bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead
Authors: Miltner Adam M. , La Torre Anna
Published: September 2018

The neurons of the retina can be affected by a wide variety of inherited or environmental degenerations that can lead to vision loss and even blindness. Retinal ganglion cell (RGC) degeneration is the hallmark of glaucoma and other optic neuropathies that affect millions of people worldwide. Numerous strategies are being trialed to replace lost neurons in different degeneration models, and in recent years, stem cell technologies have opened promising avenues to obtain donor cells for retinal repair. Stem cell–based transplantation has been most frequently used for the replacement of rod photoreceptors, but the same tools could potentially be used for other retinal cell types, including RGCs. However, RGCs are not abundant in stem cell–derived cultures, and in contrast to the short‐distance wiring of photoreceptors, RGC axons take a long and intricate journey to connect with numerous brain nuclei. Hence, a number of challenges still remain, such as the ability to scale up the production of RGCs and a reliable and functional integration into the adult diseased retina upon transplantation. In this review, we discuss the recent advancements in the development of replacement therapies for RGC degenerations and the challenges that we need to overcome before these technologies can be applied to the clinic. Developmental Dynamics 248:118–128, 2019. © 2018 Wiley Periodicals, Inc.
Allometry and integration do not strongly constrain beak shape evolution in large‐billed (Corvus macrorhynchos) and carrion crows (Corvus corone)
Authors: Yamasaki Takeshi , Aoki Sou , Tokita Masayoshi
Published: September 2018

A recent geometric morphometric study on certain landbird lineages revealed that a major part of the variation in beak shape is accounted for by skull size and cranial shape. The study interpreted this result as evidence for the presence of strong evolutionary constraints that severely prevented beak shape from evolving substantially away from predictions of allometry and morphological integration. However, there is another overlooked but similarly plausible explanation for this result: The reason why beak shape does not depart much from predictions might simply be that selection pressures favoring such changes in shape are themselves rare. Here, to evaluate the intensity of evolutionary constraints on avian beak shape more appropriately, we selected large‐billed (Corvus macrorhynchos) and carrion crows (Corvus corone) as study objects. These landbird species seem to experience selection pressures favoring a departure from an allometric trajectory. A landmark‐based geometric morphometric approach using three‐dimensional reconstructions of CT scan images revealed that only 45.4% of the total shape variation was explained by allometry and beak–braincase integration. This suggests that when a selection pressure acts in a different direction to allometry and integration, avian beak shape can react to it and evolve flexibly. As traditionally considered, evolutionary constraints on avian beak shape might not be all that strong.
Insights on the persistence of pines (Pinusspecies) in the Late Cretaceous and their increasing dominance in the Anthropocene
Authors: Singh Surendra P. , Inderjit   , Singh Jamuna S. , Majumdar Sudipto , Moyano Jaime , Nuñez Martin A. , Richardson David M.
Published: September 2018

Although gymnosperms were nearly swept away by the rise of the angiosperms in the Late Cretaceous, conifers, and pines (Pinusspecies) in particular, survived and regained their dominance in some habitats. Diversification of pines into fire‐avoiding (subgenusHaploxylon) and fire‐adapted (subgenusDiploxylon) species occurred in response to abiotic and biotic factors in the Late Cretaceous such as competition with emerging angiosperms and changing fire regimes. Adaptations/traits that evolved in response to angiosperm‐fuelled fire regimes and stressful environments in the Late Cretaceous were key to pine success and are also contributing to a new “pine rise” in some areas in the Anthropocene. Human‐mediated activities exert both positive and negative impacts of range size and expansion and invasions of pines. Large‐scale afforestation with pines, human‐mediated changes to fire regimes, and other ecosystem processes are other contributing factors. We discuss traits that evolved in response to angiosperm‐mediated fires and stressful environments in the Cretaceous and that continue to contribute to pine persistence and dominance and the numerous ways in which human activities favor pines.
Synthesis and Reactivity of Oxazinoindolones via Regioselective 6‐exo‐dig Iodolactonization
Authors: Hammoud Sokaina , Anselmi Elsa , Cherry Khalil , Kizirian Jean‐Claude , Thibonnet Jérôme
Published: September 2018

An efficient protocol for the facile construction of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones has been developed by using a regio‐ and stereoselective iodolactonization reaction. Subsequent palladium cross‐coupling reactions of 3,4‐dihydro‐10‐iodo‐3‐iodomethylene‐[1,4]‐oxazino[4,3‐a]indol‐1‐ones readily afforded functionalized oxazinoindolones.
1,2‐Diaza‐1,3‐diene‐Based Multicomponent Reactions in Sequential Protocols to Synthesize Arylamino‐5‐hydrazonothiophene‐3‐carboxylates
Authors: Mari Giacomo , De Crescentini Lucia , Favi Gianfranco , Santeusanio Stefania , Mantellini Fabio
Published: September 2018

Two unprecedented approaches to amply functionalized 2‐arylamino‐5‐hydrazonothiophene‐3‐carboxylates were reported. The first one is a useful metal‐free sequential multicomponent synthesis of readily available β‐keto esters, isothiocyanates and in situ generated 4‐unsubstituted diazadienes. The second one is the basic treatment of 2,5‐dihydrothiophenes previously prepared by means of an analogous sequential multicomponent synthesis where 4‐substituted diazadienes were employed.
Regioselective Ring Opening of 1,3‐Dioxane‐Type Acetals in Carbohydrates
Authors: Janssens Jonas , Risseeuw Martijn D. P. , Van der Eycken Johan , Van Calenbergh Serge
Published: September 2018

The (regio)selective manipulation of hydroxyl groups in carbohydrates has been a long‐standing challenge in (bio)organic chemistry and continues to trigger the creative minds of many chemists. Among the various strategies that have been developed to address these issues, mostly relying on multistep procedures involving the use of protecting groups, the regioselective ring opening of 1,3‐dioxane‐type acetals has emerged as a powerful tool. Since the first papers on this subject appeared in the 1960s, a large variety in both acetal types and reagents for their partial cleavage has come to the fore. This review aims to give an overview of the different carbohydrate‐derived ring systems, ranging from four‐ to seven‐membered rings, on which regioselective ring‐openings have been performed, along with the appropriate reagents and combinations thereof. The transformations on 1,3‐dioxane acetals fit in a larger group of ring opening reactions of structurally related cyclic functional groups, including 1,3‐dioxolanes, 1,3‐oxathianes, orthoesters, cyclic carbonates and silylene acetals, which will not be discussed in this review.
Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate
Authors: Chen Gaofeng , Wen Hairuo , Mao Zhihui , Song Jie , Jiang Hua , Wang Weifan , Yang Ying , Miao Yufa , Wang Chao , Huang Zhiying , Wang Xue
Published: September 2018

The utility and sensitivity of the newly developed flow cytometric Pig‐a gene mutation assay have become a great concern recently. In this study, we have examined the feasibility of integrating the Pig‐a assay as well as micronucleus and Comet endpoints into acute and subchronic general toxicology studies. Male Sprague–Dawley rats were treated for 3 or 28 consecutive days by oral gavage with procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum tolerated dose. The induction of CD59‐negative reticulocytes and erythrocytes, micronucleated reticulocytes in peripheral blood, micronucleated polychromatic erythrocytes in bone marrow, and Comet responses in peripheral blood, liver, kidney, and lung were evaluated at one, two, or more timepoints. Both PCZ and EC produced positive responses at most analyzed timepoints in all tissue types, both with the 3‐day and 28‐day treatment regimens. Furthermore, comparison of the magnitude of the genotoxicity responses indicated that the micronucleus and Comet endpoints generally produced greater responses with the higher dose, short‐term treatments in the 3‐day study, while the Pig‐a assay responded better to the cumulative effects of the lower dose, but repeated subchronic dosing in the 28‐day study. Collectively, these results indicate that integration of several in vivo genotoxicity endpoints into a single routine toxicology study is feasible and that the Pig‐a assay may be particularly suitable for integration into subchronic dose studies based on its ability to accumulate the mutations that result from repeated treatments. This characteristic may be especially important for assaying lower doses of relatively weak genotoxicants. Environ. Mol. Mutagen. 60:56–71, 2019. © 2018 Wiley Periodicals, Inc.
Interactions between superoxide dismutase and paraoxonase polymorphic variants in nonsyndromic cleft lip with or without cleft palate in the Brazilian population
Authors: Machado Renato Assis , de Oliveira Silva Carolina , Persuhn Darlene Camati , de Melo Cavalcanti Dantas Vanessa , de Almeida Reis Silvia Regina , Wu Tao , Line Sergio Roberto , Martelli‐Junior Hercilio , Graner Edgard , Coletta Ricardo D.
Published: September 2018

During development, oxidative stress is hypothesized to mediate embryotoxicity, which may be intensified by exposition to environmental factors and by genetic variations in the enzymes involved in protecting cells from these damaging effects, including superoxide dismutase (SOD) and paraoxonase (PON). The aim of this study was to evaluate the influence of single‐nucleotide polymorphisms (SNP) in genes associated with the neutralization of oxidative stress (SOD and PON family members) in the risk of nonsyndromic oral cleft in the Brazilian population. Initially, we tested for association between 28 SNP in SOD1, SOD2, SOD3, PON1, PON2, and PON3 among 325 nonsyndromic cleft lip with or without cleft palate (NSCL±P) case‐parent trios. Multiple logistic regression analyses were used to explore gene, GxG and GxE, involving factors that induce oxidative stress accumulation during pregnancy. Signals still significant after both Bonferroni correction and in permutation test were subsequently confirmed in an ancestry‐structured case–control analysis with 722 NSCL±P and 866 controls from the same population. In the trio sample, transmission disequilibrium test (TDT) (allele and haplotype) and GxE analysis showed no significant associations, but multiple pairwise GxG interactions involving 10 SNP in PON1, PON2, and PON3 were detected and further examined in the case–control sample. The PON1 rs2237583 and PON2 rs17166879 yielded significant evidence of SNP‐SNP interactions after adjustment for multiple tests (both Bonferroni correction and 10,000 permutation test). The C allele and the CT genotype of PON1 rs2237583 were associated with significant protective effects against NSCL±P, while rs3917490 showed a significant association only in the sample composed of patients displaying high African ancestry. Our results reveal associations between rs2237583 and rs3917490 in PON1 and GxG interactions containing rs2237583 and rs17166879 with the susceptibility of NSCL±P in the Brazilian population. Furthermore, this study underlines the recent tendency of taking into account potential GxG interactions to clarify the underlying mechanisms associated with the etiology of this common malformation. Environ. Mol. Mutagen. 60: 185–196, 2019. © 2018 Wiley Periodicals, Inc.
A Bayesian spatial hierarchical model for extreme precipitation in Great Britain
Authors: Sharkey Paul , Winter Hugo C.
Published: September 2018

Intense precipitation events are commonly known to be associated with an increased risk of flooding. As a result of the societal and infrastructural risks linked with flooding, extremes of precipitation require careful modeling. Extreme value analysis is typically used to model large precipitation events, although an independent analysis of neighboring sites can produce very different estimates of risk. In reality, one would expect neighboring locations to exhibit similar extremal behavior. A common method of inducing spatial similarity of extremal behavior is to define a spatial structure on the parameters of a generalized Pareto distribution in a Bayesian hierarchical modeling framework. These methods are often implemented under the assumption of conditional independence in time and space, with the consequence that standard errors of parameter estimates are too small. We present an approach for accounting for spatial and temporal dependence when quantifying the uncertainty in Bayesian hierarchical models when the misspecification of conditional independence has been made. We also present comparisons of performance between this class of models and alternative approaches, applied to precipitation data in Great Britain.
A Sustainable Power Supply System, Iran's Opportunities via Bioenergy
Authors: Heidari Alireza , Hajinezhad Ahmad , Aslani Alireza
Published: September 2018

Biomass as a sustainable renewable energy resource with numerous advantages in terms of storage, transportation, and conversion to gas and liquid that no other renewables can compete with bioenergy in these fields could be a proper power solution for Iran as a developing country with abundant fossil and renewable resources. Despite the lake of official statistics, a comprehensive review of biomass resource estimation of Iran has been conducted for the first time and 72 Mt animal manure, 61 Mt sewage and waste water, 19 Mt agricultural residue, 15 Mt municipal solid wastes, 4 Mt woody residues, and 1.3 Mt citrus residues are estimated. A novel biopower model structure is introduced using reference energy system modeling approach as a network representation of the technical activities to convert biomass to electricity. Therefore, 781 ML biodiesel, 5690 ML bioethanol and 20,500 MCM biogas could be extracted through the proposed structure. Thus, total biopower potential will be 63.7 TWh that is equal to 23.2% of total power generation in Iran (274.4 TWh). The sustainability assessment is conducted and the results show 79 Mt of carbon reduction, 9366 annual job creation and 0.01 USD/kWh cost reduction in order to 100% of bioenergy potential utilization, which are 79%, 22%, and 10% improve in social, environmental and economic indicators, respectively. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 171–188, 2019
The Synthesis of Carboxymethyl Cellulose‐Based Hydrogel from Sugarcane Bagasse Using Microwave‐Assisted Irradiation for Selective Adsorption of Copper(II) Ions
Authors: Baiya Chanathip , Nannuan Loetsak , Tassanapukdee Yosthanase , Chailapakul Orawon , Songsrirote Kriangsak
Published: September 2018

This study presents the sustainable applications of recycling agricultural waste. The cellulose from sugarcane bagasse (SCB) was extracted to prepare the carboxymethyl cellulose (CMC) used as the starting material for synthesizing CMC‐based hydrogel for the selective adsorption of Cu(II) ions in contaminated solution. Hydrogel fabrication was performed under microwave‐assisted irradiation, which helps to improve reaction efficiency and significantly reduces reaction time compared with using a conventional hotplate. The hydrogel of 25% CMC blended with poly(vinyl alcohol) (PVA) and using glutaraldehyde (GA) as a cross‐linking agent showed the property of selective adsorption for Cu(II) ions from the solution with an adsorption capacity of 2.3 mg/g (92.4% removal) under ambient temperature with pH 5.0. The adsorbed Cu(II) ions were effectively desorbed from the hydrogel by either 0.1 M HCl or 0.1 M EDTA. Thus, the prepared hydrogel could potentially be applied in the removal of Cu(II) ions from contaminated water, with promising potential for reuse after the regeneration process. Sugarcane bagasse was used as a starting material for the synthesis of hydrogel, which has selective adsorption property to Cu(II) ions. In addition, microwave‐assisted irradiation, technology that is able to save time and energy, was exploited for the polymer synthesis. Therefore, this study presents the sustainable applications of recycling agricultural waste for the purpose of water treatment. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S157–S165, 2019
Phytoremediation of nutrient overloaded soil by rice mill wastewater using Amaranthus palmeri and Sorghum vulgare
Authors: Umamaheswari J. , Shanthakumar S.
Published: September 2018

Paddy processing (Rice mill) industries are agro‐based industries which discharge wastewater with high organic content, cause nutrient overloading to the environment. Amaranthus palmeri and Sorghum vulgare were used to reduce the excess nutrients from the soil collected from land near a rice mill where wastewater is being disposed. Potted plant experiments were conducted for the selected species and tested for its growth potential and compared with control soil (normal soil). Absolute growth rate (AGR) of 0.52and 1.61 cm/day were obtained for A. palmeri and S. vulgare grown in contaminated soil (APCS and SVCS) which are 2.89 and 1.23 times more than that of the species grown in control soil (APC and SVC), respectively. A positive correlation was observed between AGR and their dry weights (r > 0.685; P = 0.01), and nitrogen removal (r > 0.464; P = 0.01) where it was the negative correlation in phosphate removal (AGR: r < 0.481; P = 0.01; dry weight: r < 0.245; P = 0.05). Significant ANOVA results were obtained for the interaction effect among the species and soil on the nutrient removal efficiency (RE) with respect to AGR and dry weight. It is evident that the both A. palmeri (RE: N = 98.81% and K = 72.32%) and S. vulgare (RE: N = 99.54% and K = 73.23%) are the promising species to remediate the nutrient overloaded soil. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 354–361, 2019
N2O absorption through super hydrophobic hollow fiber membrane contactor
Authors: Kartohardjono Sutrasno , Shabanindita Stephanie , Harianja Meylin , Dixon Alphasius Omega , Yuliusman Yuliusman , Saksono Nelson
Published: September 2018

Dinitrogen monoxide (N2O) is mainly produced in Horticulture and farming activities, industrial processes and combustion of fossil fuels. N2O is one of the harmful emissions and its global warming potential is 310 times greater than CO2 on a molecular basis. This research aims to absorb N2O from its mixture with air through super hydrophobic hollow membrane contactor using a mixture of 0.5M HNO3 and 0.5 wt % H2O2 solutions as absorbent. In the experiment, the feed gas flowed through the shell side of the contactor, while absorbent solution flowed through the lumen fibers. Experimental results show that the amount of N2O absorbed and N2O absorption efficiency increased with the absorbent flow rate and the number of fibers in the contactor resulting from the increase in the turbulence and surface area for gas–liquid contact, respectively. The overall mass transfer coefficient and the flux increased with the absorbent flow rate due to the decrease of the mass transfer resistance in the liquid phase. However, the overall mass transfer coefficient and the flux decreased with the number of fibers in the contactor due to the decrease of the absorbent flow rate in a single fiber. The amount of N2O absorbed and the flux increased but the N2O absorption efficiency decreased with increasing the feed gas cross flow rate. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 362–366, 2019
The inhibitory effect of graphene oxide on photocatalytic hydrogenation from organic fatty acids
Authors: Zhang Wen , Li Yang , Liu Changqing , Marhaba Taha
Published: September 2018

Two catalysts, carbon doped TiO2 (C‐TiO2) and C‐TiO2 conjugated with reduced graphene oxide (rGO)–C‐TiO2/rGO were synthesized and compared with respect to the photocatalytic hydrogen (H2) production using three organic fatty acids (OFAs) as electron donors under visible light irradiation. Our results show that the hybridization between C‐TiO2 and rGO did not subtaintially improve the production of H2 but instead elicited inhibitory effects compared to C‐TiO2. For instance, the specific H2 production on C‐TiO2 was 214 and 336 μmol·h−1·g−1 for acetic and propionic acids, respectively, whereas C‐TiO2/rGO only achieved 155 and 161 μmol·h−1·g−1, respectively. With butyric and lactic acids as electron donors, C‐TiO2 and C‐TiO2/rGO led to almost the same H2 production rates (233 and 155 μmol·h−1·g−1, respectively). The inhibitory effect of rGO on photocatalytic activity could be due to the potential deposition of OFAs on graphene sheets that may reduce the mobility and accessibility of OFAs toward catalytic reactions with C‐TiO2. The electron spin resonance spectrometry (ESR) tests revealed that and CH3• were the major radicals responsible for OFA degradation. Moreover, the produced concentration of CH3• was consistently higher in C‐TiO2 suspension than that in C‐TiO2/rGO suspension. The estimated aqueous/solid mass transfer rate constant (s−1) was lower on the catalyst surface of C‐TiO2/rGO than C‐TiO2. Consequently, the decoration of rGO sheets on C‐TiO2 may not always promote photocatalytic H2 production especially when using OFAs as electron donors. The results demonstrated hereby aim to provide new evidence on potential drawbacks of graphene‐based photocatalysis. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 410–416, 2019
Antibacterial Activity of Magnesium Oxide Nano‐hexagonal Sheets for Wastewater Remediation
Authors: Azzam Ahmed M. , Shenashen Mohamed A. , Mostafa Bayaumy B. , Kandeel Wafaa A. , El‐Safty Sherif A.
Published: September 2018

Water pollution has been rapidly intensified because of the growing population, industrial development, and improper management of water sources. In this work, we fabricated hexagonal micro/macroporous MgO nanosheets (HMM‐NSs) with an average particle size of 350 nm. HMM‐NSs served as an effective antibacterial agent with high surface reactivity due to their well‐scattered pore windows, which conferred the sheets with a large surface. Controlled HMM‐NSs create additional active sites throughout the interior/exterior sheet surface, thereby promoting the release of reactive O species (ROS). The antimicrobial activity of the designed nanosheets was tested against Gram‐positive (Staphylococcus aureus) and ‐negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. HMM‐NSs exhibited potential for bioapplication in inactivating bacterial cells by killing them through the interaction with bacterial cell membrane and internal cellular components. The reactions with cell wall proteins led to reduced permeability, while high release rates of ROS from HMM‐NSs caused damage to DNA and cellular components and eventually led to cell death. Therefore, these finding may provide an unconventional strategy for wastewater disinfection that can be used for irrigation. © 2018 American Institute of Chemical Engineers Environ Prog, 38: S260–S266, 2019
Hydrolysis of oils in the Wadi Hanifah River in Saudi Arabia by free and immobilized Staphylococcus aureus ALA1 lipase
Authors: Bacha Abir Ben , Abid Islem , Nehdi Imededdine , Horchani Habib
Published: September 2018

This study describes the biochemical properties of Staphylococcus aureus lipase immobilized by physical adsorption to assess its role in the biodegradation of oils in the Wadi Hanifah River. After optimization of the immobilization conditions, the recovered enzyme activity was 95% with appreciable increase in stability. The immobilized and free lipase retained 70% and only 10% of the initial activity after a 60‐min incubation at 80 °C, respectively. More than ~40% residual activity remained after 48 h of incubation at pH5 to 11. The immobilized enzyme retained 100% of the initial activity when used for four cycles and 42% of initial activity when stored at 25 °C for 120 days. Enzyme stability was enhanced in the presence of inactivating agents including β‐mercaptoethanol, SDS, EDTA, and Co2+. The bioremediation potential of lipid‐rich wastewater by the immobilized and free lipases was explored by analyses of chemical oxygen demand and lipid content. Both free and immobilized lipases efficiently hydrolyzed all oils tested and organic matter present in the wastewater. Overall, the results indicate the potential of immobilized S. aureus lipase in biological wastewater treatment and offer new options for several industrial applications. © 2018 American Institute of Chemical Engineers Environ Prog, 38:e13000, 2019
Anaerobic Digestion of Three Microalgae Biomasses and Assessment of Digestates as Biofertilizer for Plant Growth
Authors: Ekinci Kamil , Erdal Ibrahim , Uysal Önder , Uysal Fatma Özge , Tunce Hamdi , Doğan Ahmet
Published: September 2018

This study focused on the determination of biochemical methane potential of three different microalgae, Chlorella sp., Neochloris conjuncta, and Botryococcus braunii, and evaluation of the digestates as biofertilizers for corn growth. Biomethane Potential Test Unit consisting of twelve 2‐L flasks placed in temperature controlled water at 37°C was utilized. As Botryococcus braunii had the highest lipid content (9.54%), it also had the highest biochemical methane potential (290.63 N mL g−1 volatile solid). The digestates containing microalgae and inoculum were applied to corn plant with four application dosages (0 [control], 5, 10, and 15 t ha−1) based on dry mass. Results emphasized that the lowest dosage (5 t ha−1) of the digestates containing Chlorella sp. and inoculum (digested dairy manure with silage maize) increased plant dry weights by 9% and 23%, respectively. However, further increase in the dosages of the digestates containing Botryococcus braunii and Neochloris conjuncta resulted in a decrease of plant growth and nutrients uptake by corn plants from the soil. Results highlighted that increment of the dosages of the digestates containing Botryococcus braunii and Neochloris conjuncta led to a decrease of plant growth and nutrient uptake from soil. © 2018 American Institute of Chemical Engineers Environ Prog, 38:e13024, 2019
The evolution of the human foot
Authors: McNutt Ellison J. , Zipfel Bernhard , DeSilva Jeremy M.
Published: September 2018

There are 26 bones in each foot (52 in total), meaning that roughly a quarter of the human skeleton consists of foot bones. Yet, early hominin foot fossils are frustratingly rare, making it quite difficult to reconstruct the evolutionary history of the human foot. Despite the continued paucity of hominid or hominin foot fossils from the late Miocene and early Pliocene, the last decade has witnessed the discovery of an extraordinary number of early hominin foot bones, inviting a reassessment of how the human foot evolved, and providing fresh new evidence for locomotor diversity throughout hominin evolution. Here, we provide a review of our current understanding of the evolutionary history of the hominin foot.
Mechanisms shaping the mutational landscape of the FRA3B/FHIT‐deficient cancer genome
Authors: Saldivar Joshua C. , Park Dongju
Published: September 2018

Genome instability is an enabling characteristic of cancer that facilitates the acquisition of oncogenic mutations that drive tumorigenesis. Underlying much of the instability in cancer is DNA replication stress, which causes both chromosome structural changes and single base‐pair mutations. Common fragile sites are some of the earliest and most frequently altered loci in tumors. Notably, the fragile locus, FRA3B, lies within the fragile histidine triad (FHIT) gene, and consequently deletions within FHIT are common in cancer. We review the evidence in support of FHIT as a DNA caretaker and discuss the mechanism by which FHIT promotes genome stability. FHIT increases thymidine kinase 1 (TK1) translation to balance the deoxyribonucleotide triphosphates (dNTPs) for efficient DNA replication. Consequently, FHIT‐loss causes replication stress, DNA breaks, aneuploidy, copy‐number changes (CNCs), small insertions and deletions, and point mutations. Moreover, FHIT‐loss‐induced replication stress and DNA breaks cooperate with APOBEC3B overexpression to catalyze DNA hypermutation in cancer, as APOBEC family enzymes prefer single‐stranded DNA (ssDNA) as substrates and ssDNA is enriched at sites of both replication stress and DNA breaks. Consistent with the frequent loss of FHIT across a broad spectrum of cancer types, FHIT‐deficiency is highly associated with the ubiquitous, clock‐like mutation signature 5 occurring in all cancer types thus far examined. The ongoing destabilization of the genome caused by FHIT loss underlies recurrent inactivation of tumor suppressors and activation of oncogenes. Considering that more than 50% of cancers are FHIT‐deficient, we propose that FRA3B/FHIT fragility shapes the mutational landscape of cancer genomes.
Efficient Harvesting of Nannochloropsis Microalgae via Optimized Chitosan‐Mediated Flocculation
Authors: Chua Elvis T. , Eltanahy Eladl , Jung Heejae , Uy Manuel , Thomas‐Hall Skye R. , Schenk Peer M.
Published: September 2018

Food‐grade rather than synthetic or chemical flocculants are needed for microalgae harvesting by settling, if used for food products. Chitosan is effective in harvesting freshwater microalgae, but it is expensive and typically not suitable for marine microalgae like Nannochloropsis. To minimize costs for food‐grade flocculation, a number of potentially important parameters are considered, including chitosan solubility and optimized chitosan‐mediated flocculation of Nannochloropsis sp. BR2 by a five‐factor central composite design experiment. Results show that an optical density (440 nm) of 2 (0.23 g dry weight L−1), initial pH of 6, final pH of 10, and 22 ppm chitosan with a viscosity of 1808 cP provide optimum flocculation efficiency, which is predicted to be in the range of 97.01% to 99.93%. These predictions are verified on 4.5 and 8 L Nannochloropsis sp. BR2 cultures.
A Review of State‐of‐the‐Art Microfluidic Technologies for Environmental Applications: Detection and Remediation
Authors: Yew Maxine , Ren Yong , Koh Kai Seng , Sun Chenggong , Snape Colin
Published: September 2018

Microfluidic systems have advanced beyond natural and life science applications and lab‐on‐a‐chip uses. A growing trend of employing microfluidic technologies for environmental detection has emerged thanks to the precision, time‐effectiveness, and cost‐effectiveness of advanced microfluidic systems. This paper reviews state‐of‐the‐art microfluidic technologies for environmental applications, such as on‐site environmental monitoring and detection. Microdevices are extensively used in collecting environmental samples as a means to facilitate detection and quantification of targeted components with minimal quantities of samples. Likewise, microfluidic‐inspired approaches for separation and treatment of contaminated water and air, such as the removal of heavy metals and waterborne pathogens from wastewater and carbon capture are also investigated.
Acid Mine Drainage Treatment Using Bayer Precipitates Obtained from Seawater Neutralization of Bayer Liquor
Authors: Kaur Gurkiran , Couperthwaite Sara J. , Millar Graeme J.
Published: September 2018

Bayer precipitates from the seawater neutralization of Bayer liquor waste from the alumina industry are shown to be a prospective solution for the remediation of acid mine drainage (AMD) water. Precipitates are varied in composition, albeit they are generally comprised of hydrotalcite (Mg6Al2(OH)16CO3∙xH2O), calcite (CaCO3), aragonite (CaCO3), mixed metal hydroxides (Mg2Al(OH)7), and halite (NaCl). Brucite (Mg(OH)2) is detected for lower Bayer liquor concentrations (1–3 g L−1 Al2O3) when the concentrations of aluminum and hydroxyl species are insufficient to promote hydrotalcite formation. The neutralizing capacity of the precipitates also varies with Bayer liquor composition. Treatment of AMD water with Bayer precipitates met discharge pH guidelines. The dissolution of hydrotalcite and brucite (1–3 g L−1 Bayer precipitates only) is responsible for the Bayer precipitate's neutralizing capacity, while calcium carbonate has a buffering affect at around pH 7. Manganese ions are the most challenging species to remove because high pH values are required (pH > 9), which is not possible with all precipitates tested. One caveat is that increasing the degree of manganese removal generates issues with excessive dissolved aluminum which exceeds discharge limits. Future research should address this latter problem and facilitate implementation of this approach to AMD remediation.
Distinct patterns of glia repair and remyelination in antibody‐mediated demyelination models of multiple sclerosis and neuromyelitis optica
Authors: Liu Yiting , Given Katherine S. , Owens Gregory P. , Macklin Wendy B. , Bennett Jeffrey L.
Published: September 2018

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory demyelinating disorders of the central nervous system with evidence of antibody‐mediated pathology. Using ex vivo organotypic mouse cerebellar slice cultures, we have demonstrated that recombinant antibodies (rAbs) cloned from cerebrospinal fluid plasmablasts of MS and NMO patients target myelin‐ and astrocyte‐specific antigens to induce disease‐specific oligodendrocyte loss and myelin degradation. In this study, we examined glial cell responses and myelin integrity during recovery from disease‐specific antibody‐mediated injury. Following exposure to MS rAb and human complement (HC) in cerebellar explants, myelinating oligodendrocytes repopulated the demyelinated tissue and formed new myelin sheaths along axons. Remyelination was accompanied by pronounced microglial activation. In contrast, following treatment with NMO rAb and HC, there was rapid regeneration of astrocytes and pre‐myelinating oligodendrocytes but little formation of myelin sheaths on preserved axons. Deficient remyelination was associated with progressive axonal loss and the return of microglia to a resting state. Our results indicate that antibody‐mediated demyelination in MS and NMO show distinct capacities for recovery associated with differential injury to adjacent axons and variable activation of microglia. Remyelination was rapid in MS rAb plus HC‐induced demyelination. By contrast, oligodendrocyte maturation and remyelination failed following NMO rAb‐mediated injury despite the rapid restoration of astrocytes and preservation of axons in early lesions.
Astrocytes, the rising stars of the glioblastoma microenvironment
Authors: Brandao Mayra , Simon Thomas , Critchley Giles , Giamas Georgios
Published: September 2018

Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise ~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked. Yet, obtaining an in‐depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles.
The neural oscillatory markers of phonetic convergence during verbal interaction
Authors: Mukherjee Sankar , Badino Leonardo , Hilt Pauline M. , Tomassini Alice , Inuggi Alberto , Fadiga Luciano , Nguyen Noël , D'Ausilio Alessandro
Published: September 2018

During a conversation, the neural processes supporting speech production and perception overlap in time and, based on context, expectations and the dynamics of interaction, they are also continuously modulated in real time. Recently, the growing interest in the neural dynamics underlying interactive tasks, in particular in the language domain, has mainly tackled the temporal aspects of turn‐taking in dialogs. Besides temporal coordination, an under‐investigated phenomenon is the implicit convergence of the speakers toward a shared phonetic space. Here, we used dual electroencephalography (dual‐EEG) to record brain signals from subjects involved in a relatively constrained interactive task where they were asked to take turns in chaining words according to a phonetic rhyming rule. We quantified participants' initial phonetic fingerprints and tracked their phonetic convergence during the interaction via a robust and automatic speaker verification technique. Results show that phonetic convergence is associated to left frontal alpha/low‐beta desynchronization during speech preparation and by high‐beta suppression before and during listening to speech in right centro‐parietal and left frontal sectors, respectively. By this work, we provide evidence that mutual adaptation of speech phonetic targets, correlates with specific alpha and beta oscillatory dynamics. Alpha and beta oscillatory dynamics may index the coordination of the “when” as well as the “how” speech interaction takes place, reinforcing the suggestion that perception and production processes are highly interdependent and co‐constructed during a conversation.
Frequency‐specific age‐related decreased brain network diversity in cognitively healthy elderly: A whole‐brain data‐driven analysis
Authors: Lou Wutao , Wang Defeng , Wong Adrian , Chu Winnie C. W. , Mok Vincent C. T. , Shi Lin
Published: September 2018

Age‐related changes in functional brain network have been well documented. However, recent studies have suggested the nonstationary properties of the functional connectivity of the brain, and little is known about the changes of functional connectivity dynamics during aging. In this study, a two‐step singular value decomposition was introduced to capture the dynamic patterns of the time‐varying functional connectivity in different frequency intervals, and the whole‐brain and regional brain diversity were quantified by using Shannon entropy. The relationships between age and functional connectivity dynamics were investigated in a relatively large sample cohort of cognitively healthy elderly (N = 188, ages 65–80). The results showed an age‐related decreased diversity in the whole brain as well as in the right inferior frontal gyrus, right amygdala, right hippocampus, left parahippocampal, and left inferior parietal gyrus in the frequency interval of 0.06–0.12 Hz. In addition, the whole‐brain diversity during resting state could also reflect the general mental flexibility. This study provided the first evidence of frequency‐specific age effects on the functional connectivity dynamics in cognitively healthy elderly, and may shed new light on the dynamic functional connectivity analysis of aging and neurodegenerative diseases.
Cognitive loading via mental arithmetic modulates effects of blink‐related oscillations on precuneus and ventral attention network regions
Authors: Liu Careesa C. , Hajra Sujoy Ghosh , Song Xiaowei , Doesburg Sam M. , Cheung Teresa P. L. , D'Arcy Ryan C. N.
Published: September 2018

Blink‐related oscillations (BROs) have been linked with environmental monitoring processes associated with blinking, with cortical activations in the bilateral precuneus. Although BROs have been described under resting and passive fixation conditions, little is known about their characteristics under cognitive loading. To address this, we investigated BRO effects during both mental arithmetic (MA) and passive fixation (PF) tasks using magnetoencephalography (n =20), while maintaining the same sensory environment in both tasks. Our results confirmed the presence of BRO effects in both MA and PF tasks, with similar characteristics including blink‐related increase in global field power and blink‐related activation of the bilateral precuneus. In addition, cognitive loading due to MA also modulated BRO effects by decreasing BRO‐induced cortical activations in key brain regions including the bilateral anterior precuneus. Interestingly, blinking during MA—but not PF—activated regions of the ventral attention network (i.e., right supramarginal gyrus and inferior frontal gyrus), suggesting possible recruitment of these areas for blink processing under cognitive loading conditions. Time–frequency analysis revealed a consistent pattern of BRO‐related effects in the precuneus in both tasks, but with task‐related functional segregation within the anterior and posterior subregions. Based on these findings, we postulate a potential neurocognitive mechanism for blink processing in the precuneus. This study is the first investigation of BRO effects under cognitive loading, and our results provide compelling new evidence for the important cognitive implications of blink‐related processing in the human brain.
Reduction in gray matter of cerebellum in schizophrenia and its influence on static and dynamic connectivity
Authors: He Hui , Luo Cheng , Luo Yuling , Duan Mingjun , Yi Qizhong , Biswal Bharat B. , Yao Dezhong
Published: September 2018

Pathophysiological and atrophic changes in the cerebellum have been well‐documented in schizophrenia. Reduction of gray matter (GM) in the cerebellum was confirmed across cognitive and motor cerebellar modules in schizophrenia. Such abnormalities in the cerebellum could potentially have widespread effects on both sensorimotor and cognitive symptoms. In this study, we investigated how reduction change in the cerebellum affects the static and the dynamic functional connectivity (FC) between the cerebellum and cortical/subcortical networks in schizophrenia. Reduction of GM in the cerebellum was confirmed across the cognitive and motor cerebellar modules in schizophrenic subjects. Results from this study demonstrates that the extent of reduction of GM within cerebellum correlated with increased static FCs between the cerebellum and the cortical/subcortical networks, including frontoparietal network (FPN), and thalamus in patients with schizophrenia. Decreased GM in the cerebellum was also associated with a declined dynamic FC between the cerebellum and the FPN in schizophrenic subjects. The severity of patients' positive symptom was related to these structural‐functional coupling score of cerebellum. These findings identified potential cerebellar driven functional changes associated with positive symptom deficits. A post hoc analysis exploring the effect of changed FC within cerebellum, confirmed that a significant positive relationship, between dynamic FCs of cerebellum–thalamus and intracerebellum existed in patients, but not in controls. The reduction of GM within the cerebellum might be associated with modulation of cerebellum–thalamus, and contributes to the dysfunctional cerebellar‐cortical communication in schizophrenia. Our results provide a new insight into the role of cerebellum in understanding the pathophysiological of schizophrenia.
Morphometry Confirms Fibrosis Regression From Sustained Virologic Response to Direct‐Acting Antivirals for Hepatitis C
Authors: Pan Jason J. , Bao Fei , Du Emma , Skillin Chase , Frenette Catherine T. , Waalen Jill , Alaparthi Lakshmi , Goodman Zachary D. , Pockros Paul J.
Published: September 2018

Sustained virologic response (SVR) after direct‐acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post‐SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR. Overall, 62% had improved liver stiffness that was consistent with regression of at least one stage of fibrosis. In the cirrhosis group, 48% showed fibrosis regression by at least two stages by TE (<9.5 kPa). In the F3 fibrosis group, 39% regressed by at least two stages (<7 kPa). The median time from SVR to regression by TE was 1 year. Fifteen patients with liver biopsies prior to SVR underwent a biopsy after SVR; 13 of these patients had improved liver stiffness (to <9.5 kPa). The post‐SVR liver biopsies of only 4 patients showed F1‐F2 while 11 patients showed F3‐F4; however, morphometry of the first 11 biopsied patients revealed that 10 patients had an average 46% decrease in collagen content. Conclusion: This is the first DAA study that also has paired liver biopsies showing fibrosis regression. After SVR is achieved, improvements in liver stiffness measured by TE are seen in a majority of patients with advanced fibrosis/cirrhosis within 2 years. TE improvements are overstated when compared to histologic staging but confirmed with morphometric analysis. It is unclear whether TE following SVR can reliably predict when patients no longer require advanced fibrosis/cirrhosis monitoring after SVR.
Insight into the stable isotopic composition of glacial lakes in a tropical alpine ecosystem: Chirripó, Costa Rica
Authors: Esquivel‐Hernández Germain , Sánchez‐Murillo Ricardo , Quesada‐Román Adolfo , Mosquera Giovanny M. , Birkel Christian , Boll Jan
Published: September 2018

Tropical high‐elevation lakes are considered sentinels of global climate change. This work characterizes the hydrological conditions of tropical alpine glacial lakes located in the highlands of Chirripó, Costa Rica, using a unique data set of water stable isotopes (δ2H and δ18O) in precipitation, stream water, and lake water between September 2015 and July 2017. A combined dataset of bathymetric, hydrometric, and isotope data collected between July 2016 and July 2017 on Lake Ditkevi was used to calculate the annual water balance of the lake. Evaporation to inflow ratios from three lake systems was estimated using a linear resistance model, the experimentally estimated local evaporation line of Chirripó, and the first glacial lake water evaporation lines in the region. The temporal isotopic variations (δ18O, d‐excess, and lc‐excess) confirm variations in the dry and wet season evaporative conditions for the glacial lakes and consistently average annual low evaporation to inflow (E/I) ratios in the range of 2.0 ± 0.8% and 18.1 ± 12.2%. Lake Ditkevi's water balance indicates annual steady‐state conditions, with an estimated evaporation loss of 650 mm/year (10.0 ± 5.0% of inflow), a high‐water contribution to the catchment (90% of inflow), a residence time of 0.53 ± 0.27 years, and a catchment scale (0.289 km2) water yield or depth equivalent run‐off of 278 mm/yr. These results provide novel information about water balance and evaporation losses in tropical alpine glacial lakes, which can serve as baseline information for future isotope‐based hydro‐climate research in high‐elevation regions in the tropics and elsewhere.