bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of Diabetic Retinopathy
Authors: Moore Spencer M , Chao Daniel L 
Published: July 2020

Abstract

Diabetic retinopathy (DR) is a common, vision‐threatening microvascular complication of diabetes mellitus (DM). Early epidemiologic studies revealed a potential heritable component as differences in disease risk persisted between ethnic groups even when controlling for common diabetes risk factors. These insights spawned sib‐pair genetic linkage analyses which confirmed a genetic component to DR risk. Insights from large genome wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with DR risk, but these largely could not be replicated in other studies or across ethnic groups. Whole‐exome sequencing (WES) is an emerging technology better positioned than GWAS to identify rare variants conferring risk of DR among diabetic patients. Although the multifactorial, polygenic nature of DR complicates the search for significant genetic risk variants, advances in sequencing technology with large patient cohorts may provide novel actionable insights to improve care for DR patients.

Key Concepts

Diabetic retinopathy is the most common microvascular complication of diabetes mellitus.

Diabetic retinopathy is a leading cause of blindness worldwide.

Early epidemiologic studies suggested a strong heritable component to risk of diabetic retinopathy.

Genome wide association studies have demonstrated many weak genetic associations with risk of developing diabetic retinopathy but are difficult to reproduce across ethnic groups.

Whole exome sequencing is a newer technology that provides more detailed analysis of rare genetic variants and has revealed several diabetic retinopathy risk variants.

Epigenetics and pharmacogenomics are emerging areas of research that may guide future personalised therapies for diabetic retinopathy.

Diabetes mellitus and diabetic retinopathy are heterogeneous disorders with multifactorial causes, including environmental and genetic factors.
Recent Loss of Genetic Diversity in Eastern Gorillas
Authors: Guschanski Katerina 
Published: July 2020

Abstract

Many primate populations are declining as a result of human activities. Eastern gorillas are the most affected of all great apes. Understanding the genomic consequences of rapid declines is important for assessing conservation needs. Genomic analyses of museum specimens that predate the most recent changes allow for quantification of the genomic effects of population declines and extinctions. Grauer's gorillas, one of the two Eastern gorilla subspecies, have declined by almost 80% in the last two decades. Comparisons of genomic changes over the last 100 years revealed severe reduction in genetic diversity and increase in inbreeding and frequency of deleterious mutations. The other subspecies, the Mountain gorilla, has experienced little genomic change, possibly as a result of both long‐term evolutionary history and recent conservation efforts over the last 60 years. There is thus hope for the critically endangered species if appropriate conservation actions are taken.

Key Concepts

Wild animal populations are declining as a result of human activities.

Eastern gorillas have experienced a drastic decline in population size and are now critically endangered.

Severe declines in population size leave genomic signatures in the affected populations and can lead to population extinctions.

Samples from historical specimens can inform about genomic changes that have happened in the last few centuries.

Temporal comparisons of genome‐wide diversity and functional profiles can be used to direct conservation actions.
A Structurally Simple but High‐Performing Donor–Acceptor Polymer for Field‐Effect Transistor Applications
Authors: Aniés Filip , Wang Simeng , Hodsden Thomas , Panidi Julianna , Fei Zhuping , Jiao Xuechen , Wong Yi Hang Cherie , McNeill Christopher R. , Anthopoulos Thomas D. , Heeney Martin 
Published: July 2020

AbstractA straightforward synthesis is reported for four structurally simple donor–acceptor conjugated polymers based on an alkylated difluorobenzotriazole and either unsubstituted bithiophene (T2) or thienylvinylthiophene (TVT) co‐monomers. Two solubilizing sidechains are investigated in which the position of the branching point is moved away from the conjugated backbone. Optoelectronic measurements and density functional theory calculations show very similar energetic properties between the polymers, with a slightly narrower bandgap for the vinylene incorporating TVT polymers as a result of extended conjugation. Transistor measurements demonstrate that the simplest polymer, containing a readily available 2‐decyltetradecyl sidechain with a T2 co‐monomer, exhibits the best device performance, with an average saturated mobility of 0.2 cm2 V−1 s−1.
Monsanto's Roundup verdicts portend liability for some pesticide health damages
Authors: Centner Terence J. 
Published: July 2020

AbstractThree California juries have found that Monsanto should be liable for millions of dollars in non‐economic losses to pesticide users and punitive damages, although the verdicts are on appeal. The plaintiffs in the lawsuits claimed Monsanto was negligent in failing to provide training on how to use Roundup and for not providing adequate warnings about the product's dangers. The punitive damage awards resulted from jurors finding that the defendant had engaged in malice, oppression, or fraud. In June 2020, Monsanto's owner Bayer reached an agreement to resolve approximately 125,000 Roundup product liability claims for US$10.1 billion. The verdicts and the proffered settlement suggest that pesticide products that unduly impair human health are not acceptable under American liability principles. Manufacturers need to design products that are reasonably safe and convey sufficient warning information to minimize damages to users and property. The placement of damage costs on product manufacturers is intended to encourage the development of safer pesticide products and the development of alternative non‐chemical pest‐control measures.
The variability of SMARCA4‐related Coffin–Siris syndrome: Do nonsense candidate variants add to milder phenotypes?
Authors: Li Dong , Ahrens‐Nicklas Rebecca C. , Baker Janice , Bhambhani Vikas , Calhoun Amy , Cohen Julie S. , Deardorff Matthew A. , Fernández‐Jaén Alberto , Kamien Benjamin , Jain Mahim , Mckenzie Fiona , Mintz Mark , Motter Constance , Niles Kirsten , Ritter Alyssa , Rogers Curtis , Roifman Maian , Townshend Sharron , Ward‐Melver Catherine , Schrier Vergano Samantha A. 
Published: July 2020

AbstractSMARCA4 encodes a central ATPase subunit in the BRG1‐/BRM‐associated factors (BAF) or polybromo‐associated BAF (PBAF) complex in humans, which is responsible in part for chromatin remodeling and transcriptional regulation. Variants in this and other genes encoding BAF/PBAF complexes have been implicated in Coffin–Siris Syndrome, a multiple congenital anomaly syndrome classically characterized by learning and developmental differences, coarse facial features, hypertrichosis, and underdevelopment of the fifth digits/nails of the hands and feet. Individuals with SMARCA4 variants have been previously reported and appear to display a variable phenotype. We describe here a cohort of 15 unrelated individuals with SMARCA4 variants from the Coffin–Siris syndrome/BAF pathway disorders registry who further display variability in severity and degrees of learning impairment and health issues. Within this cohort, we also report two individuals with novel nonsense variants who appear to have a phenotype of milder learning/behavioral differences and no organ‐system involvement.
Memories of the Teratology Society: 1972–2020
Authors: Holmes Lewis B. 
Published: July 2020

AbstractBackgroundMy career goal in 1971 was to learn about the causes of malformations. Attending the annual meetings of the Teratology Society and reading the articles in Teratology exposed me to the scientists and clinicians involved in this research and the methods being used.MethodsOver a period of 49 years (1972–2020), I heard many presentations about several exposures in pregnancy that can cause birth defects. Symposia and platform presentations provided unique and stimulating information on the fetal effects of the teratogen thalidomide.ResultsI developed research studies and presented the results from our studies on teratogenic exposures, such as anticonvulsant drugs, the prenatal diagnosis procedure chorionic villus sampling, and the abortifacient misoprostol. The annual Pregnancy Registry Workshop was developed as a forum for discussing issues related to this new method of evaluating potential teratogenic exposures in pregnancy.ConclusionAttending the annual meetings and reading the articles in the journal Teratology (now Birth Defects Research) have been an instructive and enjoyable way to learn about the causes of malformations.
Update on the gestational effects of maternal hyperthermia
Authors: Graham John M. 
Published: July 2020

AbstractObjectivesI plan to review the types of defects caused by gestational hyperthermia. Hyperthermia‐induced malformations in animals and humans involve many organs and structures, particularly the central nervous system, as well as other defects. The type of defect is related to the timing of the hyperthermic insult, and the underlying mechanisms include cell death, membrane disruption, vascular disruption, and placental infarction.MethodsReview of recent epidemiologic studies (2005–2020) has confirmed an association between gestational hyperthermia and birth defects.ResultsThere are strong associations between neural tube defects and maternal fever, and other studies have demonstrated associations between first trimester hyperthermia and an increased risk for cardiovascular defects, oral clefts, isolated congenital ear defects, cataracts, hypospadias, renal anomalies, possibly anorectal malformations, and congenital anomalies in general, suggesting that this association between maternal hyperthermia and birth defects in humans is causal. The first prospective evaluation of maternal fever was reported in 1998, and this study confirmed findings from previous case‐control studies and case series regarding the magnitude and duration of elevated maternal body temperature in relation to an increased risk for neural tube defects as well as a specific pattern of malformation.ConclusionsThe consistency of findings across these different study designs supports the causal nature of the relationship between maternal fever and specific birth defects. This review summarizes the recent human evidence documenting the gestational effects of maternal hyperthermia.
Online‐based software for guiding immediate implantation to replace a tooth with root resorption in the esthetic zone
Authors: Chapanov Krasimir Ivanov , Iliev Georgi Veselinov , Kazakov Stoyan Torezov 
Published: July 2020

AbstractThis case report describes an alternative approach for the planning of immediate implant placement and provisionalization, which uses a new online dental software that predicts the esthetic outcome.
An extremely rare case of giant oncocytic adenolipoma of the parotid gland
Authors: Shakya Dipesh , Nepal Ajit 
Published: July 2020

AbstractOncocytic adenolipoma is a rare tumor to occur in the salivary gland, which can present as a giant neck mass. Until now, <20 such cases are reported. We report this rare case for surgeons to consider it as one of the differential diagnoses.
Inhibiting Effect of Ionic Liquids on the Corrosion of Mild Steel in H2S and HCl Solution
Authors: Cui Fusheng , Ni Yuqing , Jiang Juncheng , Ni Lei , Wang Zhirong 
Published: July 2020

AbstractFour imidazolium‐based ionic liquids (ILs) were selected to investigate the inhibiting effect of ILs with various alkyl chain lengths on the corrosion of mild steel in H2S and HCl solution using electrochemical experiments, weight loss and surface analyses, and quantum chemical study. The results demonstrated that these ILs acted as mixed‐type inhibitors and efficiently inhibited the corrosion of mild steel in H2S and HCl solution. Their excellent corrosion inhibition ability was due to their adsorption process on the metal surface, which followed the Langmuir adsorption isotherm. Furthermore, extending the alkyl chain length in the ILs could improve their inhibition performance.
Sensitive Detection of Motor Neuron Disease Derived Exosomal miRNA Using Electrocatalytic Activity of Gold‐Loaded Superparamagnetic Ferric Oxide Nanocubes
Authors: Masud Mostafa Kamal , Mahmudunnabi Rabbee G. , Aziz Nahian Binte , Stevens Claire H. , Do‐Ha Dzung , Yang Shu , Blair Ian P. , Hossain Md. Shahriar A. , Shim Yoon‐Bo , Ooi Lezanne , Yamauchi Yusuke , Shiddiky Muhammad J. A. 
Published: July 2020

AbstractDysregulated microRNA associated pathways contribute to the pathology of neurological disorders, hence presenting themselves as a potential candidate for motor neuron disease (MND) diagnosis. Herein, we reported an enzymatic amplification‐free approach for the electrochemical detection of exosomal microRNA (miR‐338‐3p) from preconditioned media of motor neurons obtained from amyotrophic lateral sclerosis (ALS) patients and healthy controls. Our assay utilizes a three‐step strategy that involves i) initial isolation and purification of exosomal miR‐338‐3p from patients and healthy controls using biotinylated complementary capture probe followed by heat‐release of the specific target, ii) direct adsorption of target miR‐338‐3p onto the gold‐loaded ferric oxide nanocatalyst (AuNP‐Fe2O3NC) through affinity interaction between microRNA and exposed gold surfaces within the AuNP‐Fe2O3NC, and iii) gold nanocatalyst‐induced electrocatalytic signal amplification through methylene blue‐ferricyanide redox cycling (MB/[Fe(CN)6]3−). The electrocatalytic signal is monitored by using chronocoulometry at the AuNP–Fe2O3NC‐modified screen‐printed carbon electrode (AuNP‐Fe2O3NC/SPCE). We demonstrated the detection of miR‐338‐3p as low as 100 aM in spiked buffer samples with a relative standard deviation of (%RSD) <5.0 % (n=5). We also demonstrate the successful detection of miR‐338‐3p from a small cohort of preconditioned media of motor neurons obtained from ALS patients and healthy controls. The sensor avoids the use of conventional recognition and transduction layers in hybridization‐based electrochemical miRNA biosensors, polymerase‐based amplifications. It is robust, fast (<2.5 h) and potentially applicable to a wide variety of RNA biomarker detection.
Synthesis of Recombinant Human Hemoglobin With NH2‐Terminal Acetylation in Escherichia coli
Authors: Natarajan Chandrasekhar , Signore Anthony V. , Kumar Vikas , Storz Jay F. 
Published: July 2020

AbstractThe development of new technologies for the efficient expression of recombinant hemoglobin (rHb) is of interest for experimental studies of protein biochemistry and the development of cell‐free blood substitutes in transfusion medicine. Expression of rHb in Escherichia coli host cells has numerous advantages, but one disadvantage of using prokaryotic systems to express eukaryotic proteins is that they are incapable of performing post‐translational modifications such as NH2‐terminal acetylation. One possible solution is to coexpress additional enzymes that can perform the necessary modifications in the host cells. Here, we report a new method for synthesizing human rHb with proper NH2‐terminal acetylation. Mass spectrometry experiments involving native and recombinant human Hb confirmed the efficacy of the new technique in producing correctly acetylated globin chains. Finally, functional experiments provided insights into the effects of NH2‐terminal acetylation on O2 binding properties. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Gene synthesis and cloning the cassette to the expression plasmidBasic Protocol 2: Selection of E. coli expression strains for coexpressionBasic Protocol 3: Large‐scale recombinant hemoglobin expression and purificationSupport Protocol 1: Measuring O2 equilibration curvesSupport Protocol 2: Mass spectrometry to confirm NH2‐terminal acetylation
Amelioration of ocean acidification and warming effects through physiological buffering of a macroalgae
Authors: Doo Steve S. , Leplastrier Aero , Graba‐Landry Alexia , Harianto Januar , Coleman Ross A. , Byrne Maria 
Published: July 2020

AbstractConcurrent anthropogenic global climate change and ocean acidification are expected to have a negative impact on calcifying marine organisms. While knowledge of biological responses of organisms to oceanic stress has emerged from single‐species experiments, these do not capture ecologically relevant scenarios where the potential for multi‐organism physiological interactions is assessed. Marine algae provide an interesting case study, as their photosynthetic activity elevates pH in the surrounding microenvironment, potentially buffering more acidic conditions for associated epiphytes. We present findings that indicate increased tolerance of an important epiphytic foraminifera, Marginopora vertebralis, to the effects of increased temperature (±3°C) and pCO2 (~1,000 µatm) when associated with its common algal host, Laurencia intricata. Specimens of M. vertebralis were incubated for 15 days in flow‐through aquaria simulating current and end‐of‐century temperature and pH conditions. Physiological measures of growth (change in wet weight), calcification (measured change in total alkalinity in closed bottles), photochemical efficiency (Fv/Fm), total chlorophyll, photosynthesis (oxygen flux), and respiration were determined. When incubated in isolation, M. vertebralis exhibited reduced growth in end‐of‐century projections of ocean acidification conditions, while calcification rates were lowest in the high‐temperature, low‐pH treatment. Interestingly, association with L. intricata ameliorated these stress effects with the growth and calcification rates of M. vertebralis being similar to those observed in ambient conditions. Total chlorophyll levels in M. vertebralis decreased when in association with L. intricata, while maximum photochemical efficiency increased in ambient conditions. Net production estimates remained similar between M. vertebralis in isolation and in association with L. intricata, although both production and respiration rates of M. vertebralis were significantly higher when associated with L. intricata. These results indicate that the association with L. intricata increases the resilience of M. vertebralis to climate change stress, providing one of the first examples of physiological buffering by a marine alga that can ameliorate the negative effects of changing ocean conditions.
Study on crack propagation of the CO2 presplitting blasting empty hole effect in coal seam
Authors: Pan Hongyu , Li Jingwen , Zhang Tianjun , Li Shugang , Zhang Lei 
Published: July 2020

AbstractCO2 presplitting blasting is an effective method to increase coal seams permeability and improve gas drainage efficiency. During the blasting process, the empty holes in the coal and rock mass have a significant effect on crack growth. In the experiment, a sample containing empty holes was used for CO2 presplitting blasting. The VIC‐3D was used to observe the change in the surface displacement of the sample; and the amplitude of the wave during the blasting process was collected using ultrasonic waves. Here, we calculated the attenuation coefficient α, analyzed the internal crack damage of the coal and rock mass, and compared the LS‐DYNA simulation results to analyze the empty hole effect on the crack growth of the coal and rock mass. The results show that: (a) radial tensile stress is generated due to the superposition of compression waves and reflected waves during blasting, resulting in an approximately straight main crack channel between the blast hole and the empty hole; (b) When both the stress and the attenuation coefficient reach their peaks, a main crack is formed and the most severe damage occurs inside the coal and rock mass; (c) the main crack channel was formed at 0.13 seconds, and the energy consumption reached the peak at 0.18 seconds, the negative linear correlation between energy and stress was obtained. Therefore, the empty hole effect provides a good guide for the crack propagation of the coal and rock mass and provides a new experimental scheme for increasing the permeability of coal seams.
Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end‐plate innervation
Authors: Bouçanova Filipa , Pollmeier Gill , Sandor Katalin , Morado Urbina Carlos , Nijssen Jik , Médard Jean‐Jacques , Bartesaghi Luca , Pellerin Luc , Svensson Camilla I , Hedlund Eva , Chrast Roman 
Published: July 2020

AbstractRecent studies in neuron‐glial metabolic coupling have shown that, in the CNS, astrocytes and oligodendrocytes support neurons with energy‐rich lactate/pyruvate via monocarboxylate transporters (MCTs). The presence of such transporters in the PNS, in both Schwann cells and neurons, has prompted us to question if a similar interaction may be present. Here we describe the generation and characterization of conditional knockout mouse models where MCT1 or MCT4 is specifically deleted in Schwann cells (named MCT1 and MCT4 cKO). We show that MCT1 cKO and MCT4 cKO mice develop normally and that myelin in the PNS is preserved. However, MCT1 expressed by Schwann cells is necessary for long‐term maintenance of motor end‐plate integrity as revealed by disrupted neuromuscular innervation in mutant mice, while MCT4 appears largely dispensable for the support of motor neurons. Concomitant to detected structural alterations, lumbar motor neurons from MCT1 cKO mice show transcriptional changes affecting cytoskeletal components, transcriptional regulators, and mitochondria related transcripts, among others. Together, our data indicate that MCT1 plays a role in Schwann cell‐mediated maintenance of motor end‐plate innervation thus providing further insight into the emerging picture of the biology of the axon‐glia metabolic crosstalk.
Cannabis use in patients with early psychosis is associated with alterations in putamen and thalamic shape
Authors: Sami Musa , Cole James H. , Kempton Matthew J. , Annibale Luciano , Das Debasis , Kelbrick Marlene , Eranti Savitha , Collier Tracy , Onyejiaka Chidimma , O'Neill Aisling , Lythgoe David J. , McGuire Philip , Williams Steve C. R. , Bhattacharyya Sagnik 
Published: July 2020

AbstractAround half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP − C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C − C = 22) cannabis use. We undertook vertex‐based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p < .05. We adjusted analyses for age, sex, tobacco and alcohol use. The putamen (bilaterally) and the right thalamus showed regional enlargement in PwP + C versus PwP − C. There were no areas of regional deflation. There were no significant differences between C + C and C − C. Cannabis use in participants with psychosis is associated with morphological alterations in subcortical structures. Putamen and thalamic enlargement may be related to compulsivity in patients with a history of cannabis use.