bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low metformin dose and its therapeutic serum concentration in prediabetes
Authors: Sutkowska Edyta , Fortuna Paulina , Wisniewski Jerzy , Sutkowska Karolina , Hodurek Pawel , Gamian Andrzej , Kaluza Bernadetta 
Published: June 2021

AbstractThis prospective study aimed to analyze whether the patients with pre-diabetes (pre-DM) reach the TC (therapeutic concentration) of the metformin during repeated, low, constant drug dose. The guidelines do not recommend any metformin dose for this group of patients. Based on the previous study after a dose of 1700 mg/day the patients seem to reach the therapeutic drug concentration, which guarantees the glycemic effect. Twenty patients with new-diagnosed pre-DM were treated with a 1500 mg/day regimen of the metformin for 15 weeks. The serum concentration of the drug was assessed by liquid chromatography-mass spectrometry technique at 6 and 15 week of the treatment. The correlation of the serum metformin concentration with BMI (body mass index) and patients’ weight was also performed. The mean metformin concentration was: 4.65 μmol/L (± 2.41) and 5.41 μmol/L (± 3.44) (p = 0.27) after 6 and 15 weeks of the treatment respectively. There was a positive correlation between the serum concentration of the metformin and body weight (but not BMI) in the 15th week of the therapy (p = 0.04)- the higher body weight the higher concentration of the metformin. Patients with pre-diabetes can be successfully treated with a low dose of metformin, to reach the drug’s therapeutic concentration. Body weight can impact the metformin serum concentration during long-term treatment what should be taken into consideration when choosing the dose because of its pleiotropic effect e.g. on the cardiovascular system via reduction of the oxidative stress and would be not connected with the drug’s hypoglycemic effect.ClinicalTrials.gov number: NCT03398356; date of first registration: 01/07/2018.
Automatic and unbiased segmentation and quantification of myofibers in skeletal muscle
Authors: Waisman Ariel , Norris Alessandra Marie , Elías Costa Martín , Kopinke Daniel 
Published: June 2021

AbstractSkeletal muscle has the remarkable ability to regenerate. However, with age and disease muscle strength and function decline. Myofiber size, which is affected by injury and disease, is a critical measurement to assess muscle health. Here, we test and apply Cellpose, a recently developed deep learning algorithm, to automatically segment myofibers within murine skeletal muscle. We first show that tissue fixation is necessary to preserve cellular structures such as primary cilia, small cellular antennae, and adipocyte lipid droplets. However, fixation generates heterogeneous myofiber labeling, which impedes intensity-based segmentation. We demonstrate that Cellpose efficiently delineates thousands of individual myofibers outlined by a variety of markers, even within fixed tissue with highly uneven myofiber staining. We created a novel ImageJ plugin (LabelsToRois) that allows processing of multiple Cellpose segmentation images in batch. The plugin also contains a semi-automatic erosion function to correct for the area bias introduced by the different stainings, thereby identifying myofibers as accurately as human experts. We successfully applied our segmentation pipeline to uncover myofiber regeneration differences between two different muscle injury models, cardiotoxin and glycerol. Thus, Cellpose combined with LabelsToRois allows for fast, unbiased, and reproducible myofiber quantification for a variety of staining and fixation conditions.
Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions
Authors: Rimington Rowan P. , Fleming Jacob W. , Capel Andrew J. , Wheeler Patrick C. , Lewis Mark P. 
Published: June 2021

AbstractInvestigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.
An in vivo selection system with tightly regulated gene expression enables directed evolution of highly efficient enzymes
Authors: Nearmnala Parinthon , Thanaburakorn Manutsawee , Panbangred Watanalai , Chaiyen Pimchai , Hongdilokkul Narupat 
Published: June 2021

AbstractIn vivo selection systems are powerful tools for directed evolution of enzymes. The selection pressure of the systems can be tuned by regulating the expression levels of the catalysts. In this work, we engineered a selection system for laboratory evolution of highly active enzymes by incorporating a translationally suppressingcisrepressor as well as an inducible promoter to impart stringent and tunable selection pressure. We demonstrated the utility of our selection system by performing directed evolution experiments using TEM β-lactamase as the model enzyme. Five evolutionary rounds afforded a highly active variant exhibiting 440-fold improvement in catalytic efficiency. We also showed that, without thecisrepressor, the selection system cannot provide sufficient selection pressure required for evolving highly efficient TEM β-lactamase. The selection system should be applicable for the exploration of catalytic perfection of a wide range of enzymes.
An integrative measure of cognitive performance, but not individual task performance, is linked to male reproductive output in budgerigars
Authors: Medina-García Angela , Wright Timothy F. 
Published: June 2021

AbstractCognitive abilities such as learning and memory are key for survival and reproduction. Individuals with high cognitive abilities may be more successful at attracting mates and producing offspring. However, empirical tests of and evidence supporting this hypothesis remain scarce. We measured cognitive performance of male budgerigars in four tasks: problem solving, detour reaching, seed discrimination, and spatial memory. We then tested female choice for male cognition at three stages of the mating choice process: social pairing, extra-pair mating, and continued reproductive investment with a social mate. We also measured female reproductive output. We used an integrative measure of male cognitive performance that encapsulates performance across all tasks, the ‘composite cognitive score’ by summing performance on the four tasks. In the first stage, females did not choose their social mates based on any of the measures of male cognitive performance. In the second stage, however, males with higher composite cognitive scores sired and raised more offspring. In the third stage, females increased their reproductive investment after the first breeding attempt when paired with males with higher detour-reaching scores. These results suggest that female reproductive decisions may shape overall male cognitive performance.
Connectivity adaptations in dopaminergic systems define the brain maturity of investors
Authors: Ortiz-Teran Elena , Diez Ibai , Sepulcre Jorge , Lopez-Pascual Joaquin , Ortiz Tomas 
Published: June 2021

AbstractInvestment decisions rely on perceptions from external stimuli along with the integration of inner brain-body signals, all of which are shaped by experience. As experience is capable of molding both the structure and function of the human brain, we have used a novel neuroimaging connectomic-genetic approach to investigate the influence of investment work experience on brain anatomy. We found that senior investors display higher gray matter volume and increased structural brain connectivity in dopamine-related pathways, as well as a set of genes functionally associated with adrenaline and noradrenaline biosynthesis (SLC6A3, TH and SLC18A2), which is seemingly involved in reward processing and bodily stress responses during financial trading. These results suggest the key role of catecholamines in the way senior investors harness their emotions while raising bodily awareness as they grow in investment maturity.
Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures
Authors: Saiga Rino , Uesugi Masayuki , Takeuchi Akihisa , Uesugi Kentaro , Suzuki Yoshio , Takekoshi Susumu , Inomoto Chie , Nakamura Naoya , Torii Youta , Kushima Itaru , Iritani Shuji , Ozaki Norio , Oshima Kenichi , Itokawa Masanari , Arai Makoto , Mizutani Ryuta 
Published: June 2021

AbstractBrain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7–9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.
Flexible, high mobility short-channel organic thin film transistors and logic circuits based on 4H–21DNTT
Authors: Bilgaiyan Anubha , Cho Seung-Il , Abiko Miho , Watanabe Kaori , Mizukami Makoto 
Published: June 2021

AbstractThe low mobility and large contact resistance in organic thin-film transistors (OTFTs) are the two major limiting factors in the development of high-performance organic logic circuits. Here, solution-processed high-performance OTFTs and circuits are reported with a polymeric gate dielectric and 6,6 bis (trans-4-butylcyclohexyl)-dinaphtho[2,1-b:2,1-f]thieno[3,2-b]thiophene (4H–21DNTT) for the organic semiconducting layer. By optimizing and controlling the fabrication conditions, a high saturation mobility of 8.8 cm2 V−1 s−1 was demonstrated as well as large on/off ratios (> 106) for relatively short channel lengths of 15 μm and an average carrier mobility of 10.5 cm2 V−1 s−1 for long channel length OTFTs (> 50 μm). The pseudo-CMOS inverter circuit with a channel length of 15 μm exhibited sharp switching characteristics with a high signal gain of 31.5 at a supply voltage of 20 V. In addition to the inverter circuit, NAND logic circuits were further investigated, which also exhibited remarkable logic characteristics, with a high gain, an operating frequency of 5 kHz, and a short propagation delay of 22.1 μs. The uniform and reproducible performance of 4H–21DNTT OTFTs show potential for large-area, low-cost real-world applications on industry-compatible bottom-contact substrates.
Flat hardness distribution in AA6061 joints by linear friction welding
Authors: Choi Jeong-Won , Li Weihao , Ushioda Kohsaku , Fujii Hidetoshi 
Published: June 2021

AbstractIt is known that one of the main concerns associated with the conventional welding of precipitation-strengthened Al alloys is the formation of softening regions, resulting in the deterioration of mechanical properties. In this study, we show that linear friction welding (LFW) can completely suppress softening regions in precipitation-strengthened AA6061-T6 alloy by introducing a large shear strain and by controlling the interfacial temperature. We found that the LFW process resulted in an extremely low interfacial temperature; it decreased as the applied pressure increased from 50 to 240 MPa. This approach can essentially suppress both softening and hardening regions, leading to uniform hardness distribution in Al joints. The high-pressure LFW process demonstrated here can thus provide an innovated guidance to obtain high-performance Al alloy joints and be extended to other precipitation-strengthened Al alloys, which undergo high-temperature softening.
Diet and general cognitive ability in the UK Biobank dataset
Authors: Hepsomali Piril , Groeger John A. 
Published: June 2021

AbstractAccumulating evidence suggests that dietary interventions might have potential to be used as a strategy to protect against age-related cognitive decline and neurodegeneration, as there are associations between some nutrients, food groups, dietary patterns, and some domains of cognition. In this study, we aimed to conduct the largest investigation of diet and cognition to date, through systematically examining the UK Biobank (UKB) data to find out whether dietary quality and food groups play a role on general cognitive ability. This cross-sectional population-based study involved 48,749 participants. UKB data on food frequency questionnaire and cognitive function were used. Also, healthy diet, partial fibre intake, and milk intake scores were calculated. Adjusted models included age, sex, and BMI. We observed associations between better general cognitive ability and higher intakes of fish, and unprocessed red meat; and moderate intakes of fibre, and milk. Surprisingly, we found that diet quality, vegetable intake, high and low fibre and milk intake were inversely associated with general cognitive ability. Our results suggest that fish and unprocessed red meat and/or nutrients that are found in fish and unprocessed red meat might be beneficial for general cognitive ability. However, results should be interpreted in caution as the same food groups may affect other domains of cognition or mental health differently. These discrepancies in the current state of evidence invites further research to examine domain-specific effects of dietary patterns/food groups on a wide range of cognitive and affective outcomes with a special focus on potential covariates that may have an impact on diet and cognition relationship.
Spatial ecology of cane toads (Rhinella marina) in their native range: a radiotelemetric study from French Guiana
Authors: DeVore Jayna L. , Shine Richard , Ducatez Simon 
Published: June 2021

AbstractLike most invasive species, cane toads have attracted less research in their native range than in invaded areas. We radio-tracked 34 free-ranging toads in French Guiana, a source region for most invasive populations, across two coastal and two rainforest sites. Coastal toads generally sheltered in pools of fresh or brackish water but nocturnally foraged on beaches, whereas rainforest toads sheltered in forested habitats, moving into open areas at night. Over five days of monitoring, native toads frequently re-used shelters and moved little between days (means = 10–63 m/site) compared to invasion-front toads from Australia (~ 250 m). Larger toads moved less between days, but displaced in more consistent directions. At night, foraging toads travelled up to 200 m before returning to shelters. Foraging distance was related to body condition at coastal sites, with toads in poorer body condition travelling farther. Rain increased the probability of coastal toads sheltering in the dry habitats where they foraged. Dispersal and rainfall were lower at coastal sites, and the strategies utilized by coastal toads to minimize water loss resembled those of invasive toads in semi-desert habitats. This global invader already exhibits a broad environmental niche and substantial behavioural flexibility within its native range.
Generation of restriction endonucleases barcode map to trace SARS-CoV-2 origin and evolution
Authors: Colombo Federico , Corsiero Elisa , Lewis Myles J. , Pitzalis Costantino 
Published: June 2021

AbstractSince the first report of SARS-CoV-2 in China in 2019, there has been a huge debate about the origin. In this work, using a different method we aimed to strengthen the observation that no evidence of genetic manipulation has been found by (1) detecting classical restriction site (RS) sequence in human SARS-CoV-2 genomes and (2) comparing them with other recombinant SARS-CoV-like virus created for experimental purposes. Finally, we propose a novel approach consisting in the generation of a restriction endonucleases site map of SARS-CoV-2 and other related coronavirus genomes to be used as a fingerprint to trace the virus evolution.
Gemella haemolysans inhibits the growth of the periodontal pathogen Porphyromonas gingivalis
Authors: Miyoshi Tomohiro , Oge Shogo , Nakata Satoshi , Ueno Yuji , Ukita Hidehiko , Kousaka Reiko , Miura Yuki , Yoshinari Nobuo , Yoshida Akihiro 
Published: June 2021

AbstractThe oral microbiome plays an important role in the human microbial community and in maintaining the health of an individual. Imbalances in the oral microbiome may contribute to oral and systemic diseases. The progression of periodontal disease is closely related to the growth of bacteria, such as Porphyromonas gingivalis, in the oral cavity. However, the pathogen growth mechanism specific to periodontal disease remains unknown. This study aimed to identify bacteria associated with periodontal health by focusing on hemolytic bacteria. Unstimulated saliva samples were collected from ten periodontitis patients and five healthy subjects to detect and identify the presence of hemolytic bacteria. The saliva of healthy subjects contained a higher proportion of G. haemolysans than saliva samples from patients with periodontitis. Growth inhibition assays indicated that the protein components contained in the culture supernatant of G. haemolysans directly suppressed the growth of P. gingivalis. This study shows that the presence of G. haemolysans in saliva is associated with periodontal health and that it inhibits the growth of P. gingivalis in vitro.
Antibiogram profile and virulence signatures of Pseudomonas aeruginosa isolates recovered from selected agrestic hospital effluents
Authors: Mapipa Q. , Digban T. O. , Nnolim N. E. , Nwodo U. U. 
Published: June 2021

AbstractHospital wastewater (HWW) harbours diverse microbial species and a miscellany of genome that would facilitate the emergence of novel pathogen upon genome integration that manifests novel traits in infectious pathogens. The study aimed to determine the antibiogram, and virulence signatures of Pseudomonas aeruginosa (P. aeruginosa) recovered from selected agrestic hospital effluents in Eastern Cape, South Africa. Thirty-six (36) wastewater samples were collected from selected hospital drains between February 2018 and April 2018, processed and analyzed by culture-dependent methods for the isolation of P. aeruginosa. The identity confirmation of isolates was achieved by amplification of oprl and oprL genes. Antibiogram was done using standard disk diffusion technique of Kirby–Bauer as approved by CLSI 2018 guidelines. Virulence signatures (lasA, lasB, toxA, popB) among isolates were analysed using polymerase chain reaction. A total of 54 P. aeruginosa isolates were confirmed by amplification of oprl and oprL genes in the hospital wastewater effluent samples. The isolates showed a 100% susceptibility to gentamicin, amikacin and imipenem antimicrobial agents. Ceftazidime recorded the most resistance (63%) against the isolates studied. Other antibiotics had a resistance range of 7% and 35%. The MAR index among the isolates revealed a range of 0.23 and 0.38. ToxA virulence gene was detected in all isolates while popB, lasB, lasA were detected in 82%, 75% and 54% of the isolates. This study reveals P. aeruginosa isolates with virulence traits and some strains showing multiple antibiotic resistance. The multiple antibiotic resistance index (MARI) of ≥ 0.2 indicates that the some isolates may have emerged from high-risk sources, thus projecting a risk to public health. However, with the high sensitivity pattern observed among the studied isolates, most of the antibiotics used in the susceptibility tests are not at peril. Hence, the use of these antibiotics is encouraged for treatment of infection attributed to P. aeruginosa. It is also pertinent to initiate strict control and rigid antibiotics therapeutic policy with surveillance programmes for multidrug-resistant pathogens to forestall the development and transmission of resistance traits in the pathogens.
Evolution of KIPPIS as a versatile platform for evaluating intracellularly functional peptide aptamers
Authors: Kashima Daiki , Kawahara Masahiro 
Published: June 2021

AbstractChimeric proteins have been widely used to evaluate intracellular protein–protein interactions (PPIs) in living cells with various readouts. By combining an interleukin-3-dependent murine cells and chimeric proteins containing a receptor tyrosine kinase c-kit, we previously established a c-kit-based PPI screening (KIPPIS) system to evaluate and select protein binders. In the KIPPIS components, proteins of interest are connected with a chemically inducible helper module and the intracellular domain of the growth-signaling receptor c-kit, which detects PPIs based on cell proliferation as a readout. In this system, proteins of interest can be incorporated into chimeric proteins without any scaffold proteins, which would be advantageous for evaluating interaction between small peptides/domains. To prove this superiority, we apply KIPPIS to 6 peptide aptamer–polypeptide pairs, which are derived from endogenous, synthetic, and viral proteins. Consequently, all of the 6 peptide aptamer–polypeptide interactions are successfully detected by cell proliferation. The detection sensitivity can be modulated in a helper ligand-dependent manner. The assay results of KIPPIS correlate with the activation levels of Src, which is located downstream of c-kit-mediated signal transduction. Control experiments reveal that KIPPIS clearly discriminates interacting aptamers from non-interacting ones. Thus, KIPPIS proves to be a versatile platform for evaluating the binding properties of peptide aptamers.