bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of zinc(II) from livestock and poultry sewage by a zinc(II) resistant bacteria
Authors: Huang Jiang , Wang Jihong , Jia Lan
Published: December 2020

In order to remediate Zn-contaminated livestock and poultry sewage, a zinc-resistant bacterial strain was screened and isolated from the manure of livestock and poultry and identified by molecular biology. The optimal conditions for removing zinc(II) from strain XZN4 were determined by single-factor experiments as follows: within 3 times of repeated use, pH value was 5, initial concentration of zinc(II) was 100 mg/L, the amount of bacteria was 6 g/L, the temperature was 25–30 °C, and the removal equilibrium time was 60 min. Then, through adsorption isotherm model, scanning electron microscope image, energy dispersive spectrum analysis, infrared spectrum analysis and sterilization control experiment, it was found that the removal of zinc(II) by bacteria was single-molecule layer adsorption, which was carried out in coordination with degradation. The influence of different concentrations of copper(II), ammonia nitrogen, phosphorus, and chlortetracycline on the removal of zinc(II) from livestock and poultry sewage by XZN4 strain in the actual application was discussed. The bacteria can reduce the concentration of zinc(II) from the complex livestock and poultry waste water to below the discharge standard, and has a strong environmental tolerance, the highest removal rate reached 88.6% and the highest removal amount reached 10.30 mg/L. The screening and application of XZN4 strain can thus be of great significance for the microbial treatment of zinc(II) in complex livestock and poultry sewage. The results will provide guidance for the microbial remediation of heavy metal pollution.
Degenerative cervical myelopathy presenting as subjective lower limb weakness could be a trap towards misdiagnosis
Authors: Luo Chi-An , Lu Meng-Ling , Kaliya-Perumal Arun-Kumar , Chen Lih-Huei , Chen Wen-Jer , Niu Chi-Chien
Published: December 2020

When patients presenting with subjective lower limb weakness (SLLW) are encountered, it is natural to suspect a lumbar pathology and proceed with related clinical examination, investigations and management. However, SLLW could be a sign of degenerative cervical myelopathy (DCM) due to an evolving cord compression. In such circumstances, if symptoms are not correlated to myelopathy at the earliest, there could be potential complications over time. In this study, we intend to analyse the outcomes after surgical management of the cervical or thoracic cord compression in patients with SLLW. Retrospectively, patients who presented to our center during the years 2010–2016 with sole complaint of bilateral SLLW but radiologically diagnosed to have a solitary cervical or thoracic stenosis, or tandem spinal stenosis and underwent surgical decompression procedures were selected. Their clinical presentation was categorised into three types, myelopathy was graded using Nurick’s grading and JOA scoring; in addition, their lower limb functional status was assessed using the lower extremity functional scale (LEFS). Functional recovery following surgery was assessed at 6 weeks, 3 months, 6 months, one year, and two years. Selected patients (n = 24; Age, 56.4 ± 10.1 years; range 32–78 years) had SLLW for a period of 6.4 ± 3.2 months (range 2–13 months). Their preoperative JOA score was 11.3 ± 1.8 (range 7–15), and LEFS was 34.4 ± 7.7 (range 20–46). Radiological evidence of a solitary cervical lesion and tandem spinal stenosis was found in 6 and 18 patients respectively. Patients gradually recovered after surgical decompression with LEFS 59.8 ± 2.7 (range 56–65) at 1 year and JOA score 13.6 ± 2.7 (range − 17 to 100) at 2 years. The recovery rate at final follow up was 47.5%. Our results indicate the importance of clinically suspecting SLLW as an early non-specific sign of DCM to avoid misdiagnosis, especially in patients without conventional upper motor neuron signs. In such cases, surgical management of the cord compression resulted in significant functional recovery and halted the progression towards permanent disability.
Estimating visual field loss from monoscopic optic disc photography using deep learning model
Authors: Lee Jinho , Kim Yong Woo , Ha Ahnul , Kim Young Kook , Park Ki Ho , Choi Hyuk Jin , Jeoung Jin Wook
Published: December 2020

Visual field assessment is recognized as the important criterion of glaucomatous damage judgement; however, it can show large test–retest variability. We developed a deep learning (DL) algorithm that quantitatively predicts mean deviation (MD) of standard automated perimetry (SAP) from monoscopic optic disc photographs (ODPs). A total of 1200 image pairs (ODPs and SAP results) for 563 eyes of 327 participants were enrolled. A DL model was built by combining a pre-trained DL network and subsequently trained fully connected layers. The correlation coefficient and mean absolute error (MAE) between the predicted and measured MDs were calculated. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the detection ability for glaucomatous visual field (VF) loss. The data were split into training/validation (1000 images) and testing (200 images) sets to evaluate the performance of the algorithm. The predicted MD showed a strong correlation and good agreement with the actual MD (correlation coefficient = 0.755; R2 = 57.0%; MAE = 1.94 dB). The model also accurately predicted the presence of glaucomatous VF loss (AUC 0.953). The DL algorithm showed great feasibility for prediction of MD and detection of glaucomatous functional loss from ODPs.
Application of Raman spectroscopy and Machine Learning algorithms for fruit distillates discrimination
Authors: Berghian-Grosan Camelia , Magdas Dana Alina
Published: December 2020

Through this pilot study, the association between Raman spectroscopy and Machine Learning algorithms were used for the first time with the purpose of distillates differentiation with respect to trademark, geographical and botanical origin. Two spectral Raman ranges (region I—200–600 cm−1 and region II—1200–1400 cm−1) appeared to have the higher discrimination potential for the investigated distillates. The proposed approach proved to be a very effective one for trademark fingerprint differentiation, a model accuracy of 95.5% being obtained (only one sample was misclassified). A comparable model accuracy (90.9%) was achieved for the geographical discrimination of the fruit spirits which can be considered as a very good one taking into account that this classification was made inside Transylvania region, among neighbouring areas. Because the trademark fingerprint is the prevailing one, the successfully distillate type differentiation, with respect to the fruit variety, was possible to be made only inside of each producing entity.
Marker assisted improvement of low soil phosphorus tolerance in the bacterial blight resistant, fine-grain type rice variety, Improved Samba Mahsuri
Authors: Swamy H. K. Mahadeva , Anila M. , Kale R. R. , Rekha G. , Bhadana V. P. , Anantha M. S. , Brajendra P. , Balachiranjeevi C. H. , Hajira S. K. , Prasanna B. Laxmi , Pranathi K. , Dilip T. , Kousik M. B. V. N. , Harika G. , Surekha K. , Kumar R. Mahender , Cheralu C. , Shankar V. Gouri , Laha G. S. , Prasad M. S. , Rao L. V. Subba , Madhav M. S. , Balachandran S. M. , Sundaram R. M.
Published: December 2020

Improved-Samba-Mahsuri (ISM), a high-yielding, popular bacterial blight resistant (possessing Xa21, xa13, and xa5), fine-grain type, low glycemic index rice variety is highly sensitive to low soil phosphorus (P). We have deployed marker-assisted backcross breeding (MABB) approach for targeted transfer of Pup1, a major QTL associated with low soil P tolerance, using Swarna as a donor. A new co-dominant marker, K20-1-1, which is specific for Pup1 was designed and used for foreground selection along with functional markers specific for the bacterial blight resistance genes, Xa21, xa13, and xa5. A set of 66 polymorphic SSR marker were used for the background selection along with a pair of flanking markers for the recombination selection in backcross derived progenies and in BC2F2 generation, 12 plants, which are homozygous for Pup1, all the three bacterial blight resistance genes and possessing agro-morphological traits equivalent to or better than ISM were selected and selfed to produce BC2F3s. They were evaluated in plots with low soil P and normal soil P at ICAR-IIRR, Hyderabad for their low soil P tolerance, and bacterial blight resistance and superior lines were advanced to BC2F6. One of the lines, when tested at multiple locations in India was found promising under both normal as well as low soil P conditions.
Mitochondrial dysfunction in sepsis is associated with diminished intramitochondrial TFAM despite its increased cellular expression
Authors: Rahmel Tim , Marko Britta , Nowak Hartmuth , Bergmann Lars , Thon Patrick , Rump Katharina , Kreimendahl Sebastian , Rassow Joachim , Peters Jürgen , Singer Mervyn , Adamzik Michael , Koos Björn
Published: December 2020

Sepsis is characterized by a dysregulated immune response, metabolic derangements and bioenergetic failure. These alterations are closely associated with a profound and persisting mitochondrial dysfunction. This however occurs despite increased expression of the nuclear-encoded transcription factor A (TFAM) that normally supports mitochondrial biogenesis and functional recovery. Since this paradox may relate to an altered intracellular distribution of TFAM in sepsis, we tested the hypothesis that enhanced extramitochondrial TFAM expression does not translate into increased intramitochondrial TFAM abundance. Accordingly, we prospectively analyzed PBMCs both from septic patients (n = 10) and lipopolysaccharide stimulated PBMCs from healthy volunteers (n = 20). Extramitochondrial TFAM protein expression in sepsis patients was 1.8-fold greater compared to controls (p = 0.001), whereas intramitochondrial TFAM abundance was approximate 80% less (p < 0.001). This was accompanied by lower mitochondrial DNA copy numbers (p < 0.001), mtND1 expression (p < 0.001) and cellular ATP content (p < 0.001) in sepsis patients. These findings were mirrored in lipopolysaccharide stimulated PBMCs taken from healthy volunteers. Furthermore, TFAM-TFB2M protein interaction within the human mitochondrial core transcription initiation complex, was 74% lower in septic patients (p < 0.001). In conclusion, our findings, which demonstrate a diminished mitochondrial TFAM abundance in sepsis and endotoxemia, may help to explain the paradox of lacking bioenergetic recovery despite enhanced TFAM expression.
Photoreceptor alteration in intermediate age-related macular degeneration
Authors: Borrelli Enrico , Sacconi Riccardo , Zuccaro Biancamaria , Cavalleri Michele , Bordato Alessandro , Zucchiatti Ilaria , Querques Lea , Bandello Francesco , Querques Giuseppe
Published: December 2020

The aim of this study was to analyze photoreceptor alterations occurring in eyes with intermediate age-related macular degeneration (AMD) and to investigate their associations with choriocapillaris (CC) flow. In this retrospective case–control study, we collected data from 35 eyes with intermediate AMD from 35 patients who had swept source optical coherence tomography structural and angiography imaging obtained. A control group of 35 eyes from 35 healthy subjects was included for comparison. Our main outcome measure for comparison between groups was the normalized reflectivity of en face image segmented at the ellipsoid zone (EZ) level, which was calculated to quantify the photoreceptor damage. OCTA metrics to quantify CC flow signal were also computed. These metrics were measured in a circle centered on the fovea and with a diameter of 5 mm. In intermediate AMD eyes, the macular area occupied by drusen was identified. Therefore, the EZ reflectivity and CC flow signal were separately measured in regions without drusen (“drusen-free” region). Measurements were generated using previously published algorithms. Mean ± SD age was 74.1 ± 6.8 years in the intermediate AMD group and 72.1 ± 6.0 years in the control group (p = 0.206). The normalized EZ reflectivity was 0.76 ± 0.10 in the intermediate AMD group and 0.85 ± 0.08 in the control group (p < .0001). In the “drusen-free” region, the normalized EZ reflectivity was 0.77 ± 0.10 (p < .0001  vs. healthy controls) and was positively correlated with the CC flow signal density (ρ = − 0.340 and p = 0.020). In conclusion, eyes with intermediate AMD exhibit a diffuse reduced EZ normalized reflectivity, and this reduction is correlated with CC flow signal in the regions without drusen. This study supports the concept of the damage of the unit comprised of photoreceptor, CC, and intervening tissues as an early event in AMD.
Maternal proteomic profiling reveals alterations in lipid metabolism in late-onset fetal growth restriction
Authors: Paules Cristina , Youssef Lina , Miranda Jezid , Crovetto Francesca , Estanyol Josep Maria , Fernandez Guerau , Crispi Fatima , Gratacós Eduard
Published: December 2020

Fetal growth restriction defined as the failure to achieve the fetal genetic growth potential is a major cause of perinatal morbidity and mortality. The role of maternal adaptations to placental insufficiency in this disorder is still not fully understood. We aimed to investigate the biological processes and protein–protein interactions involved in late-onset fetal growth restriction in particular. We applied 2D nano LC–MS/MS proteomics analysis on maternal blood samples collected at the time of delivery from 5 singleton pregnancies with late-onset fetal growth restriction and 5 uncomplicated pregnancies. Data were analyzed using R package “limma” and Ingenuity Pathway Analysis. 25 proteins showed significant changes in their relative abundance in late-onset fetal growth restriction (p value < 0.05). Direct protein–protein interactions network demonstrated that Neurogenic locus notch homolog protein 1 (NOTCH1) was the most significant putative upstream regulator of the observed profile. Gene ontology analysis of these proteins revealed the involvement of 14 canonical pathways. The most significant biological processes were efflux of cholesterol, efflux of phospholipids, adhesion of blood cells, fatty acid metabolism and dyslipidemia. Future studies are warranted to validate the potential role of the detected altered proteins as potential therapeutic targets in the late-onset form of fetal growth restriction.
Generation, analysis, and transformation of macro-chloroplast Potato (Solanum tuberosum) lines for chloroplast biotechnology
Authors: Occhialini Alessandro , Pfotenhauer Alexander C. , Frazier Taylor P. , Li Li , Harbison Stacee A. , Lail Andrew J. , Mebane Zachary , Piatek Agnieszka A. , Rigoulot Stephen B. , Daniell Henry , Stewart C. Neal , Lenaghan Scott C.
Published: December 2020

Chloroplast biotechnology is a route for novel crop metabolic engineering. The potential bio-confinement of transgenes, the high protein expression and the possibility to organize genes into operons represent considerable advantages that make chloroplasts valuable targets in agricultural biotechnology. In the last 3 decades, chloroplast genomes from a few economically important crops have been successfully transformed. The main bottlenecks that prevent efficient transformation in a greater number of crops include the dearth of proven selectable marker gene-selection combinations and tissue culture methods for efficient regeneration of transplastomic plants. The prospects of increasing organelle size are attractive from several perspectives, including an increase in the surface area of potential targets. As a proof-of-concept, we generatedSolanum tuberosum(potato) macro-chloroplast lines overexpressing the tubulin-like GTPase protein geneFtsZ1fromArabidopsis thaliana. Macro-chloroplast lines exhibited delayed growth at anthesis; however, at the time of harvest there was no significant difference in height between macro-chloroplast and wild-type lines. Macro-chloroplasts were successfully transformed by biolistic DNA-delivery and efficiently regenerated into homoplasmic transplastomic lines. We also demonstrated that macro-chloroplasts accumulate the same amount of heterologous protein than wild-type organelles, confirming efficient usage in plastid engineering. Advantages and limitations of using enlarge compartments in chloroplast biotechnology are discussed.
The dorsal arcopallium of chicks displays the expression of orthologs of mammalian fear related serotonin receptor subfamily genes
Authors: Fujita Toshiyuki , Aoki Naoya , Mori Chihiro , Fujita Eiko , Matsushima Toshiya , Homma Koichi J. , Yamaguchi Shinji
Published: December 2020

Fear is an adaptive emotion that elicits defensive behavioural responses against aversive threats in animals. In mammals, serotonin receptors (5-HTRs) have been shown to modulate fear-related neural circuits in the basolateral amygdala complex (BLA). To understand the phylogenetic continuity of the neural basis for fear, it is important to identify the neural circuit that processes fear in other animals. In birds, fear-related behaviours were suggested to be processed in the arcopallium/amygdala complex and modulated by the serotonin (5-HT) system. However, details about the distribution of 5-HTRs in the avian brain are very sparsely reported, and the 5-HTR that is potentially involved in fear-related behaviour has not been elucidated. In this study, we showed that orthologs of mammalian 5-HTR genes that are expressed in the BLA, namely 5-HTR1A, 5-HTR1B, 5-HTR2A, 5-HTR2C, 5-HTR3A, and 5-HTR4, are expressed in a part of the chick arcopallium/amygdala complex called the dorsal arcopallium. This suggests that serotonergic regulation in the dorsal arcopallium may play an important role in regulating fear-related behaviour in birds. Our findings can be used as a basis for comparing the processing of fear and its serotonergic modulation in the mammalian amygdala complex and avian arcopallium/amygdala complex.
Single-cell RNA-seq reveals CD16- monocytes as key regulators of human monocyte transcriptional response to Toxoplasma
Authors: Patir Anirudh , Gossner Anton , Ramachandran Prakash , Alves Joana , Freeman Tom C. , Henderson Neil C. , Watson Mick , Hassan Musa A.
Published: December 2020

Monocytes are among the major myeloid cells that respond toToxoplasma, a ubiquitous foodborne that infects ≥ 1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasmainteractions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasmainteractions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses toToxoplasmahave sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte responses to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasmaencounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report thatToxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14+CD16-monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover theToxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed toToxoplasma.
Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood
Authors: Hanel Andrea , Neme Antonio , Malinen Marjo , Hämäläinen Emmi , Malmberg Henna-Riikka , Etheve Stéphane , Tuomainen Tomi-Pekka , Virtanen Jyrki K. , Bendik Igor , Carlberg Carsten
Published: December 2020

Vitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)2D3 stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.
Deletion of the GAPDH gene contributes to genome stability in Saccharomyces cerevisiae
Authors: Hanasaki Miki , Yaku Keisuke , Yamauchi Motohiro , Nakagawa Takashi , Masumoto Hiroshi
Published: December 2020

Cellular metabolism is directly or indirectly associated with various cellular processes by producing a variety of metabolites. Metabolic alterations may cause adverse effects on cell viability. However, some alterations potentiate the rescue of the malfunction of the cell system. Here, we found that the alteration of glucose metabolism suppressed genome instability caused by the impairment of chromatin structure. Deletion of the TDH2 gene, which encodes glyceraldehyde 3-phospho dehydrogenase and is essential for glycolysis/gluconeogenesis, partially suppressed DNA damage sensitivity due to chromatin structure, which was persistently acetylated histone H3 on lysine 56 in cells with deletions of both HST3 and HST4, encoding NAD+-dependent deacetylases. tdh2 deletion also restored the short replicative lifespan of cells with deletion of sir2, another NAD+-dependent deacetylase, by suppressing intrachromosomal recombination in rDNA repeats increased by the unacetylated histone H4 on lysine 16. tdh2 deletion also suppressed recombination between direct repeats in hst3∆ hst4∆ cells by suppressing the replication fork instability that leads to both DNA deletions among repeats. We focused on quinolinic acid (QUIN), a metabolic intermediate in the de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway, which accumulated in the tdh2 deletion cells and was a candidate metabolite to suppress DNA replication fork instability. Deletion of QPT1, quinolinate phosphoribosyl transferase, elevated intracellular QUIN levels and partially suppressed the DNA damage sensitivity of hst3∆ hst4∆ cells as well as tdh2∆ cells. qpt1 deletion restored the short replicative lifespan of sir2∆ cells by suppressing intrachromosomal recombination among rDNA repeats. In addition, qpt1 deletion could suppress replication fork slippage between direct repeats. These findings suggest a connection between glucose metabolism and genomic stability.
Autophagy: a necessary defense against extreme cadmium intoxication in a multigenerational 2D experiment
Authors: Babczyńska Agnieszka , Nowak Agnieszka , Kafel Alina , Łozowski Bartosz , Rost-Roszkowska Magdalena , Tarnawska Monika , Augustyniak Maria , Sawadro Marta , Molenda Agnieszka
Published: December 2020

Autophagy is a natural process that aims to eliminate malfunctioning cell parts, organelles or molecules under physiological conditions. It is also induced in response to infection, starvation or oxidative stress to provide energy in case of an energy deficit. The aim of this 2-dimensional study was to test if, and if so, how, this process depends on the concentration of cadmium in food (with Cd concentrations from 0 to 352 μg of Cd per g of food (dry weight)—D1 dimension) and the history of selection pressure (160 vs 20 generations of exposure to Cd—D2 dimension). For the study, the 5th instar larvae of a unique strain of the moth Spodoptera exigua that was selected for cadmium tolerance for 160 generations (44 μg of Cd per g of food (dry weight)), as well as 20-generation (11, 22 and 44 μg of Cd per g of food (dry weight)) and control strains, were used. Autophagy intensity was measured by means of flow cytometry and compared with life history parameters: survivability and duration of the 3rd larval stage. The highest values of autophagy markers were found in the groups exposed to the highest Cd concentration and corresponded (with a significant correlation coefficient) to an increased development duration or decreased survivorship in the respective groups. In conclusion, autophagy is probably initiated only if any other defense mechanisms, e.g., antioxidative mechanisms, are not efficient. Moreover, in individuals from pre-exposed populations, the intensity of autophagy is lower.
Effect of immunosuppressants on a mouse model of osteogenesis imperfecta type V harboring a heterozygous Ifitm5 c.-14C > T mutation
Authors: Hanagata Nobutaka , Takemura Taro , Kamimura Keiko , Koda Toshiaki
Published: December 2020

Osteogenesis imperfecta (OI) type V is an autosomal dominant disorder caused by the c.-14C > T mutation in the interferon-induced transmembrane protein 5 gene (IFITM5), however, its onset mechanism remains unclear. In this study, heterozygous c.-14C > T mutant mice were developed to investigate the effect of immunosuppressants (FK506 and rapamycin) on OI type V. Among the mosaic mice generated by Crispr/Cas9-based technology, mice with less than 40% mosaic ratio of c.-14C > T mutation survived, whereas those with more than 48% mosaic ratio exhibited lethal skeletal abnormalities with one exception. All heterozygous mutants obtained by mating mosaic mice with wild-type mice exhibited a perinatal lethal phenotype due to severe skeletal abnormalities. Administration of FK506, a calcineurin inhibitor, in the heterozygous fetuses improved bone mineral content (BMC) of the neonates, although it did not save the neonates from the lethal effects of the mutation, whereas rapamycin, an mTOR inhibitor, reduced BMC, suggesting that mTOR signaling is involved in the bone mineralization of heterozygous mutants. These findings could clarify certain aspects of the onset mechanism of OI type V and enable development of therapeutics for this condition.
Muscle and epidermal contributions of the structural protein β-spectrin promote hypergravity-induced motor neuron axon defects in C. elegans
Authors: Kalichamy Saraswathi S. , Alcantara Alfredo V. , Kim Ban-Seok , Park Junsoo , Yoon Kyoung-hye , Lee Jin I.
Published: December 2020

Biology is adapted to Earth’s gravity force, and the long-term effects of varying gravity on the development of animals is unclear. Previously, we reported that high gravity, called hypergravity, increases defects in the development of motor neuron axons in the nematode Caenorhabditis elegans. Here, we show that a mutation in the unc-70 gene that encodes the cytoskeletal β-spectrin protein suppresses hypergravity-induced axon defects. UNC-70 expression is required in both muscle and epidermis to promote the axon defects in high gravity. We reveal that the location of axon defects is correlated to the size of the muscle cell that the axon traverses. We also show that mutations that compromise key proteins of hemidesmosomal structures suppress hypergravity-induced axon defects. These hemidesmosomal structures play a crucial role in coupling mechanical force between the muscle, epidermis and the external cuticle. We speculate a model in which the rigid organization of muscle, epidermal and cuticular layers under high gravity pressure compresses the narrow axon migration pathways in the extracellular matrix hindering proper axon pathfinding of motor neurons.
Author Correction: High PD-L1 expression is associated with therapeutic response to pembrolizumab in patients with advanced biliary tract cancer
Authors: Ahn Soomin , Lee Jong- chan , Shin Dong Woo , Kim Jaihwan , Hwang Jin‑ Hyeok
Published: December 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sustained blood glutamate scavenging enhances protection in ischemic stroke
Authors: Zaghmi Ahlem , Dopico-López Antonio , Pérez-Mato María , Iglesias-Rey Ramón , Hervella Pablo , Greschner Andrea A. , Bugallo-Casal Ana , da Silva Andrés , Gutiérrez-Fernández María , Castillo José , Pérez Francisco Campos , Gauthier Marc A.
Published: December 2020

Stroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for ~6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body.
The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity
Authors: Hendus-Altenburger Ruth , Vogensen Jens , Pedersen Emilie Skotte , Luchini Alessandra , Araya-Secchi Raul , Bendsoe Anne H. , Prasad Nanditha Shyam , Prestel Andreas , Cardenas Marité , Pedraz-Cuesta Elena , Arleth Lise , Pedersen Stine F. , Kragelund Birthe B.
Published: December 2020

Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na+/H+-exchanger 1 (NHE1) regulates intracellular pH (pHi) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE1-LID is intrinsically disordered and, in presence of membrane mimetics, forms a helical αα-hairpin co-structure with the membrane, anchoring the regulatory domain vis-a-vis the transport domain. This co-structure is fundamental for NHE1 activity, as its disintegration reduced steady-state pHi and the rate of pHi recovery after acid loading. We propose that regulatory lipid-protein co-structures may play equally important roles in other membrane proteins.
C1QTNF6 regulates cell proliferation and apoptosis of NSCLC in vitro and in vivo
Authors: Zhang Wei , Feng Ganzhu
Published: December 2020

Objectives: Lung cancer has been reported as the leading cause of cancer-associated deaths in humans, and its incidence continues to increase in the world. A growing number of studies have shown that dysregulated genes are associated with the occurrence and poor prognosis of a variety of tumors, including non-small cell lung cancer (NSCLC). C1q/tumor necrosis factor-related protein 6 (C1QTNF6), a member of the C1q/tumor necrosis factor-related protein (CTRP) family, has been revealed to play a role in carcinogenesis and cancer progression. Nevertheless, the effects and mechanisms of C1QTNF6 in NSCLC remain unrevealed. Materials and methods: MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide) and colony formation, flow cytometric and transwell assays were performed to explore the cell function. Real-time PCR (RT-PCR) and Western blot were used to analyze the mRNA and protein expression. Results: In the present study, we found that C1QTNF6 significantly promoted the proliferation of SPCA1 and A549 cells by MTT and colony formation assays. In addition, down-regulation of C1QTNF6 weakened the tumor growth in vivo. Besides, C1QTNF6 remarkably reduced apoptosis by flow cytometric analysis and TUNEL assay. Furthermore, the capability of migration and invasion was obviously enhanced on C1QTNF6 overexpression. Conclusion: Overall, our results demonstrated that inhibition of C1QTNF6 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and in vivo of NSCLC. Based on the above results, our study provided us with a new and key perspective in understanding and treating NSCLC.
Perceptual Learning of Vocoded Speech With and Without Contralateral Hearing: Implications for Cochlear Implant Rehabilitation
Authors: Chavant Martin , Hervais-Adelman Alexis , Macherey Olivier
Published: December 2020

Purpose

An increasing number of individuals with residual or even normal contralateral hearing are being considered for cochlear implantation. It remains unknown whether the presence of contralateral hearing is beneficial or detrimental to their perceptual learning of cochlear implant (CI)–processed speech. The aim of this experiment was to provide a first insight into this question using acoustic simulations of CI processing.

Method

Sixty normal-hearing listeners took part in an auditory perceptual learning experiment. Each subject was randomly assigned to one of three groups of 20 referred to as NORMAL, LOWPASS, and NOTHING. The experiment consisted of two test phases separated by a training phase. In the test phases, all subjects were tested on recognition of monosyllabic words passed through a six-channel “PSHC” vocoder presented to a single ear. In the training phase, which consisted of listening to a 25-min audio book, all subjects were also presented with the same vocoded speech in one ear but the signal they received in their other ear differed across groups. The NORMAL group was presented with the unprocessed speech signal, the LOWPASS group with a low-pass filtered version of the speech signal, and the NOTHING group with no sound at all.

Results

The improvement in speech scores following training was significantly smaller for the NORMAL than for the LOWPASS and NOTHING groups.

Conclusions

This study suggests that the presentation of normal speech in the contralateral ear reduces or slows down perceptual learning of vocoded speech but that an unintelligible low-pass filtered contralateral signal does not have this effect. Potential implications for the rehabilitation of CI patients with partial or full contralateral hearing are discussed.
Shewanella oneidensis MR‐1 in situ biosynthesis of Ag nanoparticles on TiO2 nanotubes with enhanced photocatalytic performance
Authors: Song Xiaojie , Yang Fan , Wang Xiufang , Zhang Kehua
Published: December 2020

Biogenetic nanocomposites research provides valuable methods for the green synthesis of nanomaterials. As a dissimilatory metal‐reducing bacterium, Shewanella oneidensis MR‐1 is used to reduce Ag+ to Ag nanoparticles (Ag NPs) (diameter about 10 nm) under anaerobic conditions, resulting in the in‐situ formation of Ag NPs immobilised on TiO2 nanotubes (TNTs) (Ag/TNTs nanocomposites). The loading amount of Ag nanocrystals on the TNT surface can be controlled easily through adjusting the AgNO3 concentration and further influence visible‐light absorption efficiency of Ag/TNTs nanocomposites by decreasing the Ag loading amount. Ag/TNTs nanocomposites show superior photocatalytic efficiency under simulated sunlight than single TiO2 nanomaterials. Moreover, the photocatalytic capacity of Ag/TNTs nanocomposites synergistic by S. oneidensis MR‐1 is further enhanced and the degradation ratio of methylene blue reaches 92.3% within 30 min which attributed to a synergistic effect.
Mass segregation and sequential star formation in NGC 2264 revealed by Herschel
Authors: Nony T. , Robitaille J.-F. , Motte F. , Gonzalez M. , Joncour I. , Moraux E. , Men’shchikov A. , Didelon P. , Louvet F. , Buckner A. S. M. , Schneider N. , Lumsden S. L. , Bontemps S. , Pouteau Y. , Cunningham N. , Fiorellino E. , Oudmaijer R. , André P. , Thomasson B.
Published: December 2020

Context. The mass segregation of stellar clusters could be primordial rather than dynamical. Despite the abundance of studies of mass segregation for stellar clusters, those for stellar progenitors are still scarce, so the question concerning the origin and evolution of mass segregation is still open.

Aims. Our goal is to characterize the structure of the NGC 2264 molecular cloud and compare the populations of clumps and young stellar objects (YSOs) in this region whose rich YSO population has shown evidence of sequential star formation.

Methods. We separated the Herschel column density map of NGC 2264 into three subregions and compared their cloud power spectra using a multiscale segmentation technique. We extracted compact cloud fragments from the column density image, measured their basic properties, and studied their spatial and mass distributions.

Results. In the whole NGC 2264 cloud, we identified a population of 256 clumps with typical sizes of ~0.1 pc and masses ranging from 0.08 M⊙ to 53 M⊙. Although clumps have been detected all over the cloud, most of the massive, bound clumps are concentrated in the central subregion of NGC 2264. The local surface density and the mass segregation ratio indicate a strong degree of mass segregation for the 15 most massive clumps, with a median Σ6 three times that of the whole clumps population and ΛMSR ≃ 8. We show that this cluster of massive clumps is forming within a high-density cloud ridge, which is formed and probably still fed by the high concentration of gas observed on larger scales in the central subregion. The time sequence obtained from the combined study of the clump and YSO populations in NGC 2264 suggests that the star formation started in the northern subregion, that it is now actively developing at the center, and will soon start in the southern subregion.

Conclusions. Taken together, the cloud structure and the clump and YSO populations in NGC 2264 argue for a dynamical scenario of star formation. The cloud could first undergo global collapse, driving most clumps to centrally concentrated ridges. After their main accretion phase, some YSOs, and probably the most massive, would stay clustered while others would be dispersed from their birth sites. We propose that the mass segregation observed in some star clusters is inherited from that of clumps, originating from the mass assembly phase of molecular clouds.
Sparse optimal control for a semilinear heat equation with mixed control-state constraints – regularity of Lagrange multipliers
Authors: Casas Eduardo , Tröltzsch Fredi
Published: December 2020

An optimal control problem for a semilinear heat equation with distributed control is discussed, where two-sided pointwise box constraints on the control and two-sided pointwise mixed control-state constraints are given. The objective functional is the sum of a standard quadratic tracking type part and a multiple of the L1-norm of the control that accounts for sparsity. Under a certain structural condition on almost active sets of the optimal solution, the existence of integrable Lagrange multipliers is proved for all inequality constraints. For this purpose, a theorem by Yosida and Hewitt is used. It is shown that the structural condition is fulfilled for all sufficiently large sparsity parameters. The sparsity of the optimal control is investigated. Eventually, higher smoothness of Lagrange multipliers is shown up to Hölder regularity.
Empfehlungen zur Phytotherapie in der S3-Leitlinie „Peri- und Postmenopause – Diagnostik und Interventionen“
Authors: Klose Petra , Langhorst Jost
Published: December 2020

Im Jahr 2018 wurde die „Leitlinie zur Hormontherapie in der Peri- und Postmenopause“ von 2010 erneuert, neu ausgerichtet und umbenannt. Der Schwerpunkt liegt nach wie vor auf der wissenschaftlichen Aufarbeitung der Möglichkeiten und Risiken der Hormontherapie zur Linderung von menopausalen Beschwerden. Aber im ersten Kapitel zu Diagnostik und Interventionen wird relativ ausführlich auch auf andere Therapiemöglichkeiten eingegangen. So gibt es gegen Hitzewallungen für Traubensilberkerze und Isoflavone eine neutrale sog. „Kann“-Empfehlung, die besagt, dass Evidenz vorhanden, diese aber nur für eine sogenannte „offene“ Empfehlung ausreicht. In den anschließenden Hintergrundtexten werden Traubensilberkerze, Phytoöstrogene bzw. Isoflavone und weitere Therapieoptionen wissenschaftlich beleuchtet und bewertet: Die zahlreichen Studien zu Cimicifuga und zu den phytoöstrogenreichen Pflanzen wie Soja, Rotklee, Rhapontik-Rhabarber, Leinsamen kommen zu keinem einheitlichen Bild, wobei die Wirksamkeit gegen Hitzewallungen jedoch als wahrscheinlich angesehen wird. Weitere Therapieoptionen aus dem Bereich der Phytotherapie und Naturheilkunde, die möglicherweise Wirkung zeigen, sind die Akupunktur und Johanniskraut. Zu wenige Studien gibt es zu Ginseng und zu Tiefenentspannung. Skeptisch werden TCM-Kräuterrezepturen gesehen, da die Studienlage sehr schlecht ist und wenig über Nebenwirkungen und Interaktionen bekannt ist.

Alles in allem ist es in der erneuerten Leitlinie gelungen, eine kleine Nische für die Phytotherapie und Naturheilkunde zu erobern. Insgesamt ist die Studienlage nach wie vor nicht gut oder ausreichend, um überzeugend für eine klare Empfehlung von z. B. Traubensilberkerze oder Phytoöstrogenen zu plädieren. Aber die Evidenz reicht immerhin aus, unter streng wissenschaftlichen Gesichtspunkten eine Wirksamkeit anzunehmen. Wichtig ist ebenso, dass die Sicherheit einer Einnahme untersucht und dargelegt werden konnte. So ist den Frauen und behandelnden Ärzten die Möglichkeit eröffnet, diese Phytotherapeutika oder z. B. Akupunktur gegen Hitzewallungen leitlinienkonform anzuwenden und für sich persönlich zu testen.
Healthy Aging
Authors: Gröber Uwe
Published: December 2020

Die Alterung von Körper und Gehirn wird durch mediterrane Ernährung und bedarfsgerechte Substitution von EPA und DHA in Form von Fisch-/Algenöl verlangsamt. Studien belegen die positive Wirkung einer ausreichenden Versorgung mit ω-3-Fettsäuren auf Alterungsprozesse u. a. durch antiinflammatorische Effekte und geringere Verkürzung der Telomere. Ein guter ω-3-Index reduziert deutlich das Risiko für kardiovaskuläre Erkrankungen. Vitamin D beeinflusst ebenfalls Inflammaging und Telomerlänge. Das Prohormon trägt zum Schutz vor neurodegenerativen sowie psychischen Erkrankungen bei, reduziert die allgemeine Mortalität sowie das Sterberisiko bei Darmkrebs und Metabolischem Syndrom. Positive Wirkungen auf Knochendichte und signifikante Reduktion des Sturzrisikos unterstreichen die Bedeutung des Nährstoffs für den alternden Menschen. Da insb. Ältere unzureichend mit Vitamin D versorgt sind, ist die Supplementierung eine wichtige präventivmedizinische und die Lebensqualität erhöhende Strategie.
Synthesis of Spirocyclopropane Oxindoles via Michael-Initiated Cyclopropanation of Pyridinium Salts with 3-Ylidene Oxindoles
Authors: Ren Hongjun , Zhang Jun-Qi , Gao Yujia , Song Jinyu , Hu Dandan , Miao Maozhong
Published: December 2020

A Michael-initiated ring-closure reaction of pyridinium salts with arylidene oxindoles has been developed. A wide range of aryl-substituted spirocyclopropane oxindoles has been achieved in moderate to good yields (41–99%).
This efficient strategy exhibits good functional group compatibility and may serve as an attractive method for the synthesis of diverse cyclopropanes.
Zn-Mediated Hydrodeoxygenation of Tertiary Alkyl Oxalates
Authors: Gong Hegui , Ye Yang , Ma Guobin , Yao Ken
Published: December 2020

Herein we describe a general, mild, and scalable method for hydrodeoxygenation of readily accessible tertiary alkyl oxalates by Zn/silane under Ni-catalyzed conditions. The reduction
method is suitable for an array of structural motifs derived from tertiary alcohols that bear diverse functional groups, including the synthesis of a key intermediate en route to estrone.
Asparagine Synthetase Deficiency with Intracranial Hemorrhage Can Mimic Molybdenum Cofactor Deficiency
Authors: Abdel-Salam Ghada M. H. , Abdel-Hamid Mohamed S.
Published: December 2020

Here we report a consanguineous Egyptian family with two siblings presented with congenital microcephaly, early-onset epileptic encephalopathy, feeding difficulties, and early lethality. The condition was initially diagnosed as molybdenum cofactor deficiency as the brain imaging for one of them showed brain edema and intracranial hemorrhage in addition to the hypoplastic corpus callosum, vermis hypoplasia, and small-sized pons. Subsequently, whole exome sequencing identified a novel homozygous missense variant in exon 4 of ASNS gene c.397_398GT > CA (p.Val133Gln) confirming the diagnosis of asparagine synthetase deficiency syndrome. No discernible alternative cause for the intracranial hemorrhage was found. Our patient is the second to show asparagine synthetase deficiency and intracranial hemorrhage, thus confirming the involvement of ASNS gene. As such, it is important to consider asparagine synthetase deficiency syndrome in patients with microcephaly, brain edema, and neonatal intracranial hemorrhage.
Negative Pressure Pulmonary Edema as a Cause of Diffuse Alveolar Hemorrhage in the Newborn
Authors: Donoso Alejandro , Tomarelli Gianfranco , Arriagada Daniela
Published: December 2020

Negative pressure pulmonary edema (NPPE) is a rare entity that can become life threatening. Its development in neonates is very rare, and its presentation as alveolar hemorrhage is uncommon. We report a case of a newborn 23 days old, previously healthy, who presented an episode of choking during breastfeeding. This progressed to acute respiratory failure due to diffuse alveolar hemorrhage. A few hours after admission, the newborn developed refractory hypoxemia, requiring high-frequency oscillatory ventilation and nitric oxide therapy for 24 hours. NPPE was postulated as a diagnosis of exclusion. The newborn recovered completely. NPPE should always be considered in a case with recent obstruction of the upper airway, even in unusual age groups. Sometimes it can manifest as alveolar hemorrhage.