bluuebunny/crossref_metadata_2025 huggingface dataset:
Micropropagation and HPLC-DAD, UPLC MS/MS analysis of oenothein B and phenolic acids in shoot cultures and in regenerated plants of fireweed (Chamerion angustifolium (L.) Holub)
Authors: Dreger Mariola , Gryszczyńska Agnieszka , Szalata Milena , Wielgus Karolina
Published: October 2020

In this study, a micropropagation protocol using nodal explants from in vitro grown plants of Chamerion angustifolium (L.) Holub was developed and analysis of oenothein B and selected phenolic acids in shoot cultures was performed for the first time. For shoot induction and multiplication Murashige and Skoog’s (MS) basal medium supplemented with 2-isopentenyladenine (2iP), zeatin (Z) and 6-benzyloaminopurine (BAP) was used. 2iP was the most responsive in terms of promoting shoots per explant with the maximum (6.57 ± 1.14) recorded at a concentration of 2.0 mg L−1 after 6 weeks of culture. After two subcultures the multiplication rate was increased up to 19 shoots per explant on medium with 2iP (1.0 mg L−1). To prevent tissue browning, ascorbic acid and casein hydrolysate were added to the induction medium, resulting in a reduction of browning by 30%. The rooted plantlets were successfully transferred to soil and acclimatized with 97% frequency. Quantitative and qualitative assessments of oenothein B and phenolic acid contents in in vitro regenerated shoots as well as in ex vitro plants were performed using high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC MS/MS) methods. Oenothein B (1.62‒4.55 g 100 g−1 DW), ellagic acid, gallic and caffeic acids were identified in in vitro regenerated plants. The results of this study confirm that the oenothein B-producing plantlets can be obtained using the micropropagation method with axillary shoots being a valuable source of oenothein B and phenolic acids.
Prehistoric exploitation of minerals resources. Experimentation and use-wear analysis of grooved stone tools from Grotta della Monaca (Calabria, Italy)
Authors: Caricola Isabella , Breglia Francesco , Larocca Felice , Hamon Caroline , Lemorini Cristina , Giligny François
Published: October 2020

The Calabria region of Southern Italy is rich in mineralisation. Unfortunately, no consistent data are available about mineral exploitation in the later prehistoric periods. The Grotta della Monaca mine in Calabria is a prehistoric site that is characterised by the mineralisation of iron ores (such as goethite) and copper carbonates (malachite and azurite). For this reason, the site provides an exceptional opportunity to study a prehistoric mine in which several minerals were exploited during the late Neolithic and early Chalcolithic. In this study, we present the results of an experimental protocol and use-wear analysis conducted using macro-lithic tool replicas to extract mineral resources. The experimental test aimed at reconstructing the function of grooved stone tools found at Grotta della Monaca. Use-wear observation, through a combined low- and high-power approach on experimental and archaeological objects, allowed us to define different extraction techniques and methods of mineral treatments. These data enhance our understanding and reconstruction of the chaîne opératoires, economic choices, and cultural aspects that characterised prehistoric miners in Southern Italy.
Development of a Situational Awareness Estimation Model Considering Traffic Environment for Unscheduled Takeover Situations
Authors: Hayashi Hiroaki , Oka Naoki , Kamezaki Mitsuhiro , Sugano Shigeki
Published: October 2020

In semi-autonomous vehicles (SAE level 3) that requires drivers to takeover (TO) the control in critical situations, a system needs to judge if the driver have enough situational awareness (SA) for manual driving. We previously developed a SA estimation system that only used driver’s glance data. For deeper understanding of driver’s SA, the system needs to evaluate the relevancy between driver’s glance and surrounding vehicle and obstacles. In this study, we thus developed a new SA estimation model considering driving-relevant objects and investigated the relationship between parameters. We performed TO experiments in a driving simulator to observe driver’s behavior in different position of surrounding vehicles and TO performance such as the smoothness of steering control. We adopted support vector machine to classify obtained dataset into safe and dangerous TO, and the result showed 83% accuracy in leave-one-out cross validation. We found that unscheduled TO led to maneuver error and glance behavior differed from individuals.
Changes in pneumatization of the maxillary air sinuses in Korean adults following biomimetic oral appliance therapy
Authors: Singh G. Dave , Kim Hee Nam
Published: October 2020

Objective

For the treatment of obstructive sleep apnea in adults, mandibular advancement devices (MADs) are often used. Since adults with a prognathic mandibular phenotype are at risk of developing an unfavorable facial profile, midfacial development using biomimetic oral appliance therapy might provide a suitable alternative. However, the effect of this procedure on the maxillary air sinuses is unknown; therefore, changes in sinus pneumatization were investigated in this study.

Methods

After obtaining informed consent, 16 consecutive Korean adults with midfacial hypoplasia had 3D cone‐beam (CB) CT scans taken, and biomimetic upper appliances (DNA appliance®, Vivos Therapeutics, Inc., USA) were constructed.

All subjects were instructed to wear the device 12–16 h/day. Each month, examination for the progress of midfacial development was recorded. Post‐treatment, a follow‐up 3D CBCT scan was undertaken with no device in the patient's mouth. Pre‐ and post‐treatment linear and volumetric measurements were obtained using appropriate software, and compared statistically using t‐tests.

Results

The mean age of the sample was 25.0 yrs ± 8.7. The mean treatment time was 15.5 mths ± 5.2. Post‐treatment, the transpalatal bone width increased from 35.3 mm ± 3.0 to 38.5 mm ± 2.0 (P < 0.001); the maxillary air sinus volume on the left side increased from 18.8 cm3 ± 6.5 to 20.0 cm3 ± 6.0 (P < 0.05), and from 18.5 cm3 ± 5.7 to 19.7 cm3 ± 5.8 (P < 0.05) on the right side.

Conclusions

Biomimetic oral appliance therapy may be able to increase the maxillary air sinus volume in adults. In view of these preliminary findings, further studies on the effect of enhanced pneumatization on paranasal sinus function and sleep parameters are warranted.
The Theology of the Books of Haggai and Zechariah
Authors: Foster Robert
Published: October 2020

Tucked away at the end of the Minor Prophets, the Books of Haggai and Zechariah offer messages of challenge and hope to residents of the small district of Yehud in the Persian Empire in the generations after the return from Babylonian exile. In this volume, Robert Foster focuses on the distinct theological message of each book. The Book of Haggai uses Israel's foundational event - God's salvation of Israel from Egypt - to exhort the people to finish building the Second Temple. The Book of Zechariah argues that the hopes the people had in the prophet Zechariah's days did not come true because the people failed to keep God's long-standing demand for justice, though hope still lies in the future because of God's character. Each chapter in this book closes with a substantive reflection of the ethics of the major sections of the Books of Haggai and Zechariah and their implications for contemporary readers.
Changing ice and changing light: trends in solar heat input to the upper Arctic ocean from 1988 to 2014
Authors: Perovich Donald , Light Bonnie , Dickinson Suzanne
Published: October 2020

The Arctic sea-ice cover has undergone a significant decline in recent decades. The melt season is starting earlier, ice is thinner and seasonal ice dominates. Here we examine the effects of these changes on the solar heat input to the upper ocean in ice-covered Arctic waters from 1985 to 2014. Satellite observations of ice concentration, onset dates of melt and freeze-up and ice age, are combined with ice thicknesses from the PIOMAS model and incident solar irradiance from reanalysis products to calculate the contributions of open ocean and ice to the solar heat input in the upper ocean. Of the total, 86% of the area has positive trends for solar heat input to the ocean through leads due to decreases in ice concentration. Only 62% of the area shows positive trends of solar heat input to the ocean explicitly through the ice. Positive trends are due to thinning ice, while negative trends occur in regions where the ice-free season has lengthened. The annual total solar heat input to the ocean exhibits positive trends in 82% of the area. The spatial pattern of the cumulative annual total solar heat input is similar to the pattern of solar heat input directly to leads.
Empiricism, Constructivism, and Grand Theory in Sociological Approaches to Law: The Case of Transnational Private Regulation
Authors: Kampourakis Ioannis
Published: October 2020

Sociological approaches to law in both Germany and the UK have been characterized by internal divisions and divergent methodologies and aspirations. While, in the UK, empirical socio-legal studies have been a prominent way of studying how law shapes and is shaped by social institutions, in Germany, the “grand theory” of systemtheoretical approaches to law has had a lasting impact. In this Article, I discuss the epistemological contrast between these two sociological approaches to law by focusing on how they address transnational private regulation. Empirical socio-legal studies share an epistemic commitment to an objective and knowable social reality, and they tend to see human actors as the motors of history. Thus they focus on the interrelational dynamics within Global Value Chains (GVCs), searching for “what works” in transnational private regulation. On the contrary, systemstheory oriented sociological jurisprudence views social reality as constructed and fragmented into the epistemes of different social systems. GVCs are understood as selfreferential normative orders, in which the question of agency and human actors is secondary—the emphasis is on communications and anonymous forces of ordering. Attempting to inspect the possibilities for synthesis, I ask how “big” we can and should think in law and society. I thus attempt to outline an approach that starts from the materiality of social structures to investigate processes beyond individual agency and to uncover elements of normative reconstruction of the particular area of social activity.
Euromaidan Abroad: The Social Movement Motivations of Young Ukrainian Immigrants
Authors: Korzh Alla , Kovalchuk Serhiy , Marshall Adj
Published: October 2020

This article examines the motivations of young Ukrainian immigrants to support the Euromaidan from abroad. Existing research has documented social movements within their national boundaries and the participation of young people in them. However, it has rarely examined the expansion of social movements beyond their national boundaries and the engagement of young immigrants in such movements. Drawing on a larger qualitative study, this article presents the findings about what motivated 24 young Ukrainian immigrants residing in the USA to support the Euromaidan movement of 2013–2014 and compares their motivations to those of the protestors in Ukraine. We argue that motivations of young Ukrainian immigrants to support the Euromaidan from abroad manifest themselves in symbolic or psychological causes. Our findings demonstrate that the individual motivations were driven by an ideological commitment to systemic change in Ukraine, manifested through young Ukrainian immigrants’ (1) desire to end injustice, (2) solidarity with fellow Ukrainians, (3) moral obligation to raise awareness among the US public, and, most prominently, (4) sense of agency to contribute to the long-awaited change in the homeland. Our findings also show that overall, the motivations of young Ukrainian immigrants to join the movement aligned with those of the protestors in Ukraine.
Democracy and Depression: A Cross-National Study of Depressive Symptoms and Nonparticipation
Authors: LANDWEHR CLAUDIA , OJEDA CHRISTOPHER
Published: October 2020

Depression is the most common mental health disorder. It has consequences not only on individuals but also on social and political levels. We argue that depressive symptoms impair political participation by reducing the motivation and physical energy of sufferers. We test our hypotheses by conducting regression analyses of four nationally representative cross-sectional and longitudinal surveys that collectively span many democracies. Our results are threefold. First, we find that the severest depressive symptoms lower the probability of voting by 0.05–0.25 points, an effect that is exceeded only by education and age. Second, we show that depressive symptoms negatively affect political interest and internal efficacy, thereby confirming that they diminish political motivation. Third, we find that depressive symptoms most strongly affect physically demanding acts, thereby confirming that they reduce the physical energy required for participation. We conclude by urging scholars to take depressive symptoms seriously in the study of political behavior.
Long-term insights into marine turtle sightings, strandings and captures around the UK and Ireland (1910–2018)
Authors: Botterell Zara L. R. , Penrose Rod , Witt Matthew J. , Godley Brendan J.
Published: October 2020

With over a century of records, we present a detailed analysis of the spatial and temporal occurrence of marine turtle sightings and strandings in the UK and Ireland between 1910 and 2018. Records of hard-shell turtles, including loggerhead turtles (Caretta caretta, N = 240) and Kemp's ridley turtles (Lepidochelys kempii, N = 61), have significantly increased over time. However, in the most recent years there has been a notable decrease in records. The majority of records of hard-shell turtles were juveniles and occurred in the boreal winter months when the waters are coolest in the North-east Atlantic. They generally occurred on the western aspects of the UK and Ireland highlighting a pattern of decreasing records with increasing latitude, supporting previous suggestions that juvenile turtles arrive in these waters via the North Atlantic current systems. Similarly, the majority of the strandings and sightings of leatherback turtles (Dermochelys coriacea, N = 1683) occurred on the western aspects of the UK and the entirety of Ireland's coastline. In contrast to hard-shell turtles, leatherback turtles were most commonly recorded in the boreal summer months with the majority of strandings being adult sized, of which there has been a recent decrease in annual records. The cause of the recent annual decreases in turtle strandings and sightings across all three species is unclear; however, changes to overall population abundance, prey availability, anthropogenic threats and variable reporting effort could all contribute. Our results provide a valuable reference point to assess species range modification due to climate change, identify possible evidence of anthropogenic threats and to assess the future trajectory of marine turtle populations in the North Atlantic.
p67: a cryptic lysosomal hydrolase in Trypanosoma brucei?
Authors: Koeller Carolina M. , Smith Terry K. , Gulick Andrew M. , Bangs James D.
Published: October 2020

p67 is a type I transmembrane glycoprotein of the terminal lysosome of African trypanosomes. Its biosynthesis involves transport of an initial gp100 ER precursor to the lysosome, followed by cleavage to N-terminal (gp32) and C-terminal (gp42) subunits that remain non-covalently associated. p67 knockdown is lethal, but the only overt phenotype is an enlarged lysosome (~250 to >1000 nm). Orthologues have been characterized in Dictyostelium and mammals. These have processing pathways similar to p67, and are thought to have phospholipase B-like (PLBL) activity. The mouse PLBD2 crystal structure revealed that the PLBLs represent a subgroup of the larger N-terminal nucleophile (NTN) superfamily, all of which are hydrolases. NTNs activate by internal autocleavage mediated by a nucleophilic residue, i.e. Cys, Ser or Thr, on the upstream peptide bond to form N-terminal α (gp32) and C-terminal β (gp42) subunits that remain non-covalently associated. The N-terminal residue of the β subunit is then catalytic in subsequent hydrolysis reactions. All PLBLs have a conserved Cys/Ser dipeptide at the α/β junction (Cys241/Ser242 in p67), mutation of which renders p67 non-functional in RNAi rescue assays. p67 orthologues are found in many clades of parasitic protozoa, thus p67 is the founding member of a group of hydrolases that likely play a role broadly in the pathogenesis of parasitic infections.
A non-increasing tree growth process for recursive trees and applications
Authors: Eslava Laura
Published: October 2020

We introduce a non-increasing tree growth process
$((T_n,{\sigma}_n),\, n\ge 1)$
, where Tn is a rooted labelled tree on n vertices and σn is a permutation of the vertex labels. The construction of (Tn, σn) from (Tn−1, σn−1) involves rewiring a random (possibly empty) subset of edges in Tn−1 towards the newly added vertex; as a consequence Tn−1 ⊄ Tn with positive probability. The key feature of the process is that the shape of Tn has the same law as that of a random recursive tree, while the degree distribution of any given vertex is not monotone in the process.

We present two applications. First, while couplings between Kingman’s coalescent and random recursive trees were known for any fixed n, this new process provides a non-standard coupling of all finite Kingman’s coalescents. Second, we use the new process and the Chen–Stein method to extend the well-understood properties of degree distribution of random recursive trees to extremal-range cases. Namely, we obtain convergence rates on the number of vertices with degree at least
$c\ln n$
, c ∈ (1, 2), in trees with n vertices. Further avenues of research are discussed.
Mixing properties of colourings of the ℤd lattice
Authors: Alon Noga , Briceño Raimundo , Chandgotia Nishant , Magazinov Alexander , Spinka Yinon
Published: October 2020

We study and classify proper q-colourings of the ℤd lattice, identifying three regimes where different combinatorial behaviour holds. (1) When
$q\le d+1$
, there exist frozen colourings, that is, proper q-colourings of ℤd which cannot be modified on any finite subset. (2) We prove a strong list-colouring property which implies that, when
$q\ge d+2$
, any proper q-colouring of the boundary of a box of side length
$n \ge d+2$
can be extended to a proper q-colouring of the entire box. (3) When
$q\geq 2d+1$
, the latter holds for any
$n \ge 1$
. Consequently, we classify the space of proper q-colourings of the ℤd lattice by their mixing properties.
Perforated posterior mitral leaflet aneurysm in an 8-month-old infant
Authors: Nagaoka Kota , Ibuki Keijiro , Miyahara Yoshinori
Published: October 2020

Mitral valve aneurysm not associated with infective endocarditis is rarely reported in children. We report a case of perforated posterior mitral leaflet aneurysm in an infant with reference to surgical and histopathological findings. Although its aetiology remains unclear, we suggest to include mitral valve aneurysm in differential diagnosis as a cause of mitral regurgitation in children.
ON PRICE DYNAMICS WITH SEARCH AND BARGAINING IN THE PRODUCT MARKET
Authors: Abbritti Mirko , Trani Tommaso
Published: October 2020

We introduce business-to-business (B2B) relationships into an otherwise standard model to revisit two aspects of price dynamics in a unified analysis. On one side, the pass-through of cost shocks to prices is empirically incomplete. On the other side, the literature contains conjectures that long-term relationships may reduce the allocative role of price changes. After a partial equilibrium analysis of these aspects, we consider the general equilibrium effects. The formation of B2B relationships implies that the trade of intermediate goods depends on search, bargaining, and the adjustment along the intensive margin as opposed to the extensive margin. We find that, when this adjustment is costly, retailers have a relatively high bargaining power, and mismatch shocks are possible, the model can account for the second moments of the US producer price index and other variables. In this case, although its allocative role is low, the intermediate goods price affects the allocation of goods through the search externalities and is sufficiently volatile. The analysis includes several sensitivity tests and comparisons.
A preliminary study of group therapy intervention for bipolar disorder based on the integrative cognitive model
Authors: Maçkalı Zeynep , Güneri Gülin , Korkmaz Arın , Çakır Sibel
Published: October 2020

The main aim of this research was to investigate the effect of the 8-week group therapy intervention based on the integrative cognitive model (ICM) of bipolar disorder. The sample was composed of 10 patients with bipolar I and bipolar II diagnoses. The group sessions were held once a week for 1.5 hours. For the quantitative measures, the group participants were assessed during pre-test, post-test and 3-month follow-up using the Turkish versions of the Beck Depression Inventory, the Hypomanic Attitudes and Positive Predictions Inventory, the Psychological Well-being Scale and the Satisfaction with Life Scale. Quantitative analyses revealed that a reliable change was seen only in pre-test and post-test depression scores. However, this change could not be maintained at 3-month follow-up. For the qualitative analyses, data collected during semi-structured interviews were used. The thematic analyses results showed that the 8-week ICM-based group therapy was found to help participants make sound observations about their behaviors, decrease their feelings of loneliness and increase self-acceptance, and acceptance of the role of mood swings in their lives. Moreover, the results showed that participants found the following activities very beneficial: describing their emotions, evaluating the intensity of their emotions, identifying their life goals, coping with interpersonal conflicts, evaluating resources and going over strengths. In conclusion, the 8-week ICM-based group therapy had a positive impact on participants’ self-awareness, self-acceptance and self-perception.

Key learning aims

(1)

To learn more about the integrative cognitive model and how it has been reconceptualized for group-based intervention.

(2)

To understand the structure and content of group CBT protocol for bipolar disorders based on the integrative cognitive model.

(3)

To consider possible advantages of group CBT for bipolar disorders during the recovery process.
Comment on “High‐Resolution, Multilayer Modeling of Singapore's Urban Climate Incorporating Local Climate Zones” by Mughal et al. (2019)
Authors: Velasco Erik
Published: October 2020

Weather forecasting models coupled with canopy layer schemes are frequently used to assess the urban heat island (UHI) phenomenon through sensitivity analysis. These models are valuable tools if they are properly tested against field observations. Mughal et al. (2019) (https://doi.org/10.1029/2018JD029796) followed this approach to investigate Singapore's UHI effect within the urban canopy layer. But a lack of field observations for evaluating the model's performance led to simplistic assumptions and wrong interpretations. The major flaws triggered by both circumstances are exposed with the aim that future research does not repeat the same mistakes and can provide the scientific basis to formulate effective mitigation measures.
Effect of Sediment Supply on Cyclic Fluctuations of the Disequilibrium Ratio and Threshold Transport Discharge, Inferred From Bedload Transport Measurements Over 27 Years at the Swiss Erlenbach Stream
Authors: Rickenmann Dieter
Published: October 2020

Bedload transport in natural channels typically shows large fluctuations even for constant hydraulic forcing. It has been shown that the threshold shear stress for initiation of motion depends, for example, on the bed morphology and on channel slope and that it may be influenced by flood history effects. This study is based on a unique data set of continuous field observations of bedload transport acquired during 27 years with impact plate measurements and involving more than 500 sediment‐transporting flood events. A disequilibrium ratio is defined which represents the observed bedload mass per event divided by the bedload mass calculated via a bedload transport equation integrated over the time of a flood event. The disequilibrium ratio varies in a cyclic behavior around equilibrium conditions defined by its median value. The mean duration of a cycle depends on upstream sediment supply or availability on the bed, and longer cycles are associated with a larger active layer on the bed. A memory effect is evident regarding the temporal evolution of both disequilibrium ratio and bed state as reflected by threshold transport conditions, determined from the observations as the critical discharge at the start and at the end of a bedload‐transporting event. The disequilibrium ratio and the threshold transport discharge are inversely correlated with each other, likely providing a feedback mechanism governing the fluctuations around an equilibrium state. Accounting for the memory effect, that is, for the bed state after the previous event, improves the prediction of bedload transport for the following event.
Genetic association of FMRP targets with psychiatric disorders
Authors: Clifton Nicholas E. , Rees Elliott , Holmans Peter A. , Pardiñas Antonio F. , Harwood Janet C. , Di Florio Arianna , Kirov George , Walters James T. R. , O’Donovan Michael C. , Owen Michael J. , Hall Jeremy , Pocklington Andrew J.
Published: October 2020

Genes encoding the mRNA targets of fragile X mental retardation protein (FMRP) are enriched for genetic association with psychiatric disorders. However, many FMRP targets possess functions that are themselves genetically associated with psychiatric disorders, including synaptic transmission and plasticity, making it unclear whether the genetic risk is truly related to binding by FMRP or is alternatively mediated by the sampling of genes better characterised by another trait or functional annotation. Using published common variant, rare coding variant and copy number variant data, we examined the relationship between FMRP binding and genetic association with schizophrenia, major depressive disorder and bipolar disorder. High-confidence targets of FMRP, derived from studies of multiple tissue types, were enriched for common schizophrenia risk alleles, as well as rare loss-of-function and de novo nonsynonymous variants in schizophrenia cases. Similarly, through common variation, FMRP targets were associated with major depressive disorder, and we present novel evidence of association with bipolar disorder. These relationships could not be explained by other functional annotations known to be associated with psychiatric disorders, including those related to synaptic structure and function. This study reinforces the evidence that targeting by FMRP captures a subpopulation of genes enriched for genetic association with a range of psychiatric disorders.
APC loss induces Warburg effect via increased PKM2 transcription in colorectal cancer
Authors: Cha Pu-Hyeon , Hwang Jeong-Ha , Kwak Dong-Kyu , Koh Eunjin , Kim Kyung-Sup , Choi Kang-Yell
Published: October 2020

Background

Most cancer cells employ the Warburg effect to support anabolic growth and tumorigenesis. Here, we discovered a key link between Warburg effect and aberrantly activated Wnt/β-catenin signalling, especially by pathologically significant APC loss, in CRC.

Methods

Proteomic analyses were performed to evaluate the global effects of KYA1797K, Wnt/β-catenin signalling inhibitor, on cellular proteins in CRC. The effects of APC-loss or Wnt ligand on the identified enzymes, PKM2 and LDHA, as well as Warburg effects were investigated. A linkage between activation of Wnt/β-catenin signalling and cancer metabolism was analysed in tumour of Apcmin/+ mice and CRC patients. The roles of PKM2 in cancer metabolism, which depends on Wnt/β-catenin signalling, were assessed in xenograft-tumours.

Results

By proteomic analysis, PKM2 and LDHA were identified as key molecules regulated by Wnt/β-catenin signalling. APC-loss caused the increased expression of metabolic genes including PKM2 and LDHA, and increased glucose consumption and lactate secretion. Pathological significance of this linkage was indicated by increased expression of glycolytic genes with Wnt target genes in tumour of Apcmin/+ mice and CRC patients. Warburg effect and growth of xenografted tumours-induced by APC-mutated-CRC cells were suppressed by PKM2-depletion.

Conclusions

The β-catenin-PKM2 regulatory axis induced by APC loss activates the Warburg effect in CRC.
The SUMO pathway in pancreatic cancer: insights and inhibition
Authors: Schneeweis Christian , Hassan Zonera , Schick Markus , Keller Ulrich , Schneider Günter
Published: October 2020

An urgent medical need to develop novel treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) exists. However, despite various efforts in the histopathological and molecular subtyping of PDAC, novel targeted or specific therapies have not been established. Posttranslational modifications (PTMs) with ubiquitin-like proteins, including small ubiquitin-like modifiers (SUMOs), mediate numerous processes that can contribute to the fitness and survival of cancer cells. The contribution of SUMOylation to transcriptional control, DNA repair pathways, mitotic progression, and oncogenic signalling has been described. Here we review functions of the SUMO pathway in PDAC, with a special focus on its connection to an aggressive subtype of the disease characterised by high MYC activity, and discuss SUMOylation inhibitors under development for precise PDAC therapies.
Implications of metabolism-driven myeloid dysfunctions in cancer therapy
Authors: Strauss Laura , Guarneri Valentina , Gennari Alessandra , Sica Antonio
Published: October 2020

Immune homeostasis is maintained by an adequate balance of myeloid and lymphoid responses. In chronic inflammatory states, including cancer, this balance is lost due to dramatic expansion of myeloid progenitors that fail to mature to functional inflammatory neutrophils, macrophages, and dendritic cells (DCs), thus giving rise to a decline in the antitumor effector lymphoid response. Cancer-related inflammation orchestrates the production of hematopoietic growth factors and cytokines that perpetuate recruitment and activation of myeloid precursors, resulting in unresolved and chronic inflammation. This pathologic inflammation creates profound alterations in the intrinsic cellular metabolism of the myeloid progenitor pool, which is amplified by competition for essential nutrients and by hypoxia-induced metabolic rewiring at the tumor site. Therefore, persistent myelopoiesis and metabolic dysfunctions contribute to the development of cancer, as well as to the severity of a broad range of diseases, including metabolic syndrome and autoimmune and infectious diseases. The aims of this review are to (1) define the metabolic networks implicated in aberrant myelopoiesis observed in cancer patients, (2) discuss the mechanisms underlying these clinical manifestations and the impact of metabolic perturbations on clinical outcomes, and (3) explore new biomarkers and therapeutic strategies to restore immunometabolism and differentiation of myeloid cells towards an effector phenotype to increase host antitumor immunity. We propose that the profound metabolic alterations and associated transcriptional changes triggered by chronic and overactivated immune responses in myeloid cells represent critical factors influencing the balance between therapeutic efficacy and immune-related adverse effects (irAEs) for current therapeutic strategies, including immune checkpoint inhibitor (ICI) therapy.
Chromosome-level genome assembly of a parent species of widely cultivated azaleas
Authors: Yang Fu-Sheng , Nie Shuai , Liu Hui , Shi Tian-Le , Tian Xue-Chan , Zhou Shan-Shan , Bao Yu-Tao , Jia Kai-Hua , Guo Jing-Fang , Zhao Wei , An Na , Zhang Ren-Gang , Yun Quan-Zheng , Wang Xin-Zhu , Mannapperuma Chanaka , Porth Ilga , El-Kassaby Yousry Aly , Street Nathaniel Robert , Wang Xiao-Ru , Van de Peer Yves , Mao Jian-Feng
Published: October 2020

Azaleas (Ericaceae) comprise one of the most diverse ornamental plants, renowned for their cultural and economic importance. We present a chromosome-scale genome assembly for Rhododendron simsii, the primary ancestor of azalea cultivars. Genome analyses unveil the remnants of an ancient whole-genome duplication preceding the radiation of most Ericaceae, likely contributing to the genomic architecture of flowering time. Small-scale gene duplications contribute to the expansion of gene families involved in azalea pigment biosynthesis. We reconstruct entire metabolic pathways for anthocyanins and carotenoids and their potential regulatory networks by detailed analysis of time-ordered gene co-expression networks. MYB, bHLH, and WD40 transcription factors may collectively regulate anthocyanin accumulation in R. simsii, particularly at the initial stages of flower coloration, and with WRKY transcription factors controlling progressive flower coloring at later stages. This work provides a cornerstone for understanding the underlying genetics governing flower timing and coloration and could accelerate selective breeding in azalea.
Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
Authors: Wessel Alex W. , Kose Nurgun , Bombardi Robin G. , Roy Vicky , Chantima Warangkana , Mongkolsapaya Juthathip , Edeling Melissa A. , Nelson Christopher A. , Bosch Irene , Alter Galit , Screaton Gavin R. , Fremont David H. , Crowe James E. , Diamond Michael S.
Published: October 2020

There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.
Author Correction: Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology
Authors: Elouej Sahar , Harhouri Karim , Mao Morgane Le , Baujat Genevieve , Nampoothiri Sheela , Kayserili Hϋlya , Menabawy Nihal Al , Selim Laila , Paneque Arianne Llamos , Kubisch Christian , Lessel Davor , Rubinsztajn Robert , Charar Chayki , Bartoli Catherine , Airault Coraline , Deleuze Jean-François , Rötig Agnes , Bauer Peter , Pereira Catarina , Loh Abigail , Escande-Beillard Nathalie , Muchir Antoine , Martino Lisa , Gruenbaum Yosef , Lee Song-Hua , Manivet Philippe , Lenaers Guy , Reversade Bruno , Lévy Nicolas , De Sandre-Giovannoli Annachiara
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Fabrication of high-performance dual carbon Li-ion hybrid capacitor: mass balancing approach to improve the energy-power density and cycle life
Authors: Panja Tandra , Ajuria Jon , Díez Noel , Bhattacharjya Dhrubajyoti , Goikolea Eider , Carriazo Daniel
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Environmental influences on foraging effort, success and efficiency in female Australian fur seals
Authors: Speakman Cassie N. , Hoskins Andrew J. , Hindell Mark A. , Costa Daniel P. , Hartog Jason R. , Hobday Alistair J. , Arnould John P. Y.
Published: October 2020

Understanding the factors which influence foraging behaviour and success in marine mammals is crucial to predicting how their populations may respond to environmental change. The Australian fur seal (Arctocephalus pusillus doriferus, AUFS) is a predominantly benthic forager on the shallow continental shelf of Bass Strait, and represents the greatest biomass of marine predators in south-eastern Australia. The south-east Australian region is experiencing rapid oceanic warming, predicted to lead to substantial alterations in prey diversity, distribution and abundance. In the present study, foraging effort and indices of foraging success and efficiency were investigated in 138 adult female AUFS (970 foraging trips) during the winters of 1998–2019. Large scale climate conditions had a strong influence on foraging effort, foraging success and efficiency. Foraging effort and foraging success were also strongly influenced by winter chlorophyll-a concentrations and sea-surface height anomalies in Bass Strait. The results suggest increasing foraging effort and decreasing foraging success and efficiency under anticipated environmental conditions, which may have population-level impacts.
Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia
Authors: Bailey G. D. , Doolan L. , Baskar A. , Smith L. C. , Seedhouse C. H.
Published: October 2020

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1–10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance.
Force-of-infection of Taenia solium porcine cysticercosis: a modelling analysis to assess global incidence and prevalence trends
Authors: Dixon Matthew A. , Winskill Peter , Harrison Wendy E. , Whittaker Charles , Schmidt Veronika , Sarti Elsa , Bawm Saw , Dione Michel M. , Thomas Lian F. , Walker Martin , Basáñez Maria-Gloria
Published: October 2020

The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.
In situ breast cancer incidence patterns in Iceland and differences in ductal carcinoma in situ treatment compared to Sweden
Authors: Agustsson Arnar S. , Birgisson Helgi , Agnarsson Bjarni A. , Jonsson Thorvaldur , Stefansdottir Hrefna , Wärnberg Fredrik , Lambe Mats , Tryggvadottir Laufey , Sverrisdottir Asgerdur
Published: October 2020

The purpose was to review the incidence of in situ carcinoma in Iceland after initiating population-based mammography screening in 1987 and to compare management of ductal carcinoma in situ (DCIS) between Iceland and the Uppsala–Örebro region (UÖR) in Central Sweden. The Icelandic Cancer Registry provided data on in situ breast carcinomas for women between 1957 and 2017. Clinical data for women with DCIS between 2008 and 2014 was extracted from hospital records and compared to women diagnosed in UÖR. In Iceland, in situ carcinoma incidence increased from 7 to 30 per 100 000 women per year, following the introduction of organised mammography screening. The proportion of in situ carcinoma of all breast carcinomas increased from 4 to 12%. More than one third (35%) of women diagnosed with DCIS in Iceland were older than 70 years versus 18% in UÖR. In Iceland, 49% of all DCIS women underwent mastectomy compared to 40% in UÖR. The incidence of in situ carcinoma in Iceland increased four-fold after the uptake of population-based mammography screening causing considerable risk of overtreatment. Differences in treatment of DCIS were seen between Iceland and UÖR, revealing the importance of quality registration for monitoring patterns of management.
Cytoskeletal disorganization underlies PABPN1-mediated myogenic disability
Authors: Olie Cyriel Sebastiaan , van der Wal Erik , Cikes Domagoj , Maton Loes , de Greef Jessica C. , Lin I.-Hsuan , Chen Yi-Fan , Kareem Elsayad , Penninger Josef M. , Kessler Benedikt M. , Raz Vered
Published: October 2020

Muscle wasting and atrophy are regulated by multiple molecular processes, including mRNA processing. Reduced levels of the polyadenylation binding protein nucleus 1 (PABPN1), a multifactorial regulator of mRNA processing, cause muscle atrophy. A proteomic study in muscles with reduced PABPN1 levels suggested dysregulation of sarcomeric and cytoskeletal proteins. Here we investigated the hypothesis that reduced PABPN1 levels lead to an aberrant organization of the cytoskeleton. MURC, a plasma membrane-associated protein, was found to be more abundant in muscles with reduced PABPN1 levels, and it was found to be expressed at regions showing regeneration. A polarized cytoskeletal organization is typical for muscle cells, but muscle cells with reduced PABPN1 levels (named as shPAB) were characterized by a disorganized cytoskeleton that lacked polarization. Moreover, cell mechanical features and myogenic differentiation were significantly reduced in shPAB cells. Importantly, restoring cytoskeletal stability, by actin overexpression, was beneficial for myogenesis, expression of sarcomeric proteins and proper localization of MURC in shPAB cell cultures and in shPAB muscle bundle. We suggest that poor cytoskeletal mechanical features are caused by altered expression levels of cytoskeletal proteins and contribute to muscle wasting and atrophy.
Pain management of unicompartmental (UKA) vs. total knee arthroplasty (TKA) based on a matched pair analysis of 4144 cases
Authors: Leiss Franziska , Götz Julia Sabrina , Maderbacher Günther , Zeman Florian , Meissner Winfried , Grifka Joachim , Benditz Achim , Greimel Felix
Published: October 2020

Unicompartmental knee arthroplasty and total knee arthroplasty are well established treatment options for end-stage osteoarthritis, UKA still remains infrequently used if you take all knee arthroplasties into account. An important factor following knee arthroplasty is pain control in the perioperative experience, as high postoperative pain level is associated with persistent postsurgical pain. There is little literature which describes pain values and the need for pain medication following UKA and/or TKA. So far, no significant difference in pain has been found between UKA and TKA. The aim of the study was to evaluate differences in the postoperative course in unicompartmental knee arthroplasty vs. total knee arthroplasty regarding the need for pain medication and patient-reported outcomes including pain scores and side effects. We hypothesized that unicompartmental knee arthroplasty is superior to total knee arthroplasty in terms of postoperative pain values and the need of pain medication. In this project, we evaluated 2117 patients who had unicompartmental knee arthroplasty and 3798 who had total knee arthroplasty performed, from 2015 to 2018. A total of 4144 patients could be compared after performing the matched pair analysis. A professional team was used for data collection and short patient interviews to achieve high data quality on the first postoperative day. Parameters were compared after performing a 1:1 matched pair analysis, multicenter-wide in 14 orthopedic departments. Pain scores were significantly lower for the UKA group than those of the TKA group (p < 0.001 respectively for activity pain, minimum and maximum pain). In the recovery unit, there was less need for pain medication in patients with UKA (p = 0.004 for non-opioids). The opiate consumption was similarly lower for the UKA group, but not statistically significant (p = 0.15). In the ward, the UKA group needed less opioids (p < 0.001). Patient subjective parameters were significantly better for UKA. After implantation of unicompartmental knee arthroplasty, patients showed lower pain scores, a reduced need for pain medication and better patient subjective parameters in the early postoperative course in this study.
A study on the effects of tumor-derived exosomes on hepatoma cells and hepatocytes by atomic force microscopy
Authors: Ju Tuoyu , Wang Shuwei , Wang Jiajia , Yang Fan , Song Zhengxun , Xu Hongmei , Chen Yujuan , Zhang Jingran , Wang Zuobin
Published: October 2020

The effect of HCC-LM3-exos on the mechanical properties of heptoma cells (HCC-LM3, SMCC-7721) and heptocytes (HL-7702) were detected by atomic force microscopy.
Evolution of strept(avidin)-based artificial metalloenzymes in organometallic catalysis
Authors: Mukherjee Prasun , Maiti Debabrata
Published: October 2020

Construction of strept(avidin)-based artificial metalloenzymes and enhancement of their catalytic activity towards a wide range of synthetic transformationsviachemical and genetic optimizations.
Polar CsPbBr3-based Dion–Jacobson hybrid for promising UV photodetection
Authors: Fu Dongying , Wu Shichao , Xin Jianli , Zhang Xinyuan , Han Gaoyi , Zhang Xian-Ming
Published: October 2020

A CsPbBr3-based polar single crystal of 2D bilayered Dion–Jacobson type hybrid perovskites has been for the first time discovered for promising UV photodetection.
Ultra-stable Pickering emulsion stabilized by a natural particle bilayer
Authors: Tao Shengnan , Jiang Hang , Wang Rongjie , Yang Cheng , Li Yunxing , Ngai To
Published: October 2020

An all-natural Pickering emulsion with a Janus interface of particle bilayer is prepared, which has unprecedented stability.
Detection of an alcohol-associated cancer marker by single-molecule quantum sequencing
Authors: Komoto Yuki , Ohshiro Takahito , Taniguchi Masateru
Published: October 2020

N2-Ethyl-2′-deoxyguanosine, a promising biomarker of ethanol-derived cancers, was detected using a single-molecule quantum sequencer and discriminated from deoxyguanosine.