatigue, stiffness, and pain of the jaw. Sixty‐eight percent of the patients had symptoms of TMD before oncological treatment and 94% and 81% had symptoms at the 6‐ and 12‐month follow‐up, respectively.

Conclusion

The signs and symptoms of TMD escalate after radiotherapy, with symptoms peaking at 6 months after radiotherapy. Most commonly, patients suffer from restricted mouth opening, stiffness, fatigue, and pain of the jaw.
Thermal slip and radiative heat transfer effects on electro‐osmotic magnetonanoliquid peristaltic propulsion through a microchannel
Authors: Prakash J. , Siva E. P. , Tripathi D. , Bég O. Anwar
Published: July 2019

A mathematical study is described to examine the concurrent influence of thermal radiation and thermal wall slip on the dissipative magnetohydrodynamic electro‐osmotic peristaltic propulsion of a viscous nanoliquid in an asymmetric microchannel under the action of an axial electric field and transverse magnetic field. Convective boundary conditions are incorporated in the model and the case of forced convection is studied, that is, thermal and species (nanoparticle volume fraction) buoyancy forces neglected. The heat source and sink effects are also included and the diffusion flux approximation is employed for radiative heat transfer. The transport model comprises the continuity, momentum, energy, nanoparticle volume fraction, and electric potential equations with appropriate boundary conditions. These are simplified by negating the inertial forces and invoking the Debye–Hückel linearization. The resulting governing equations are reduced into a system of nondimensional simultaneous ordinary differential equations, which are solved analytically. Numerical evaluation is conducted with symbolic software (MATLAB). The impact of different control parameters (Hartmann number, electro‐osmosis parameter, slip parameter, Helmholtz–Smoluchowski velocity, Biot numbers, Brinkman number, thermal radiation, and Prandtl number) on the heat, mass, and momentum characteristics (velocity, temperature, Nusselt number, etc) are presented graphically. Increasing Brinkman number is found to elevate temperature magnitudes. For positive Helmholtz–Smoluchowski velocity (reverse axial electrical field) temperature is strongly reduced, whereas for negative Helmholtz–Smoluchowski velocity (aligned axial electrical field), it is significantly elevated. With increasing thermal slip, nanoparticle volume fraction is also increased. Heat source elevates temperatures, whereas heat sink depresses them, across the microchannel span. Conversely, heat sink elevates nanoparticle volume fraction, whereas heat source decreases it. Increasing Hartmann (magnetic) parameter and Prandtl number enhance the nanoparticle volume fraction. Furthermore, with increasing radiation parameter, the Nusselt number is reduced at the extremities of the microchannel, whereas it is elevated at intermediate distances. The results reported provide a good insight into biomimetic energy systems exploiting electromagnetics and nanotechnology, and, furthermore, they furnish a useful benchmark for experimental and more advanced computational multiphysics simulations.
Viscosity and thermal conductivity comparative study for hybrid nanofluid in binary base fluids
Authors: Kumar Vikash , Sahoo Rashmi Rekha
Published: July 2019

Thermal conductivity and viscosity analysis of Al2O
3/CuO (50/50) hybrid nanofluid in various mass fractions of ethylene glycol (EG) and propylene glycol (PG) binary base fluid have been investigated in the present work. Hybrid nanofluid with vol. fraction range limited to 1.5% and within the higher temperature range of 50°C to 70°C is considered for thermal conductivity and viscosity analysis. Impact on viscosity and conductivity models with various shape nanoparticles, i.e, spherical, cylindrical, brick, platelets, and blades have been discussed and were compared in EG and PG binary base fluids. Also, the analysis extends to the prediction for the stability with zeta potential and synthesis of spherical shape Al2O3/CuO hybrid nanofluid with X‐ray diffraction (XRD) and scanning electron microscope (SEM). The theoretical analysis revealed that thermal conductivity of Al2O3/CuO hybrid nanofluid in EG binary base fluid is lower compared to in PG binary base fluid. The thermal conductivity is observed to be higher in spherical and cylindrical shape nanoparticle compared to bricks, blades, and platelets shape nanoparticles. Optimum viscosity of Al2O3/CuO hybrid nanofluid is observed at 50%EG and 30%PG of the binary base fluid. Hybrid nanofluid in 30% of PG as binary base fluid results 16.2% higher dynamic viscosity compared to pure PG base fluid for a volume concentration of 2%. Zeta potential measurement results in the stability of spherical Al2O3‐CuO/ (50/50) EG/W hybrid nanofluid, and it may be considered as a heat transfer fluid.
Epidemiological survey of antinuclear antibodies in healthy population and analysis of clinical characteristics of positive population
Authors: Li Xiaoyan , Liu Xin , Cui Jingjing , Song Wenjie , Liang Ying , Hu Yue , Guo Yaping
Published: July 2019

Background

In China, the incidence of autoimmune diseases is gradually increasing. To decrease the misdiagnosis rate of autoimmune diseases, we conducted an epidemiological investigation about the presence of antinuclear antibody (ANA) in healthy populations and analyzed the clinical characteristics of healthy population with both high titer of ANA and positive anti‐SSA and AMA‐M2.

Methods

Serum ANA titers were detected by indirect immunofluorescence (IIF), and other 15 types of ANA‐specific antibodies were detected by line immunoassays.

Results

In 25 110 individuals for routine examination, the positive rate of ANA titer >1:100 was 14.01%, of which the positive rate of female (19.05%) was higher than that of male (9.04%; P < 0.01). The positive rate of ANA titer >1:320 was 5.93%, of which the positive rate of female (8.68%) was higher than that of male (3.21%; P < 0.01). The specific antibodies were detected in 1489 of ANA‐positive people with titer >1:320, and the top three detected antibodies were anti‐Ro‐52 (212), AMA‐M2 (189), and anti‐SSA (144). The abnormal rate of blood routine test, liver function test, and other clinical indicators in AMA‐M2–positive population was significantly different from those in the control group. The abnormal rate of blood routine test, liver function test, and immune index in anti‐SSA–positive population was higher than those in control group.

Conclusion

There was a high prevalence of ANA positive in healthy population. To avoid misdiagnosis, those who had symptoms of abdominal discomfort, pruritus, or fatigue with abnormal results of blood routine and liver function test should be examined for ANA, AMA‐M2, anti‐SSA as early as possible.
YAP1 is required for the angiogenesis in retinal microvascular endothelial cells via the inhibition of MALAT1‐mediated miR‐200b‐3p in high glucose‐induced diabetic retinopathy
Authors: Han Ning , Tian Wen , Yu Na , Yu Li
Published: July 2019

Diabetic retinopathy (DR) is one of the severest complications in the development of diabetes with a characteristic of intraretinal new vessel formation. Our present study attempts to probe into the involvement of Yes‐associated protein 1 (YAP1) in retinal microvascular endothelial cells (RMECs) and the underlying mechanism. The DR mouse model was induced by streptozotocin injection and a high‐glucose/high‐fat diet. After that, with the utilization of the Pearson's correlation analysis, the correlation between YAP1 and metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) was analyzed. The relationship between microRNA‐200b‐3p (miR‐200b‐3p) and MALAT1 or vascular endothelial growth factor A (VEGFA) was then validated. Finally, the cellular processes including the abilities of proliferation, migration, as well as tube formation, were evaluated after the alteration of YAP1, MALAT1, and miR‐200b‐3p expression. YAP1 was observed to be highly expressed in retinas from DR mice, which promoted the cellular processes of RMECs through upregulating the MALAT1 expression. It was further confirmed that MALAT1 could sponge miR‐200b‐3p, and miR‐200b‐3p directly targeted VEGFA. When YAP1 was silenced, the RMEC proliferation, migration, and angiogenesis in the retina of DR mice were reduced. From these data, we conclude that YAP1 may exert some promotive effects on the development of DR through its regulation of the MALAT1/miR‐200b‐3p/VEGFA axis, highlighting that YAP1 silencing may be instrumental for the therapeutic targeting of DR.
Inhibition of KHSRP sensitizes colorectal cancer to 5‐fluoruracil through miR‐501‐5p‐mediated ERRFI1 mRNA degradation
Authors: Pan Ruijun , Cai Wei , Sun Jing , Yu Chaoran , Li Peiyong , Zheng Minhua
Published: July 2019

K‐homology (KH)‐type splicing regulatory protein (KHSRP) is an RNA binding protein that participates in RNA variable splicing and stability, and facilitates the biogenesis of miRNAs that target mRNA. However, to date, the role of KHSRP in colorectal cancer (CRC) progression has not been reported. In this study, the function of KHSRP in CRC proliferation and 5‐fluoruracil (5‐FU) resistance was investigated. The upregulation of KHSRP expression was confirmed in CRC patient tissues and two CRC cell lines. Manipulating KHSRP expression altered cell proliferation and 5‐FU resistance in CRC cells. ERRFI1, a downstream effector of KHSRP in CRC cells, reduced CRC cell proliferation. Sensitivity to 5‐FU mediated by KHSRP knockdown was reversed by ERRFI1 knockdown. We found that KHSRP decreased ERRFI1 mRNA expression indirectly. By screening KHSRP‐regulated miRNAs, we further found that miR‐501‐5p directly combines with KHSRP in CRC cells. Mechanistically, the results of a luciferase assay suggested that miR‐501‐5p directly binds to the ERRFI1 3′‐untranslated region. Taken together, our data indicated that modification of ERRFI1 by KHSRP occurs through miR‐501‐5p, an essential mechanism driving CRC proliferation and 5‐FU resistance. Insight into this mechanism may provide novel targets for overcoming drug resistance in CRC.
Evaluation of the biocompatibility of resin composite‐based dental materials with gingival mesenchymal stromal cells
Authors: Cândea Ciurea Andreea , Şurlin Petra , Stratul Ştefan‐Ioan , Soancă Andrada , Roman Alexandra , Moldovan Mărioara , Tudoran B. Lucian , Pall Emoke
Published: July 2019

Resin composite‐based dental materials can leach certain components into the oral environment, causing potentially harmful gingival biological effect. Gingival tissue is a rich source of mesenchymal stem cells (MSCs) that is easily accessible, and can be used as a complementary approach for the investigation of dental material biocompatibility. Using gingival MSCs (gMSCs), the present study aimed to investigate the cytotoxicity of two classes of restorative dental materials (ormocers and resin composites) used to restore class II cavities close to the gingival margin, in addition to analyzing the leached compounds from these resin composite‐based materials. Functionality assays (Colony‐forming unit, migratory potential, and proliferation assays) and a viability assay (MTT) were employed. Cells' aspect was observed by scanning electron microscopy (SEM). Leached monomers were also quantitated using high‐performance liquid chromatography (HPLC). The cytotoxicity of the biomaterials was highlighted by impaired functionality and diminished viability of gMSCs. Despite being variants of the same commercial material, the two ormocers behaved differently one material having a more negative impact on cell functionality than the other. Cells appeared to attach well to all materials. Main monomer molecules were mostly released by the tested materials. For all samples, an increased elution of monomers was recorded in artificial saliva as compared with culture medium. One composite material has released nearly eight times more urethane dimetacrylate in artificial saliva than in culture medium. Significantly lower gMSC viability scores were recorded for all the investigated samples in comparison with the control.
Difficulties adapting to Nail‐Patella syndrome: A qualitative study of patients' perspectives
Authors: Geerts‐Crabbé Laura , Antoine Pascal , Brugallé Elodie , Ghoumid Jamal , Bellengier Laurence , Edery Patrick , Heron Delphine , Manouvrier‐Hanu Sylvie , Fantini‐Hauwel Carole
Published: July 2019

Nail‐Patella syndrome (NPS) is a genetic disorder generating physical malformations and, in approximately one in three cases, ocular and renal damage. The present research aimed to deeply understand patients' subjective experience with NPS, particularly the aspects of the syndrome that affect patients' adaptation and to propose interventions that can improve genetic and psychological counseling and help patients cope with their condition. Semi‐structured interviews of nine people diagnosed with NPS were analyzed using interpretative phenomenological analysis. Results highlighted attempts to look like a person without disabilities by hiding malformations and not telling the truth about symptoms' genetic origin because of patients' poor self‐esteem, negative self‐cognition, and social isolation experienced from childhood to adulthood. Difficulties of adaptation to physical limits and pain were also identified. The majority of participants who were not diagnosed at birth tended to consider physical symptoms as “birth malformations” without imagining other potential implications until receiving a diagnosis. Despite the diagnosis, the majority continued to minimize the potential complications by considering NPS as a “physical difference” and not adhering to medical surveillance.
Ring Opening and Recyclization Reactions of 3‐Nitrochromone with Some Nucleophilic Reagents
Authors: Ibrahim Magdy A. , Alnamer Youssef A.
Published: July 2019

The chemical reactivity of 3‐nitrochromone (1) was studied towards some nucleophilic reagents. Reaction of 3‐nitrochromone (1) with some carbon nucleophiles revealed existence of ring‐opening ring‐closure reactions, and the mode of cyclization depends on the nucleophile used. Treatment of 3‐nitrochromone (1) with malononitrile and ethyl cyanoacetate produced benzoxocinone derivatives 2 and 3, respectively. Boiling compound 1 with cyanoacetamide and 2‐aminoprop‐1‐ene‐1,1,3‐tricarbonitrile afforded pyridine derivatives 4 and 5, respectively. Reaction of compound 1 with 1H‐benzimidazol‐2‐ylacetonitrile, 5‐amino‐2,4‐dihydro‐3H‐pyrazol‐3‐one, and dimedone led to pyrido[1,2‐a]benzimidazole 6, pyrazolo[3,4‐b]pyridine 7, and chromenone 8, respectively. Treating 3‐nitrochromone (1) with heterocyclic amines gave enaminones 11 and 12 via nucleophilic attack at C‐2 position with ring opening. The structures of the newly synthesized products were deduced on the basis of their analytical and spectral data.
An Efficient Access to Pyrimidine‐based Polyfunctional Heterocycles with Anticipated Antibacterial Activity
Authors: Mourad Asmaa Kamal , Mohammed Fatehia K. , Tammam Gamal Hassan , Mohammed Shimaa Rabie
Published: July 2019

6‐Amino‐2‐thioxotetrahydropyrimidine‐5‐carbonitrile derivative 2 was synthesized in a good yield via refluxing a mixture of arylidene 1 and thiourea in a highly basic sodium ethoxide solution. Subsequently, the synthesized pyrimidine‐2‐thione derivative 2 was allowed to interact with diversified nucleophiles and electrophiles under various reaction conditions in order to have a feasible access to further new and assorted fused heterocycles. Finally, the biological activity of the newly synthesized fused pyrimidines was screened in vitro against four different Gram‐positive and Gram‐negative bacterial strains. All the developed heterocycles were adequately characterized utilizing 1H‐NMR, 13C‐NMR, Fourier transform infrared, elemental analysis, and electrospray ionization–mass spectrum and tested for their antibacterial activity.
Synthesis, antimicrobial activity, and molecular docking study of formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamides
Authors: Muluk Mahesh B. , Dhumal Sambhaji T. , Phatak Pramod S. , Rehman Naziya N. M. A. , Dixit Prashant P. , Choudhari Prafulla B. , Mane Ramrao A. , Haval Kishan P.
Published: July 2019

In the present study, substituted formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamide derivatives (6a–k) have been designed and synthesized employing click chemistry approach and evaluated for their in vitro antifungal and antibacterial activities. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral techniques. Among the screened compounds, 6d, 6e, 6j, and 6k have shown good antifungal and antibacterial activities. Compound 6k has shown very effective antimicrobial activity. We further performed exploratory docking studies on microbial DNA gyrase to rationalize the in vitro biological data and to demonstrate the mechanism of antimicrobial activity. This is the first report to demonstrate the formylnaphthalenyloxymethyl, triazole, and N‐phenylacetamide hybrids as potential antimicrobial agents.
Frontline Science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes
Authors: Miranda Mariana Camila Gonçalves , Oliveira Rafael Pires , Torres Lícia , Aguiar Sarah Leão Fiorini , Pinheiro-Rosa Natalia , Lemos Luísa , Guimarães Mauro Andrade , Reis Daniela , Silveira Tatiany , Ferreira Ênio , Moreira Thaís Garcias , Cara Denise Carmona , Maioli Tatiani Uceli , Kelsall Brian L , Carlos Daniela , Faria Ana Maria Caetano
Published: July 2019

Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria-bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre-diabetic NOD mice, and cross-fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.
Sensitivity of Kupffer cells and liver sinusoidal endothelial cells to ricin toxin and ricin toxin–Ab complexes
Authors: Mooney Bridget , Torres-Velez Fernando J , Doering Jennifer , Ehrbar Dylan J , Mantis Nicholas J
Published: July 2019

Ricin toxin is a plant-derived, ribosome-inactivating protein that is rapidly cleared from circulation by Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs)—with fatal consequences. Rather than being inactivated, ricin evades normal degradative pathways and kills both KCs and LSECs with remarkable efficiency. Uptake of ricin by these 2 specialized cell types in the liver occurs by 2 parallel routes: a “lactose-sensitive” pathway mediated by ricin's galactose/N-acetylgalactosamine-specific lectin subunit (RTB), and a “mannose-sensitive” pathway mediated by the mannose receptor (MR; CD206) or other C-type lectins capable of recognizing the mannose-side chains displayed on ricin's A (RTA) and B subunits. In this report, we investigated the capacity of a collection of ricin-specific mouse MAb and camelid single-domain (VHH) antibodies to protect KCs and LSECs from ricin-induced killing. In the case of KCs, individual MAbs against RTA or RTB afforded near complete protection against ricin in ex vivo and in vivo challenge studies. In contrast, individual MAbs or VHHs afforded little (<40%) or even no protection to LSECs against ricin-induced death. Complete protection of LSECs was only achieved with MAb or VHH cocktails, with the most effective mixtures targeting RTA and RTB simultaneously. Although the exact mechanisms of protection of LSECs remain unknown, evidence indicates that the Ab cocktails exert their effects on the mannose-sensitive uptake pathway without the need for Fcγ receptor involvement. In addition to advancing our understanding of how toxins and small immune complexes are processed by KCs and LSECs, our study has important implications for the development of Ab-based therapies designed to prevent or treat ricin exposure should the toxin be weaponized.
Malt1 deficient mice develop osteoporosis independent of osteoclast-intrinsic effects of Malt1 deficiency
Authors: Monajemi Mahdis , Fisk Shera , Pang Yvonne C F , Leung Jessica , Menzies Susan C , Ben-Othman Rym , Cai Bing , Kollmann Tobias R , Rozmus Jacob , Sly Laura M
Published: July 2019

This study tested the hypothesis that mucosa associated lymphoid tissue 1 (Malt1) deficiency causes osteoporosis in mice by increasing osteoclastogenesis and osteoclast activity. A patient with combined immunodeficiency (CID) caused by MALT1 deficiency had low bone mineral density resulting in multiple low impact fractures that was corrected by hematopoietic stem cell transplant (HSCT). We have reported that Malt1 deficient Mϕs, another myeloid cell type, are hyper-responsive to inflammatory stimuli. Our objectives were to determine whether Malt1 deficient mice develop an osteoporosis-like phenotype and whether it was caused by Malt1 deficiency in osteoclasts. We found that Malt1 deficient mice had low bone volume by 12 weeks of age, which was primarily associated with reduced trabecular bone. Malt1 protein is expressed and active in osteoclasts and is induced by receptor activator of NF-κB ligand (RANKL) in preosteoclasts. Malt1 deficiency did not impact osteoclast differentiation or activity in vitro. However, Malt1 deficient (Malt1−/−) mice had more osteoclasts in vivo and had lower levels of serum osteoprotegerin (OPG), an endogenous inhibitor of osteoclastogenesis. Inhibition of Malt1 activity in Mϕs induced MCSF production, required for osteoclastogenesis, and decreased OPG production in response to inflammatory stimuli. In vitro, MCSF increased and OPG inhibited osteoclastogenesis, but effects were not enhanced in Malt1 deficient osteoclasts. These data support the hypothesis that Malt1 deficient mice develop an osteoporotic phenotype with increased osteoclastogenesis in vivo, but suggest that this is caused by inflammation rather than an effect of Malt1 deficiency in osteoclasts.
Isolation of aristolochic acid I from herbal plant using molecular imprinted polymer composited ionic liquid‐based zeolitic imidazolate framework‐67
Authors: Fang Luwei , Tian Minglei , Row Kyung Ho , Yan Xuemin , Xiao Wei
Published: July 2019

Aristolochic acid I is a toxic compound found in the genus of Aristolochia plants, which are commonly used as herbal cough treatment medicines. To remove the aristolochic acid I in extract efficiently and selectively, a molecularly imprinted polymer composed of ethylimidazole ionic liquid‐based zeolitic imidazolate framework‐67 was synthesized and used as the adsorbent. Under the conditions optimized by the software design expert, the sorbent showed highest adsorption amount of 34.25 mg/g in methanol/water (95:5, v/v) at 39°C for 138 min. The sorbent was then applied to solid phase extraction to isolate aristolochic acid I from the extract of the herbal plant Fibraurea Recisa Pierre. 0.043 mg/g of aristolochic acid I was obtained after the loading, washing, and elution processes. The limit of detection of 2.41 × 10−5 mg/mL and good recoveries provided evidence for the accuracy of this method.
Review of the effects of barred owls on spotted owls
Authors: Long Linda L. , Wolfe Jared D.
Published: July 2019

Barred owls (Strix varia) are forest‐dwelling owls, native to eastern North America, with populations that expanded westward into the range of the spotted owl (Strix occidentalis). Barred owls exert an overwhelmingly negative influence on spotted owls, thereby threatening spotted owl population viability where the species co‐occur. In this review, we provide an overview of the barred owl's range expansion and detail and synthesize previously published literature on spotted and barred owls within the range of the spotted owl as related to potential future outcomes for the northern spotted owl (S. o. caurina). We include research on diet, habitat use and selection, effects of barred owls on spotted owl demography and behavior, hybridization with spotted owls, parasites, contemporary management, and future research needs for spotted owl populations given continued barred owl expansion throughout western North America. Our literature review and synthesis should provide managers with the information necessary to develop strategies that mitigate deleterious effects of barred owls at local and landscape scales. © 2019 The Wildlife Society.
Motor function and the probability of prodromal Parkinson's disease in older adults
Authors: Maraki Maria I. , Stefanis Leonidas , Yannakoulia Mary , Kosmidis Mary H. , Xiromerisiou Georgia , Dardiotis Efthimios , Hadjigeorgiou Georgios M. , Sakka Paraskevi , Scarmeas Nikolaos , Stamelou Maria
Published: July 2019

Background

Identification and characterization of Parkinson's disease (PD) in its prodromal stage is crucial.

Objective

The objective of this study was to investigate the association between motor function and the probability of prodromal PD in a community‐dwelling older population.

Methods

We used data from a population‐based cohort of older adults (HELIAD study). Subjective motor function was evaluated with a 12‐item motor symptoms questionnaire and objective motor function indirectly with a physical activity questionnaire and two gait speed tests. The probability of prodromal PD was calculated according to the Movement Disorder Society research criteria for n = 1731 without PD. Regression multiadjusted models were used to investigate the associations between each motor measure and prodromal PD probability.

Results

For each unit increase in motor symptoms score and for each kcal/kg/day lower energy expenditure (corresponding to 20 minutes of light walking/day for a 75‐kg man) there was a 27% and 3% higher probability for prodromal PD, respectively (P < 0.001). Having at least one subjective motor symptom increased the odds of having possible/probable prodromal PD (n = 49; P < 0.05). Including subjective and indirect motor variables in the same model showed that both (symptoms and physical activity) contributed significantly to the model (P < 0.01). Excluding subthreshold parkinsonism from the calculation showed that gait speed less than 0.8 m/s was also associated with a higher prodromal PD probability score (P < 0.001).

Conclusions

Subjective motor symptoms as well as simple objective motor measures of physical activity or gait speed are associated with a higher probability of prodromal PD in older adults. These data may serve to enable the early identification of prodromal PD cohorts, particularly if they are confirmed in longitudinal studies. © 2019 International Parkinson and Movement Disorder Society