bluuebunny/crossref_metadata_2025 huggingface dataset:
Thamnolecania yunusii(Ramalinaceae) – A new species of lichenised fungus from Horseshoe Island (Antarctic Peninsula)
Authors: Halici Mehmet Gökhan , Güllü Mithat , Bölükbaşi Ekrem , Kahraman Yiğit Merve
Published: November 2023

The new terricolous lichen speciesThamnolecania yunusiiHalıcı, Güllü, Bölükbaşı & Kahraman, which is characterised by its cream to greyish brown granulose-crustose thallus without vegetative propagules, is described from Horseshoe Island in the South-West Antarctic Peninsula region. AllThamnolecaniaspecies are known only from the Antarctic. The only species of the genus with a crustose thallus isT.racovitzae, but it differs fromT.yunusiiby growing on rocks, having an effuse to subeffigurate thallus that is sometimes isidiate and with shorter and narrower ascospores (c.15 × 3.5 µmvs.15.5–19.5 × 3.5–5.5 µm). The nrITS, mtSSU and RPB1 gene regions of the new species were studied and the phylogenetic position of the species was shown to be in the same clade asThamnolecania gerlachei,T.brialmontiiandT.racovitzae, but occurs on a different branch from these species. AsT.yunusiiis an Antarctic endemic, like the otherThamnolecaniaspecies, and most of the morphological characters fit well with this genus, we describe this new species under the genusThamnolecania.
Clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia combined with left ventricular non-compaction
Authors: Xu Bihe , Yang Jing , Liu Fang , Lv Tingting , Li Kun , Yuan Yifang , Li Siyuan , Liu Yuanwei , Zhang Ping
Published: November 2023

Background:

Catecholaminergic polymorphic ventricular tachycardia is an ion channelopathy, caused by mutations in genes coding for calcium-handling proteins. It can coexist with left ventricular non-compaction. We aim to investigate the clinical and genetic characteristics of this co-phenotype.

Methods:

Medical records of 24 patients diagnosed with catecholaminergic polymorphic ventricular tachycardia in two Chinese hospitals between September, 2005, and January, 2020, were retrospectively reviewed. We evaluated their clinical and genetic characteristics, including basic demographic data, electrocardiogram parameters, medications and survival during follow-up, and their gene mutations. We did structural analysis for a novel variant ryanodine receptor 2-E4005V.

Results:

The patients included 19 with catecholaminergic polymorphic ventricular tachycardia mono-phenotype and 5 catecholaminergic polymorphic ventricular tachycardia-left ventricular non-compaction overlap patients. The median age of onset symptoms was 9.0 (8.0,13.5) years. Most patients (91.7%) had cardiac symptoms, and 50% had a family history of syncope. Overlap patients had lower peak heart rate and threshold heart rate for ventricular tachycardia and ventricular premature beat during the exercise stress test (p < 0.05). Sudden cardiac death risk may be higher in overlap patients during follow-up. Gene sequencing revealed 1 novel ryanodine receptor 2 missense mutation E4005V and 1 mutation previously unreported in catecholaminergic polymorphic ventricular tachycardia, but no left ventricular non-compaction-causing mutations were observed. In-silico analysis showed the novel mutation E4005V broke down the interaction between two charged residues.

Conclusions:

Catecholaminergic polymorphic ventricular tachycardia overlapping with left ventricular non-compaction may lead to ventricular premature beat/ventricular tachycardia during exercise stress test at lower threshold heart rate than catecholaminergic polymorphic ventricular tachycardia alone; it may also indicate a worse prognosis and requires strict follow-up. ryanodine receptor 2 mutations disrupted interactions between residues and may interfere the function of ryanodine receptor 2.
Associations between early infections and childhood cognition in the Newcastle Thousand Families Study birth cohort
Authors: Pennock Erin , Slack Emma L. , Grebby Jess A. , Forster Lara N. , Pearce Mark S.
Published: November 2023

Childhood infections have been shown to stunt growth, contribute to malnutrition and reduce cognition in early adulthood. This study aimed to assess relationships between early life infections and childhood cognition at age 11 years in the Newcastle Thousand Families Study (NTFS). The analysis included 741 members from the NTFS who had complete data for infections between birth and 5 years, and the 11-plus examinations. School records from the 11-plus examinations showed cognitive (IQ), English (EQ) and arithmetic (AQ) abilities. Housing conditions, overcrowding, birth order and social class were recorded at birth. Helicobacter pylori seropositivity was measured at age 49–51 years. Multivariable linear regression was used to examine relationships between infections and cognition. The total number of infections in the first 5 years of life was not significantly associated with IQ, EQ or AQ, nor were there significant relationships between cognitive outcomes and most infections. Tonsillitis did display a positive, significant association with IQ after adjustment for confounders (b = 6.43, 95% CI 0.92, 11.94, p = 0.022). Lower respiratory tract infections (LRTIs) showed significant negative relationships with all cognitive outcomes. H. pylori seropositivity at age 50 exhibited negative, significant relationships with EQ (p = 0.014) and AQ (p = 0.024) after adjustment for confounders. Although no significant relationship between overall infections and cognition were found, there were indications that LRTIs and gastrointestinal system infections may limit cognitive development. Given these infections remain prevalent, further research regarding severity and recurrence of infections and how they affect childhood cognition is needed.
Steps towards inclusivity: modifying challenging content, navigating pedagogical materials and initiating student reflection within the Classics classroom
Authors: Peddar David
Published: November 2023

Although there is plenty of scholarship regarding the concerns of addressing controversial and sensitive subject manner in the Classics classroom, and I have considered these to quite an extent, my own interest in these practices emerged where they matter the most: my own experiences within the classroom. For me, it came to a head with one pupil who demonstrated an active enthusiasm for Latin study and the classical world at large, but was slowly becoming disheartened after several classes, despite not displaying any overt academic challenges to any of the presented material. When I brought this issue up privately with her, she said: ‘Sir, it sucks that this culture and language which I adore, wouldn't value me as much I value it.’ She also expressed regret at choosing Latin, as she felt ‘it seems to be a subject where only boys can succeed.’ It also became apparent that this consensus was common, and shared with several of her friends and peers. This paper describes some of the actions I undertook to address their sensitivities in the Classics classroom.
State‐Dependence of the Equilibrium Climate Sensitivity in a Clear‐Sky GCM
Authors: Henry Matthew , Vallis Geoffrey K. , Lutsko Nicholas J. , Seeley Jacob T. , McKim Brett A.
Published: November 2023

The climate sensitivity peaks around 310 K in a wide variety of climate models, ranging from idealized single column models to fully comprehensive climate models. Here, we increase CO2 using a clear‐sky three‐dimensional atmospheric model with a radiation scheme which maintains accuracy for high CO2 and temperature levels. In contrast, the Equilibrium Climate Sensitivity (ECS) of our model plateaus around 310 K. We show that this is due to the moistening of the subtropical regions caused by a slowdown in atmospheric circulation, which increases the ECS at very high CO2 values. When relative humidity is fixed, the ECS peak is consistent with single column model results. This work does not rule out that clouds or other complex processes impact the ECS in comprehensive climate models. Though the changes in CO2 here are extreme, this study underlines the importance of changes in atmospheric circulation and relative humidity in quantitative assessments of climate sensitivity.
Structure of the Martian Crust Below InSight From Surface Waves and Body Waves Generated by Nearby Meteoroid Impacts
Authors: Drilleau Mélanie , Beucler Éric , Shi Jing , Knapmeyer‐Endrun Brigitte , Garcia Raphaël F. , Ansan Véronique , Kim Doyeon , Lognonné Philippe , Banerdt William B.
Published: November 2023

We measure group velocity dispersion of surface waves generated by two meteoroid impacts on Mars close to the lander of the InSight mission. This allows us to probe the crustal structure in the first few kilometers beneath the InSight lander. In combination with body wave arrival times from five impact events, we obtain direct seismic constraints on the seismic velocity of the crust in the vicinity of the InSight landing site. We confirm the existence of a uppermost low‐velocity layer with a mean thickness of ∼1.2 km, interpreted as layered volcanic materials, possibly interstratified with sedimentary and altered materials. Our joint inversion of surface and body waves shows a four‐layer model for the Martian crust, compatible with high‐ and low‐frequency P‐to‐S receiver functions estimated in previous studies.
A North–South Dipole Response of the South Atlantic Convergence Zone During the Mid‐Holocene
Authors: Wong Minn Lin , Battisti David S. , Liu Xiaojuan , Ding Qinghua , Wang Xianfeng
Published: November 2023

The South Atlantic Convergence Zone (SACZ) profoundly modulates precipitation from central to southeastern Brazil in the present‐day climate. However, the understanding of its long‐term behavior responding to various climate forcings remains limited. Here, we use an isotope‐enabled atmospheric general circulation model (ECHAM4.6) to examine the precipitation response of the SACZ during the mid‐Holocene about six thousand years ago. The model simulates a northward intensification of the SACZ in the mid‐Holocene, resulting in a dipole anomaly pattern relative to today's climate. The mid‐Holocene precipitation increased along the northern margin of the SACZ due to the strengthening of easterly winds across the tropical Atlantic, while an eastward deflection of the South American low‐level jet reduced moisture transport to southern Brazil, resulting in reduced precipitation along the southern margins of the SACZ. The north–south dipole response in precipitation is consistent with the mid‐Holocene hydroclimate change observed in proxy records from the region.
Assessing Latent and Kinetic Energy Trend Changes in Extratropical Cyclones From 1940 to 2020: Results From ERA‐5 Reanalysis
Authors: Dzambo Andrew , McFarquhar Greg , Sledd Anne , L’Ecuyer Tristan
Published: November 2023

Baroclinic or extratropical cyclones (ETCs) transport heat and moisture to higher latitudes, making it fundamentally important to understand how their influence changes as Earth's climate evolves. A 2–8‐day Lanzcos bandpass filter is applied to European Center for Medium Range Weather Forecasting 5th Generation Reanalysis latent energy (LE) and kinetic energy (KE) data to assess how ETCs have changed from 1940 to 2020 relative to full‐scale changes in LE and KE. Full‐scale KE trends are more positive at high latitudes relative to mid‐latitudes, confirming several previous studies that ETCs have shifted poleward. LE increases have occurred globally, and trends in both full‐scale LE and KE are statistically significant in the southern high latitudes. The high relative fractional contribution of 2–8‐day LE wave power and trend clearly suggest that ETCs have an increasingly important role in poleward moisture transport but are not solely responsible for the observed statistically significant increases.
The Role of Passive Cloud Volumes in the Transition From Shallow to Deep Atmospheric Convection
Authors: Vraciu Cristian V. , Kruse Irene L. , Haerter Jan O.
Published: November 2023

Properly capturing the transition from shallow to deep convection remains a major shortcoming of numerical weather and climate models due to poor understanding of the physical processes controlling this transition. Although recent studies suggest shallow preconditioning and cold pool feedbacks to be important, these studies are unable to explain the initial phase of the transition. We identify an additional mechanism, namely the interaction between passive cloud volumes (PCV)—old cumulus cloud volumes in the decaying stage—and updrafts, and discuss the potential role of this mechanism in the transition from shallow to deep convection. We show that the number of updrafts interacting with PCV is very large during the transition and the updrafts better preserve their buoyancy due to entrainment of much moister air. We argue that PCV might play an important role in the transition and cumulus parameterizations could therefore benefit from including them.
The Role of Subslab Low‐Velocity Anomalies Beneath the Nazca Ridge and Iquique Ridge on the Nazca Plate and Their Possible Contribution to the Subduction Angle
Authors: Lee Hwaju , Kim YoungHee , Bezada Maximiliano J. , Clayton Robert W.
Published: November 2023

Subducting the buoyant crustal material of an aseismic oceanic ridge has been regarded as a dominant contributor to flat slab subduction. However, normal‐dip subduction is also observed in some cases where ridges are subducting. In this study, we compare the subduction of two ridges on the Nazca Plate: Nazca Ridge (flat slab) and Iquique Ridge (normal‐dip slab). Anisotropy determined by shear wave splitting observation suggests that the low‐velocity anomalies found beneath the ridges are mapping anisotropic structure into isotropic velocities. After a tomographic inversion incorporating anisotropy models for both ridges, we find that the low‐velocity anomalies found beneath the Nazca Ridge are not anisotropic and therefore likely represent warm mantle, and those beneath the Iquique Ridge are caused by anisotropy. We conclude that subslab mantle buoyancy has a larger impact on the subduction angle than the crustal material of the ridge.
Interdecadal Variations of Radiative Feedbacks Associated With the El Niño and Southern Oscillation (ENSO) in CMIP6 Models
Authors: Tsuchida Ko , Mochizuki Takashi , Kawamura Ryuichi , Kawano Tetsuya
Published: November 2023

Internally generated radiative feedback at interannual timescales can influence climate sensitivity estimates. This study has clarified the mechanisms of variability in radiative feedback associated with the El Niño and Southern Oscillation based on preindustrial control simulations for Coupled Model Intercomparison Project Phase 6. Radiative feedback showed large modulation with a comparable magnitude to the intermodel uncertainty associated with internal changes in the zonal gradient of the ocean thermocline and sea surface temperature (SST) in the equatorial Pacific on interdecadal timescales. When the interdecadal SST anomalies in the eastern and western equatorial Pacific were simulated as positive and negative, respectively, the statistical properties of the interannual variations were also modified with diminished Walker circulation changes per unit of global mean surface temperature rise. Meanwhile, the enhanced local Hadley circulation led to a middle‐to upper‐level cloud decrease and a low‐level cloud increase in the subtropics, causing enhanced negative radiative feedback as a global average.
Emergence of Unstable Focused Flow Induced by Variable‐Density Flows in Vertical Fractures
Authors: Cao Hongfan , Yoon Seonkyoo , Xu Zhenyu , Pyrak‐Nolte Laura J. , Bresciani Etienne , Kang Peter K.
Published: November 2023

Fluids with different densities often coexist in subsurface fractures and lead to variable‐density flows that control subsurface processes such as seawater intrusion, contaminant transport, and geologic carbon sequestration. In nature, fractures have dip angles relative to gravity, and density effects are maximized in vertical fractures. However, most studies on flow and transport through fractures are often limited to horizontal fractures. Here, we study the mixing and transport of variable‐density fluids in vertical fractures by combining three‐dimensional (3D) pore‐scale numerical simulations and visual laboratory experiments. Two miscible fluids with different densities are injected through two inlets at the bottom of a fracture and exit from an outlet at the top of the fracture. Laboratory experiments show the emergence of an unstable focused flow path, which we term a “runlet.” We successfully reproduce the unstable runlet using 3D numerical simulations and elucidate the underlying mechanisms triggering the runlet. Dimensionless number analysis shows that the runlet instability arises due to the Rayleigh‐Taylor instability (RTI), and flow topology analysis is applied to identify 3D vortices that are caused by the RTI. Even under laminar flow regimes, fluid inertia is shown to control the runlet instability by affecting the size and movement of vortices. Finally, we confirm the emergence of a runlet in rough‐walled fractures. Since a runlet dramatically affects fluid distribution, residence time, and mixing, the findings in this study have direct implications for the management of groundwater resources and subsurface applications.
Portable visual and electrochemical detection of hydrogen peroxide release from living cells based on dual-functional Pt-Ni hydrogels
Authors: Li Guanglei , Chen Yao , Liu Fei , Bi Wenhua , Wang Chenxin , Lu Danfeng , Wen Dan
Published: November 2023

It is important to monitor the intra-/extracellular concentration of hydrogen peroxide (H2O2) in biological processes. However, miniaturized devices that enable portable and accurate H2O2 measurement are still in their infancy because of the difficulty of developing facile sensing strategies and highly integrated sensing devices. In this work, portable H2O2 sensors based on Pt-Ni hydrogels with excellent peroxidase-like and electrocatalytic activities are demonstrated. Thus, simple and sensitive H2O2 sensing is achieved through both colorimetric and electrochemical strategies. The as-fabricated H2O2 sensing chips exhibit favorable performance, with low detection limits (0.030 μM & 0.15 μM), wide linearity ranges (0.10 μM–10.0 mM & 0.50 μM–5.0 mM), outstanding long-term stability (up to 60 days), and excellent selectivity. With the aid of an M5stack development board, portable visual and electrochemical H2O2 sensors are successfully constructed without complicated and expensive equipment or professional operators. When applied to the detection of H2O2 released from HeLa cells, the results obtained by the developed sensors are in good agreement with those from an ultraviolet‒visible spectrophotometer (UV‒vis) (1.97 μM vs. 2.08 μM) and electrochemical station (1.77 μM vs. 1.84 μM).
UBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance
Authors: Rodriguez Tirado Carla , Wang Choushi , Li Xiaoling , Deng Su , Gonzalez Julisa , Johnson Nickolas A. , Xu Yaru , Metang Lauren A. , Sundar Rajan Medha , Yang Yuqiu , Yin Yi , Hofstad Mia , Raj Ganesh V. , Zhang Song , Lemoff Andrew , He Wei , Fan Jie , Wang Yunguan , Wang Tao , Mu Ping
Published: November 2023

Prostate cancer (PCa) is primarily driven by aberrant Androgen Receptor (AR) signaling. Although there has been substantial advancement in antiandrogen therapies, resistance to these treatments remains a significant obstacle, often marked by continuous or enhanced AR signaling in resistant tumors. While the dysregulation of the ubiquitination-based protein degradation process is instrumental in the accumulation of oncogenic proteins, including AR, the molecular mechanism of ubiquitination-driven AR degradation remains largely undefined. We identified UBE2J1 as the critical E2 ubiquitin-conjugating enzyme responsible for guiding AR ubiquitination and eventual degradation. The absence of UBE2J1, found in 5–15% of PCa patients, results in disrupted AR ubiquitination and degradation. This disruption leads to an accumulation of AR proteins, promoting resistance to antiandrogen treatments. By employing a ubiquitination-based AR degrader to adeptly restore AR ubiquitination, we reestablished AR degradation and inhibited the proliferation of antiandrogen-resistant PCa tumors. These findings underscore the fundamental role of UBE2J1 in AR degradation and illuminate an uncharted mechanism through which PCa maintains heightened AR protein levels, fostering resistance to antiandrogen therapies.
The RORɣ/SREBP2 pathway is a master regulator of cholesterol metabolism and serves as potential therapeutic target in t(4;11) leukemia
Authors: Erkner Estelle , Hentrich Thomas , Schairer Rebekka , Fitzel Rahel , Secker-Grob Kathy-Ann , Jeong Johan , Keppeler Hildegard , Korkmaz Fulya , Schulze-Hentrich Julia M. , Lengerke Claudia , Schneidawind Dominik , Schneidawind Corina
Published: November 2023

Dysregulated cholesterol homeostasis promotes tumorigenesis and progression. Therefore, metabolic reprogramming constitutes a new hallmark of cancer. However, until today, only few therapeutic approaches exist to target this pathway due to the often-observed negative feedback induced by agents like statins leading to controversially increased cholesterol synthesis upon inhibition. Sterol regulatory element-binding proteins (SREBPs) are key transcription factors regulating the synthesis of cholesterol and fatty acids. Since SREBP2 is difficult to target, we performed pharmacological inhibition of retinoic acid receptor (RAR)-related orphan receptor gamma (RORγ), which acts upstream of SREBP2 and serves as master regulator of the cholesterol metabolism. This resulted in an inactivated cholesterol-related gene program with significant downregulation of cholesterol biosynthesis. Strikingly, these effects were more pronounced than the effects of fatostatin, a direct SREBP2 inhibitor. Upon RORγ inhibition, RNA sequencing showed strongly increased cholesterol efflux genes leading to leukemic cell death and cell cycle changes in a dose- and time-dependent manner. Combinatorial treatment of t(4;11) cells with the RORγ inhibitor showed additive effects with cytarabine and even strong anti-leukemia synergism with atorvastatin by circumventing the statin-induced feedback. Our results suggest a novel therapeutic strategy to inhibit tumor-specific cholesterol metabolism for the treatment of t(4;11) leukemia.
CASC4/GOLM2 drives high grade serous carcinoma anoikis resistance through the recycling of EGFR
Authors: Bapat Jaidev , Yamamoto Tomomi M. , Woodruff Elizabeth R. , Qamar Lubna , Mikeska Railey G. , Aird Katherine M. , Watson Zachary L. , Brubaker Lindsay W. , Bitler Benjamin G.
Published: November 2023

Ovarian cancer is the deadliest gynecological malignancy, and accounts for over 150,000 deaths per year worldwide. The high grade serous ovarian carcinoma (HGSC) subtype accounts for almost 70% of ovarian cancers and is the deadliest. HGSC originates in the fimbria of the fallopian tube and disseminates through the peritoneal cavity. HGSC survival in peritoneal fluid requires cells to resist anoikis (anchorage-independent apoptosis). Most anoikis resistant mechanisms are dependent on microenvironment interactions with cell surface-associated proteins, such as integrins and receptor tyrosine kinases (RTKs). We previously identified the gene CASC4 as a driver of anoikis resistance. CASC4 is predicted to be a Golgi-associated protein that may regulate protein trafficking to the plasma membrane, but CASC4 is largely uncharacterized in literature; thus, we sought to determine how CASC4 confers anoikis resistance to HGSC cells. Mining of publicly available ovarian cancer datasets (TCGA) showed that CASC4 is associated with worse overall survival and increased resistance to platinum-based chemotherapies. For experiments, we cultured three human HGSC cell lines (PEO1, CaOV3, OVCAR3), and a murine HGSC cell line, (ID8) with shRNA-mediated CASC4 knockdowns (CASC4 KD) in suspension, to recapitulate the peritoneal fluid environment in vitro. CASC4 KD significantly inhibited cell proliferation and colony formation ability, and increased apoptosis. A Reverse Phase Protein Assay (RPPA) showed that CASC4 KD resulted in a broad re-programming of membrane-associated proteins. Specifically, CASC4 KD led to decreased protein levels of the RTK Epidermal Growth Factor Receptor (EGFR), an initiator of several oncogenic signaling pathways, leading us to hypothesize that CASC4 drives HGSC survival through mediating recycling and trafficking of EGFR. Indeed, loss of CASC4 led to a decrease in both EGFR membrane localization, reduced turnover of EGFR, and increased EGFR ubiquitination. Moreover, a syngeneic ID8 murine model of ovarian cancer showed that knocking down CASC4 leads to decreased tumor burden and dissemination.
Vancomycin tolerance of adherent Staphylococcus aureus is impeded by nanospike-induced physiological changes
Authors: Hayles Andrew , Bright Richard , Nguyen Ngoc Huu , Truong Vi Khanh , Wood Jonathan , Palms Dennis , Vongsvivut Jitraporn , Barker Dan , Vasilev Krasimir
Published: November 2023

Bacterial colonization of implantable biomaterials is an ever-pervasive threat that causes devastating infections, yet continues to elude resolution. In the present study, we report how a rationally designed antibacterial surface containing sharp nanospikes can enhance the susceptibility of pathogenic bacteria to antibiotics used in prophylactic procedures. We show that Staphylococcus aureus, once adhered to a titanium surface, changes its cell-surface charge to increase its tolerance to vancomycin. However, if the Ti surface is modified to bear sharp nanospikes, the activity of vancomycin is rejuvenated, leading to increased bacterial cell death through synergistic activity. Analysis of differential gene expression provided evidence of a set of genes involved with the modification of cell surface charge. Synchrotron-sourced attenuated Fourier-transform infrared microspectroscopy (ATR-FTIR), together with multivariate analysis, was utilized to further elucidate the biochemical changes of S. aureus adhered to nanospikes. By inhibiting the ability of the pathogen to reduce its net negative charge, the nanoengineered surface renders S. aureus more susceptible to positively charged antimicrobials such as vancomycin. This finding highlights the opportunity to enhance the potency of prophylactic antibiotic treatments during implant placement surgery by employing devices having surfaces modified with spike-like nanostructures.
Compressive strength degradation of engineered bamboo subjected to fungal attack
Authors: Chen C. Q. , Zhang S. J. , Kong Y. B. H. , Ji T. , Huang W. W. , Hu Y. T. , Zhang D. W. , Xiao Y.
Published: November 2023

Glue laminated bamboo (glubam) is a type of engineered bamboo material developed for applications in building structures and interiors. This paper focuses on the fungal (Aspergillus niger) colonization from 14 to 56 days in thick- and thin-strip glubam board with the investigation of physical, mechanical (compression), and microcosmic properties. Two-degree of carbonization treatment was employed to improve the antifungal property of the thick-strip glubam. After 56 days of infection, the deep-degree carbonized thick-strip glubam presents better anti-mold properties than medium and non-carbonized specimens. For thin-strip glubam, both parallel and perpendicular to the main bamboo fiber direction were considered. The longitudinal thin-strip glubam retains decent compressive properties, while the transverse specimens stay a stable compressive strength along all fungal tests. The paper reports the experimental values of mass loss, color changes, compressive strengths, modulus of elasticity in compression, and microstructure observations from optical and SEM microscopy at different fungal exposure timespans.
Pesticide use negatively affects bumble bees across European landscapes
Authors: Nicholson Charlie C. , Knapp Jessica , Kiljanek Tomasz , Albrecht Matthias , Chauzat Marie-Pierre , Costa Cecilia , De la Rúa Pilar , Klein Alexandra-Maria , Mänd Marika , Potts Simon G. , Schweiger Oliver , Bottero Irene , Cini Elena , de Miranda Joachim R. , Di Prisco Gennaro , Dominik Christophe , Hodge Simon , Kaunath Vera , Knauer Anina , Laurent Marion , Martínez-López Vicente , Medrzycki Piotr , Pereira-Peixoto Maria Helena , Raimets Risto , Schwarz Janine M. , Senapathi Deepa , Tamburini Giovanni , Brown Mark J. F. , Stout Jane C. , Rundlöf Maj
Published: November 2023

Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species1,2, leading to restrictions on these compounds3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes4–9 and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestris colonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.
Landscape dynamics and the Phanerozoic diversification of the biosphere
Authors: Salles Tristan , Husson Laurent , Lorcery Manon , Hadler Boggiani Beatriz
Published: November 2023

The long-term diversification of the biosphere responds to changes in the physical environment. Yet, over the continents, the nearly monotonic expansion of life started later in the early part of the Phanerozoic eon1 than the expansion in the marine realm, where instead the number of genera waxed and waned over time2. A comprehensive evaluation of the changes in the geodynamic and climatic forcing fails to provide a unified theory for the long-term pattern of evolution of life on Earth. Here we couple climate and plate tectonics models to numerically reconstruct the evolution of the Earth’s landscape over the entire Phanerozoic eon, which we then compare to palaeo-diversity datasets from marine animal and land plant genera. Our results indicate that biodiversity is strongly reliant on landscape dynamics, which at all times determine the carrying capacity of both the continental domain and the oceanic domain. In the oceans, diversity closely adjusted to the riverine sedimentary flux that provides nutrients for primary production. On land, plant expansion was hampered by poor edaphic conditions until widespread endorheic basins resurfaced continents with a sedimentary cover that facilitated the development of soil-dependent rooted flora, and the increasing variety of the landscape additionally promoted their development.
Gridded livestock density database and spatial trends for Kazakhstan
Authors: Kolluru Venkatesh , John Ranjeet , Saraf Sakshi , Chen Jiquan , Hankerson Brett , Robinson Sarah , Kussainova Maira , Jain Khushboo
Published: November 2023

Livestock rearing is a major source of livelihood for food and income in dryland Asia. Increasing livestock density (LSKD) affects ecosystem structure and function, amplifies the effects of climate change, and facilitates disease transmission. Significant knowledge and data gaps regarding their density, spatial distribution, and changes over time exist but have not been explored beyond the county level. This is especially true regarding the unavailability of high-resolution gridded livestock data. Hence, we developed a gridded LSKD database of horses and small ruminants (i.e., sheep & goats) at high-resolution (1 km) for Kazakhstan (KZ) from 2000–2019 using vegetation proxies, climatic, socioeconomic, topographic, and proximity forcing variables through a random forest (RF) regression modeling. We found high-density livestock hotspots in the south-central and southeastern regions, whereas medium-density clusters in the northern and northwestern regions of KZ. Interestingly, population density, proximity to settlements, nighttime lights, and temperature contributed to the efficient downscaling of district-level censuses to gridded estimates. This database will benefit stakeholders, the research community, land managers, and policymakers at regional and national levels.
Lower cardiotoxicity of CPX-351 relative to daunorubicin plus cytarabine free-drug combination in hiPSC-derived cardiomyocytes in vitro
Authors: Fortin Marie C. , LaCroix Andrew S. , Grammatopoulos Tom N. , Tan Lei , Wang Qi , Manca Dino
Published: November 2023

Liposomal formulations are hypothesized to alleviate anthracycline cardiotoxicity, although this has only been documented clinically for doxorubicin. We developed an in vitro multiparametric model using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to assess the relative toxicity of anthracyclines across formulations. Proof of concept was established by treating hiPSC-CM with equivalent concentrations of free and liposomal doxorubicin. The study was then repeated with free daunorubicin plus cytarabine and CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine. hiPSC-CM were treated with free-drug or liposomal formulations for 24 h on Days 1, 3, and 5 at equivalent concentrations ranging from 0 to 1000 ng/mL and assessed on subsequent days. Free-drug treatment resulted in concentration-dependent cumulative cytotoxicity (microscopy), more profound decrease in ATP levels, and significant time- and concentration-dependent decreases in oxygen consumption versus liposomal formulations (p < 0.01). Repeated free-drug exposure also resulted in greater release of biomarkers (cardiac troponin I, FABP3) and lactate dehydrogenase, as well as in a biphasic rhythmicity response (initial increase followed by slowing/quiescence of beating) indicating significant injury, which was not observed after repeated exposure to liposomal formulations. Overall, liposomal formulations were considerably less toxic to hiPSC-CM than their free-drug counterparts. Clinical data will be needed to confirm findings for CPX-351.
Assessing the potential of composite confining systems for secure and long-term CO2 retention in geosequestration
Authors: Bakhshian Sahar , Bump Alexander P. , Pandey Shaunak , Ni Hailun , Hovorka Susan D.
Published: November 2023

A potential geologic target for CO2 storage should ensure secure containment of injected CO2. Traditionally, this objective has been achieved by targeting reservoirs with overlying seals-regionally extensive, low permeability units that have been proven capable of retaining buoyant fluid accumulations over geologic time. However, considering that the amount of CO2 is limited by a decadal injection period, vertical migration of CO2 can be effectively halted by a composite system of discontinuous shale/silt/mudstone barriers in bedded sedimentary rocks. Here, we studied the impact of depositional architectures in a composite confining system on CO2 migration and confinement at reservoir scale. We stochastically generated lithologically heterogeneous reservoir models containing discontinuous barriers consistent with statistical distributions of net-sand-to-gross-shale ratio (NTG) and horizontal correlation lengths derived from well log data and observations of producing hydrocarbon fields in Southern Louisiana. We then performed an extensive suite of reservoir simulations of CO2 injection and post-injection to evaluate the sensitivity of CO2 plume migration and pressure response of the composite system to a series of geologic and fluid parameters including the lateral continuity of barriers, NTG, permeability anisotropy within the sand body, and capillary pressure contrast between the sand and shale facies. The results indicate that lateral continuity of barriers and NTG are the dominant controls on CO2 plume geometry and pressure build-up in the reservoir, while the impact of NTG is particularly pronounced. The significance of intraformational barriers becomes apparent as they facilitate the local capillary trapping of CO2. Those barriers improve the pore space occupancy by promoting a more dispersed shape of the plume and ultimately retard the buoyancy-driven upward migration of the plume post injection.
Consequences of load distribution in selected vehicles in the context of changing the position of the vehicle’s centre of gravity
Authors: Synák František , Smolková Alexandra , Žúžiová Klára
Published: November 2023

The position of the vehicle’s centre of gravity has an impact on its driving performances, and it also affects the vehicle’s impact on its surroundings. Therefore, the study pays attention to the change in the centre of gravity’s position due to different load distribution. The research was performed by wide-ranging experimental measurements with three different vehicles, i.e. with a passenger car, a van and a truck. The measurement results and their analysis point to the rate of change in the centre of gravity’s position due to different load distribution, and to the fact that a vehicle axle can be overloaded even when the vehicle load capacity is not used completely. In addition, the contribution of the study is a database which can be used for other research via modelling.
On the inadequacy of nominal assortativity for assessing homophily in networks
Authors: Karimi Fariba , Oliveira Marcos
Published: November 2023

Nominal assortativity (or discrete assortativity) is widely used to characterize group mixing patterns and homophily in networks, enabling researchers to analyze how groups interact with one another. Here we demonstrate that the measure presents severe shortcomings when applied to networks with unequal group sizes and asymmetric mixing. We characterize these shortcomings analytically and use synthetic and empirical networks to show that nominal assortativity fails to account for group imbalance and asymmetric group interactions, thereby producing an inaccurate characterization of mixing patterns. We propose the adjusted nominal assortativity and show that this adjustment recovers the expected assortativity in networks with various level of mixing. Furthermore, we propose an analytical method to assess asymmetric mixing by estimating the tendency of inter- and intra-group connectivities. Finally, we discuss how this approach enables uncovering hidden mixing patterns in real-world networks.
A common timing mechanism across different millisecond domains: evidence from perceptual and motor tasks
Authors: Stanczyk Magdalena , Szelag Elzbieta , Krystecka Klaudia , Szymaszek Aneta
Published: November 2023

Temporal information processing (TIP) constitutes a complex construct that underlies many cognitive functions and operates in a few hierarchically ordered time domains. This study aimed to verify the relationship between the tens of milliseconds and hundreds of milliseconds domains, referring to perceptual and motor timing, respectively. Sixty four young healthy individuals participated in this study. They underwent two auditory temporal order judgement tasks to assess their performance in the tens of milliseconds domain; on this basis, groups of high-level performers (HLP) and low-level performers (LLP) were identified. Then, a maximum tapping task was used to evaluate performance in the hundreds of milliseconds domain. The most remarkable result was that HLP achieved a faster tapping rate and synchronised quicker with their “internal clock” during the tapping task than did LLP. This result shows that there is a relationship between accuracy in judging temporally asynchronous stimuli and ability to achieve and maintain the pace of a movement adequate to one’s internal pacemaker. This could indicate the strong contribution of a common timing mechanism, responsible for temporal organisation and coordination of behaviours across different millisecond domains.
An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence
Authors: Riviere-Cazaux Cecile , Carlstrom Lucas P. , Neth Bryan J. , Olson Ian E. , Rajani Karishma , Rahman Masum , Ikram Samar , Mansour Moustafa A. , Mukherjee Bipasha , Warrington Arthur E. , Short Susan C. , von Zglinicki Thomas , Brown Desmond A. , Burma Sandeep , Tchkonia Tamar , Schafer Marissa J. , Baker Darren J. , Kizilbash Sani H. , Kirkland James L. , Burns Terry C.
Published: November 2023

High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments. Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype (SASP) induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence. Moreover, senescent tumor cells could spur the growth of their non-senescent counterparts, thereby accelerating recurrence. In this review, we highlight emerging evidence supporting the use of senolytic agents to ablate latent, senescent-like cells that could contribute to tumor recurrence. We also discuss how senescent cell clearance can decrease the SASP within the tumor microenvironment thereby reducing tumor aggressiveness at recurrence. Finally, senolytics could improve the long-term sequelae of prior therapy on cognition and bone marrow function. We critically review the senolytic drugs currently under preclinical and clinical investigation and the potential challenges that may be associated with deploying senolytics against latent glioma. In conclusion, senescence in glioma and the microenvironment are critical and potential targets for delaying or preventing tumor recurrence and improving patient functional outcomes through senotherapeutics.
Functional analysis of recurrent CDC20 promoter variants in human melanoma
Authors: Godoy Paula M. , Oyedeji Abimbola , Mudd Jacqueline L. , Morikis Vasilios A. , Zarov Anna P. , Longmore Gregory D. , Fields Ryan C. , Kaufman Charles K.
Published: November 2023

Small nucleotide variants in non-coding regions of the genome can alter transcriptional regulation, leading to changes in gene expression which can activate oncogenic gene regulatory networks. Melanoma is heavily burdened by non-coding variants, representing over 99% of total genetic variation, including the well-characterized TERT promoter mutation. However, the compendium of regulatory non-coding variants is likely still functionally under-characterized. We developed a pipeline to identify hotspots, i.e. recurrently mutated regions, in melanoma containing putatively functional non-coding somatic variants that are located within predicted melanoma-specific regulatory regions. We identified hundreds of statistically significant hotspots, including the hotspot containing the TERT promoter variants, and focused on a hotspot in the promoter of CDC20. We found that variants in the promoter of CDC20, which putatively disrupt an ETS motif, lead to lower transcriptional activity in reporter assays. Using CRISPR/Cas9, we generated an indel in the CDC20 promoter in human A375 melanoma cell lines and observed decreased expression ofCDC20, changes in migration capabilities, increased growth of xenografts, and an altered transcriptional state previously associated with a more proliferative and less migratory state. Overall, our analysis prioritized several recurrent functional non-coding variants that, through downregulation ofCDC20, led to perturbation of key melanoma phenotypes.
Twenty-four-hour rhythmicities in disorders of consciousness are associated with a favourable outcome
Authors: Gobert Florent , Corneyllie Alexandra , Bastuji Hélène , Berthomier Christian , Thevenet Marc , Abernot Jonas , Raverot Véronique , Dailler Frédéric , Guérin Claude , Gronfier Claude , Luauté Jacques , Perrin Fabien
Published: November 2023

Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening.
Cell-compatible isotonic freezing media enabled by thermo-responsive osmolyte-adsorption/exclusion polymer matrices
Authors: Kato Yui , Matsuda Yuya , Uto Takuya , Tanaka Daisuke , Ishibashi Kojiro , Ishizaki Takeru , Ohta Akio , Kobayashi Akiko , Hazawa Masaharu , Wong Richard W. , Ninomiya Kazuaki , Takahashi Kenji , Hirata Eishu , Kuroda Kosuke
Published: November 2023

During the long-term storage of cells, it is necessary to inhibit ice crystal formation by adding cryoprotectants. Non-cell-permeable cryoprotectants have high osmotic pressure which dehydrates cells, indirectly suppressing intracellular ice crystal formation. However, the high osmotic pressure and dehydration often damage cells. Emerging polymer-type non-cell-permeable cryoprotectants form matrices surrounding cells. These matrices inhibit the influx of extracellular ice nuclei that trigger intracellular ice crystal formation. However, these polymer-type cryoprotectants also require high osmotic pressure to exert an effective cryoprotecting effect. In this study, we designed a poly(zwitterion) (polyZI) that forms firm matrices around cells based on their high affinity to cell membranes. The polyZI successfully cryopreserved freeze-vulnerable cells under isotonic conditions. These matrices also controlled osmotic pressure by adsorbing and desorbing NaCl depending on the temperature, which is a suitable feature for isotonic cryopreservation. Although cell proliferation was delayed by the cellular matrices, washing with a sucrose solution improved proliferation.