bluuebunny/crossref_metadata_2025 huggingface dataset:
A strong alcoholic drink does not influence self-assessments of the big five personality traits
Authors: Paruzel-Czachura Mariola , Sorokowska Agnieszka , Bianga Paweł , Sorokowski Piotr , Gosling Sam
Published: November 2022

cAlohol affects how people think, feel, and behave, and how they perceive the physical and social world around them. But does alcohol also influence how people perceive themselves? Past work points to a number of possibilities, suggesting intoxication could lead to positive biases, to negative biases, or have no effects on self-assessments at all. Here we tested whether alcoholic intoxication affects self-assessments of personality within the Big Five personality framework. We hypothesized that intoxicated participants would see themselves more positively than non-intoxicated individuals would. We conducted a preregistered laboratory experiment on participants divided into three groups: alcohol intoxication (n = 106), placebo (n = 114), and control conditions (n = 109). Contrary to predictions, we found no differences in self-assessments of personality across conditions. Findings point to the possibility that self-assessments of personality may be too stable to be affected by the momentary changes in thoughts and feelings caused by alcoholic intoxication.
Decision support for efficient XAI services - A morphological analysis, business model archetypes, and a decision tree
Authors: Gerlach Jana , Hoppe Paul , Jagels Sarah , Licker Luisa , Breitner Michael H.
Published: November 2022

The black-box nature of Artificial Intelligence (AI) models and their associated explainability limitations create a major adoption barrier. Explainable Artificial Intelligence (XAI) aims to make AI models more transparent to address this challenge. Researchers and practitioners apply XAI services to explore relationships in data, improve AI methods, justify AI decisions, and control AI technologies with the goals to improve knowledge about AI and address user needs. The market volume of XAI services has grown significantly. As a result, trustworthiness, reliability, transferability, fairness, and accessibility are required capabilities of XAI for a range of relevant stakeholders, including managers, regulators, users of XAI models, developers, and consumers. We contribute to theory and practice by deducing XAI archetypes and developing a user-centric decision support framework to identify the XAI services most suitable for the requirements of relevant stakeholders. Our decision tree is founded on a literature-based morphological box and a classification of real-world XAI services. Finally, we discussed archetypical business models of XAI services and exemplary use cases.
The northernmost Eurasian Miocene beavers: Euroxenomys (Castoridae, Mammalia) from Olkhon Island, Lake Baikal (Eastern Siberia)
Authors: Mörs Thomas , Hägglund Signe , Erbajeva Margarita A. , Alexeeva Nadezhda , Shchetnikov Alexander A. , Daxner-Höck Gudrun
Published: November 2022

The castorid dental material described in this paper derives from Miocene, fossiliferous deposits of the Baikal rift valley, exposed at Tagay Bay on Olkhon Island in the Lake Baikal, in eastern Siberia. It consists of maxillary fragments and isolated upper and lower teeth of the small trogontheriine beaver Euroxenomys minutus (von Meyer, 1838). It is the first record of the species in Asia and at the same time the northernmost occurrence of Eurasian Miocene beavers. The magnetostratigraphic correlation of the Tagay -1 section, indicates a late Burdigalian, Early/early Middle Miocene age of ~16.5 to ~16.3 Ma that corresponds to the Mammalian Neogene zone MN4/5. The presence of E. minutus in Tagay is an indicator for an Orleanian European-Siberian bioprovince during the Mid-Miocene Climate Optimum, and for a continuous belt of humid, warm-temperate to subtropical forests, stretching from Europe to Siberia, and probably further to East and South-Eastern Asia. In Eurasia, beaver remains are an indicator of permanent water bodies, which is in agreement with the palaeoenvironment of the Tagay locality.
On the time dependence of the photon Compton wavelength
Authors: Fiordilino E
Published: November 2022

The Proca equation is a generalisation of the Maxwell equations that modifies the potential of a constant charge at rest from the Coulomb to the Yukawa form and describes massive photons. In this paper, we assume time-dependent photon mass and solve the Proca equation for a charge at rest. It is found that the vector potential is non-vanishing and that the scalar potential has the form$$\Phi \bigl (r,x^0\bigr )=f\bigl (r,x^0\bigr )/r$$Φ(r,x0)=f(r,x0)/rwith$$x^0=ct$$x0=ctand, thus, is space-time dependent. The solution shows that an oscillating potential pulse leaves the charge at$$x^0=0$$x0=0and propagates with the speed of the light to modify the initial Yukawa potential. Experimentally the change of sign of the potential field at the charge location can be interpreted as a change of the sign of the charge. The picture that emerges from the theory is, then, that of charges that at the initial time emit massive radiation that fills the Universe. The period of the field oscillation is, however, increasing and suggests that after a long time the potential may become stabilised. A noteworthy consequence of the theory is that the present form of the Maxwell electrodynamics is only temporarily true.
Differences in Cognitive Triad, Biased Information Processing, and Metacognitive Beliefs Between Women with Depression and Premenstrual Syndrome
Authors: Śliwerski Andrzej , Koszałkowska Karolina , Mrowicka Aleksandra , Szafran Marta
Published: November 2022

The timing of premenstrual syndrome (PMS) suggests that hormonal fluctuations are a key component in its pathogenesis. Unfortunately, women with PMS cannot be distinguished from asymptomatic women regarding biological markers. Research suggests that increased susceptibility to hormonal changes among women with PMS may be explained by the theory of cognitive vulnerability to affective disorders. The study group comprised 127 women (aged 19–35). The participants were divided into four groups: asymptomatic, nondepressed with PMS, depressed without PMS, and both depressed and with PMS. PMS was diagnosed by prospective daily reports, and depression by SCID-IV. All participants completed the Cognitive triad inventory (CTI), Metacognitive belief questionnaire (MCQ-30), and the self-referent information processing task (SRET) randomly either in the follicular or luteal phase. Findings indicated that only the asymptomatic women differed in cognitive processing from the depressed women. Those with PMS, despite demonstrating a slightly greater intensity of distorted cognitive processing, did not differ significantly from the asymptomatic participants; however, they differed from those with depression regarding in the cognitive triad. The phase of the cycle was not a significant factor in differentiating distorted cognitive processing. Depressed women have more distorted cognitive processes than non-depressed women. Women with PMS appear to be a group that lies between asymptomatic women and those who suffer from depression. Moreover, among women with depression, those with PMS have even more severe distorted cognitive processing than those without PMS.
RNA Structural Dynamics Modulate EGFR-TKI Resistance Through Controlling YRDC Translation in NSCLC Cells
Authors: Shi Boyang , An Ke , Wang Yueqin , Fei Yuhan , Guo Caixia , Cliff Zhang Qiangfeng , Yang Yun-Gui , Tian Xin , Kan Quancheng
Published: November 2022

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N  6  -threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3′ UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
Handbook of Hydraulic Geometry
Authors: Singh Vijay
Published: November 2022

Hydraulic geometry describes the relations between stable channel characteristics and discharge and adjustments made by a stream in response to changes in river discharge and sediment load. This book introduces hydraulic geometry and discusses different theories and their applications in river engineering, thus providing a comprehensive summary for hydraulic engineers, as well as graduate students and researchers in fluvial geomorphology and hydraulic and environmental engineering. Topics covered include the basis of power form of hydraulic geometry relations, validity and stability of power relations, state and assumption of equilibrium, variability of exponents, variation of channel width and velocity, and the effect of stream size and river channel patterns.
Investigating the English public's awareness of the Bern Convention and their education on environmental issues and laws
Authors: Dunn Rachel , Wyatt Tanya , Johnson Luke , Willis Callam , Millar Hannah
Published: November 2022

This paper investigates the knowledge of the general public on the legislative framework relating to wildlife conservation in England, with a specific focus on the Bern Convention and the public's awareness of the treaty, as well as the domestic legislation transposing it. By creating a publicly available survey, the study determined the environmental attitudes of the public and their knowledge of the legislative regime relating to wildlife conservation. Whilst the majority of the public displayed pro-environmental attitudes and support for greater efforts towards the conservation of flora and fauna, the overall awareness of the legislation was worryingly low, with only 5.6% of respondents recognising the Bern Convention. Accordingly, the study investigated how awareness of environmental legislation may be increased. Ultimately, the paper concludes that formal environmental education, including legislation, must be optimised, and the domestic legislative framework should be further consolidated.
Caring Piously: New Institutionalisation of Childcare Services in Turkey
Authors: Dedeoğlu Saniye , Şahankaya Adar Aslı
Published: November 2022

In Turkey, Early Childcare and Education (ECCE) policy has never been prioritised in the social policy agenda and was even further pushed back with the welfare state’s weakening role in the 2000s. The private sector, inaccessible for many, particularly low-income households, has tried to fill the significant gap in the supply side of these services. Municipalities and the Presidency of Religious Affairs (PoRA) have also recently become new actors in the provision of low-cost ‘care services’. This article compares the quality of these services by examining the number of students served, regulations, infrastructure, curricula, cost, and staff. Although neoliberalism has had an impact on welfare regimes in the European Union (EU) context, more established welfare and gender equality regimes have modified those impacts, resulting in a new institutionalisation, based on non-institutionalisation, of childcare services in Turkey’s national policy frame.
Ultraviolet Autofluorescence Microscopy of Nanotyrannus lancensis Sections Reveals Blood Clots in Vessel Canals
Authors: Armitage Mark H
Published: November 2022

Theropod dinosaurs have captured the imagination of the public and paleontologists alike. Histology of the bones of theropods has revealed much about dinosaur physiology, behavior, and growth. Histology and ultraviolet fluorescence (UVFL) microscopy of one controversial dinosaur, Nanotyrannus lancensis, reveals the presence of blood clots in post-fixed vessel canals of claw, vertebra, and other isolated post-cranial elements collected at Hell Creek, MT. These clots are thicker, more closely adherent to canal walls, and more reactive to 347 nm UVFL incident light than unfixed specimens. Theropod histology images in the literature display similar clots, and those should be subjected to UVFL for confirmation. In addition, nematodes are evidently preserved in vessel canals of dinosaurs.
Voices of resilience: The perspective of persons with disabilities in armed conflict
Authors: Hocq Nicolas , Assaf Nour
Published: November 2022

Novyi Bug is a town with a population of more than 15,000 residents. It is situated in the Bashtan district of the Mykolaiv region, in Ukraine. The situation in Novyi Bug remains very unpredictable. At the end of May 2022 there were attacks on the town of Novyi Bug and the Mykolaiv region was hit by rockets and missiles. Many civilian infrastructures, including inclusive resource centers, houses and hospital premises were either destroyed or damaged.
Cavitation‐Associated Water Evaporation From Porous Media Through In Situ NMR Characterization
Authors: Zhang Yadong , Li Hongxia , Haile Natnael F. , Alketbi Afra S. , AlAmoodi Nahla , Zhang TieJun
Published: November 2022

Evaporation of water from porous media is essential for a large variety of applications, whereas the opacity of porous matrix imposes considerable challenges in unveiling complicated phase‐change phenomena. Air invasion was previously reported as the major desaturation mechanism, while cavitation in porous media is not well studied. Herein we characterize the transient distribution and evaporation of water in homogeneous tight porous media with nondestructive nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). By monitoring the amplitude change of NMR transverse relaxation time T2, we investigate the dynamical pore filling status and water content during evaporation. Interestingly, we find that the T2 spectrum shifts immediately after the evaporation starts, indicating the emptying of big pores from the entire medium. Disconnected void clusters at different depths in the porous medium are also observed from MRI scanning and optical images. These observations indicate the emergence of cavitation across the entire porous media along with the evaporation from open surface. Cavitation occurs when the water is stretched to metastable state by large capillary pressure from the evaporating meniscus. By studying the evaporation from hydrophilic membrane‐separated porous media, we further demonstrate the existence of cavitation‐associated evaporation. The preferential water vaporization from the bottom part can still be found from T2 spectrum analysis and optical imaging even when the water‐permeable membrane cuts off possible air invasion. Our findings confirm cavitation‐associated evaporation is one of the primary mechanisms for tight porous media, which provides valuable guidance for evaporation and moisture control.
Assessing Predictability of Marine Heatwaves With Random Forests
Authors: Giamalaki K. , Beaulieu C. , Prochaska J. X.
Published: November 2022

Marine heatwaves (MHWs) have increased in frequency and duration over the last century and are expected to intensify in the future. Such events have become an increasing threat for marine ecosystems and subsequently the economies and populations that rely on them. Here we apply random forests to assess skill in forecasting MHWs onset and severity at multiple prediction lead times. Random forests models are trained on a range of atmospheric and oceanic conditions to identify precursors of MHWs. The best performing random forest model accurately captures (76%) MHW presence/absence in the northeast Pacific and is capable of forecasting realistic extreme sea surface temperature patterns at weekly lead times. However, the total accuracy drops to 38% when forecasting MHW severity. Machine learning algorithms affirm further exploration as forecasting tools and have the potential to accelerate our predictive ability and preparedness against upcoming extreme climate changes.
Cobalamin Co‐Limits Phytoplankton and Bacterial Biomass and Activity in Eastern Mediterranean Coastal Waters
Authors: Rahav Eyal , Silverman Jacob
Published: November 2022

In this study, we examined the response of phytoplankton and heterotrophic bacteria to B12 amendments in microcosm experiments in the coastal southeastern Mediterranean Sea (SEMS) during the summer, where ambient levels of dissolved B12 ranged from as low as ∼2 pmol L−1 to 60 pmol L−1 (median 5.3 pmol L−1). Additions of B12 (20 pmol L−1) to surface seawater triggered a 4‐fold increase in NO3+NO2 uptake compared to unamended seawater, resulting in proliferation of mainly pico/nano‐eukaryotic phytoplankton (∼30%) and increase in primary and bacterial productivity (40%–50%). Complimentary experiments that tested the combined effects of nutrient (NO3 and PO4) and B12 additions suggest that phytoplankton were primarily NO3 and B12 co‐limited, whereas heterotrophic bacteria were PO4 and B12 co‐limited. These results provide valuable information about the marine distribution of nutrient limitation in low nutrients low chlorophyll (LNLC) environments such as the SEMS, and how bacterioplankton might respond to environmental perturbations.
Does Uranus' Asymmetric Magnetic Field Produce a Relatively Weak Proton Radiation Belt?
Authors: Masters A. , Ioannou C. , Rayns N.
Published: November 2022

Since the Voyager 2 flyby in 1986 the radiation belts of Uranus have presented a problem for physicists. The observations indicate the electron radiation belt is far more intense than the proton radiation belt, and while the electron intensities are close to the upper theoretical limit, proton intensities are well below. Here we propose the relatively weak proton radiation belt could be due to Uranus' asymmetric magnetic field. We model test particle motion through the field to show that perturbations arising from asymmetry are greater the larger the particle gyroradius, predominantly affecting 100‐keV protons. For these particles, more rapid changes in maximum distance from the planet during a bounce motion promote trajectory evolution into regions where they could be lost through impact with the rings, impact with the atmosphere, or to the distant magnetosphere and solar wind. We suggest this could explain a relatively weak proton radiation belt at Uranus.
Common Error Patterns in the Regional Atmospheric Circulation Simulated by the CMIP Multi‐Model Ensemble
Authors: Brands Swen
Published: November 2022

The ability of global climate models to reproduce recurrent regional atmospheric circulation types is introduced as an overarching concept to explore potential dependencies between these models. If this approach is applied on a sufficiently large spatial domain, the similarity of the resulting error pattern can be compared from one model to another. By computing a pattern correlation matrix for a large multi‐model ensemble from the Coupled Model Intercomparison Project Phases 5 and 6, groups of comparatively strong correlation coefficients are obtained for those models working with similar atmospheric components. Thereby, frequent shared error patterns are found within the ensemble, which also occur for nominally different atmospheric component models. The error pattern correlation coefficients describing these similarities are nearly unrelated to model performance and can be used as statistical dependency weights.
Depth‐Varying Friction on a Ramp‐Flat Fault Illuminated by ∼3‐Year InSAR Observations Following the 2017 Mw 7.3 Sarpol‐e Zahab Earthquake
Authors: Guo Zelong , Motagh Mahdi , Hu Jyr‐Ching , Xu Guangyu , Haghighi Mahmud Haghshenas , Bahroudi Abbas , Fathian Aram , Li Shaoyang
Published: November 2022

We use interferometric synthetic aperture radar observations to investigate the fault geometry and afterslip evolution within 3 years after a mainshock. The postseismic observations favor a ramp‐flat structure in which the flat angle should be lower than 10°. The postseismic deformation is dominated by afterslip, while the viscoelastic response is negligible. A multisegment, stress‐driven afterslip model (hereafter called the SA‐2 model) with depth‐varying frictional properties better explains the spatiotemporal evolution of the postseismic deformation than a two‐segment, stress‐driven afterslip model (hereafter called the SA‐1 model). Although the SA‐2 model does not improve the misfit significantly, this multisegment fault with depth‐varying friction is more physically plausible given the depth‐varying mechanical stratigraphy in the region. Compared to the kinematic afterslip model, the mechanical afterslip models with friction variation tend to underestimate early postseismic deformation to the west, which may indicate more complex fault friction than we expected. Both the kinematic and stress‐driven models can resolve downdip afterslip, although it could be affected by data noise and model resolution. The transition depth of the sedimentary cover basement interface inferred by afterslip models is ∼12 km in the seismogenic zone, which coincides with the regional stratigraphic profile. Because the coseismic rupture propagated along a basement‐involved fault while the postseismic slip may activate the frontal structures and/or shallower detachments in the sedimentary cover, the 2017 Sarpol‐e Zahab earthquake may have acted as a typical event that contributed to both thick‐ and thin‐skinned shortening of the Zagros in both seismic and aseismic ways.
A Multi‐Layer Linear Rossby Wave Dispersion Relation for Vertical Tilt of Mesoscale Eddies
Authors: Li Hong , Xu Fanghua , Wang Guihua , Shi Ruizi
Published: November 2022

Vertical tilt of mesoscale eddies has been frequently observed in world oceans. The observations of composite eddies, individual eddies from an oceanic reanalysis product, and idealized numerical experiments of mesoscale eddies all show that the eddy vertical tilt is gradually increased with time in eddy mature stage, implying that the eddy translation speed changes with depth. However, eddy vertical tilt cannot be explained by the classic linear Rossby wave dispersion relation, since the classic zonal translation speed () of linear Rossby waves is depth‐independent from the quasi‐geostrophic potential vorticity (QGPV) equation. To deduce a depth‐dependent linear Rossby wave dispersion relation, we solved the QGPV equation by assuming that the stratified water column in oceans can be separated into a number of fine layers with constant stratification in each layer, whereas the stratification changes among layers. A multi‐layer linear Rossby wave (MLRW) dispersion relation in stratified oceans is then deduced. The MLRW dispersion relation shows that changes with depth. In each layer, is proportional to stratification and layer thickness but inversely proportional to Earth's rotation. The estimated structure from the MLRW dispersion relation is consistent with the structure of eddies in numerical experiments and the observed composite eddies. Noticeably, there are some discrepancies between the theoretical estimates and those from observations and numerical simulations, primarily due to the sensitivity of the theoretical estimates to layer thickness. The study attempts to provide an approach to describe and predict mesoscale eddy vertical tilt.
Oncosuppressive miRNAs loaded in lipid nanoparticles potentiate targeted therapies in BRAF-mutant melanoma by inhibiting core escape pathways of resistance
Authors: Fattore Luigi , Cafaro Giordana , Di Martile Marta , Campani Virginia , Sacconi Andrea , Liguoro Domenico , Marra Emanuele , Bruschini Sara , Stoppoloni Daniela , Cirombella Roberto , De Nicola Francesca , Pallocca Matteo , Ruggiero Ciro F. , Castaldo Vittorio , Catizone Angiolina , Del Bufalo Donatella , Viglietto Giuseppe , Vecchione Andrea , Blandino Giovanni , Aurisicchio Luigi , Fanciulli Maurizio , Ascierto Paolo A. , De Rosa Giuseppe , Mancini Rita , Ciliberto Gennaro
Published: November 2022

BRAF-mutated melanoma relapsing after targeted therapies is an aggressive disease with unmet clinical need. Hence the need to identify novel combination therapies able to overcome drug resistance. miRNAs have emerged as orchestrators of non-genetic mechanisms adopted by melanoma cells to challenge therapies. In this context we previously identified a subset of oncosuppressor miRNAs downregulated in drug-resistant melanomas. Here we demonstrate that lipid nanoparticles co-encapsulating two of them, miR-199-5p and miR-204-5p, inhibit tumor growth both in vitro and in vivo in combination with target therapy and block the development of drug resistance. Mechanistically they act by directly reducing melanoma cell growth and also indirectly by hampering the recruitment and reprogramming of pro-tumoral macrophages. Molecularly, we demonstrate that the effects on macrophages are mediated by the dysregulation of a newly identified miR-204-5p-miR-199b-5p/CCL5 axis. Finally, we unveiled that M2 macrophages programs are molecular signatures of resistance and predict response to therapy in patients. Overall, these findings have strong translational implications to propose new combination therapies making use of RNA therapeutics for metastatic melanoma patients.
Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer
Authors: Huang Shujun , Hu Pingzhao , Lakowski Ted M.
Published: November 2022

Our previous studies demonstrated that the FOXM1 pathway is upregulated and the PPARA pathway downregulated in breast cancer (BC), and especially in the triple negative breast cancer (TNBC) subtype. Targeting the two pathways may offer potential therapeutic strategies to treat BC, especially TNBC which has the fewest effective therapies available among all BC subtypes. In this study we identified small molecule compounds that could modulate the PPARA and FOXM1 pathways in BC using two methods. In the first method, data were initially curated from the Connectivity Map (CMAP) database, which provides the gene expression profiles of MCF7 cells treated with different compounds as well as paired controls. We then calculated the changes in the FOXM1 and PPARA pathway activities from the compound-induced gene expression profiles under each treatment to identify compounds that produced a decreased activity in the FOXM1 pathway or an increased activity in the PPARA pathway. In the second method, the CMAP database tool was used to identify compounds that could reverse the expression pattern of the two pathways in MCF7 cells. Compounds identified as repressing the FOXM1 pathway or activating the PPARA pathway by the two methods were compared. We identified 19 common compounds that could decrease the FOXM1 pathway activity scores and reverse the FOXM1 pathway expression pattern, and 13 common compounds that could increase the PPARA pathway activity scores and reverse the PPARA pathway expression pattern. It may be of interest to validate these compounds experimentally to further investigate their effects on TNBCs.
Caspase-8 is required for HSV-1-induced apoptosis and promotes effective viral particle release via autophagy inhibition
Authors: Marino-Merlo Francesca , Klett Anusha , Papaianni Emanuela , Drago Selene Francesca Anna , Macchi Beatrice , Rincón María Gabriela , Andreola Federica , Serafino Annalucia , Grelli Sandro , Mastino Antonio , Borner Christoph
Published: November 2022

Regulated cell death (RCD) plays an important role in the progression of viral replication and particle release in cells infected by herpes simplex virus-1 (HSV-1). However, the kind of RCD (apoptosis, necroptosis, others) and the resulting cytopathic effect of HSV-1 depends on the cell type and the species. In this study, we further investigated the molecular mechanisms of apoptosis induced by HSV-1. Although a role of caspase-8 has previously been suggested, we now clearly show that caspase-8 is required for HSV-1-induced apoptosis in a FADD-/death receptor-independent manner in both mouse embryo fibroblasts (MEF) and human monocytes (U937). While wild-type (wt) MEFs and U937 cells exhibited increased caspase-8 and caspase-3 activation and apoptosis after HSV-1 infection, respective caspase-8-deficient (caspase-8−/−) cells were largely impeded in any of these effects. Unexpectedly, caspase-8−/− MEF and U937 cells also showed less virus particle release associated with increased autophagy as evidenced by higher Beclin-1 and lower p62/SQSTM1 levels and increased LC3-I to LC3-II conversion. Confocal and electron microscopy revealed that HSV-1 stimulated a strong perinuclear multivesicular body response, resembling increased autophagy in caspase-8−/− cells, entrapping virions in cellular endosomes. Pharmacological inhibition of autophagy by wortmannin restored the ability of caspase-8−/− cells to release viral particles in similar amounts as in wt cells. Altogether our results support a non-canonical role of caspase-8 in both HSV-1-induced apoptosis and viral particle release through autophagic regulation.
Structural basis of tankyrase activation by polymerization
Authors: Pillay Nisha , Mariotti Laura , Zaleska Mariola , Inian Oviya , Jessop Matthew , Hibbs Sam , Desfosses Ambroise , Hopkins Paul C. R. , Templeton Catherine M. , Beuron Fabienne , Morris Edward P. , Guettler Sebastian
Published: November 2022

The poly-ADP-ribosyltransferase tankyrase (TNKS, TNKS2) controls a wide range of disease-relevant cellular processes, including WNT–β-catenin signalling, telomere length maintenance, Hippo signalling, DNA damage repair and glucose homeostasis1,2. This has incentivized the development of tankyrase inhibitors. Notwithstanding, our knowledge of the mechanisms that control tankyrase activity has remained limited. Both catalytic and non-catalytic functions of tankyrase depend on its filamentous polymerization3–5. Here we report the cryo-electron microscopy reconstruction of a filament formed by a minimal active unit of tankyrase, comprising the polymerizing sterile alpha motif (SAM) domain and its adjacent catalytic domain. The SAM domain forms a novel antiparallel double helix, positioning the protruding catalytic domains for recurring head-to-head and tail-to-tail interactions. The head interactions are highly conserved among tankyrases and induce an allosteric switch in the active site within the catalytic domain to promote catalysis. Although the tail interactions have a limited effect on catalysis, they are essential to tankyrase function in WNT–β-catenin signalling. This work reveals a novel SAM domain polymerization mode, illustrates how supramolecular assembly controls catalytic and non-catalytic functions, provides important structural insights into the regulation of a non-DNA-dependent poly-ADP-ribosyltransferase and will guide future efforts to modulate tankyrase and decipher its contribution to disease mechanisms.
The encoding of touch by somatotopically aligned dorsal column subdivisions
Authors: Turecek Josef , Lehnert Brendan P. , Ginty David D.
Published: November 2022

The somatosensory system decodes a range of tactile stimuli to generate a coherent sense of touch. Discriminative touch of the body depends on signals conveyed from peripheral mechanoreceptors to the brain through the spinal cord dorsal column and its brainstem target, the dorsal column nuclei (DCN)1,2. Models of somatosensation emphasize that fast-conducting low-threshold mechanoreceptors (LTMRs) innervating the skin drive the DCN3,4. However, postsynaptic dorsal column (PSDC) neurons within the spinal cord dorsal horn also collect mechanoreceptor signals and form a second major input to the DCN5–7. The significance of PSDC neurons and their contributions to the coding of touch have remained unclear since their discovery. Here we show that direct LTMR input to the DCN conveys vibrotactile stimuli with high temporal precision. Conversely, PSDC neurons primarily encode touch onset and the intensity of sustained contact into the high-force range. LTMR and PSDC signals topographically realign in the DCN to preserve precise spatial detail. Different DCN neuron subtypes have specialized responses that are generated by distinct combinations of LTMR and PSDC inputs. Thus, LTMR and PSDC subdivisions of the dorsal column encode different tactile features and differentially converge in the DCN to generate specific ascending sensory processing streams.
Organization of residential space, site function variability, and seasonality of activities among MIS 5 Iberian Neandertals
Authors: Deschamps Marianne , Martín-Lerma Ignacio , Linares-Matás Gonzalo , Zilhão João
Published: November 2022

Whether ethnoarcheological models of hunter-gatherer mobility, landscape use, and structuration of the inhabited space are relevant to the archeology of Neandertals and the Middle Paleolithic remains controversial. The thin lenses of hearth-associated stone tools and faunal remains excavated in sub-complex AS5 of Cueva Antón (Murcia, Spain) significantly advance these debates. Dated to 77.8–85.1 ka, these living floors are interstratified in river-accumulated sands and were buried shortly after abandonment by low-energy inundation events, with minimal disturbance and negligible palimpsest formation. Stone tools were made and ergonomically modified to fit tasks; their spatial distributions and use-wear reveal hearth-focused activities and a division of the inhabited space into resting and working areas. Site function varied with season of the year: units III-i/j1 and III-i/j2-3 record winter visits focused on filleting and hide processing, while woodworking predominated in unit III-b/d, which subsumes visits to the site over the course of at least one winter, one spring, and one summer. These snapshots of Neandertal behavior match expectations derived from the ethnographic and Upper Paleolithic records for the lifeways of hunter-gatherers inhabiting temperate regions with a markedly seasonal climate.
Arc discharge rapid synthesis of engineered copper oxides nano shapes with potent antibacterial activity against multi-drug resistant bacteria
Authors: Elwakil Bassma H. , Toderas M. , El-Khatib Mostafa
Published: November 2022

Nowadays Nano metals have received an eminent compromise of attention. Even though different nanostructure of same metal maybe gives different results in wide range applications. Copper oxide (CuO-NPs) and Copper Nano wires (CuO-NWs) were prepared in controlled size via the alternating current Arc discharge process. Deionized water and argon gas were the chosen dielectric medium during the process to obtain 2 different forms of copper oxides. By changing the dielectric material from deionized water to argon gas the shape of CuO nanoparticles changed from spherical (CuO-NPs) to wires (CuO-NWS). The yield prepared depicted the purity of the prepared CuO, and their diameters were about 10 ± 5 nm and 30 ± 3 nm for CuO-NWs and CuO-NPs respectively. In vitro cytotoxic effect of the prepared CuO-NWs & CuO-NPs using human normal lung fibroblast cell line (WI-38 cells) revealed that CuO-NWs & CuO-NPs CC50 values were 458.8 and 155.6 µg/mL respectively. Both yields showed potent antibacterial activity against different multi-drug resistant Acinetobacter baumannii strains. A complete eradication of the bacterial growth was noticed after 4 Hrs incubation with CuO-NWs. Moreover, CuO-NWs showed superior antibacterial activity (with minimum inhibitory concentration reached 1.8 µg/mL) over CuO-NPs. The detailed antibacterial activity mechanism of CuO-NWs was further investigated; data proved the precipitation and adsorption of the nanoparticles on the bacterial cell surface leading to cell deformation with reactive oxygen species increment. The results explicated that the nanoparticles shape plays an essential role in the antibacterial activity. Rotational Arc discharge machine might be a promising tool to obtain various metal nanostructures with low cost and environmentally friendly with potent activity.
Detecting hierarchical organization of pervasive communities by modular decomposition of Markov chain
Authors: Okamoto Hiroshi , Qiu Xule
Published: November 2022

Connecting nodes that contingently co-appear, which is a common process of networking in social and biological systems, normally leads to modular structure characterized by the absence of definite boundaries. This study seeks to find and evaluate methods to detect such modules, which will be called ‘pervasive’ communities. We propose a mathematical formulation to decompose a random walk spreading over the entire network into localized random walks as a proxy for pervasive communities. We applied this formulation to biological and social as well as synthetic networks to demonstrate that it can properly detect communities as pervasively structured objects. We further addressed a question that is fundamental but has been little discussed so far: What is the hierarchical organization of pervasive communities and how can it be extracted? Here we show that hierarchical organization of pervasive communities is unveiled from finer to coarser layers through discrete phase transitions that intermittently occur as the value for a resolution-controlling parameter is quasi-statically increased. To our knowledge, this is the first elucidation of how the pervasiveness and hierarchy, both hallmarks of community structure of real-world networks, are unified.
Bacterial etiology and risk factors among newborns suspected of sepsis at Hawassa, Ethiopia
Authors: Worku Endale , Fenta Demissie Assegu , Ali Musa Mohammed
Published: November 2022

Neonatal sepsis is a systemic infection that occurs at an early age. Its etiology varies from one region to the other. The contribution of sepsis to neonatal mortality and morbidity is significant in resource-limited countries; however, there is limited information about the etiology of sepsis in Sidama Regional State, Ethiopia. The aim of this study was to determine the prevalence of bacterial caused newborn sepsis, associated factors, and the antimicrobial susceptibility profile of bacteria. A hospital-based prospective cross-sectional study was conducted among 392 sepsis suspected newborns admitted to the neonatal intensive care unit of Hawassa University Comprehensive Specialized Hospital from March 2021 to November 2021. Blood specimens were collected and bacteria were isolated using the standard culture method. The drug resistance profile of bacteria was evaluated using the disk diffusion method. The socio-demographic and clinical parameters of participants were gathered using a questionnaire. Binary logistic regression was used to determine the determinants of sepsis. A variable with a p < 0.05 was considered a significant determinant of neonatal sepsis with a 95% confidence level. The prevalence of sepsis caused by bacteria among newborns was 143 (36.5%); 95% CI (31.3–41.4). The predominant bacteria was Klebsiella species (n = 61; 42.65%), followed by non-lactose fermenting Gram-negative bacteria (n = 27; 18.88%) and Enterococcus species (n = 26; 18.18%). The overall proportions of antimicrobial resistance of Gram-negative bacteria range from 10.2 to 99.1%. All Klebsiella species were resistant to ceftriaxone. Ppremature rupture of membrane [AOR = 12.7 (95% CI 6.430–25.106)], absence of respiratory support [AOR = 3.53 (95% CI 1.840–6.759)], sex of newborns [AOR = 2.10 (1.214–3.560)] and reason for admission [AOR = 3.17 (95% CI 1.278–7.859)] were significantly associated with culture-confirmed neonatal sepsis. This study indicated the contribution of bacteria in causing sepsis among newborns; the majority of them were Gram-negative bacteria. Most recovered bacteria were resistant to commonly used antibiotics. Pre-term, mode of delivery and types of respiratory support were significantly associated with the occurrence of sepsis caused by bacteria.
Suicide trends among Australian construction workers during years 2001–2019
Authors: Maheen Humaira , Taouk Yamna , LaMontagne Anthony D. , Spittal Matthew , King Tania
Published: November 2022

In many Western countries, including Australia, construction workers have been identified as being at elevated risk of suicide compared to other workers. A variety of suicide prevention initiatives have been implemented and expanded to reduce suicide in this occupational group; however, the net effect of these is unknown. Using 19 years of national suicide data, this study examined the suicide mortality of Australian male construction workers relative to all other working males, and compared suicide rates over time between the two groups. Age-standardized suicide rates were calculated for construction workers and those employed in other occupations. 2001–2019 trends in age-standardized rates of suicide mortality were analyzed by joinpoint regression analysis. The annual average percentage change (AAPC) measure was calculated for both groups to quantify change over time within each group, complemented by a pair-wise AAPC comparison of changes in trends between the two groups over the 2001–2019 period. Australian male construction workers' overall age-standardized suicide rate was 26.6 per 100,000 persons compared to 13.2 per 100,000 for male workers employed in other occupations (pooled over the entire 2001–2019 period). Over time, the suicide mortality rate declined in both construction workers and those working in other occupations; however, the decline in suicide mortality was greater in construction workers (AAPC: −3.0; 95%CI −4.0, −2.0) compared to other workers (AAPC: 1.5; 95%CI −2.1, −1.0). The AAPC pair-wise comparison showed a significant difference between the rate of decline among construction versus other workers over the 19-year study period (AAPC: −1.4; 95%CI 0.4, 2.5), confirming a rapid decline among construction versus other male workers. This study provides evidence of a decline in suicide rates among Australian construction workers over the last two decades. This decline may be attributable to the combined effects of population-wide, male-specific, and sector-specific suicide prevention efforts over this same period, suggesting that the continuation or expansion of such efforts may lead to further declines.
Ascorbic acid does not necessarily interfere with the electrochemical detection of dopamine
Authors: Rantataro Samuel , Ferrer Pascual Laura , Laurila Tomi
Published: November 2022

It is widely stated that ascorbic acid (AA) interferes with the electrochemical detection of neurotransmitters, especially dopamine, because of their overlapping oxidation potentials on typical electrode materials. As the concentration of AA is several orders of magnitude higher than the concentration of neurotransmitters, detection of neurotransmitters is difficult in the presence of AA and requires either highly stable AA concentration or highly selective neurotransmitter sensors. In contrast to the common opinion, we show that AA does not always interfere electrochemical detection of neurotransmitters. The decay of AA is rapid in cell culture medium, having a half-time of 2.1 hours, according to which the concentration decreases by 93% in 8 hours and by 99.75% in 18 hours. Thus, AA is eventually no longer detected by electrodes and the concentration of neurotransmitters can be effectively monitored. To validate this claim, we used unmodified single-wall carbon nanotube electrode to measure dopamine at physiologically relevant concentration range (25–1000 nM) from human midbrain organoid medium with highly linear response. Finally, AA is known to affect dopamine oxidation current through regeneration of dopamine, which complicates precise detection of small amounts of dopamine. By designing experiments as described here, this complication can be completely eliminated.
Retinal Layer Separation (ReLayS) method enables the molecular analysis of photoreceptor segments and cell bodies, as well as the inner retina
Authors: Todorova Vyara , Merolla Luca , Karademir Duygu , Wögenstein Gabriele M. , Behr Julian , Ebner Lynn J. A. , Samardzija Marijana , Grimm Christian
Published: November 2022

Understanding the physiology of the retina, and especially of the highly polarized photoreceptors, is essential not only to broaden our knowledge of the processes required for normal vision, but also to develop effective therapies to prevent or slow retinal degenerative diseases. However, the molecular analysis of photoreceptors is a challenge due to the heterogeneity of the retinal tissue and the lack of easy and reliable methods for cell separation. Here we present the ReLayS method—a simple technique for the separation of photoreceptor segments (PS) containing both inner and outer segments, outer nuclear layer (ONL), and inner retina (InR) that contains the remaining retinal layers. The layer-specific material isolated from a mouse half-retina with the ReLayS method was sufficient for protein isolation and Western blotting or RNA isolation and real-time PCR studies. The separation of PS, ONL, and InR was successfully validated by Western blotting and real-time PCR using proteins and genes with known expression profiles within the retina. Furthermore, the separation of the PS from the ONL enabled the detection of light-driven translocation of transducin from the PS to the soma. ReLayS is a simple and useful method to address protein and possibly metabolites distribution in photoreceptor compartments in various situations including development, ageing, and degenerative diseases.
GltS regulates biofilm formation in methicillin-resistant Staphylococcus aureus
Authors: Shibamura-Fujiogi Miho , Wang Xiaogang , Maisat Wiriya , Koutsogiannaki Sophia , Li Yunan , Chen Yue , Lee Jean C. , Yuki Koichi
Published: November 2022

Biofilm-based infection is a major healthcare burden. Methicillin-resistant Staphylococcus aureus (MRSA) is one of major organisms responsible for biofilm infection. Although biofilm is induced by a number of environmental signals, the molecule responsible for environmental sensing is not well delineated. Here we examined the role of ion transporters in biofilm formation and found that the sodium-glutamate transporter gltS played an important role in biofilm formation in MRSA. This was shown by gltS transposon mutant as well as its complementation. The lack of exogenous glutamate also enhanced biofilm formation in JE2 strain. The deficiency of exogenous glutamate intake accelerated endogenous glutamate/glutamine production, which led to the activation of the urea cycle. We also showed that urea cycle activation was critical for biofilm formation. In conclusion, we showed that gltS was a critical regulator of biofilm formation by controlling the intake of exogenous glutamate. An intervention to target glutamate intake may be a potential useful approach against biofilm.