bluuebunny/crossref_metadata_2025 huggingface dataset:
Intercellular and intracellular cilia orientation is coordinated by CELSR1 and CAMSAP3 in oviduct multi-ciliated cells
Authors: Usami Fumiko Matsukawa , Arata Masaki , Shi Dongbo , Oka Sanae , Higuchi Yoko , Tissir Fadel , Takeichi Masatoshi , Fujimori Toshihiko
Published: January 2021

The molecular mechanisms by which cilia orientation is coordinated within and between multi-ciliated cells (MCCs) are not fully understood. In the mouse oviduct, MCCs exhibit a characteristic basal body (BB) orientation and microtubule gradient along the tissue axis. The intracellular polarities were moderately maintained in cells lacking CELSR1 (cadherin EGF LAG seven-pass G-type receptor 1), a planar cell polarity (PCP) factor involved in tissue polarity regulation, although the intercellular coordination of the polarities was disrupted. However, CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a microtubule minus-end regulator, was found to be critical for determining the intracellular BB orientation. CAMSAP3 localized to the base of cilia in a polarized manner, and its mutation led to the disruption of intracellular coordination of BB orientation, as well as the assembly of microtubules interconnecting BBs, without affecting PCP factor localization. Thus, both CELSR1 and CAMSAP3 are responsible for BB orientation but in distinct ways; their cooperation should therefore be critical for generating functional multi-ciliated tissues.
Ipomoeassin-F inhibits the in vitro biogenesis of the SARS-CoV-2 spike protein and its host cell membrane receptor
Authors: O'Keefe Sarah , Roboti Peristera , Duah Kwabena B. , Zong Guanghui , Schneider Hayden , Shi Wei Q. , High Stephen
Published: January 2021

In order to produce proteins essential for their propagation, many pathogenic human viruses, including SARS-CoV-2, the causative agent of COVID-19 respiratory disease, commandeer host biosynthetic machineries and mechanisms. Three major structural proteins, the spike, envelope and membrane proteins, are amongst several SARS-CoV-2 components synthesised at the endoplasmic reticulum (ER) of infected human cells prior to the assembly of new viral particles. Hence, the inhibition of membrane protein synthesis at the ER is an attractive strategy for reducing the pathogenicity of SARS-CoV-2 and other obligate viral pathogens. Using an in vitro system, we demonstrate that the small molecule inhibitor ipomoeassin F (Ipom-F) potently blocks the Sec61-mediated ER membrane translocation and/or insertion of three therapeutic protein targets for SARS-CoV-2 infection; the viral spike and ORF8 proteins together with angiotensin-converting enzyme 2, the host cell plasma membrane receptor. Our findings highlight the potential for using ER protein translocation inhibitors such as Ipom-F as host-targeting, broad-spectrum antiviral agents.

This article has an associated First Person interview with the first author of the paper.
A questão do negro na autocracia burguesa brasileira: as contribuições sociopolíticas de Florestan Fernandes e Clóvis Moura
Authors: Sartoretto Leonardo
Published: January 2021

O presente artigo debate a inserção histórica do negro na dominação de classe brasileira. Evocando o conceito de autocracia em Florestan Fernandes, por ser quem mais o atrela à questão do negro como categoria social sob viés marxista, busca-se também em Clóvis Moura contribuições que demonstram como o negro representa estruturalmente o grupo mais explorado pelo capitalismo brasileiro. Contudo, a discussão indica que o negro deve, por isso mesmo, trazer a radicalidade de suas demandas para o âmbito classista da luta, pois é nesse sentido - da criação de uma frente articulada de grupos subalternos para formar uma objetiva e necessária consciência de classe - que apontam os esforços de vida dos dois sociólogos que mais combateram a chamada democracia racial, legitimadora desse passado.
Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis
Authors: Syahrul Syahrul , Maliga Helnida Anggun , Ilmawan Muhammad , Fahriani Marhami , Mamada Sukamto S. , Fajar Jonny Karunia , Frediansyah Andri , Syahrul Faza Nabila , Imran Imran , Haris Salim , Rambe Aldy Safruddin , Emran Talha Bin , Rabaan Ali A. , Tiwari Ruchi , Dhama Kuldeep , Nainu Firzan , Mutiawati Endang , Harapan Harapan
Published: January 2021

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease.

Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated.

Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%;I2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%;I2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively.

Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted.

PROSPERO registration:CRD42020224470 (04/12/20)
A REFORMA DO ENSINO MÉDIO EM QUESTÃO: ENTRE FALÁCIAS E DESAFIOS
Authors: Furtado José Henrique de Lacerda
Published: January 2021

Em uma conjuntura nacional de aprofundamento da crise política e econômica no país, em que diversas medidas de cunho neoliberal vêm sendo implementadas, uma nova organização do ensino médio é propostanão só, ignorando os diversos problemas reais enfrentados cotidianamente pelas escolas brasileiras, mas também, evidenciando a lógica mercantilista com que a educação vem sendo conduzida ao longo dos anos no Brasil. Ressalta-se ainda, o contexto marcado por um cenário imbricado de interesses em disputa em que ela foi sendo formulada. Neste sentido, a reforma do ensino médio, aprovada através da Lei nº 13.415/2017, preconiza uma série de mudanças no mínimo, controversas, tendo como palavra de ordem a sugestiva e questionável flexibilização. Sendo assim, o presente artigo tem como objetivo central discutir acerca deste cenário de disputas em que a reforma do ensino médio se apresenta, destacando a importância da educação em uma perspectiva emancipatória para a formação do indivíduo. A partir das discussões apresentadas, fica evidente a perspectiva regressiva adotada na formulação do novo modelo de ensino médio, que ignora a importância do relevante papel que pode ser desempenhado por ele na transformação social e no desenvolvimento do pensamento crítico e reflexivo dos estudantes. Nesse contexto de retrocessos, faz-se imprescindível e urgente, portanto, que a sociedade como um todo se organize, assumindo o protagonismo na luta pela manutenção dos direitos conquistados e pelo controle dos rumos da educação dos jovens brasileiros, na busca constante por uma sociedade mais justa e menos desigual.
DESAFIOS DOCENTES NO ENSINO MÉDIO INTEGRADO: DIÁLOGOS INTERCULTURAIS NAS PRÁTICAS EDUCATIVAS
Authors: Menezes Graziela Ninck Dias , Rios Jane Adriana Vasconcelos Pacheco
Published: January 2021

O texto discute resultados de uma pesquisa que cartografou a profissão docente na Educação Profissional Técnica a partir de experiências educativas com a diversidade. De base qualitativa, o trabalho mapeou dimensões da profissão por meio de questionário survey e constituiu espaços de escuta e análises colaborativas com os participantes da pesquisa – professores que atuam no Ensino Médio Integrado -, de dois campi de um instituto federal, por meio de rodas de conversa e de cartas pedagógicas. As análises indicaram que os docentes vivem uma crise profissional, considerando seus processos formativos e os modos como a política de atenção à diversidade da instituição é produzida, diante o atual contexto sócio-educacional, em que os sujeitos da diversidade reivindicam o reconhecimento de suas existências. Nesse sentido, os docentes são desafiados a reinvenção de práticas educativas que dialoguem com as singularidades constitutivas de cada sujeito por meio de um diálogo intercultural.
AS REDES SOCIAIS E A POPULARIZAÇÃO DO CONHECIMENTO CIENTÍFICO: METODOLOGIA PARA O ENSINO DE FÍSICA
Authors: Oliveira Ana Maria Silva
Published: January 2021

Com as mudanças propostas na reforma curricular do Ensino Médio, o ensino de Física, Química e Biologia foram unificados em um único bloco denominado itinerário formativo de Ciências da Natureza. Considerado como difícil e desmotivante pelo público estudantil, o ensino de Física necessitará de novos caminhos pedagógicos para contemplar as demandas da educação básica contemporânea, considerando sua relação interdisciplinar e conectiva com o mundo do trabalho. Essa proposta pedagógica emerge do desafio de motivar o interesse dos estudantes do curso técnico em cozinha (PROEJA), modalidade integrada, pelos conhecimentos de Física, discutindo caminhos que promovam o diálogo entre os conteúdos e a prática do trabalho. O uso pedagógico das redes sociais é o elemento central da proposta metodológica, servindo de “pano de fundo” para aproximação da população da zona rural com os espaços digitais. Pretende-se, a partir do diálogo entre a Física, enquanto disciplina propedêutica, e as disciplinas técnicas do curso, promover uma aproximação do conhecimento científico com o “saber fazer” do estudante, resignificando sua prática laboral e contribuindo para sua formação omnilateral, enquanto cidadão crítico e capaz de influenciar e promover mudanças.
PENSARNOS Y PROYECTARNOS COMOREGIÓN BIOMA PAMPA DE EDUCACIÓN SUPERIOR
Authors: Ubal Wilson Marcelo
Published: January 2021

O presente artigo se baseia em uma experiência em construção na região sul do Rio Grande do Sul (Brasil) e Noroeste do Uruguai denominada Projeto Região Bioma Pampa de Instituições Públicas de Educação Superior (RBPIPES). O projeto que reúne as principais instituições públicas de Ensino Superior da região com o fim de aprofundar o vínculo acadêmico, contém uma potencialidade modelar em seu desenho e metodologia. Por este motivo, pode servir de orientação para projetos territoriais de características análogas. Começamos pela contextualização de nossa região e uma breve apresentação do Bioma Pampa. Continuamos historicizando um movimento que tem gerado entre as instituições públicas de nossa região um compartilhamento de princípios e êxitos alcançados. Com a posterior abordagem das potencialidades e desafios do projeto, culminamos o trabalho comum a utopia humanizadora: constituirmos um centro de Educação Superior de referência continental e mundial em um conjunto de temáticas estratégicas para o desenvolvimento sustentável de nossa região, sem perder de vista o necessário aprofundamento dos processos de justiça social para os homens e mulheres destas latitudes do continente.
Editorial
Authors: Gama Zacarias
Published: January 2021

.
Transformational Leadership at Times of Crisis: The Case of School Leaders in Greece
Authors: Menon Maria Eliophotou
Published: January 2021

The paper aims to investigate the extent to which school leaders adopt transformational leadership behaviors at times of crisis. The emphasis on restructuring in the educational policy environment in recent decades has led to an increased interest in transformational leadership in education, resulting in a large number of studies. In order to investigate the adoption of transformational leadership behaviors/practices at times of crisis, qualitative research was conducted with 30 primary school teachers in Greece. The schools were selected based on the extent to which they had been affected by the financial crisis. Greece has faced major challenges in the last ten years, including the financial crisis and the influx of immigrants. These changes have had a profound effect on the Greek educational system. In this context, the paper examines the extent to which school leaders in Greece adopt transformational leadership practices in order to deal with the impact of the crisis on their school unit. The findings of the research are used to draw conclusions and implications regarding educational policy as well as future research on the topic.
Under different umbrellas: intersectionality and alliances in US feminist politics
Authors: Ferree Myra Marx
Published: January 2021

Macro-level forms of inequality work intersectionally to establish democracy normatively, as well as shape its institutions. Liberal democracies, once revolutionarily new political formations, rest on an equally revolutionary understanding of male domination based not on descent, but on economic arrangements (the new ‘breadwinner’ role) and political institutions (the ‘brotherhood’ national state). Over time, social movements have diminished liberal democracy’s original exclusions of women and minority ethnic men so that many citizens’ daily lives now contradict this once hegemonic normative order. The US party binary pushes contemporary movements to transform or restore this understanding of democracy under the political umbrellas of the competing Democratic and Republican parties. This polarisation then contributes to the gendering of movement claims and political representation. Gendered polarisation creates opportunities for cohesion among movements on both sides and yet blocks more fundamental reforms of US democracy.
Theoretical investigations of a modified compressed ultrafast photography method suitable for single-shot fluorescence lifetime imaging
Authors: Li Yahui , Tian Jinshou , Li David Day-Uei
Published: January 2021

A single-shot fluorescence lifetime imaging (FLIM) method based on the
compressed ultrafast photography (CUP) is proposed, named
space-restricted CUP (srCUP). srCUP is suitable for imaging objects
moving slowly (

<∼
150

/

M

m
m

/

s

,

M

is the magnification of the objective
lens) in the field of view with the intensity changing within
nanoseconds in a measurement window around 10 ns. We used synthetic
datasets to explore the performances of srCUP compared with CUP and
TCUP (a variant of CUP). srCUP not only provides superior
reconstruction performances, but its reconstruction speed is also
twofold and threefold faster than CUP and TCUP, respectively. The
lifetime determination performances were assessed by estimating
lifetime components, amplitude- and intensity-weighted average
lifetimes (

τ
A

and

τ
I

), with the reconstructed scenes using
the least squares method based on a bi-exponential model. srCUP has
the best accuracy and precision for lifetime determinations with a
relative bias less than 7% and a coefficient of variation less than 7%
for

τ
A

, and a relative bias less than 10%
and a coefficient of variation less than 11% for

τ
I

.
In-line characterization of nanostructures produced by roll-to-roll nanoimprinting
Authors: Skovlund Madsen Jonas , Geisler Mathias , Berri Lotz Mikkel , Zalkovskij Maksim , Bilenberg Brian , Korhonen Raimo , Peltonen Petri , Erik Hansen Poul , Alkærsig Jensen Søren
Published: January 2021

We present an in-line metrology solution for dimensional characterization of roll-to-roll imprinted nanostructures. The solution is based on a scatterometric analysis of optical data from a hyperspectral camera deployed at a production facility, where nanostructures are produced at speeds of 10m/min. The system combines the ease of use of a real-space imaging system with the spectral information used in scatterometry. We present nanoscale dimensional measurements on one-dimensional line gratings with various periods and orientations. The depths of the produced structures are accurately characterized with uncertainties on the scale of a few nanometers. The hyperspectral imaging capabilities of the system can also be used to avoid vibrational effects.
Controlled unidirectional reflection in cold atoms via the spatial Kramers-Kronig relation
Authors: Zhang Yan , Wu Jin-Hui , Artoni M. , La Rocca G. C.
Published: January 2021

It is known that the Kramers-Kronig (KK) relation between real and imaginary parts of the optical susceptibility in the frequency domain can also be realized in the space domain, as first proposed in [Nat. Photonics 9(7), 436 (2015)10.1038/nphoton.2015.106]. We here study a mechanism to implement spatial KK relations in a cold atomic sample and use it to control unidirectional reflectionless for probe light incident from either the left or right side of the sample at will. In our model, the complex frequency dependent atomic susceptibility is mapped into a spatially dependent one, employing a far-detuned driving field of intensity linearly varied in space. The reflection of an incident light from one side of the sample can then be set to vanish over a specific frequency band directly by changing the driving field parameters, such as its intensity and frequency. Also, by incorporating the Bragg scattering into the spatial KK relation, the reflectivity from the opposite side of the sample, though typically small for realistic atomic densities, can be made to increase to improve the reflectivity contrast. The present scheme bears potentials for all-optical network applications that require controllable unidirectional light propagation.
Non-diffracting states at exceptional points
Authors: Yuce Cem , Ramezani Hamidreza
Published: January 2021

We propose to use exceptional points (EPs) to construct diffraction-free beam propagation and localized power oscillation in lattices. We specifically consider two systems to utilize EPs for diffraction-free beam propagation, one in synthetic gauge lattices and the other in unidirectionally coupled resonators where each resonator individually is capable of creating orbital angular momentum (OAM) beams. In the second system, we introduce the concept of robust and tunable OAM beam propagation in discrete lattices. We show that one can create robust OAM beams in an arbitrary number of sites of a photonic lattice. Furthermore, we report power oscillation at the EP of a non-Hermitian lattice. Our research widens the study and application of EPs in different photonic systems including OAM beams and their associated dynamics in discrete lattices.
GeSn lateral p-i-n waveguide photodetectors for mid-infrared integrated photonics
Authors: Tsai Cheng-Hsun , Lin Kuan-Chih , Cheng Chin-Yuan , Lee Kuo-Chih , Cheng H. H. , Chang Guo-En
Published: January 2021

In this Letter, we demonstrate mid-infrared (MIR) lateralp−i−nGeSn waveguide photodetectors (WGPDs) on silicon, to the best of our knowledge for the first time, as a key enabler of MIR electronic–photonic integrated circuits (EPICs). Narrow-bandgap GeSn alloys were employed as the active material to enable efficient photodetection in the MIR region. A lateralp−i−nhomojunction diode was designed and fabricated to significantly enhance the optical confinement factor of the guided modes and thus enhance the optical responsivity. Thus, a photodetection range of up to 1950 nm and a good responsivity of 0.292 A/W at 1800 nm were achieved. These results demonstrate the feasibility of planar GeSn WGPDs for monolithic MIR EPICs on silicon.
Time-resolved study of laser emission in nitrogen gas pumped by two near IR femtosecond laser pulses
Authors: Danylo Rostyslav , Lambert Guillaume , Liu Yi , Tikhonchuk Vladimir , Houard Aurélien , Mysyrowicz André
Published: January 2021

The time profile of a lasing signal at 391.4 nm emitted by a weakly ionized gas of nitrogen molecules at low pressure is measured under double excitation with intense femtosecond laser pulses at 800 nm. An abrupt decrease in emission occurs at the time of arrival of the second pulse. It is explained by a transfer of population from ground to first excited ionic level and by a disruption of coherence, terminating the conditions for lasing in a V-scheme without population inversion.
Tunable sub-300  fs soliton and switchable dual-wavelength pulse generation from a mode-locked fiber oscillator around 2.8  µm
Authors: Luo Hongyu , Yang Jian , Li Jianfeng , Liu Yong
Published: January 2021

In this Letter, we demonstrate, for the first time, to the best of our knowledge, tunable soliton and switchable dual-wavelength pulse generation from a nonlinear polarization rotation mode-locked

E
r

3
+

-doped fluoride fiber oscillator around 2.8 µm, employing a

L
i
N
b
O

3

birefringent plate (BFP)-based Lyot filter. In the single soliton state, the wavelength can be continuously tuned in the region of

2752.4

∼

2807.2

n
m

(

∼

55

n
m

) with a pulse width between 199 and 270 fs, by rotating the BFP with the aid of its spectral filtering effect. At higher pump levels, two kinds of dual-wavelength synchronous mode-locking states (i.e., 2746.4/2782.0 and 2787.2/2825.2 nm) are observed, and can be flexibly switched by adjusting the rotation angle of the BFP. This approach opens up new opportunities for the development of versatile mid-infrared ultrashort laser sources.
Phase-controlled dual-wavelength resonance in a self-coupling whispering-gallery-mode microcavity
Authors: Xie Ran-Ran , Qin Guo-Qing , Zhang Hao , Wang Min , Li Gui-Qin , Ruan Dong , Long Gui-Lu
Published: January 2021

We report a novel, to the best of our knowledge, way to achieve phase-controlled dual-wavelength resonance based on whispering-gallery-mode (WGM) microcavities experimentally. With the help of a feedback waveguide, not only two optical pathways but also a unidirectional coupling between counter-propagating waves are formed, which is the requirement of all-optical analogues of electromagnetically induced transparency and Autler–Townes splitting. By adjusting the accumulating phase introduced from the fiber waveguide, we observe the signal lineshape changes from symmetric to asymmetric, i.e., the resonant transmission and extinction ratio of two splitting modes can be controlled, which brings a new degree of freedom to the WGM resonator system. These results may boost the development of quantum state control and pave the way for reconfiguring devices such as narrow-band filters.
Deep reinforcement learning control of white-light continuum generation
Authors: Valensise Carlo M. , Giuseppi Alessandro , Cerullo Giulio , Polli Dario
Published: January 2021

White-light continuum (WLC) generation in bulk media finds numerous applications in ultrafast optics and spectroscopy. Due to the complexity of the underlying spatiotemporal dynamics, WLC optimization typically follows empirical procedures. Deep reinforcement learning (RL) is a branch of machine learning dealing with the control of automated systems using deep neural networks. In this Letter, we demonstrate the capability of a deep RL agent to generate a long-term-stable WLC from a bulk medium without any previous knowledge of the system dynamics or functioning. This work demonstrates that RL can be exploited effectively to control complex nonlinear optical experiments.
Phosphor-free microLEDs with ultrafast and broadband features for visible light communications
Authors: Tian Zhenhuan , Li Qiang , Wang Xuzheng , Zhang Mingyin , Su Xilin , Zhang Ye , Li Yufeng , Yun Feng , Lee S. W. Ricky
Published: January 2021

Modulation bandwidth and the emission region are essential features for the widespread use of visible light communications (VLC). This paper addresses the contradictory requirements to achieve broadband and proposes ultrafast, asymmetric pyramids grown on adjacent deep concave holes via lateral overgrowth. Multicolor emission with an emission region between 420 nm and 600 nm is obtained by controlling the growth rate at different positions on the same face, which also can provide multiple subcarrier frequency points for the employment of wavelength division multiplexing technology. The spontaneous emission rate distinction is narrowed by lowering the number of the crystal plane, ensuring a high modulation bandwidth over broadband. More importantly, the residual stress and dislocation density were minimized by employing a patterned substrate, and lateral overgrowth resulted in a further enhancement of the recombination rate. Finally, the total modulation bandwidth of multiple subcarriers of the asymmetric pyramids is beyond GHz. These ultrafast, multicolor microLEDs are viable for application in VLC systems and may also enable applications for intelligent lighting and display.
A novel terpene synthase controls differences in anti-aphrodisiac pheromone production between closely related Heliconius butterflies
Authors: Darragh Kathy , Orteu Anna , Black Daniella , Byers Kelsey J. R. P. , Szczerbowski Daiane , Warren Ian A. , Rastas Pasi , Pinharanda Ana , Davey John W. , Fernanda Garza Sylvia , Abondano Almeida Diana , Merrill Richard M. , McMillan W. Owen , Schulz Stefan , Jiggins Chris D.
Published: January 2021

Plants and insects often use the same compounds for chemical communication, but not much is known about the genetics of convergent evolution of chemical signals. The terpene (E)-β-ocimene is a common component of floral scent and is also used by the butterflyHeliconius melpomeneas an anti-aphrodisiac pheromone. While the biosynthesis of terpenes has been described in plants and microorganisms, few terpene synthases (TPSs) have been identified in insects. Here, we study the recent divergence of 2 species,H.melpomeneandHeliconius cydno, which differ in the presence of (E)-β-ocimene; combining linkage mapping, gene expression, and functional analyses, we identify 2 novel TPSs. Furthermore, we demonstrate that one, HmelOS, is able to synthesise (E)-β-ocimene in vitro. We find no evidence for TPS activity in HcydOS (HmelOS ortholog ofH.cydno), suggesting that the loss of (E)-β-ocimene in this species is the result of coding, not regulatory, differences. The TPS enzymes we discovered are unrelated to previously described plant and insect TPSs, demonstrating that chemical convergence has independent evolutionary origins.
Genome-wide prediction of topoisomerase IIβ binding by architectural factors and chromatin accessibility
Authors: Martínez-García Pedro Manuel , García-Torres Miguel , Divina Federico , Terrón-Bautista José , Delgado-Sainz Irene , Gómez-Vela Francisco , Cortés-Ledesma Felipe
Published: January 2021

DNA topoisomerase II-β (TOP2B) is fundamental to remove topological problems linked to DNA metabolism and 3D chromatin architecture, but its cut-and-reseal catalytic mechanism can accidentally cause DNA double-strand breaks (DSBs) that can seriously compromise genome integrity. Understanding the factors that determine the genome-wide distribution of TOP2B is therefore not only essential for a complete knowledge of genome dynamics and organization, but also for the implications of TOP2-induced DSBs in the origin of oncogenic translocations and other types of chromosomal rearrangements. Here, we conduct a machine-learning approach for the prediction of TOP2B binding using publicly available sequencing data. We achieve highly accurate predictions, with accessible chromatin and architectural factors being the most informative features. Strikingly, TOP2B is sufficiently explained by only three features: DNase I hypersensitivity, CTCF and cohesin binding, for which genome-wide data are widely available. Based on this, we develop a predictive model for TOP2B genome-wide binding that can be used across cell lines and species, and generate virtual probability tracks that accurately mirror experimental ChIP-seq data. Our results deepen our knowledge on how the accessibility and 3D organization of chromatin determine TOP2B function, and constitute a proof of principle regarding the in silico prediction of sequence-independent chromatin-binding factors.
Rosetta design with co-evolutionary information retains protein function
Authors: Schmitz Samuel , Ertelt Moritz , Merkl Rainer , Meiler Jens
Published: January 2021

Computational protein design has the ambitious goal of crafting novel proteins that address challenges in biology and medicine. To overcome these challenges, the computational protein modeling suite Rosetta has been tailored to address various protein design tasks. Recently, statistical methods have been developed that identify correlated mutations between residues in a multiple sequence alignment of homologous proteins. These subtle inter-dependencies in the occupancy of residue positions throughout evolution are crucial for protein function, but we found that three current Rosetta design approaches fail to recover these co-evolutionary couplings. Thus, we developed the Rosetta method ResCue (residue-coupling enhanced) that leverages co-evolutionary information to favor sequences which recapitulate correlated mutations, as observed in nature. To assess the protocols via recapitulation designs, we compiled a benchmark of ten proteins each represented by two, structurally diverse states. We could demonstrate that ResCue designed sequences with an average sequence recovery rate of 70%, whereas three other protocols reached not more than 50%, on average. Our approach had higher recovery rates also for functionally important residues, which were studied in detail. This improvement has only a minor negative effect on the fitness of the designed sequences as assessed by Rosetta energy. In conclusion, our findings support the idea that informing protocols with co-evolutionary signals helps to design stable and native-like proteins that are compatible with the different conformational states required for a complex function.
Disease-driven reduction in human mobility influences human-mosquito contacts and dengue transmission dynamics
Authors: Schaber Kathryn L. , Perkins T. Alex , Lloyd Alun L. , Waller Lance A. , Kitron Uriel , Paz-Soldan Valerie A. , Elder John P. , Rothman Alan L. , Civitello David J. , Elson William H. , Morrison Amy C. , Scott Thomas W. , Vazquez-Prokopec Gonzalo M.
Published: January 2021

Heterogeneous exposure to mosquitoes determines an individual’s contribution to vector-borne pathogen transmission. Particularly for dengue virus (DENV), there is a major difficulty in quantifying human-vector contacts due to the unknown coupled effect of key heterogeneities. To test the hypothesis that the reduction of human out-of-home mobility due to dengue illness will significantly influence population-level dynamics and the structure of DENV transmission chains, we extended an existing modeling framework to include social structure, disease-driven mobility reductions, and heterogeneous transmissibility from different infectious groups. Compared to a baseline model, naïve to human pre-symptomatic infectiousness and disease-driven mobility changes, a model including both parameters predicted an increase of 37% in the probability of a DENV outbreak occurring; a model including mobility change alone predicted a 15.5% increase compared to the baseline model. At the individual level, models including mobility change led to a reduction of the importance of out-of-home onward transmission (R, the fraction of secondary cases predicted to be generated by an individual) by symptomatic individuals (up to -62%) at the expense of an increase in the relevance of their home (up to +40%). An individual’s positive contribution to R could be predicted by a GAM including a non-linear interaction between an individual’s biting suitability and the number of mosquitoes in their home (>10 mosquitoes and 0.6 individual attractiveness significantly increased R). We conclude that the complex fabric of social relationships and differential behavioral response to dengue illness cause the fraction of symptomatic DENV infections to concentrate transmission in specific locations, whereas asymptomatic carriers (including individuals in their pre-symptomatic period) move the virus throughout the landscape. Our findings point to the difficulty of focusing vector control interventions reactively on the home of symptomatic individuals, as this approach will fail to contain virus propagation by visitors to their house and asymptomatic carriers.
Another dengue fever outbreak in Eastern Ethiopia—An emerging public health threat
Authors: Gutu Mulugeta Asefa , Bekele Alemayehu , Seid Yimer , Mohammed Yusuf , Gemechu Fekadu , Woyessa Abyot Bekele , Tayachew Adamu , Dugasa Yohanis , Gizachew Lehageru , Idosa Moti , Tokarz Ryan E. , Sugerman David
Published: January 2021

Background

Dengue Fever (DF) is a viral disease primarily transmitted by Aedes (Ae.) aegypti mosquitoes. Outbreaks in Eastern Ethiopia were reported during 2014–2016. In May 2017, we investigated the first suspected DF outbreak from Kabridahar Town, Somali region (Eastern Ethiopia) to describe its magnitude, assess risk factors, and implement control measures.

Methods

Suspected DF cases were defined as acute febrile illness plus ≥2 symptoms (headache, fever, retro-orbital pain, myalgia, arthralgia, rash, or hemorrhage) in Kabridahar District residents. All reported cases were identified through medical record review and active searches. Severe dengue was defined as DF with severe organ impairment, severe hemorrhage, or severe plasma leakage. We conducted a neighborhood-matched case-control study using a subset of suspected cases and conveniently-selected asymptomatic community controls and interviewed participants to collect demographic and risk factor data. We tested sera by RT-PCR to detect dengue virus (DENV) and identify serotypes. Entomologists conducted mosquito surveys at community households to identify species and estimate larval density using the house index (HI), container index (CI) and Breteau index (BI), with BI≥20 indicating high density.

Results

We identified 101 total cases from May 12–31, 2017, including five with severe dengue (one death). The attack rate (AR) was 17/10,000. Of 21 tested samples, 15 (72%) were DENV serotype 2 (DENV 2). In the case-control study with 50 cases and 100 controls, a lack of formal education (AOR [Adjusted Odds Ratio] = 4.2, 95% CI [Confidence Interval] 1.6–11.2) and open water containers near the home (AOR = 3.0, 95% CI 1.2–7.5) were risk factors, while long-lasting insecticide treated-net (LLITN) usage (AOR = 0.21, 95% CI 0.05–0.79) was protective. HI and BI were 66/136 (49%) and 147 per 100 homes (147%) respectively, with 151/167 (90%) adult mosquitoes identified as Ae. aegypti.

Conclusion

The epidemiologic, entomologic, and laboratory investigation confirmed a DF outbreak. Mosquito indices were far above safe thresholds, indicating inadequate vector control. We recommended improved vector surveillance and control programs, including best practices in preserving water and disposal of open containers to reduce Aedes mosquito density.
The cholera risk assessment in Kano State, Nigeria: A historical review, mapping of hotspots and evaluation of contextual factors
Authors: Ngwa Moise Chi , Ihekweazu Chikwe , Okwor Tochi , Yennan Sebastian , Williams Nanpring , Elimian Kelly , Karaye Nura Yahaya , Bello Imam Wada , Sack David A.
Published: January 2021

Nigeria is endemic for cholera since 1970, and Kano State report outbreaks annually with high case fatality ratios ranging from 4.98%/2010 to 5.10%/2018 over the last decade. However, interventions focused on cholera prevention and control have been hampered by a lack of understanding of hotspot Local Government Areas (LGAs) that trigger and sustain yearly outbreaks. The goal of this study was to identify and categorize cholera hotspots in Kano State to inform a national plan for disease control and elimination in the State. We obtained LGA level confirmed and suspected cholera data from 2010 to 2019 from the Nigeria Centre for Disease Control (NCDC) and Kano State Ministry of Health. Data on inland waterbodies and population numbers were obtained from online sources and NCDC, respectively. Clusters (hotspots) were identified using SaTScan through a retrospective analysis of the data for the ten-year period using a Poisson discrete space-time scan statistic. We also used a method newly proposed by the Global Task Force on Cholera Control (GTFCC) to identify and rank hotspots based on two epidemiological indicators including mean annual incidence per 100 000 population of reported cases and the persistence of cholera for the study period. In the ten-year period, 16,461 cholera cases were reported with a case fatality ratio of 3.32% and a mean annual incidence rate of 13.4 cases per 100 000 population. Between 2010 and 2019, the most severe cholera exacerbations occurred in 2014 and 2018 with annual incidence rates of 58.01 and 21.52 cases per 100 000 inhabitants, respectively. Compared to 2017, reported cases and deaths increased by 214.56% and 406.67% in 2018. The geographic distribution of outbreaks revealed considerable spatial heterogeneity with the widest in 2014. Space-time clustering analysis identified 18 out of 44 LGAs as high risk for cholera (hotspots) involving both urban and rural LGAs. Cholera clustered around water bodies, and the relative risk of having cholera inside the hotspot LGA were 1.02 to 3.30 times higher than elsewhere in the State. A total of 4,894,144 inhabitants were in these hotspots LGAs. Of these, six LGAs with a total population of 1.665 million had a relative risk greater than 2 compared to the state as a whole. The SaTScan (statistical) and GTFCC methods were in agreement in hotspots identification. This study identified cholera hotspots LGAs in Kano State from 2010–2019. Hotspots appeared in both urban and rural settings. Focusing control strategies on these hotspots will facilitate control and eliminate cholera from the State.
Coffee consumption and risk of breast cancer: A Mendelian randomization study
Authors: Ellingjord-Dale Merete , Papadimitriou Nikos , Katsoulis Michail , Yee Chew , Dimou Niki , Gill Dipender , Aune Dagfinn , Ong Jue-Sheng , MacGregor Stuart , Elsworth Benjamin , Lewis Sarah J. , Martin Richard M. , Riboli Elio , Tsilidis Konstantinos K.
Published: January 2021

Background

Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer.

Methods

We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations.

Results

One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80–1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79–1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75–1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80–1.25), weighted median (OR: 0.97, 95% CI: 0.89–1.05) and weighted mode (OR: 1.00, CI: 0.93–1.07).

Conclusions

The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
Availability and factors influencing community level handwashing facility in Ethiopia: Implication for prevention of infectious diseases
Authors: Odo Daniel Bogale , Mekonnen Alemayehu Gonie
Published: January 2021

Background

Handwashing is one of the most effective ways to prevent transmission of infectious diseases. A substantial body of research has examined the status and determinants of handwashing facilities in healthcare settings and schools. However, its status at home in the community, especially in developing countries, remains unclear. This study aimed to examine the availability and factors influencing basic handwashing facilities at households in Ethiopia.

Method

We analysed the 2016 Ethiopian Demographic and Health Survey (EDHS) data. EDHS employed a two-stage stratified cluster sampling technique. Data were collected from the lowest administrative unit (kebele). A multivariable logistic regression model that allowed cluster-level random effects was employed to examine factors that affect the availability of basic handwashing facilities (water plus soap) at households. Estimates from the regression model are reported as odds ratios (ORs) with standard errors clustered at the DHS cluster level to account for a sampling methodology.

Results

In our sample, only 1292 (8% [95% CI, 7.6%–8.4%]) of the households had basic handwashing facilities. Compared with head of household who had no formal education, the odds of having basic handwashing facilities was higher among head of household who completed secondary level of education (adjusted odds ratio [AOR] = 1.83; 95% CI: 1.35–2.49) and higher level of education (AOR = 2.35; 95% CI: 1.63–3.39). Odds of having basic handwashing facilities was increased with having radio (AOR = 1.32; 95% CI: 1.10–1.63) and television (AOR = 1.49; 95% CI: 1.10–2.02) at home. Households that had improved latrine were two times more likely to have basic handwashing facilities (AOR = 2.09; 95% CI: 1.56–2.80). Being at higher household wealth quintiles was associated with increased odds of having basic handwashing facilities.

Conclusion

Very low basic handwashing facilities was demonstrated by this study, whereas, awareness and socio-economic related factors were identified as a determinants for its availability in the household. Greater efforts are needed to increase the coverage of community-level handwashing facilities.
Public support for restoration: Does including ecosystem services as a goal engage a different set of values and attitudes than biodiversity protection alone?
Authors: Matzek Virginia , Wilson Kerrie A.
Published: January 2021

The ecosystem services concept has come into wide use in conservation and natural resource management, partly due to its appeal as an anthropocentric rationale for protecting and restoring nature. Proponents of the ecosystem services concept expect that presenting these arguments alongside biodiversity arguments should lead to a broader base of support for conservation. This raises the question of whether support for activities that ensure ecosystem service provision relates to different sets of core values, or environmental attitudes, than support for biodiversity protection. We surveyed adult Australians to evaluate the influence of values and attitudes on willingness to pay for different habitat restoration outcomes. We hypothesized that when restoration is framed with an anthropocentric rationale (such as ecosystem service provision), support for restoration would align more strongly with anthropocentric or self-centered values and attitudes. Specifically, we tested if preference for ecosystem service benefits over biodiversity attributes, as indicated by willingness to pay in different restoration scenarios, is more strongly associated with self-enhancing (Egoistic) than self-transcending (Altruistic and Biospheric) values, and more associated with a pro-use attitude towards nature (Utilization) than an anti-use attitude (Preservation). We found that support for habitat restoration is generally based on ecocentric values and attitudes, but that positive associations between pro-environmental behavior and Egoistic values emerge when emphasis is placed on ecosystem service outcomes. Individuals scoring higher on Egoistic/Utilization metrics were also more likely to anticipate disservices from restoration. Attitudes predicted behavioral intention (willingness to pay) better than core values. Our results support the notion that the ecosystem services concept garners nontraditional backers and broadens the appeal of ecological restoration.
Hepatic steatosis relates to gastrointestinal microbiota changes in obese girls with polycystic ovary syndrome
Authors: Jobira Beza , Frank Daniel N. , Silveira Lori J. , Pyle Laura , Kelsey Megan M. , Garcia-Reyes Yesenia , Robertson Charles E. , Ir Diana , Nadeau Kristen J. , Cree-Green Melanie
Published: January 2021

Objective

Hepatic steatosis (HS) is common in adolescents with obesity and polycystic ovary syndrome (PCOS). Gut microbiota are altered in adults with obesity, HS, and PCOS, which may worsen metabolic outcomes, but similar data is lacking in youth.

Methods

Thirty-four adolescents with PCOS and obesity underwent stool and fasting blood collection, oral glucose tolerance testing, and MRI for hepatic fat fraction (HFF). Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing.

Results

50% had HS (N = 17, age 16.2±1.5 years, BMI 38±7 kg/m2, HFF 9.8[6.5, 20.7]%) and 50% did not (N = 17, age 15.8±2.2 years, BMI 35±4 kg/m2, HFF 3.8[2.6, 4.4]%). The groups showed no difference in bacterial α-diversity (richness p = 0.202; evenness p = 0.087; and diversity p = 0.069) or global difference in microbiota (β-diversity). Those with HS had lower % relative abundance (%RA) of Bacteroidetes (p = 0.013), Bacteroidaceae (p = 0.009), Porphyromonadaceae (p = 0.011), and Ruminococcaceae (p = 0.008), and higher Firmicutes:Bacteroidetes (F:B) ratio (47.8% vs. 4.3%, p = 0.018) and Streptococcaceae (p = 0.034). Bacterial taxa including phyla F:B ratio, Bacteroidetes, and family Bacteroidaceae, Ruminococcaceae and Porphyromonadaceae correlated with metabolic markers.

Conclusions

Obese adolescents with PCOS and HS have differences in composition of gut microbiota, which correlate with metabolic markers, suggesting a modifying role of gut microbiota in HS and PCOS.