bluuebunny/crossref_metadata_2025 huggingface dataset:
Singular cases of Alzheimer’s disease disclose new and old genetic “acquaintances”
Authors: Coppola Cinzia , Saracino Dario , Oliva Mariano , Cipriano Lorenzo , Puoti Gianfranco , Pappatà Sabina , Di Fede Giuseppe , Catania Marcella , Ricci Martina , Cimini Sara , Giaccone Giorgio , Bonavita Simona , Rossi Giacomina
Published: October 2020

Background

Alzheimer’s disease (AD) is the most common age-related dementia. Besides its typical presentation with amnestic syndrome at onset, atypical AD cases are being increasingly recognized, often in presenile age.

Objectives

To provide an extensive clinical and genetic characterization of six AD patients carrying one or more singular features, including age of onset, atypical phenotype and disease progression rate. By reviewing the pertinent literature and accessing publicly available databases, we aimed to assess the frequency and the significance of the identified genetic variants.

Methods

Biomarkers of amyloid-β deposition and neurodegeneration were used to establish the in vivo diagnosis of probable AD, in addition to neurological and neuropsychological evaluation, extensive laboratory assays and neuroradiological data. Considering the presenile onset of the majority of the cases, we hypothesized genetically determined AD and performed extensive genetic analyses by both Sanger sequencing and next generation sequencing (NGS).

Results

We disclosed two known missense variants, one in PSEN1 and the other in PSEN2, and a novel silent variant in PSEN2. Most notably, we identified several additional variants in other dementia-related genes by NGS. Some of them have never been reported in any control or disease databases, representing variants unique to our cases.

Conclusions

This work underlines the difficulties in reaching a confident in vivo diagnosis in cases of atypical dementia. Moreover, a wider genetic analysis by NGS approach may prove to be useful in specific cases, especially when the study of the so-far known AD causative genes produces negative or conflicting results.
Managing collaborative research: insights from a multi-consortium programme on climate adaptation across Africa and South Asia
Authors: Currie-Alder Bruce , Cundill Georgina , Scodanibbio Lucia , Vincent Katharine , Prakash Anjal , Nathe Nathalie
Published: October 2020

Collaborative research requires synergy among diverse partners, overall direction, and flexibility at multiple levels. There is a need to learn from practical experience in fostering cooperation towards research outcomes, coordinating geographically dispersed teams, and bridging distinct incentives and ways of working. This article reflects on the experience of the Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA), a multi-consortium programme which sought to build resilience to regional climate change. Participants valued the consortium as a network that provided connections with distinct sources of expertise, as a means to gain experience and skills beyond the remit of their home organisation. Consortia were seen as an avenue for reaching scale both in terms of working across regions, as well as in terms of moving research into practice. CARIAA began with programme-level guidance on climate hotspots and collaboration, alongside consortium-level visions on research agenda and design. Consortia created and implemented work plans defining each organisation’s role and responsibilities and coordinated activities across numerous partners, dispersed locations, and diverse cultural settings. Nested committees provided coherence and autonomy at the programme, consortium, and activity-level. Each level had some discretion in how to deploy funding, creating multiple collaborative spaces that served to further interconnect participants. The experience of CARIAA affirms documented strategies for collaborative research, including project vision, partner compatibility, skilled managers, and multi-level planning. Collaborative research also needs an ability to revise membership and structures as needed in response to changing involvement of partners over time.
A coarsening algorithm on adaptive red-green-blue refined meshes
Authors: Funken Stefan A. , Schmidt Anja
Published: October 2020

Adaptive meshing is a fundamental component of adaptive finite element methods. This includes refining and coarsening meshes locally. In this work, we are concerned with the red-green-blue refinement strategy in two dimensions and its counterpart-coarsening. In general, coarsening algorithms are mostly based on an explicitly given refinement history. In this work, we present a coarsening algorithm on adaptive red-green-blue meshes in two dimensions without explicitly knowing the refinement history. To this end, we examine the local structure of these meshes, find an easy-to-verify criterion to adaptively coarsen red-green-blue meshes, and prove that this criterion generates meshes with the desired properties. We present a MATLAB implementation built on the red-green-blue refinement routine of the -package (Funken and Schmidt 2018, 2019).
Wirklich irrelevant?
Authors: Fürst Silke , Vogler Daniel , Sörensen Isabel , Schäfer Mike S. , Eisenegger Mark
Published: October 2020

In jüngster Zeit wird verstärkt über die gesellschaftliche Wahrnehmung und Relevanz der Medien- und Kommunikationswissenschaft (MuK) diskutiert. Viele ForscherInnen kritisieren, dass das Fach sich zu wenig in öffentliche Debatten einmische und in den Nachrichtenmedien kaum sichtbar sei. Den zahlreichen Diagnosen stehen allerdings kaum Studien gegenüber, die die externe Wahrnehmung des Faches empirisch erfassen. Insbesondere mangelt es an Trendanalysen. Daher stellt die vorliegende Studie Resultate einer automatisierten Inhaltsanalyse zur Mediensichtbarkeit und thematischen Einordnung des Faches in Schweizer Printmedien vor. Mit einer Vollerhebung der Berichterstattung sieben überregionaler Zeitungen wird die Visibilität der Medien- und Kommunikationswissenschaft zwischen 1999 und 2018 analysiert und mit derjenigen der Nachbardisziplinen Politikwissenschaft und Soziologie verglichen. Zudem wird die Berichterstattung über das Fach mittels Topic Modeling mit Latent Dirichlet Allocation vertiefend untersucht. Unsere Studie zeigt, dass die öffentliche Sichtbarkeit der Kommunikations- und Medienwissenschaft deutlich hinter jener der Politikwissenschaft und Soziologie zurücksteht. Beide Vergleichsfächer konnten ihre Visibilität kontinuierlich steigern, während jene der MuK auf einem tieferen Niveau weitgehend stagniert. Thematisch wird über die Kommunikations- und Medienwissenschaft insbesondere im Kontext der Entwicklung der Presseauflage, von Studium und Lehre sowie von Medienpolitik, Medienregulierung und Service Public berichtet. Erstaunlicherweise berichteten Journalisten über das Fach eher selten im Kontext der Digitalisierung – und diese Kontextualisierung nimmt über die Zeit auch nicht zu. Die Studie legt nahe, dass Maßnahmen zur Stärkung der gesellschaftlichen Sichtbarkeit und Legitimation des Fachs sinnvoll wären.
Evaluating the Role of Parental Education and Adolescent Health Problems in Educational Attainment
Authors: Mikkonen Janne , Remes Hanna , Moustgaard Heta , Martikainen Pekka
Published: October 2020

This article reconsiders the role of social origin in health selection by examining whether parental education moderates the association between early health and educational attainment and whether health problems mediate the intergenerational transmission of education. We used longitudinal register data on Finns born in 1986–1991 (n = 352,899). We measured the completion of secondary and tertiary education until age 27 and used data on hospital care and medication reimbursements to assess chronic somatic conditions, frequent infections, and mental disorders at ages 10–16. We employed linear probability models to estimate the associations between different types of health problems and educational outcomes and to examine moderation by parental education, both overall in the population and comparing siblings with and without health problems. Finally, we performed a mediation analysis with g-computation to simulate whether a hypothetical eradication of health problems would weaken the association between parental and offspring education. All types of health problems reduced the likelihood of secondary education, but mental disorders were associated with the largest reductions. Among those with secondary education, there was further evidence of selection to tertiary education. High parental education buffered against the negative impact of mental disorders on completing secondary education but exacerbated it in the case of tertiary education. The simulated eradication of health problems slightly reduced disparities by parental education in secondary education (up to 10%) but increased disparities in tertiary education (up to 2%). Adolescent health problems and parental education are strong but chiefly independent predictors of educational attainment.
The Enduring Case for Fertility Desires
Authors: Yeatman Sara , Trinitapoli Jenny , Garver Sarah
Published: October 2020

Persistently high levels of unintended fertility, combined with evidence that over- and underachieved fertility are typical and not exceptional, have prompted researchers to question the utility of fertility desires writ large. In this study, we elaborate this paradox: widespread unintendedness and meaningful, highly predictive fertility desires can and do coexist. Using data from Malawi, we demonstrate the predictive validity of numeric fertility timing desires over both four-month and one-year periods. We find that fertility timing desires are highly predictive of pregnancy and that they follow a gradient wherein the likelihood of pregnancy decreases in correspondence with desired time to next birth. This finding holds despite the simultaneous observation of high levels of unintended pregnancy in our sample. Discordance between desires and behaviors reflects constraints to achieving one’s fertility and the fluidity of desires but not their irrelevance. Fertility desires remain an essential—if sometimes blunt—tool in the demographers’ toolkit.
EU Membership: Formal and Substantive Dimensions
Authors: CRAIG Paul
Published: October 2020

Membership is central to the EU, as it is to any other international organisation. Withdrawal has assumed centre-stage through Brexit. While there is literature that is relevant to membership, most notably through academic discourse on differentiated integration, there is little more general inquiry concerning membership, the concept of which has importance and implications over and beyond more particular avenues of scholarship. This article examines the formal and substantive dimensions of membership and withdrawal in the EU.
Hemispherotomy for Epilepsy: The Procedure Evolution and Outcome
Authors: Alotaibi Faisal , Albaradie Raidah , Almubarak Salah , Baeesa Saleh , Steven David A. , Girvin John P.
Published: October 2020

Hemispherectomy is a unique epilepsy surgery procedure that has undergone significant modification and evolution since Dandy’s early description. This procedure is mainly indicated to treat early childhood and infancy medically intractable epilepsy. Various epileptic syndromes have been treated with this procedure, including hemimegalencephaly (HME), Rasmussen’s encephalitis, Sturge–Weber syndrome (SWS), perinatal stroke, and hemispheric cortical dysplasia. In terms of seizure reduction, hemispherectomy remains one of the most successful epilepsy surgery procedures. The modification of this procedure over many years has resulted in lower mortality and morbidity rates. HME might increase morbidity and lower the success rate. Future studies should identify the predictors of outcomes based on the pathology and the type of hemispherectomy. Here, based on a literature review, we discuss the evolution of hemispherectomy techniques and their outcomes and complications.
ISLAM AND ANTI-COLONIAL REBELLIONS IN NORTH AND WEST AFRICA, 1914–1918
Authors: KRAUSE JONATHAN
Published: October 2020

European empires experienced widespread anti-colonial rebellions during the First World War. These rebellions occurred for many different reasons, reflecting the diversity of context and history across colonial societies in Africa and Asia. Religion naturally played a strong role in most of the anti-colonial rebellions during the First World War, most prominently Islam. This article looks at the role Islam played in two key anti-colonial rebellions in North and West Africa: the rebellions in Batna, Algeria, and the Kaocen War in Niger, respectively. The article examines how Islam was instrumentalized by rebels, imperial collaborators, and French officers and administrators to further their own ends. Rebels called upon Islam to help inspire anti-colonial movements, to bind together diverse populations, and to contextualize their actions in wider socio-political conflicts. Imperial collaborators likewise called on religious authority to assist with European imperial recruitment efforts. French officers and administrators used Islam both as a justification and a target for collective punishment and repression after the rebellions were put down from 1917. This repression is still under-studied in a period usually portrayed as evidencing broad imperial harmony, rather than violent extraction and oppression.
Implementation of fictitious absorbing layers with deceleration effects for one-dimensional Schrödinger equations
Authors: Kanai Hitoshi , Tatsuno Tomo
Published: October 2020

Absorbing boundary conditions or layers are used in simulations to reduce or eliminate wave reflections from the boundary; one of the most widely used absorbing layers is Berenger's perfectly matched layer (PML). In this paper, PML is extended to a compound absorbing layer which has multiple effects of damping and deceleration, and is applied to linear and nonlinear Schrödinger equations. The deceleration extends the time to damp out the modes with higher phase velocities, leading to remarkably reduced total reflection for dispersive waves. By invoking the two effects independently, the flexibility and performance are enhanced. Since this method is based on the WKB formalism, it requires an absorbing layer of a moderate size.
Arg-substituted VmCT1 analogs reveals promising candidate for the development of new antichagasic agent
Authors: Pedron Cibele Nicolaski , Freire Katielle Albuquerque , Torres Marcelo Der Torossian , Lima Dânya Bandeira , Monteiro Marília Lopes , Menezes Ramon Róseo Paula Pessoa Bezerra de , Martins Alice Maria Costa , Oliveira Vani Xavier
Published: October 2020

VmCT1 is an antimicrobial peptide (AMP) isolated from the venom of the scorpion Vaejovis mexicanus with antimicrobial, anticancer and antimalarial activities, which the rational design with Arg-substitution has yielded AMPs with higher antimicrobial activity than VmCT1. Chagas is a neglected tropical disease, becoming the development of new antichagasic agents is urgent. Thus, we aimed to evaluate the antichagasic effect of VmCT1 and three Arg-substituted analogues, as well their action mechanism. Peptides were tested against the epimastigote, trypomastigote, amastigote forms of Trypanossoma cruzi Y strain and against LLC-MK2 mammalian cells. The mechanism of action of these peptides was evaluated by means of flow cytometry and scanning electron microscopy. VmCT1 presented activity against all three forms of T. cruzi, with EC50 against trypomastigote forms of 1.37 μmol L−1 and selectivity index (SI) of 58. [Arg]3-VmCT1, [Arg]7-VmCT1 and [Arg]11-VmCT1 also showed trypanocidal effect, but [Arg]11-VmCT1 had the best effect, being able to decrease the EC50 against trypomastigote forms to 0.8 μmol L−1 and increase SI to 175. Necrosis was cell death pathway of VmCT1, as well [Arg]7-VmCT1 and [Arg]11-VmCT1, such as observed by membrane damage in flow cytometry analyses and scanning-electron-microscopy. In conclusion, [Arg]11-VmCT1 revealed promising as a candidate for new antichagasic therapeutics.
Where the UN Has Failed to Live Up to Its Mission: Looking Back to Look Forward
Authors: Jain Devaki
Published: October 2020

In its seventy-fifth year, the UN needs to reflect more seriously on its value in the current global scenario, the current flow of ideas, and the current flow of power that is prevalent in the world. It is important to recall that the UN was founded after World War II as a way of addressing conflict at the negotiating table rather than on the battlefield. Negotiating peace, attempting to provide some form of justice, and affirmation of human rights seemed to be the aspiration. It is within this context that women engaged in affirming their own special location in society and economy. However, over the years the UN has revealed its inability to fulfill these goals. Perhaps in the midst of all these failures, the only category of people that has drawn strength from the UN, but now has to leave it behind, are women. Scattered as they were across a world of distances, women of different cultures and classes found strength in numbers and, through the UN system and the conferences they convened, became a power of their own. As part of the special issue on “The United Nations at Seventy-Five: Looking Back to Look Forward,” this essay argues that today, however, women do not need and cannot have their aspirations be facilitated by the UN, because in their engagement with one another they have also recognized their differences. Being of similar gender does not necessarily overcome other oppressive differences.
The United Nations at Seventy-Five: Where Are the Women in The United Nations Now?
Authors: Haack Kirsten , Karns Margaret P. , Murray Jean-Pierre
Published: October 2020

Following the unsuccessful attempt to get a woman appointed as UN secretary-general in 2016 and the drop in women in senior posts in 2015, it appeared that gender equality at the UN was as distant as ever. Yet, gender equality within the Secretariat and UN system has been on the organization's agenda since 1970, with goals and target dates set for the level of women's participation and achievement. These have been met in some issue areas (for example, in so-called feminine portfolios) and organizations, but not others. As part of the special issue on “The United Nations at Seventy-Five: Looking Back to Look Forward,” this essay traces the evolution of efforts to increase the representation of women in the UN system and takes stock of their current representation therein, analyzing the data on the Secretariat and appointments to senior posts as well as in various operations and programs.
Constructing Universal Values? A Practical Approach
Authors: Lang Anthony F.
Published: October 2020

This essay explores the possibility of universal values. Universal values do not exist as Platonic ideals nor do they exist in clearly defined lists of rules or laws. Rather, universal ethical claims are constructed through the actions of individual political leaders, scholars, and activists. This essay explores how such normative constructions take place. It uses an initiative undertaken by the UN Office of Drugs and Crime to further education around corruption as an example of how such universal values come into existence. The initiative focused on developing teaching materials for higher education. The essay focuses on two particular modules, both their content and the process by which they were written.
Climate Change May Shift Coral Population Dynamics
Authors: Norris Scott
Published: October 2020

New paleoceanographic research indicates that warming waters may contribute to fewer coral reefs but to a flourishing presence of soft-bodied corals.
Implications of Sea Ice Management for Arctic Biogeochemistry
Authors: Miller Lisa , Fripiat Francois , Moreau Sebastien , Nomura Daiki , Stefels Jacqueline , Steiner Nadja , Tedesco Letizia , Vancoppenolle Martin
Published: October 2020

Geoengineering strategies to slow sea ice melting would affect not only Earth's climate but also the biology and chemistry of the oceans, atmosphere, and ice.
Slow‐to‐Fast Deformation in Mafic Fault Rocks on an Active Low‐Angle Normal Fault, Woodlark Rift, SE Papua New Guinea
Authors: Mizera M. , Little T. , Boulton C. , Prior D. , Watson E. , Biemiller J. , White J. , Shigematsu Norio
Published: October 2020

Slip on the active Mai'iu low‐angle normal fault in Papua New Guinea that dips 15–24° at the surface has exhumed in its footwall a single, continuous fault surface across a >25‐km‐wide dome. Derived from a metabasaltic protolith, the fault zone consists of a <3‐m‐thick zone of gouges and cataclasites that overprint a structurally underlying carapace of extensional mylonites. Detailed microstructural and geochemical data, combined with chlorite‐based geothermometry, reveal changing deformation processes and conditions in the Mai'iu fault rocks as they were exhumed. The microstructure of nonplastically deformed actinolite grains inherited from the fine‐grained (6–35 µm) metabasaltic protolith indicates that shearing at depth was controlled by diffusion creep accompanied by grain‐boundary sliding of these grains together with chlorite neo‐crystallization at T > 275°C–370°C. In a foliated cataclasite unit at shallower crustal levels (T ≈ 150°C–275°C), metasomatic reactions accompanied fluid‐assisted mass transfer processes that accommodated aseismic, distributed shearing; pseudotachylites and ultracataclasites in the same unit indicate that such creep was punctuated by episodes of seismic slip—after which creep resumed. At the shallowest levels (T < 150°C), gouges contain abundant saponite, a frictionally weak mineral that promotes creep on the shallowest dipping (≤24°), most poorly oriented part of the Mai'iu fault. Our field, microstructural and geochemical data of freshly exhumed fault rocks support geodetic, seismological, and geomorphic evidence for mixed seismic‐to‐aseismic slip on this active low‐angle normal fault.
Gravity Hydraulic Fracturing: A Method to Create Self‐Driven Fractures
Authors: Salimzadeh Saeed , Zimmerman Robert W. , Khalili Nasser
Published: October 2020

In this study, we investigate the possibility of using a high‐density fluid to induce downward fracture growth in a hydraulic fracturing process. We propose a mathematical model to calculate the minimum amount of a dense fluid required to trigger downward fracture propagation under gravity forces, and we verify the calculated minimum volume of the fluid through numerical simulations. Results show that when the injected fluid exceeds the minimum amount, a steady downward growth of the hydraulic fracture is obtained. The fracture propagation consists of two distinct responses: The first response can occur under either toughness‐dominated, viscosity‐dominated, or an intermediate hydraulic fracturing regime, depending on fluid rheology, rock properties, and injection scenario. The second response occurs mainly under the toughness‐dominated regime, meaning the predominant energy dissipation mechanism is to overcome the fracture toughness and break the rock. In the latter, the speed of the downward fracture growth depends on the viscosity and fluid weight.
Long‐Term Temporal Scale‐Dependent Warming Effects on the Mass Balance in the Dongkemadi Glacier, Tibetan Plateau
Authors: Liang Liqiao , Cuo Lan , Liu Qiang
Published: October 2020

Understanding how climate change impacts glaciers is important in predicting their prospective response and crucial in forecasting water supplies and potential influences within surrounding lowland areas. This study evaluated annual, seasonal, and monthly warming effects on the mass balance in the Dongkemadi (DKMD) Glacier throughout 1960–2009. Results showed an increasing trend in annual, seasonal, and monthly scale air temperature variation: high during the cool season (0.0347°C a−1) and low during the warm season (0.0222°C a−1). Warming rates variability effects at all three scales were roughly the same. Seasonal and monthly warming rates produced roughly the same effect on glacier mass balance, while the annual warming rate overestimated annual mass balance by 20.0%. July produced the largest monthly warming effect overestimation at an annual warming rate (11.9 mm w.e.; 29.3%), followed by August and June. Furthermore, increases in annual melt energy (approximately 70%) throughout the study period primarily resulted from increases in net radiation and turbulent heat flux, which mainly occurred during the warm season (>96%). Proportional increases in warming‐induced rainfall caused a decrease in mass balance while contributing to differing warming rate effects through reductions in mass inputs and albedo rather than through increases in rain‐induced heat flux. Results confirmed the effectiveness of using seasonal scale warming rates to investigate warming effects on glacier and meltwater changes in the Dongkemadi Glacier. This study provides valuable information to accurately evaluate warming effects on energy/mass balance of glaciers worldwide.
Sulforaphane-cysteine inhibited migration and invasion via enhancing mitophagosome fusion to lysosome in human glioblastoma cells
Authors: Zhou Yan , Wang Yalin , Wu Sai , Yan Yuting , Hu Yabin , Zheng Zhongnan , Li Juntao , Wu Wei
Published: October 2020

Here we uncovered the involved subcellular mechanisms that sulforaphane-cysteine (SFN-Cys) inhibited invasion in human glioblastoma (GBM). SFN-Cys significantly upregulated 45 and downregulated 14 microtubule-, mitophagy-, and invasion-associated proteins in GBM cells via HPLC–MS/MS and GEO ontology analysis; SFN-Cys disrupted microtubule by ERK1/2 phosphorylation-mediated downregulation of α-tubulin and Stathmin-1 leading to the inhibition of cell migration and invasion; SFN-Cys downregulated invasion-associated Claudin-5 and S100A4, and decreased the interaction of α-tubulin to Claudin-5. Knockdown of Claudin-5 and S100A4 significantly reduced the migration and invasion. Besides, SFN-Cys lowered the expressions of α-tubulin-mediated mitophagy-associated proteins Bnip3 and Nix. Transmission electron microscopy showed more membrane-deficient mitochondria and accumulated mitophagosomes in GBM cells, and mitochondria fusion might be downregulated because that SFN-Cys downregulated mitochondrial fusion protein OPA1. SFN-Cys increased the colocalization and interplay of LC3 to lysosomal membrane-associated protein LAMP1, aggravating the fusion of mitophagosome to lysosome. Nevertheless, SFN-Cys inhibited the lysosomal proteolytic capacity causing LC3II/LC3I elevation but autophagy substrate SQSTM1/p62 was not changed, mitophagosome accumulation, and the inhibition of migration and invasion in GBM cells. These results will help us develop high-efficiency and low-toxicity anticancer drugs to inhibit migration and invasion in GBM.
BAFF-driven NLRP3 inflammasome activation in B cells
Authors: Lim Ken-Hong , Chen Lih-Chyang , Hsu Kate , Chang Chia-Ching , Chang Chia-Yu , Kao Chen-Wei , Chang Yi-Fang , Chang Ming-Chih , Chen Caleb Gonshen
Published: October 2020

BAFF supports B-cell survival and homeostasis by activating the NF-κB pathway. While NF-κB is also involved in the priming signal of NLRP3 inflammasome, the role of BAFF in NLRP3 inflammasome regulation is unknown. Here we report BAFF engagement to BAFF receptor elicited both priming and activating signals for NLRP3 inflammasomes in primary B cells and B lymphoma cell lines. This induction of NLRP3 inflammasomes by BAFF led to increased NLRP3 and IL-1β expression, caspase-1 activation, IL-1β secretion, and pyroptosis. Mechanistically, BAFF activated NLRP3 inflammasomes by promoting the association of cIAP-TRAF2 with components of NLRP3 inflammasomes, and by inducing Src activity-dependent ROS production and potassium ion efflux. B-cell receptor (BCR) stimulation on the Lyn signaling pathway inhibited BAFF-induced Src activities and attenuated BAFF-induced NLRP3 inflammasome activation. These findings reveal an additional function of BAFF in B-cell homeostasis that is associated with BCR activities.
Regulation of fruit ripening by the brassinosteroid biosynthetic gene SlCYP90B3 via an ethylene-dependent pathway in tomato
Authors: Hu Songshen , Liu Lihong , Li Shuo , Shao Zhiyong , Meng Fanliang , Liu Haoran , Duan Wenyi , Liang Dongyi , Zhu Changqing , Xu Tao , Wang Qiaomei
Published: October 2020

The essential role of ethylene in fruit ripening has been thoroughly studied. However, the involvement of brassinosteroids (BRs) in the regulation of fruit ripening and their relationship with the ethylene pathway are poorly understood. In the current study, we found that BRs were actively synthesized during tomato fruit ripening. We then generated transgenic lines overexpressing or silencing SlCYP90B3, which encodes a cytochrome P450 monooxygenase that catalyzes the rate-limiting step of BR synthesis. The expression level of SlCYP90B3 was positively related to the contents of bioactive BRs as well as the ripening process in tomato fruit, including enhanced softening and increased soluble sugar and flavor volatile contents. Both carotenoid accumulation and ethylene production were strongly correlated with the expression level of SlCYP90B3, corroborated by the altered expression of carotenoid biosynthetic genes as well as ethylene pathway genes in transgenic tomato fruits. However, the application of the ethylene perception inhibitor 1-methycyclopropene (1-MCP) abolished the promotion effect of SlCYP90B3 overexpression on carotenoid accumulation. Taken together, these results increase our understanding of the involvement of SlCYP90B3 in bioactive BR biosynthesis as well as fruit ripening in tomato, thus making SlCYP90B3 a target gene for improvement of visual, nutritional and flavor qualities of tomato fruits with no yield penalty.
Depicting the battle between nectarine and Monilinia laxa: the fruit developmental stage dictates the effectiveness of the host defenses and the pathogen’s infection strategies
Authors: Balsells-Llauradó Marta , Silva Christian J. , Usall Josep , Vall-llaura Núria , Serrano-Prieto Sandra , Teixidó Neus , Mesquida-Pesci Saskia D. , de Cal Antonieta , Blanco-Ulate Barbara , Torres Rosario
Published: October 2020

Infections by the fungus Monilinia laxa, the main cause of brown rot in Europe, result in considerable losses of stone fruit. Herein, we present a comprehensive transcriptomic approach to unravel strategies deployed by nectarine fruit and M. laxa during their interaction. We used M. laxa-inoculated immature and mature fruit, which was resistant and susceptible to brown rot, respectively, to perform a dual RNA-Seq analysis. In immature fruit, host responses, pathogen biomass, and pathogen transcriptional activity peaked at 14–24 h post inoculation (hpi), at which point M. laxa appeared to switch its transcriptional response to either quiescence or death. Mature fruit experienced an exponential increase in host and pathogen activity beginning at 6 hpi. Functional analyses in both host and pathogen highlighted differences in stage-dependent strategies. For example, in immature fruit, M. laxa unsuccessfully employed carbohydrate-active enzymes (CAZymes) for penetration, which the fruit was able to combat with tightly regulated hormone responses and an oxidative burst that challenged the pathogen’s survival at later time points. In contrast, in mature fruit, M. laxa was more dependent on proteolytic effectors than CAZymes, and was able to invest in filamentous growth early during the interaction. Hormone analyses of mature fruit infected with M. laxa indicated that, while jasmonic acid activity was likely useful for defense, high ethylene activity may have promoted susceptibility through the induction of ripening processes. Lastly, we identified M. laxa genes that were highly induced in both quiescent and active infections and may serve as targets for control of brown rot.
Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae
Authors: Dorman Matthew J. , Domman Daryl , Poklepovich Tomás , Tolley Charlotte , Zolezzi Gisella , Kane Leanne , Viñas María Rosa , Panagópulo Marcela , Moroni Miriam , Binsztein Norma , Caffer María Inés , Clare Simon , Dougan Gordon , Salmond George P. C. , Parkhill Julian , Campos Josefina , Thomson Nicholas R.
Published: October 2020

In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992–1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992–1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics.
Influence of interapplicator distance on multibipolar radiofrequency ablation during physiological and interrupted liver perfusion in an in vivo porcine model
Authors: Poch F. G. M. , Neizert C. A. , Geyer B. , Gemeinhardt O. , Bruder L. , Niehues S. M. , Vahldiek J. L. , Bressem K. K. , Kreis M. E. , Lehmann K. S.
Published: October 2020

Radiofrequency ablation (RFA) is a curative treatment option for early stage hepatocellular carcinoma (HCC). Vascular inflow occlusion to the liver (Pringle manoeuvre) and multibipolar RFA (mbRFA) represent possibilities to generate large ablations. This study evaluated the impact of different interapplicator distances and a Pringle manoeuvre on ablation area and geometry of mbRFA. 24 mbRFA were planned in porcine livers in vivo. Test series with continuous blood flow had an interapplicator distance of 20 mm and 15 mm, respectively. For a Pringle manoeuvre, interapplicator distance was predefined at 20 mm. After liver dissection, ablation area and geometry were analysed macroscopically and histologically. Confluent and homogenous ablations could be achieved with a Pringle manoeuvre and an interapplicator distance of 15 mm with sustained hepatic blood flow. Ablation geometry was inhomogeneous with an applicator distance of 20 mm with physiological liver perfusion. A Pringle manoeuvre led to a fourfold increase in ablation area in comparison to sustained hepatic blood flow (p < 0.001). Interapplicator distance affects ablation geometry of mbRFA. Strict adherence to the planned applicator distance is advisable under continuous blood flow. The application of a Pringle manoeuvre should be considered when compliance with the interapplicator distance cannot be guaranteed.
The neurophysiological architecture of semantic dementia: spectral dynamic causal modelling of a neurodegenerative proteinopathy
Authors: Benhamou Elia , Marshall Charles R. , Russell Lucy L. , Hardy Chris J. D. , Bond Rebecca L. , Sivasathiaseelan Harri , Greaves Caroline V. , Friston Karl J. , Rohrer Jonathan D. , Warren Jason D. , Razi Adeel
Published: October 2020

The selective destruction of large-scale brain networks by pathogenic protein spread is a ubiquitous theme in neurodegenerative disease. Characterising the circuit architecture of these diseases could illuminate both their pathophysiology and the computational architecture of the cognitive processes they target. However, this is challenging using standard neuroimaging techniques. Here we addressed this issue using a novel technique—spectral dynamic causal modelling—that estimates the effective connectivity between brain regions from resting-state fMRI data. We studied patients with semantic dementia—the paradigmatic disorder of the brain system mediating world knowledge—relative to healthy older individuals. We assessed how the effective connectivity of the semantic appraisal network targeted by this disease was modulated by pathogenic protein deposition and by two key phenotypic factors, semantic impairment and behavioural disinhibition. The presence of pathogenic protein in SD weakened the normal inhibitory self-coupling of network hubs in both antero-mesial temporal lobes, with development of an abnormal excitatory fronto-temporal projection in the left cerebral hemisphere. Semantic impairment and social disinhibition were linked to a similar but more extensive profile of abnormally attenuated inhibitory self-coupling within temporal lobe regions and excitatory projections between temporal and inferior frontal regions. Our findings demonstrate that population-level dynamic causal modelling can disclose a core pathophysiological feature of proteinopathic network architecture—attenuation of inhibitory connectivity—and the key elements of distributed neuronal processing that underwrite semantic memory.
Arabidopsis, tobacco, nightshade and elm take insect eggs as herbivore alarm and show similar transcriptomic alarm responses
Authors: Lortzing Tobias , Kunze Reinhard , Steppuhn Anke , Hilker Monika , Lortzing Vivien
Published: October 2020

Plants respond to insect eggs with transcriptional changes, resulting in enhanced defence against hatching larvae. However, it is unknown whether phylogenetically distant plant species show conserved transcriptomic responses to insect eggs and subsequent larval feeding. We used Generally Applicable Gene set Enrichment (GAGE) on gene ontology terms to answer this question and analysed transcriptome data from Arabidopsis thaliana, wild tobacco (Nicotiana attenuata), bittersweet nightshade (Solanum dulcamara) and elm trees (Ulmus minor) infested by different insect species. The different plant–insect species combinations showed considerable overlap in their transcriptomic responses to both eggs and larval feeding. Within these conformable responses across the plant–insect combinations, the responses to eggs and feeding were largely analogous, and about one-fifth of these analogous responses were further enhanced when egg deposition preceded larval feeding. This conserved transcriptomic response to eggs and larval feeding comprised gene sets related to several phytohormones and to the phenylpropanoid biosynthesis pathway, of which specific branches were activated in different plant–insect combinations. Since insect eggs and larval feeding activate conserved sets of biological processes in different plant species, we conclude that plants with different lifestyles share common transcriptomic alarm responses to insect eggs, which likely enhance their defence against hatching larvae.
Presence of bacterial DNA in thrombotic material of patients with myocardial infarction
Authors: Piñon-Esteban P. , Núñez L. , Moure R. , Marrón-Liñares G. M. , Flores-Rios X. , Aldama-Lopez G. , Salgado-Fernandez J. , Calviño-Santos R. , Rebollal-Leal F. , Pan-Lizcano R. , Vazquez-Gonzalez N. , Bou G. , Tomás M. , Hermida-Prieto M. , Vazquez-Rodriguez J. M.
Published: October 2020

Infectious agents have been suggested to be involved in etiopathogenesis of Acute Coronary Syndrome (ACS). However, the relationship between bacterial infection and acute myocardial infarction (AMI) has not yet been completely clarified. The objective of this study is to detect bacterial DNA in thrombotic material of patients with ACS with ST-segment elevation (STEMI) treated with Primary Percutaneous Coronary Intervention (PPCI). We studied 109 consecutive patients with STEMI, who underwent thrombus aspiration and arterial peripheral blood sampling. Testing for bacterial DNA was performed by probe-based real-time Polymerase Chain Reaction (PCR). 12 probes and primers were used for the detection of Aggregatibacteractinomycetemcomitans, Chlamydiapneumoniae, viridans group streptococci, Porphyromonasgingivalis, Fusobacteriumnucleatum, Tannarellaforsythia, Treponemadenticola, Helycobacterpylori, Mycoplasmapneumoniae, Staphylococusaureus,  Prevotella intermedia and Streptococcusmutans. Thus, DNA of four species of bacteria was detected in 10 of the 109 patients studied. The most frequent species was viridans group streptococci (6 patients, 5.5%), followed by Staphylococusaureus (2 patients, 1.8%). Moreover, a patient had DNA of Porphyromonasgingivalis (0.9%); and another patient had DNA of Prevotella intermedia (0.9%). Bacterial DNA was not detected in peripheral blood of any of our patients. In conclusion, DNA of four species of endodontic and periodontal bacteria was detected in thrombotic material of 10 STEMI patients. Bacterial DNA was not detected in the peripheral blood of patients with bacterial DNA in their thrombotic material. Bacteria could be latently present in plaques and might play a role in plaque instability and thrombus formation leading to ACS.
Top-ranked expressed gene transcripts of human protein-coding genes investigated with GTEx dataset
Authors: Tung Kuo-Feng , Pan Chao-Yu , Chen Chao-Hsin , Lin Wen-chang
Published: October 2020

With considerable accumulation of RNA-Seq transcriptome data, we have extended our understanding about protein-coding gene transcript compositions. However, alternatively compounded patterns of human protein-coding gene transcripts would complicate gene expression data processing and interpretation. It is essential to exhaustively interrogate complex mRNA isoforms of protein-coding genes with an unified data resource. In order to investigate representative mRNA transcript isoforms to be utilized as transcriptome analysis references, we utilized GTEx data to establish a top-ranked transcript isoform expression data resource for human protein-coding genes. Distinctive tissue specific expression profiles and modulations could be observed for individual top-ranked transcripts of protein-coding genes. Protein-coding transcripts or genes do occupy much higher expression fraction in transcriptome data. In addition, top-ranked transcripts are the dominantly expressed ones in various normal tissues. Intriguingly, some of the top-ranked transcripts are noncoding splicing isoforms, which imply diverse gene regulation mechanisms. Comprehensive investigation on the tissue expression patterns of top-ranked transcript isoforms is crucial. Thus, we established a web tool to examine top-ranked transcript isoforms in various human normal tissue types, which provides concise transcript information and easy-to-use graphical user interfaces. Investigation of top-ranked transcript isoforms would contribute understanding on the functional significance of distinctive alternatively spliced transcript isoforms.
The allosteric activation mechanism of a phospholipase A2-like toxin from Bothrops jararacussu venom: a dynamic description
Authors: Gomes Antoniel A. S. , Cardoso Fabio F. , Souza Maximilia F. , Oliveira Cristiano L. P. , Perahia David , Magro Angelo J. , Fontes Marcos R. M.
Published: October 2020

The activation process of phospholipase A2-like (PLA2-like) toxins is a key step in their molecular mechanism, which involves oligomeric changes leading to the exposure of specific sites. Few studies have focused on the characterization of allosteric activators and the features that distinguish them from inhibitors. Herein, a comprehensive study with the BthTX-I toxin fromBothrops jararacussuvenom bound or unbound to α-tocopherol (αT) was carried out. The oligomerization state of BthTX-I bound or unbound to αT in solution was studied and indicated that the toxin is predominantly monomeric but tends to oligomerize when complexed with αT. In silico molecular simulations showed the toxin presents higher conformational changes in the absence of αT, which suggests that it is important to stabilize the structure of the toxin. The transition between the two states (active/inactive) was also studied, showing that only the unbound BthTX-I system could migrate to the inactive state. In contrast, the presence of αT induces the toxin to leave the inactive state, guiding it towards the active state, with more regions exposed to the solvent, particularly its active site. Finally, the structural determinants necessary for a molecule to be an inhibitor or activator were analyzed in light of the obtained results.
Bandgap and refractive index estimates of InAlN and related nitrides across their full composition ranges
Authors: Alam Shahab N. , Zubialevich Vitaly Z. , Ghafary Bijan , Parbrook Peter J.
Published: October 2020

III-Nitride bandgap and refractive index data are of direct relevance for the design of (In, Ga, Al)N-based photonic and electronic devices. The bandgaps and bandgap bowing parameters of III-nitrides across the full composition range are reviewed with a special emphasis on InxAl1−xN, where less consensus was reached in the literature previously. Considering the available InAlN data, including those recently reported for low indium contents, empirical formulae for InAlN bandgap and bandgap bowing parameter are proposed. Applying the generalised bandgap data, the refractive index dispersion data available in the literature for III-N alloys is fitted using the Adachi model. For this purpose, a formalism involving a parabolic dependence of the Adachi parameters on the dimensionless bandgap $${\xi }_{{E}_{\mathrm{g}}}=\left({E}_{\mathrm{g}, {\mathrm{A}}_{x}{\mathrm{B}}_{1-x}\mathrm{N}}-{E}_{\mathrm{g},\mathrm{ BN}}\right)/\left({E}_{\mathrm{g}, \mathrm{AN}}-{E}_{\mathrm{g},\mathrm{ BN}}\right)$$

ξ

E
g

=

E

g
,

A
x

B

1
-
x

N

-

E

g
,
BN

/

E

g
,
AN

-

E

g
,
BN

of the corresponding ternary alloys is used rather than one directly invoking the alloy composition.
Determination of the Raman polarizability tensor in the optically anisotropic crystal potassium dihydrogen phosphate and its deuterated analog
Authors: Kosc T. Z. , Huang H. , Kessler T. J. , Negres R. A. , Demos S. G.
Published: October 2020

The Raman tensor of the dominant A1 modes of the nonlinear optical crystalline material potassium dihydrogen phosphate and its 70% deuterated analog have been ascertained. Challenges in determining the A1 mode tensor element values based on previous reports have been resolved using a specially designed experimental setup that makes use of spherical crystal samples. This novel experimental design enabled the determination of measurement artifacts, including polarization rotation of the pump and/or scattered light propagating through the sample and the contribution of additional overlapping phonon modes, which have hindered previous efforts. Results confirmed that the polarization tensor is diagonal, and matrix elements were determined with high accuracy.