bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition and Dispersion of Radio‐Cesium Released due to the Fukushima Nuclear Accident: 2. Sensitivity to Aerosol Microphysical Properties of Cs‐Bearing Microparticles (CsMPs)
Authors: Kajino Mizuo , Adachi Kouji , Igarashi Yasuhito , Satou Yukihiko , Sawada Morihiro , Thomas Sekiyama Tsuyoshi , Zaizen Yuji , Saya Akane , Tsuruta Haruo , Moriguchi Yuichi
Published: December 2020

The dispersion and deposition of radio‐cesium (137Cs) carried by two types (type A and type B) of water‐insoluble Cs‐bearing solid microparticles (CsMPs) released due to the Fukushima nuclear accident were simulated for the first time. The presence of type B CsMPs (70–400 μm found in soil and 1–5 μm found in air), associated with the hydrogen explosion of Unit 1 in the afternoon of March 12, could partly explain the simulated underestimation of total deposition over land by assuming that 100% of the Cs carriers were water‐soluble submicron particles (WSPs). Type A CsMPs (0.1–10 μm), released from Units 2 or 3 in the midnight between March 14 and 15, traveled over the Kanto Plain, the most populated plain in Japan. Differences in the size distribution of type A CsMPs altered the surface air concentration over Kanto substantially, by up to more than one order of magnitude. The major deposition mechanisms varied among dry, wet, and fog (and/or cloud) depositions depending on the size distribution and locations. The simulated activity fractions due to the CsMPs in the total deposition were compared to those observed in surface soil for the first time. The observations could be explained by the simulations for the locations under the influence of type B CsMPs. However, the simulations were substantially underestimated for the locations influenced by type A CsMPs. There could be more fractions of type A CsMPs emission in the source term and/or the simulated deposition rates of type A CsMPs were underestimated.
Coupling of the CAS‐LSM Land‐Surface Model With the CAS‐FGOALS‐g3 Climate System Model
Authors: Xie Jinbo , Xie Zhenghui , Jia Binghao , Qin Peihua , Liu Bin , Wang Longhuan , Wang Yan , Li Ruichao , Chen Si , Liu Shuang , Zeng Yujing , Gao Junqiang , Li Lijuan , Yu Yongqiang , Dong Li , Wang Bin , Xie Zhipeng
Published: December 2020

The land‐surface model of the Chinese Academy of Sciences (CAS‐LSM), which includes lateral flow, water use, nitrogen discharge and river transport, soil freeze‐thaw front dynamics, and urban planning, was implemented in the Flexible Global Ocean‐Atmosphere‐Land System model, grid‐point version 3 (CAS‐FGOALS‐g3) to investigate the climatic effects of eco‐hydrological processes and human activities. Simulations were conducted using the land‐atmospheric component setup of CAS‐FGOALS‐g3 with given sea‐surface temperatures and sea‐ice distributions to assess its new capabilities. It was shown that anthropogenic groundwater use led to increased latent heat flux of about 20 W∙m−2 in three groundwater overexploitation areas: North India, northern China, and central United States. The groundwater lateral flow accompanied by this exploitation has led to deepening water table depth in these regions. The derived permafrost extent from the soil freeze‐thaw front (FTF) was comparable to observations, and the inclusion of FTF dynamics enabled simulations of seasonal variations in freeze‐thaw processes and related eco‐hydrological effects. Inclusion of riverine nitrogen transport and its joint implementation with the human activity scheme showed large dissolved inorganic nitrogen concentrations in major rivers around the globe, including western Europe, eastern China, and the U.S. Midwest, which were affected by nitrogen retention and surface water use during transport. The results suggest that the model is a useful tool for studying the effects of land‐surface processes on global climate, especially those influenced by human interventions.
Detecting Shallow Groundwater From Spaceborne Soil Moisture Observations
Authors: Soylu Mehmet E. , Bras Rafael L.
Published: December 2020

In order to accurately estimate surface fluxes, groundwater levels need to be specified accurately. However, monitoring Groundwater (GW) is challenging. The main goal of this study is to develop an innovative, yet simple, approach to detect shallow GW based solely on spaceborne soil moisture observations and apply this approach to improve the lower boundary conditions of soil moisture models. We simulated the influence of shallow GW on surface soil moisture under various environmental conditions and the results showed that the mean soil moisture and its Coefficient of Variation (CV) are both sensitive to shallow GW. Using those observations, we developed an algorithm that uses empirical functions calculating thresholds of mean soil moisture and CV to detect occurrence of shallow GW. We tested this algorithm in five different locations representing various climatic regions across the US, Argentina, and Australia. The algorithm performed well by correctly identifying periods of GW influence 92.4% of the time. We confirmed the algorithm by applying it over two regions: The Pampas, Argentina, and Southwestern Australia. The results indicate that our SMAP‐based algorithm successfully detects the shallow groundwater influenced time periods and significantly improves one particular soil moisture model output when the lower boundary conditions are adjusted according to the detection of shallow groundwater. The SMAP‐based method presented here addresses the growing need for observation‐based approaches to detect shallow groundwater at regional to global scales that may be beneficial to improving land surface and Earth system models.
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation
Authors: Coni Sonia , Serrao Silvia Maria , Yurtsever Zuleyha Nihan , Di Magno Laura , Bordone Rosa , Bertani Camilla , Licursi Valerio , Ianniello Zaira , Infante Paola , Moretti Marta , Petroni Marialaura , Guerrieri Francesca , Fatica Alessandro , Macone Alberto , De Smaele Enrico , Di Marcotullio Lucia , Giannini Giuseppe , Maroder Marella , Agostinelli Enzo , Canettieri Gianluca
Published: December 2020

Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, polyamine homeostasis, energy metabolism, and plays a role in cancer. However, the effects of EIF5A inhibition in preclinical cancer models, the mechanism of action, and specific translational targets are still poorly understood. We show here that hypusinated EIF5A promotes growth of colorectal cancer (CRC) cells by directly regulating MYC biosynthesis at specific pausing motifs. Inhibition of EIF5A hypusination with the DHPS inhibitor GC7 or through lentiviral-mediated knockdown of DHPS or EIF5A reduces the growth of various CRC cells. Multiplex gene expression analysis reveals that inhibition of hypusination impairs the expression of transcripts regulated by MYC, suggesting the involvement of this oncogene in the observed effect. Indeed, we demonstrate that EIF5A regulates MYC elongation without affecting its mRNA content or protein stability, by alleviating ribosome stalling at five distinct pausing motifs in MYC CDS. Of note, we show that blockade of the hypusination axis elicits a remarkable growth inhibitory effect in preclinical models of CRC and significantly reduces the size of polyps in APCMin/+ mice, a model of human familial adenomatous polyposis (FAP). Together, these data illustrate an unprecedented mechanism, whereby the tumor-promoting properties of hypusinated EIF5A are linked to its ability to regulate MYC elongation and provide a rationale for the use of DHPS/EIF5A inhibitors in CRC therapy.
Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency
Authors: Ouwendijk Werner J. D. , Depledge Daniel P. , Rajbhandari Labchan , Lenac Rovis Tihana , Jonjic Stipan , Breuer Judith , Venkatesan Arun , Verjans Georges M. G. M. , Sadaoka Tomohiko
Published: December 2020

Varicella-zoster virus (VZV) establishes lifelong neuronal latency in most humans world-wide, reactivating in one-third to cause herpes zoster and occasionally chronic pain. How VZV establishes, maintains and reactivates from latency is largely unknown. VZV transcription during latency is restricted to the latency-associated transcript (VLT) and RNA 63 (encoding ORF63) in naturally VZV-infected human trigeminal ganglia (TG). While significantly more abundant, VLT levels positively correlated with RNA 63 suggesting co-regulated transcription during latency. Here, we identify VLT-ORF63 fusion transcripts and confirm VLT-ORF63, but not RNA 63, expression in human TG neurons. During in vitro latency, VLT is transcribed, whereas VLT-ORF63 expression is induced by reactivation stimuli. One isoform of VLT-ORF63, encoding a fusion protein combining VLT and ORF63 proteins, induces broad viral gene transcription. Collectively, our findings show that VZV expresses a unique set of VLT-ORF63 transcripts, potentially involved in the transition from latency to lytic VZV infection.
An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake
Authors: Zhang Jia , Chen Dan , Sweeney Patrick , Yang Yunlei
Published: December 2020

It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. However, the feeding circuit for the VMH regulation of food intake remains to be defined. Here, we combine fiber photometry, chemo/optogenetics, virus-assisted retrograde tracing, ChR2-assisted circuit mapping and behavioral assays to show that selective activation of VMH neurons expressing steroidogenic factor 1 (SF1) rapidly inhibits food intake, VMH SF1 neurons project dense fibers to the paraventricular thalamus (PVT), selective chemo/optogenetic stimulation of the PVT-projecting SF1 neurons or their projections to the PVT inhibits food intake, and chemical genetic inactivation of PVT neurons diminishes SF1 neural inhibition of feeding. We also find that activation of SF1 neurons or their projections to the PVT elicits a flavor aversive effect, and selective optogenetic stimulation of ChR2-expressing SF1 projections to the PVT elicits direct excitatory postsynaptic currents. Together, our data reveal a neural circuit from VMH to PVT that inhibits food intake.
Inhibition of protein glycosylation is a novel pro-angiogenic strategy that acts via activation of stress pathways
Authors: Zhong Cuiling , Li Pin , Argade Sulabha , Liu Lixian , Chilla’ Anastasia , Liang Wei , Xin Hong , Eliceiri Brian , Choudhury Biswa , Ferrara Napoleone
Published: December 2020

Endothelial cell (EC) metabolism is thought to be one of the driving forces for angiogenesis. Here we report the identification of the hexosamine D-mannosamine (ManN) as an EC mitogen and survival factor for bovine and human microvascular EC, with an additivity with VEGF. ManN inhibits glycosylation in ECs and induces significant changes in N-glycan and O-glycan profiles. We further demonstrate that ManN and two N-glycosylation inhibitors stimulate EC proliferation via both JNK activation and the unfolded protein response caused by ER stress. ManN results in enhanced angiogenesis in a mouse skin injury model. ManN also promotes angiogenesis in a mouse hindlimb ischemia model, with accelerated limb blood flow recovery compared to controls. In addition, intraocular injection of ManN induces retinal neovascularization. Therefore, activation of stress pathways following inhibition of protein glycosylation can promote EC proliferation and angiogenesis and may represent a therapeutic strategy for treatment of ischemic disorders.
Consistent effects of pesticides on community structure and ecosystem function in freshwater systems
Authors: Rumschlag Samantha L. , Mahon Michael B. , Hoverman Jason T. , Raffel Thomas R. , Carrick Hunter J. , Hudson Peter J. , Rohr Jason R.
Published: December 2020

Predicting ecological effects of contaminants remains challenging because of the sheer number of chemicals and their ambiguous role in biodiversity-ecosystem function relationships. We evaluate responses of experimental pond ecosystems to standardized concentrations of 12 pesticides, nested in four pesticide classes and two pesticide types. We show consistent effects of herbicides and insecticides on ecosystem function, and slightly less consistent effects on community composition. Effects of pesticides on ecosystem function are mediated by alterations in the abundance and community composition of functional groups. Through bottom-up effects, herbicides reduce respiration and primary productivity by decreasing the abundance of phytoplankton. The effects of insecticides on respiration and primary productivity of phytoplankton are driven by top-down effects on zooplankton composition and abundance, but not richness. By demonstrating consistent effects of pesticides on communities and ecosystem functions and linking pesticide-induced changes in functional groups of organisms to ecosystem functions, the study suggests that ecological risk assessment of registered chemicals could be simplified to synthetic chemical classes or types and groups of organisms with similar functions and chemical toxicities.
Laser reprogramming magnetic anisotropy in soft composites for reconfigurable 3D shaping
Authors: Deng Heng , Sattari Kianoosh , Xie Yunchao , Liao Ping , Yan Zheng , Lin Jian
Published: December 2020

Responsive soft materials capable of exhibiting various three-dimensional (3D) shapes under the same stimulus are desirable for promising applications including adaptive and reconfigurable soft robots. Here, we report a laser rewritable magnetic composite film, whose responsive shape-morphing behaviors induced by a magnetic field can be digitally and repeatedly reprogrammed by a facile method of direct laser writing. The composite film is made from an elastomer and magnetic particles encapsulated by a phase change polymer. Once the phase change polymer is temporarily melted by transient laser heating, the orientation of the magnetic particles can be re-aligned upon change of a programming magnetic field. By the digital laser writing on selective areas, magnetic anisotropies can be encoded in the composite film and then reprogrammed by repeating the same procedure, thus leading to multimodal 3D shaping under the same actuation magnetic field. Furthermore, we demonstrated their functional applications in assembling multistate 3D structures driven by the magnetic force-induced buckling, fabricating multistate electrical switches for electronics, and constructing reconfigurable magnetic soft robots with locomotion modes of peristalsis, crawling, and rolling.
Experimental protection of quantum coherence by using a phase-tunable image drive
Authors: Bertaina S. , Vezin H. , De Raedt H. , Chiorescu I.
Published: December 2020

The protection of quantum coherence is essential for building a practical quantum computer able to manipulate, store and read quantum information with a high degree of fidelity. Recently, it has been proposed to increase the operation time of a qubit by means of strong pulses to achieve a dynamical decoupling of the qubit from its environment. We propose and demonstrate a simple and highly efficient alternative route based on Floquet modes, which increases the Rabi decay time ($$T_R$$

T
R

) in a number of materials with different spin Hamiltonians and environments. We demonstrate the regime $$T_R \approx T_1$$

T
R

≈

T
1

with $$T_1$$

T
1

the relaxation time, thus providing a route for spin qubits and spin ensembles to be used in quantum information processing and storage.
A longitudinal analysis of loneliness, social isolation and falls amongst older people in England
Authors: Bu Feifei , Abell Jessica , Zaninotto Paola , Fancourt Daisy
Published: December 2020

Loneliness and social isolation have been identified as important predictors of various health outcomes, but little research has investigated their influence on falls. This study aimed to investigate the longitudinal association between loneliness, social isolation and falls amongst older adults in England, looking at both self-reported falls and falls that require hospital admissions. This study drew on large scale, nationally representative data from the English Longitudinal Study of Ageing linked with Hospital Episode Statistics. Data were analysed using survival analysis, with self-reported falls (total sample = 4013) and falls require hospital admission being modelled separately (total sample = 9285). There was a 5% increase in the hazard of self-reported falls relative to one point increase in loneliness independent of socio-demographic factors (HR: 1.05, 95% CI: 1.02–1.08), but the association was explained away by individual differences in health and life-style measures (HR: 1.03, 95% CI: 1.00–1.07). Both living alone (HR: 1.18, 95% CI: 1.07–1.32) and low social contact (HR: 1.04, 95% CI: 1.01–1.07) were associated with a greater hazard of self-reported falls even after controlling for socio-demographic, health and life-style differences. Similar results were also found for hospital admissions following a fall. Our findings were robust to a variety of model specifications.
Pragmatic spatial sampling for wearable MEG arrays
Authors: Tierney Tim M. , Mellor Stephanie , O’Neill George C. , Holmes Niall , Boto Elena , Roberts Gillian , Hill Ryan M. , Leggett James , Bowtell Richard , Brookes Matthew J. , Barnes Gareth R.
Published: December 2020

Several new technologies have emerged promising new Magnetoencephalography (MEG) systems in which the sensors can be placed close to the scalp. One such technology, Optically Pumped MEG (OP-MEG) allows for a scalp mounted system that provides measurements within millimetres of the scalp surface. A question that arises in developing on-scalp systems is: how many sensors are necessary to achieve adequate performance/spatial discrimination? There are many factors to consider in answering this question such as the signal to noise ratio (SNR), the locations and depths of the sources, density of spatial sampling, sensor gain errors (due to interference, subject movement, cross-talk, etc.) and, of course, the desired spatial discrimination. In this paper, we provide simulations which show the impact these factors have on designing sensor arrays for wearable MEG. While OP-MEG has the potential to provide high information content at dense spatial samplings, we find that adequate spatial discrimination of sources (< 1 cm) can be achieved with relatively few sensors (< 100) at coarse spatial samplings (~ 30 mm) at high SNR. After this point approximately 50 more sensors are required for every 1 mm improvement in spatial discrimination. Comparable discrimination for traditional cryogenic systems require more channels by these same metrics. We also show that sensor gain errors have the greatest impact on discrimination between deep sources at high SNR. Finally, we also examine the limitation that aliasing due to undersampling has on the effective SNR of on-scalp sensors.
Dynamic changes in cell size and corresponding cell fate after optic nerve injury
Authors: Davis Benjamin M. , Guo Li , Ravindran Nivedita , Shamsher Ehtesham , Baekelandt Veerle , Mitchell Hannah , Bharath Anil A. , De Groef Lies , Cordeiro M. Francesca
Published: December 2020

Identifying disease-specific patterns of retinal cell loss in pathological conditions has been highlighted by the emergence of techniques such as Detection of Apoptotic Retinal Cells and Adaptive Optics confocal Scanning Laser Ophthalmoscopy which have enabled single-cell visualisation in vivo. Cell size has previously been used to stratify Retinal Ganglion Cell (RGC) populations in histological samples of optic neuropathies, and early work in this field suggested that larger RGCs are more susceptible to early loss than smaller RGCs. More recently, however, it has been proposed that RGC soma and axon size may be dynamic and change in response to injury. To address this unresolved controversy, we applied recent advances in maximising information extraction from RGC populations in retinal whole mounts to evaluate the changes in RGC size distribution over time, using three well-established rodent models of optic nerve injury. In contrast to previous studies based on sampling approaches, we examined the whole Brn3a-positive RGC population at multiple time points over the natural history of these models. The morphology of over 4 million RGCs was thus assessed to glean novel insights from this dataset. RGC subpopulations were found to both increase and decrease in size over time, supporting the notion that RGC cell size is dynamic in response to injury. However, this study presents compelling evidence that smaller RGCs are lost more rapidly than larger RGCs despite the dynamism. Finally, using a bootstrap approach, the data strongly suggests that disease-associated changes in RGC spatial distribution and morphology could have potential as novel diagnostic indicators.
Cathepsin S provokes interleukin-6 (IL-6) trans-signaling through cleavage of the IL-6 receptor in vitro
Authors: Flynn Charlotte M. , Garbers Yvonne , Düsterhöft Stefan , Wichert Rielana , Lokau Juliane , Lehmann Christian H. K. , Dudziak Diana , Schröder Bernd , Becker-Pauly Christoph , Rose-John Stefan , Aparicio-Siegmund Samadhi , Garbers Christoph
Published: December 2020

The cytokine interleukin-6 (IL-6) fulfills its pleiotropic functions via different modes of signaling. Regenerative and anti-inflammatory activities are mediated via classic signaling, in which IL-6 binds to the membrane-bound IL-6 receptor (IL-6R). For IL-6 trans-signaling, which accounts for the pro-inflammatory properties of the cytokine, IL-6 activates its target cells via soluble forms of the IL-6R (sIL-6R). We have previously shown that the majority of sIL-6R in human serum originates from proteolytic cleavage and mapped the cleavage site of the IL-6R. The cleavage occurs between Pro-355 and Val-356, which is the same cleavage site that the metalloprotease ADAM17 uses in vitro. However, sIL-6R serum levels are unchanged in hypomorphic ADAM17ex/exmice, making the involvement of ADAM17 questionable. In order to identify other proteases that could be relevant for sIL-6R generation in vivo, we perform a screening approach based on the known cleavage site. We identify several candidate proteases and characterize the cysteine protease cathepsin S (CTSS) in detail. We show that CTSS is able to cleave the IL-6R in vitro and that the released sIL-6R is biologically active and can induce IL-6 trans-signaling. However, CTSS does not use the Pro-355/Val-356 cleavage site, and sIL-6R serum levels are not altered inCtss−/−mice. In conclusion, we identify a novel protease of the IL-6R that can induce IL-6 trans-signaling, but does not contribute to steady-state sIL-6R serum levels.
Effects of solid oxygen fertilizers and biochars on nitrous oxide production from agricultural soils in Florida
Authors: Bera Tanumoy , Inglett Kanika S. , Liu Guodong D.
Published: December 2020

Elevated levels of nitrous oxide (N2O) emissions are a matter of concern in agricultural soils especially when flooding (hypoxic conditions) results from over irrigation or frequent rains. This study is the first to report the use of two solid oxygen fertilizers (SOFs, calcium peroxide and magnesium peroxide) to reduce N2O production in mineral and organic soils amended with N fertilizer in a short-term laboratory incubation besides two biochars. In general, organic soil had greater N2O production than mineral soil. Soils amended with nitrogen fertilizer exhibited increased N2O production, by 74 times in mineral soil and 2 times in organic soil. Both solid oxygen fertilizers in mineral soil (98–99%) and calcium peroxide in organic soil (25%) successfully reduced N2O production than corresponding N fertilized treatments. Additionally, a greater level of available nitrate–N (52–57 and 225 mg kg−1 in mineral and organic soil, respectively) was recorded with the solid oxygen fertilizers. Corn residue biochar with N fertilizer increased N2O production in mineral soil but decreased in organic soil, while pine bark biochar with N did not affect the N2O production in either soil. Depending on soil, appropriate SOFs applied were able to reduce N2O production and maintain greater nitrate–N levels in flooded soil. Thus, solid oxygen fertilizers can potentially be used as an effective way to reduce N2O emission from hypoxic soil in agricultural production systems.
Atoms in separated resonators can jointly absorb a single photon
Authors: Garziano Luigi , Ridolfo Alessandro , Miranowicz Adam , Falci Giuseppe , Savasta Salvatore , Nori Franco
Published: December 2020

The coherent nonlinear process where a single photon simultaneously excites two or more two-level systems (qubits) in a single-mode resonator has recently been theoretically predicted. Here we explore the case where the two qubits are placed in different resonators in an array of two or three weakly coupled resonators. Investigating different setups and excitation schemes, we show that this process can still occur with a probability approaching one under specific conditions. The obtained results provide interesting insights into subtle causality issues underlying the simultaneous excitation processes of qubits placed in different resonators.
Anti-oxidant copper layer by remote mode N2 plasma for low temperature copper–copper bonding
Authors: Park Haesung , Seo Hankyeol , Kim Sarah Eunkyung
Published: December 2020

An anti-oxidant Cu layer was achieved by remote mode N2 plasma. Remote mode plasma treatment offers the advantages of having no defect formation, such as pinholes, by energetic ions. In this study, an activated Cu surface by Ar plasma chemically reacted with N free radicals to evenly form Cu nitride passivation over the entire Cu surface. According to chemical state analysis using XPS, Cu oxidation was effectively prevented in air, and the thickness of the Cu nitride passivation was within 3 nm. Based on statistical analysis using the DOE technique with N2 plasma variables, namely, RF power, working pressure, and plasma treatment time, we experimentally demonstrated that a lower RF power is the most effective for forming uniform Cu nitride passivation because of a lower plasma density. When the N2 plasma density reached approximately 109 cm−3 in which the remote mode was generated, high energy electrons in the plasma were significantly reduced and the amount of oxygen detected on the Cu surface was minimized. Finally, low temperature (300 °C) Cu–Cu bonding was performed with a pair of the anti-oxidant Cu layers formed by the remote mode N2 plasma. Cu atomic diffusion with new grains was observed across the bonded interface indicating significantly improved bonding quality over bare Cu–Cu bonding.
Mammary epithelial morphogenesis in 3D combinatorial microenvironments
Authors: Luisier Raphaelle , Girgin Mehmet , Lutolf Matthias P. , Ranga Adrian
Published: December 2020

Human mammary epithelial cells can proliferate and reorganize into polarized multi-cellular constructs in-vitro, thereby functioning as an important model system in recapitulating key steps of in-vivo morphogenesis. Current approaches to constructing such three-dimensional mimics of the in-vivo microenvironment have involved the use of complex and ill-defined naturally derived matrices, whose properties are difficult to manipulate independently, and which have therefore limited our ability to understand the extrinsic regulation of morphogenesis. Here, we employ an automated, high-throughput approach to array modular building blocks of synthetic components, and develop a systematic approach to analyze colonies resulting from these varied microenvironmental combinations. This methodology allows us to systematically map the relationship between microenvironmental properties and ensuing morphogenetic phenotypes. Our analysis reveals that apico-basal polarity of mammary epithelial cells occurs within a narrow range of matrix stiffness, and that phenotypic homogeneity is favored in matrices which are insensitive to MMP-mediated degradation. Furthermore, combinations of extracellular proteins in the matrix finely tune the morphology of the mammary colonies, suggesting that subtle disregulations of the microenvironment may play a significant role in pathological disease states. This approach, which leverages the combinatorial possibilities of modular synthetic artificial extracellular matrices with an automated technology platform, demonstrates how morphogenesis can be assessed systematically in 3D, and provides new insights into mammary epithelial multicellularity.
A novel nerve transection and repair method in mice: histomorphometric analysis of nerves, blood vessels, and muscles with functional recovery
Authors: Lee Jung Il , Gurjar Anagha A. , Talukder M. A. Hassan , Rodenhouse Andrew , Manto Kristen , O’Brien Mary , Govindappa Prem Kumar , Elfar John C.
Published: December 2020

Peripheral nerve transection is associated with permanent functional deficit even after advanced microsurgical repair. While it is difficult to investigate the reasons of poor functional outcomes of microsurgical repairs in humans, we developed a novel pre-clinical nerve transection method that allows reliable evaluation of nerve regeneration, neural angiogenesis, muscle atrophy, and functional recovery. Adult male C57BL/6 mice were randomly assigned to four different types of sciatic nerve transection: Simple Transection (ST), Simple Transection & Glue (TG), Stepwise Transection and Sutures (SU), and Stepwise Transection and Glue (STG). Mice were followed for 28 days for sciatic function index (SFI), and sciatic nerves and hind limb muscles were harvested for histomorphological and cellular analyses. Immunohistochemistry revealed more directional nerve fiber growth in SU and STG groups compared with ST and TG groups. Compared to ST and TG groups, optimal neural vessel density and branching index in SU and STG groups were associated with significantly decreased muscle atrophy, increased myofiber diameter, and improved SFI. In conclusion, our novel STG method represents an easily reproducible and reliable model with close resemblance to the pathophysiological characteristics of SU model, and this can be easily reproduced by any lab.
Death by SARS-CoV 2: a Romanian COVID-19 multi-centre comorbidity study
Authors: Pantea Stoian Anca , Pricop-Jeckstadt Mihaela , Pana Adrian , Ileanu Bogdan-Vasile , Schitea Ruxandra , Geanta Marius , Catrinoiu Doina , Suceveanu Andra Iulia , Serafinceanu Cristian , Pituru Silviu , Poiana Catalina , Timar Bogdan , Nitipir Cornelia , Parvu Simona , Arsene Andreea , Mazilu Laura , Toma Antonela , Hainarosie Razvan , Ceriello Antonio , Rizzo Manfredi , Jinga Viorel
Published: December 2020

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.
Impact of a recolonizing, cross-border carnivore population on ungulate harvest in Scandinavia
Authors: Wikenros Camilla , Sand Håkan , Månsson Johan , Maartmann Erling , Eriksen Ane , Wabakken Petter , Zimmermann Barbara
Published: December 2020

Predation from large carnivores and human harvest are the two main mortality factors affecting the dynamics of many ungulate populations. We examined long-term moose (Alces alces) harvest data from two countries that share cross-border populations of wolves (Canis lupus) and their main prey moose. We tested how a spatial gradient of increasing wolf territory density affected moose harvest density and age and sex composition of the harvested animals (n = 549,310), along a latitudinal gradient during 1995–2017. In areas containing average-sized wolf territories, harvest density was on average 37% (Norway) and 51% (Sweden) lower than in areas without wolves. In Sweden, calves made up a higher proportion of the moose harvest than in Norway, and this proportion was reduced with increased wolf territory density, while it increased in Norway. The proportion of females in the adult harvest was more strongly reduced in Sweden than in Norway as a response to increased wolf territory density. Moose management in both countries performed actions aimed to increase productivity in the moose population, in order to compensate for the increased mortality caused by wolves. These management actions are empirical examples of an adaptive management in response to the return of large carnivores.
Serotonin 2A (5-HT2A) receptor affects cell–matrix adhesion and the formation and maintenance of stress fibers in HEK293 cells
Authors: John Jayakumar Joe Anand Kumar , Panicker Mitradas. M. , Basu Basudha
Published: December 2020

5-HT2A, a G-protein coupled receptor, is widely expressed in the human body, including in the gastrointestinal tract, platelets and the nervous system. It mediates various functions, for e.g. learning, memory, mood regulation, platelet aggregation and vasoconstriction, but its involvement in cell-adhesion remains largely unknown. Here we report a novel role for 5-HT2A in cell–matrix adhesion.

In HEK293 cells, which are loosely adherent, expression and stimulation of human or rat 5-HT2A receptor by agonists such as serotonin or 2,5-dimethoxy-4-iodoamphetamine (DOI) led to a significant increase in adhesion, while inhibition of 5-HT2A by antipsychotics, such as risperidone, olanzapine or chlorpromazine prevented it. 5-HT2A activation gave rise to stress fibers in these cells and was also required for their maintenance. Mechanistically, the 5-HT2A-mediated adhesion was mediated by downstream PKC and Rho signaling. Since 5-HT2A is associated with many disorders such as dementia, depression and schizophrenia, its role in cell–matrix adhesion could have implications for neural circuits.
Selective hepatitis B and D virus entry inhibitors from the group of pentacyclic lupane-type betulin-derived triterpenoids
Authors: Kirstgen Michael , Lowjaga Kira Alessandra Alicia Theresa , Müller Simon Franz , Goldmann Nora , Lehmann Felix , Alakurtti Sami , Yli-Kauhaluoma Jari , Glebe Dieter , Geyer Joachim
Published: December 2020

Current treatment options against hepatitis B and D virus (HBV/HDV) infections have only limited curative effects. Identification of Na+/taurocholate co-transporting polypeptide (NTCP) as the high-affinity hepatic receptor for both viruses in 2012 enables target-based development of HBV/HDV cell-entry inhibitors. Many studies already identified appropriate NTCP inhibitors. However, most of them interfere with NTCP’s physiological function as a hepatic bile acid transporter. To overcome this drawback, the present study aimed to find compounds that specifically block HBV/HDV binding to NTCP without affecting its transporter function. A novel assay was conceptualized to screen for both in parallel; virus binding to NTCP (measured via binding of a preS1-derived peptide of the large HBV/HDV envelope protein) and bile acid transport via NTCP. Hits were subsequently validated by in vitro HDV infection studies using NTCP-HepG2 cells. Derivatives of the birch-derived pentacyclic lupane-type triterpenoid betulin revealed clear NTCP inhibitory potency and selectivity for the virus receptor function of NTCP. Best performing compounds in both aspects were 2, 6, 19, and 25. In conclusion, betulin derivatives show clear structure–activity relationships for potent and selective inhibition of the HBV/HDV virus receptor function of NTCP without tackling its physiological bile acid transport function and therefore are promising drug candidates.
Studying the effect of lockdown using epidemiological modelling of COVID-19 and a quantum computational approach using the Ising spin interaction
Authors: Padhi Anshuman , Pradhan Sudev , Sahoo Pragna Paramita , Suresh Kalyani , Behera Bikash K. , Panigrahi Prasanta K.
Published: December 2020

COVID-19 is a respiratory tract infection that can range from being mild to fatal. In India, the countrywide lockdown has been imposed since 24th march 2020, and has got multiple extensions with different guidelines for each phase. Among various models of epidemiology, we use the SIR(D) model to analyze the extent to which this multi-phased lockdown has been active in ‘flattening the curve’ and lower the threat. Analyzing the effect of lockdown on the infection may provide a better insight into the evolution of epidemic while implementing the quarantine procedures as well as improving the healthcare facilities. For accurate modelling, incorporating various parameters along with sophisticated computational facilities are required. Parallel to SIRD modelling, we tend to compare it with the Ising model and derive a quantum circuit that incorporates the rate of infection and rate of recovery, etc as its parameters. The probabilistic plots obtained from the circuit qualitatively resemble the shape of the curve for the spread of Coronavirus. We also demonstrate how the curve flattens when the lockdown is imposed. This kind of quantum computational approach can be useful in reducing space and time complexities of a huge amount of information related to the epidemic.
Effects of disturbances by forest elephants on diversity of trees and insects in tropical rainforests on Mount Cameroon
Authors: Maicher Vincent , Delabye Sylvain , Murkwe Mercy , Doležal Jiří , Altman Jan , Kobe Ishmeal N. , Desmist Julie , Fokam Eric B. , Pyrcz Tomasz , Tropek Robert
Published: December 2020

Natural disturbances are essential for tropical forests biodiversity. In the Afrotropics, megaherbivores have played a key role before their recent decline. Contrastingly to savanna elephants, forest elephants’ impact on ecosystems remains poorly studied. Few decades ago, forests on Mount Cameroon were divided by lava flows, not being crossed by a local population of forest elephants until now. We assessed communities of trees, butterflies and two guilds of moths in the disturbed and undisturbed forests split by the longest lava flow. We surveyed 32 plots, recording 2025 trees of 97 species, and 7853 insects of 437 species. The disturbed forests differed in reduced tree density, height, and high canopy cover, and in increased DBH. Forest elephants’ selective browsing and foraging also decreased tree species richness and altered their composition. The elephant disturbance increased butterfly species richness and had various effects on species richness and composition of the insect groups. These changes were likely caused by disturbance-driven alterations of habitats and species composition of trees. Moreover, the abandonment of forests by elephants led to local declines of range-restricted butterflies. The recent declines of forest elephants across the Afrotropics probably caused similar changes in forest biodiversity and should be reflected by conservation actions.
Mechanical and structural characterisation of the dural venous sinuses
Authors: Walsh Darragh R. , Lynch James J. , O’ Connor David T. , Newport David T. , Mulvihill John J. E.
Published: December 2020

The dural venous sinuses play an integral role in draining venous blood from the cranial cavity. As a result of the sinuses anatomical location, they are of significant importance when evaluating the mechanopathology of traumatic brain injury (TBI). Despite the importance of the dural venous sinuses in normal neurophysiology, no mechanical analyses have been conducted on the tissues. In this study, we conduct mechanical and structural analysis on porcine dural venous sinus tissue to help elucidate the tissues’ function in healthy and diseased conditions. With longitudinal elastic moduli values ranging from 33 to 58 MPa, we demonstrate that the sinuses exhibit higher mechanical stiffness than that of native dural tissue, which may be of interest to the field of TBI modelling. Furthermore, by employing histological staining and a colour deconvolution protocol, we show that the sinuses have a collagen-dominant extracellular matrix, with collagen area fractions ranging from 84 to 94%, which likely explains the tissue’s large mechanical stiffness. In summary, we provide the first investigation of the dural venous sinus mechanical behaviour with accompanying structural analysis, which may aid in understanding TBI mechanopathology.
DendroScan: an open source tool to conduct comparative statistical tests and dendrogrammatic analyses on particle morphometry
Authors: Dürig T. , Schmidt L. S. , White J. D. L. , Bowman M. H.
Published: December 2020

Quantitative shape analysis of juvenile pyroclasts is applied in volcanology to reconstruct the dynamics and styles of eruptions, and to explore the details of tephra transport, dispersal, and emplacement. Morphometric analyses often include comparison of multiple data sets with a set of dimensionless shape parameters. Here we present “DendroScan”, an open source Matlab program that provides the user with all the multivariate statistical methods needed to produce such morphometric comparisons. Serving as a statistical “toolbox”, DendroScan conducts Levene-, t-, and equivalence tests, presenting the results in ad hoc interpretable graphs. Furthermore, it is designed to conduct dendrogrammatic analyses of particle morphometry, a recently developed approach for the inter-comparison of multiple morphometric data sets. DendroScan produces tree diagrams, in which the analysed samples are sorted according to their morphometric dissimilarity, allowing the user to identify, e.g., samples that are statistically equivalent. To demonstrate DendroScan’s potential, ten experimental samples are compared with volcanic ash samples generated by the Havre 2012 deep-sea eruption in the Kermadec arc (New Zealand). We show how, using DendroScan-based results, information on the eruptive mechanism can be inferred, and how the cooling history of the experimental melt is reflected in the dissimilarity of thermally granulated fragments.
Impacts of low-head hydropower plants on cyprinid-dominated fish assemblages in Lithuanian rivers
Authors: Virbickas Tomas , Vezza Paolo , Kriaučiūnienė Jūratė , Akstinas Vytautas , Šarauskienė Diana , Steponėnas Andrius
Published: December 2020

The meso-scale habitat simulation model MesoHABSIM was applied in three Lithuanian lowland rivers to study the effect of low-head hydropower plants (HPPs) on the fish habitats. Stream flow time series on a daily scale for the period 1970–2015 were used to describe flow regime downstream of HPPs for periods before and after their installation. Conditional habitat suitability criteria were developed for 4 species of cyprinid fish, schneider (Alburnoides bipunctatus), dace (Leuciscus leuciscus), roach (Rutilus rutilus) and vimba (Vimba vimba) to simulate their available habitat at different water discharges. Modelling results showed that HPPs have a significant impact on habitat availability in the low flow period in dry years below HPPs due to insufficient released flow. The environmental flow, as prescribed by the Lithuanian national law, is estimated between 80 and 95% exceedance probability of the mean minimum discharge of 30 days. This flow leads to a significant reduction in frequency and duration of available suitable habitats for vimba and schneider during low flow period. The roach habitat is the least affected. The results of habitat modelling are in line with the actual data on the occurrence and relative abundance of considered fish species in the studied river stretches. A general comparison of the relative abundance of modelled fish species in 42 natural river stretches and 20 stretches below the HPPs also showed that the relative abundance of roach is significantly higher, and that of schneider is significantly lower in river sections below the HPPs than the abundance in natural river sections. All results indicate that the current environmental flow does not secure survival of certain fish species. The applicability of the average low flow release during summer could be a plausible alternative to the current environmental flow in order to maintain ecosystem health and services.
Zika virus exposure affects neuron-glia communication in the hippocampal slices of adult rats
Authors: Bobermin Larissa Daniele , Quincozes-Santos André , Santos Camila Leite , Varela Ana Paula M. , Teixeira Thais F. , Wartchow Krista Minéia , Lissner Lílian Juliana , da Silva Amanda , Thomaz Natalie K. , Santi Lucélia , Beys-da-Silva Walter O. , Roehe Paulo M. , Sesterheim Patrícia , Guimarães Jorge A. , Gonçalves Carlos-Alberto , Souza Diogo Onofre
Published: December 2020

Zika virus (ZIKV) infection during pregnancy was associated with microcephaly in neonates, but clinical and experimental evidence indicate that ZIKV also causes neurological complications in adults. However, the changes in neuron-glial communication, which is essential for brain homeostasis, are still unknown. Here, we report that hippocampal slices from adult rats exposed acutely to ZIKV showed significant cellular alterations regarding to redox homeostasis, inflammatory process, neurotrophic functions and molecular signalling pathways associated with neurons and glial cells. Our findings support the hypothesis that ZIKV is highly neurotropic and its infection readily induces an inflammatory response, characterized by an increased expression and/or release of pro-inflammatory cytokines. We also observed changes in neural parameters, such as adenosine receptor A2a expression, as well as in the release of brain-derived neurotrophic factor and neuron-specific enolase, indicating plasticity synaptic impairment/neuronal damage. In addition, ZIKV induced a glial commitment, with alterations in specific and functional parameters such as aquaporin 4 expression, S100B secretion and glutathione synthesis. ZIKV also induced p21 senescence-associated gene expression, indicating that ZIKV may induce early senescence. Taken together, our results indicate that ZIKV-induced neuroinflammation, involving nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NFκB) pathways, affects important aspects of neuron-glia communication. Therefore, although ZIKV infection is transient, long-term consequences might be associated with neurological and/or neurodegenerative diseases.