bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dynamics of CO2‐Driven Granular Flows in Gullies on Mars
Authors: Roelofs Lonneke , Conway Susan J. , van Dam Bas , van Eijk Arjan , Merrison Jonathan P. , Iversen Jens Jacob , Sylvest Matthew , Patel Manish R. , Markies Henk , van Maarseveen Marcel , McElwaine Jim , Kleinhans Maarten G. , de Haas Tjalling
Published: June 2024

Martian gullies are landforms consisting of an erosional alcove, a channel, and a depositional apron. A significant proportion of Martian gullies at the mid‐latitudes is active today. The seasonal sublimation of CO2 ice has been suggested as a driver behind present‐day gully activity. However, due to a lack of in situ observations, the actual processes causing the observed changes remain unresolved. Here, we present results from flume experiments in environmental chambers in which we created CO2‐driven granular flows under Martian atmospheric conditions. Our experiments show that under Martian atmospheric pressure, large amounts of granular material can be fluidized by the sublimation of small quantities of CO2 ice in the granular mixture (only 0.5% of the volume fraction of the flow) under slope angles as low as 10°. Dimensionless scaling of the CO2‐driven granular flows shows that they are dynamically similar to terrestrial two‐phase granular flows, that is, debris flows and pyroclastic flows. The similarity in flow dynamics explains the similarity in deposit morphology with levees and lobes, supporting the hypothesis that CO2‐driven granular flows on Mars are not merely modifying older landforms, but they are actively forming them. This has far‐reaching implications for the processes thought to have formed these gullies over time. For other planetary bodies in our solar system, our experimental results suggest that the existence of gully like landforms is not necessarily evidence for flowing liquids but that they could also be formed or modified by sublimation‐driven flow processes.
Revealing the Local Time Structure of the Alfvén Radius in Jupiter's Magnetosphere Through High‐Resolution Simulations
Authors: Xu Yan , Ray Licia , Yao Zhonghua , Zhang Binzheng , Bonfond Bertrand , Badman Sarah , Grodent Denis , Feng Enhao , Qin Tianshu , Wei Yong
Published: June 2024

In the context of planetary magnetospheres, the Alfvén radius plays a critical role as the demarcation line where the planet's magnetosphere and ionosphere effectively decouple. This boundary is pivotal in understanding the complex interactions between planetary magnetic fields and space plasma environments. This study presents a dynamic analysis of the Alfvén radius within Jupiter's magnetosphere using high‐resolution simulations to capture its temporal variability. Our simulations reveal that the Alfvén radius presents a dynamic behavior, which is strongly modulated by planetary rotation. However, when averaged over one Jovian rotation period, the location of the Alfvén radius displays striking similarities to that described by the statistical models proposed by Jenkins et al. (2024, 10.17635/lancaster/researchdata/661). Specifically, our averaged results highlight a prominent outward bulge in the radius location toward ∼03 local time with a notable absence of the radius between the noon and dusk sectors. The absence of the Alfvén radius suggests the higher Alfvén velocities in the noon‐to‐dusk sector associated with strong magnetic fields. These results suggest that while short‐term dynamics are present, the average position of the Alfvén radius over a rotation period roughly remains consistent with previous steady‐state models, providing an enhanced understanding of the long‐term behavior exhibited by the magnetospheric plasma environment in Jupiter's magnetosphere. Importantly, the dynamic location of the Alfvén radius and the observed asymmetry after averaging over one rotation period could demonstrate a significant correlation with the complex evolution of the auroral enhancement.
Breastfeeding duration and brain-body development in 9–10-year-olds: modulating effect of socioeconomic levels
Authors: Rajagopalan Vidya , Hsu Eustace , Luo Shan
Published: June 2024

Objective

To investigate relationships of breastfeeding duration with brain structure and adiposity markers in youth and how these relationships are modified by neighborhood socioeconomic environments (SEEs).

Methods

This was a cross-sectional study of youth enrolled in the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 7511). Mixed effects models examined associations of breastfeeding duration with global brain measures and adiposity markers, adjusting for sociodemographic, pre- and post-natal covariates. Stratified analysis was performed by area deprivation index (ADI) tertiles.

Results

Total cortical surface area (SA) (False Discovery Rate - FDR corrected P < 0.001), cortical (FDR corrected P < 0.001) and subcortical gray matter (GM) volume (FDR corrected P < 0.001) increased with increased breastfeeding duration. Body mass index (BMI) z-scores (FDR corrected P = 0.001), waist circumference (FDR corrected P = 0.002) and waist-to-height ratio (WHtR) (FDR corrected P = 0.001) decreased with increased breastfeeding duration. Breastfeeding duration was inversely associated with adiposity in youth from high- and medium- ADI neighborhoods, but positively associated with SA across ADI tertiles.

Conclusions

In this cross-sectional study, longer breastfeeding duration was associated with lower adiposity indices, particularly in youth from lower SEEs and greater SA across SEE levels. Longer breastfeeding duration showed long-term associations with brain and body development for offspring.

Impact

Building on previous findings that longer breastfeeding duration is associated with healthier weight gain, lower obesity risk, and brain white matter development in infancy, our results find longer breastfeeding duration to be associated with lower adiposity indices and greater cortical and subcortical gray matter volume, and cortical surface area during peri-adolescence.

Children from lower socioeconomic environments (SEEs) demonstrated stronger negative associations of breastfeeding duration and adiposity indices, and children across SEEs showed positive relationships between breastfeeding duration and cortical surface area.

Promoting breastfeeding, particularly among women from lower SEEs would confer long-term benefits to offspring.
CDK4/6 inhibitors dephosphorylate RNF26 to stabilize TSC1 and increase the sensitivity of ccRCC to mTOR inhibitors
Authors: Liu Xinlin , Li Wei , Yi Lu , Wang Jianxi , Liu Wentao , Cheng Hongtao , Ren Shangqing
Published: June 2024

Background

The combined use of CDK4/6 inhibitors and mTOR inhibitors has achieved some clinical success in ccRCC. Exploring the underlying mechanism of the CDK4/6 pathway in cancer cells and the drug interactions of CDK4/6 inhibitors in combination therapy could help identify new therapeutic strategies for ccRCC. Notably, CDK4/6 inhibitors inactivate the mTOR pathway by increasing the protein levels of TSC1, but the mechanism by which CDK4/6 inhibitors regulate TSC1 is still unclear.

Methods

Mass spectrometry analysis, coimmunoprecipitation analysis, GST pull-down assays, immunofluorescence assays, Western blot analysis and RT‒qPCR analysis were applied to explore the relationships among CDK4, RNF26 and TSC1. Transwell assays, tube formation assays, CCK-8 assays, colony formation assays and xenograft assays were performed to examine the biological role of RNF26 in renal cancer cells.TCGA-KIRC dataset analysis and RT‒qPCR analysis were used to examine the pathways affected by RNF26 silencing.

Results

CDK4/6 inhibitors stabilized TSC1 in cancer cells. We showed that CDK4 enhances the interaction between TSC1 and RNF26 and that RNF26 activates the mTOR signaling pathway in ccRCC, contributes to ccRCC progression and angiogenesis, and promotes tumorigenesis. We then found that RNF26 functions as an E3 ligase of TSC1 to regulate CDK4-induced TSC1. This finding suggested that RNF26 promotes ccRCC progression and angiogenesis to some extent by negatively regulating TSC1.

Conclusion

Our results revealed a novel CDK4/RNF26/TSC1 axis that regulates the anticancer efficacy of CDK4/6 inhibitors and mTOR inhibitors in ccRCC.
Regulation of primary cilia disassembly through HUWE1-mediated TTBK2 degradation plays a crucial role in cerebellar development and medulloblastoma growth
Authors: Lin I-Hsuan , Li Yue-Ru , Chang Chia-Hsiang , Cheng Yu-Wen , Wang Yu-Ting , Tsai Yu-Shuen , Lin Pei-Yi , Kao Chien-Han , Su Ting-Yu , Hsu Chih-Sin , Tung Chien-Yi , Hsu Pang-Hung , Ayrault Olivier , Chung Bon-chu , Tsai Jin-Wu , Wang Won-Jing
Published: June 2024

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation. We show that TTBK2 is highly expressed in proliferating GNPs under Sonic Hedgehog (SHH) signaling, coinciding with active GNP proliferation and the presence of primary cilia. TTBK2 stabilizes primary cilia by inhibiting their disassembly, thereby promoting GNP proliferation in response to SHH. Mechanistically, we identify HUWE1 as a novel centrosomal E3 ligase that facilitates primary cilia disassembly by targeting TTBK2 degradation. Disassembly of primary cilia serves as a trigger for GNP differentiation, allowing their migration from the external granule layer (EGL) of the cerebellum to the internal granule layer (IGL) for subsequent maturation. Moreover, we have established a link between TTBK2 and SHH-type medulloblastoma (SHH-MB), a tumor characterized by uncontrolled GNP proliferation. TTBK2 depletion inhibits SHH-MB proliferation, indicating that TTBK2 may be a potential therapeutic target for this cancer type. In summary, our findings reveal the mechanism governing cerebellar development and highlight a potential anti-cancer strategy for SHH-MB.
Trpv6 channel targeting using monoclonal antibody induces prostate cancer cell apoptosis and tumor regression
Authors: Haustrate Aurélien , Cordier Clément , Shapovalov George , Mihalache Adriana , Desruelles Emilie , Soret Benjamin , Essonghé Nadège Charlène , Spriet Corentin , Yassine Maya , Barras Alexandre , Marines Johanna , Alcaraz Lindsay B. , Szunerits Sabine , Robin Gautier , Gosset Pierre , Prevarskaya Natalia , Lehen’kyi V’yacheslav
Published: June 2024

TRPV6 calcium channel is a prospective target in prostate cancer (PCa) since it is not expressed in healthy prostate while its expression increases during cancer progression. Despite the role of TRPV6 in PCa cell survival and apoptotic resistance has been already established, no reliable tool to target TRPV6 channel in vivo and thus to reduce tumor burden is known to date. Here we report the generation of mouse monoclonal antibody mAb82 raised against extracellular epitope of the pore region of the channel. mAb82 inhibited TRPV6 currents by 90% at 24 µg/ml in a dose-dependent manner while decreasing store-operated calcium entry to 56% at only 2.4 µg/ml. mAb82 decreased PCa survival rate in vitro by 71% at 12 µg/ml via inducing cell death through the apoptosis cascade via activation of the protease calpain, following bax activation, mitochondria enlargement, and loss of cristae, Cyt C release, pro-caspase 9 cleavage with the subsequent activation of caspases 3/7. In vivo, mice bearing either PC3Mtrpv6+/+ or PC3Mtrpv6-/-+pTRPV6 tumors were successfully treated with mAb82 at the dose as low as 100 µg/kg resulting in a significant reduction tumor growth by 31% and 90%, respectively. The survival rate was markedly improved by 3.5 times in mice treated with mAb82 in PC3Mtrpv6+/+ tumor group and completely restored in PC3Mtrpv6-/-+pTRPV6 tumor group. mAb82 showed a TRPV6-expression dependent organ distribution and virtually no toxicity in the same way as mAbAU1, a control antibody of the same Ig2a isotype. Overall, our data demonstrate for the first time the use of an anti-TRPV6 monoclonal antibody in vitro and in vivo in the treatment of the TRPV6-expressing PCa tumors.
Anyon quantum dimensions from an arbitrary ground state wave function
Authors: Liu Shang
Published: June 2024

Realizing topological orders and topological quantum computation is a central task of modern physics. An important but notoriously hard question in this endeavor is how to diagnose topological orders that lack conventional order parameters. A breakthrough in this problem is the discovery of topological entanglement entropy, which can be used to detect nontrivial topological order from a ground state wave function, but is far from enough for fully determining the topological order. In this work, we take a key step further in this direction: We propose a simple entanglement-based protocol for extracting the quantum dimensions of all anyons from a single ground state wave function in two dimensions. The choice of the space manifold and the ground state is arbitrary. This protocol is both validated in the continuum and verified on lattices, and we anticipate it to be realizable in various quantum simulation platforms.
Acoustic ejection mass spectrometry empowers ultra-fast protein biomarker quantification
Authors: Van Puyvelde Bart , Hunter Christie L. , Zhgamadze Maxim , Savant Sudha , Wang Y. Oliver , Hoedt Esthelle , Raedschelders Koen , Pope Matt , Huynh Carissa A. , Ramanujan V. Krishnan , Tourtellotte Warren , Razavi Morteza , Anderson N. Leigh , Martens Geert , Deforce Dieter , Fu Qin , Dhaenens Maarten , Van Eyk Jennifer E.
Published: June 2024

The global scientific response to COVID 19 highlighted the urgent need for increased throughput and capacity in bioanalytical laboratories, especially for the precise quantification of proteins that pertain to health and disease. Acoustic ejection mass spectrometry (AEMS) represents a much-needed paradigm shift for ultra-fast biomarker screening. Here, a quantitative AEMS assays is presented, employing peptide immunocapture to enrich (i) 10 acute phase response (APR) protein markers from plasma, and (ii) SARS-CoV-2 NCAP peptides from nasopharyngeal swabs. The APR proteins were quantified in 267 plasma samples, in triplicate in 4.8 h, with %CV from 4.2% to 10.5%. SARS-CoV-2 peptides were quantified in triplicate from 145 viral swabs in 10 min. This assay represents a 15-fold speed improvement over LC-MS, with instrument stability demonstrated across 10,000 peptide measurements. The combination of speed from AEMS and selectivity from peptide immunocapture enables ultra-high throughput, reproducible quantitative biomarker screening in very large cohorts.
Additive manufacturing of an ultrastrong, deformable Al alloy with nanoscale intermetallics
Authors: Shang Anyu , Stegman Benjamin , Choy Kenyi , Niu Tongjun , Shen Chao , Shang Zhongxia , Sheng Xuanyu , Lopez Jack , Hoppenrath Luke , Zhang Bohua Peter , Wang Haiyan , Bellon Pascal , Zhang Xinghang
Published: June 2024

Light-weight, high-strength, aluminum (Al) alloys have widespread industrial applications. However, most commercially available high-strength Al alloys, like AA 7075, are not suitable for additive manufacturing due to their high susceptibility to solidification cracking. In this work, a custom Al alloy Al92Ti2Fe2Co2Ni2 is fabricated by selective laser melting. Heterogeneous nanoscale medium-entropy intermetallic lamella form in the as-printed Al alloy. Macroscale compression tests reveal a combination of high strength, over 700 MPa, and prominent plastic deformability. Micropillar compression tests display significant back stress in all regions, and certain regions have flow stresses exceeding 900 MPa. Post-deformation analyses reveal that, in addition to abundant dislocation activities in Al matrix, complex dislocation structures and stacking faults form in monoclinic Al9Co2 type brittle intermetallics. This study shows that proper introduction of heterogeneous microstructures and nanoscale medium entropy intermetallics offer an alternative solution to the design of ultrastrong, deformable Al alloys via additive manufacturing.
Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate
Authors: Sastre Diego E. , Sultana Nazneen , V. A. S. Navarro Marcos , Huliciak Maros , Du Jonathan , Cifuente Javier O. , Flowers Maria , Liu Xu , Lollar Pete , Trastoy Beatriz , Guerin Marcelo E. , Sundberg Eric J.
Published: June 2024

Bacteroidales (syn. Bacteroidetes) are prominent members of the human gastrointestinal ecosystem mainly due to their efficient glycan-degrading machinery, organized into gene clusters known as polysaccharide utilization loci (PULs). A single PUL was reported for catabolism of high-mannose (HM) N-glycan glyco-polypeptides in the gut symbiont Bacteroides thetaiotaomicron, encoding a surface endo-β-N-acetylglucosaminidase (ENGase), BT3987. Here, we discover an ENGase from the GH18 family in B. thetaiotaomicron, BT1285, encoded in a distinct PUL with its own repertoire of proteins for catabolism of the same HM N-glycan substrate as that of BT3987. We employ X-ray crystallography, electron microscopy, mass spectrometry-based activity measurements, alanine scanning mutagenesis and a broad range of biophysical methods to comprehensively define the molecular mechanism by which BT1285 recognizes and hydrolyzes HM N-glycans, revealing that the stabilities and activities of BT1285 and BT3987 were optimal in markedly different conditions. BT1285 exhibits significantly higher affinity and faster hydrolysis of poorly accessible HM N-glycans than does BT3987. We also find that two HM-processing endoglycosidases from the human gut-resident Alistipes finegoldii display condition-specific functional properties. Altogether, our data suggest that human gut microbes employ evolutionary strategies to express distinct ENGases in order to optimally metabolize the same N-glycan substrate in the gastroinstestinal tract.
Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence
Authors: Li Jinhui , Deng Zhengyi , Soerensen Simon John Christoph , Kachuri Linda , Cardenas Andres , Graff Rebecca E. , Leppert John T. , Langston Marvin E. , Chung Benjamin I.
Published: June 2024

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 μg/m3 increase in PM2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 μg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM2.5 levels to 5.8 μg/m3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.
Kinetics and mapping of Ca-driven calmodulin conformations on skeletal and cardiac muscle ryanodine receptors
Authors: Rebbeck Robyn T. , Svensson Bengt , Zhang Jingyan , Samsó Montserrat , Thomas David D. , Bers Donald M. , Cornea Razvan L.
Published: June 2024

Calmodulin transduces [Ca2+] information regulating the rhythmic Ca2+ cycling between the sarcoplasmic reticulum and cytoplasm during contraction and relaxation in cardiac and skeletal muscle. However, the structural dynamics by which calmodulin modulates the sarcoplasmic reticulum Ca2+ release channel, the ryanodine receptor, at physiologically relevant [Ca2+] is unknown. Using fluorescence lifetime FRET, we resolve different structural states of calmodulin and Ca2+-driven shifts in the conformation of calmodulin bound to ryanodine receptor. Skeletal and cardiac ryanodine receptor isoforms show different calmodulin-ryanodine receptor conformations, as well as binding and structural kinetics with 0.2-ms resolution, which reflect different functional roles of calmodulin. These FRET methods provide insight into the physiological calmodulin-ryanodine receptor structural states, revealing additional distinct structural states that complement cryo-EM models that are based on less physiological conditions. This technology will drive future studies on pathological calmodulin-ryanodine receptor interactions and dynamics with other important ryanodine receptor bound modulators.
A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses
Authors: Wang Yingdan , Hao Aihua , Ji Ping , Ma Yunping , Zhang Zhaoyong , Chen Jiali , Mao Qiyu , Xiong Xinyi , Rehati Palizhati , Wang Yajie , Wang Yanqun , Wen Yumei , Lu Lu , Chen Zhenguo , Zhao Jincun , Wu Fan , Huang Jinghe , Sun Lei
Published: June 2024

The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.
Fusaric acid mediates the assembly of disease-suppressive rhizosphere microbiota via induced shifts in plant root exudates
Authors: Jin Xue , Jia Huiting , Ran Lingyi , Wu Fengzhi , Liu Junjie , Schlaeppi Klaus , Dini-Andreote Francisco , Wei Zhong , Zhou Xingang
Published: June 2024

The plant health status is determined by the interplay of plant-pathogen-microbiota in the rhizosphere. Here, we investigate this tripartite system focusing on the pathogenFusarium oxysporumf. sp.lycopersici(FOL) and tomato plants as a model system. First, we explore differences in tomato genotype resistance to FOL potentially associated with the differential recruitment of plant-protective rhizosphere taxa. Second, we show the production of fusaric acid by FOL to trigger systemic changes in the rhizosphere microbiota. Specifically, we show this molecule to have opposite effects on the recruitment of rhizosphere disease-suppressive taxa in the resistant and susceptible genotypes. Last, we elucidate that FOL and fusaric acid induce changes in the tomato root exudation with direct effects on the recruitment of specific disease-suppressive taxa. Our study unravels a mechanism mediating plant rhizosphere assembly and disease suppression by integrating plant physiological responses to microbial-mediated mechanisms in the rhizosphere.
Functional group tolerant hydrogen borrowing C-alkylation
Authors: Bailey Elliot P. , Donohoe Timothy J. , Smith Martin D.
Published: June 2024

Hydrogen borrowing is an attractive and sustainable strategy for carbon–carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed.
G6PD and ACSL3 are synthetic lethal partners of NF2 in Schwann cells
Authors: Kyrkou Athena , Valla Robert , Zhang Yao , Ambrosi Giulia , Laier Stephanie , Müller-Decker Karin , Boutros Michael , Teleman Aurelio A.
Published: June 2024

Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.
A versatile automated pipeline for quantifying virus infectivity by label-free light microscopy and artificial intelligence
Authors: Petkidis Anthony , Andriasyan Vardan , Murer Luca , Volle Romain , Greber Urs F.
Published: June 2024

Virus infectivity is traditionally determined by endpoint titration in cell cultures, and requires complex processing steps and human annotation. Here we developed an artificial intelligence (AI)-powered automated framework for ready detection of virus-induced cytopathic effect (DVICE). DVICE uses the convolutional neural network EfficientNet-B0 and transmitted light microscopy images of infected cell cultures, including coronavirus, influenza virus, rhinovirus, herpes simplex virus, vaccinia virus, and adenovirus. DVICE robustly measures virus-induced cytopathic effects (CPE), as shown by class activation mapping. Leave-one-out cross-validation in different cell types demonstrates high accuracy for different viruses, including SARS-CoV-2 in human saliva. Strikingly, DVICE exhibits virus class specificity, as shown with adenovirus, herpesvirus, rhinovirus, vaccinia virus, and SARS-CoV-2. In sum, DVICE provides unbiased infectivity scores of infectious agents causing CPE, and can be adapted to laboratory diagnostics, drug screening, serum neutralization or clinical samples.
Unpredictable benefits of social information can lead to the evolution of individual differences in social learning
Authors: van den Berg Pieter , Vu TuongVan , Molleman Lucas
Published: June 2024

Human ecological success is often attributed to our capacity for social learning, which facilitates the spread of adaptive behaviours through populations. All humans rely on social learning to acquire culture, but there is substantial variation across societies, between individuals and over developmental time. However, it is unclear why these differences exist. Here, we present an evolutionary model showing that individual variation in social learning can emerge if the benefits of social learning are unpredictable. Unpredictability selects for flexible developmental programmes that allow individuals to update their reliance on social learning based on previous experiences. This developmental flexibility, in turn, causes some individuals in a population to end up consistently relying more heavily on social learning than others. We demonstrate this core evolutionary mechanism across three scenarios of increasing complexity, investigating the impact of different sources of uncertainty about the usefulness of social learning. Our results show how evolution can shape how individuals learn to learn from others, with potentially profound effects on cultural diversity.
Intra-islet α-cell Gs signaling promotes glucagon release
Authors: Liu Liu , El Kimberley , Dattaroy Diptadip , Barella Luiz F. , Cui Yinghong , Gray Sarah M. , Guedikian Carla , Chen Min , Weinstein Lee S. , Knuth Emily , Jin Erli , Merrins Matthew J. , Roman Jeffrey , Kaestner Klaus H. , Doliba Nicolai , Campbell Jonathan E. , Wess Jürgen
Published: June 2024

Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell Gs signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell Gs signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α−cell Gs-coupled A2A adenosine receptors. Studies with α-cell-specific Gαs knockout mice showed that α-cell Gs also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched Gs-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.
Resilient, environment tolerant and biocompatible electroluminescent devices with enhanced luminance based on compliant and self-adhesive electrodes
Authors: Lu Ya , Chen Yuanyuan , Sun Haoyu , Deng Fang , Mei Changtong , Xu Xinwu , Wu Qinglin , Xiao Huining , Yue Yiying , Han Jingquan
Published: June 2024

Electroluminescent (EL) devices are of great significance for expanding the application range of optoelectronics. However, the realization of EL devices with environment-tolerance, stretchability, mechanical cycling stability, self-adhesion, biocompatibility, and high dielectric constant still remains a challenge. Herein, a type of EL device with enhanced comprehensive performances composing of a chlorinated barium titanate/phosphor/polydimethylsiloxane (Cl-BT/phosphor/PDMS) luminescent layer sandwiched between two silver nanowire-cellulose nanocrystal with II crystalline allomorph/Triton X-100 modified polydimethylsiloxane (AgNW-CNC II/TX-PDMS) electrodes fabricated through a full solution-processing strategy is proposed. Environmentally-friendly CNC II with high transmittance acts as an antioxidant, dispersant and film-former for AgNWs. The hydrophilic modification of TX to PDMS imparts the electrodes with self-adhesion, high stretchability, as well as strong interfacial bonding between TX-PDMS and AgNW-CNC II. The electrodes achieve skin-like modulus by adjusting TX content, endowing the EL devices with a high compliance (186 kPa of Young’s modulus). The luminescent layer with Cl-BT exhibits a high dielectric constant (19) and luminance (up to 72 cd m−2). The assembled EL device with excellent cyclic stability (luminance retention 85% after 400 cycles), durability (luminance retention >94% after 400 min) and stretchability (88% luminance at 200% strain) can work properly at broad temperatures (−20 ~ 70 °C) and underwater. This biocompatible and self-adhesive EL device demonstrates great potential for implantable biomedical devices and wearable displays under harsh environments.
Excitation/inhibition imbalance in schizophrenia: a meta-analysis of inhibitory and excitatory TMS-EMG paradigms
Authors: Lányi Orsolya , Koleszár Boróka , Schulze Wenning Alexander , Balogh David , Engh Marie Anne , Horváth András Attila , Fehérvari Péter , Hegyi Péter , Molnár Zsolt , Unoka Zsolt , Csukly Gábor
Published: June 2024

Cortical excitation-inhibition (E/I) imbalance is a potential model for the pathophysiology of schizophrenia. Previous research using transcranial magnetic stimulation (TMS) and electromyography (EMG) has suggested inhibitory deficits in schizophrenia. In this meta-analysis we assessed the reliability and clinical potential of TMS-EMG paradigms in schizophrenia following the methodological recommendations of the PRISMA guideline and the Cochrane Handbook. The search was conducted in three databases in November 2022. Included articles reported Short-Interval Intracortical Inhibition (SICI), Intracortical Facilitation (ICF), Long-Interval Intracortical Inhibition (LICI) and Cortical Silent Period (CSP) in patients with schizophrenia and healthy controls. Meta-analyses were conducted using a random-effects model. Subgroup analysis and meta-regressions were used to assess heterogeneity. Results of 36 studies revealed a robust inhibitory deficit in schizophrenia with a significant decrease in SICI (Cohen’s d: 0.62). A trend-level association was found between SICI and antipsychotic medication. Our findings support the E/I imbalance hypothesis in schizophrenia and suggest that SICI may be a potential pathophysiological characteristic of the disorder.
Decoding the hallmarks of allograft dysfunction with a comprehensive pan-organ transcriptomic atlas
Authors: Robertson Harry , Kim Hani Jieun , Li Jennifer , Robertson Nicholas , Robertson Paul , Jimenez-Vera Elvira , Ameen Farhan , Tran Andy , Trinh Katie , O’Connell Philip J. , Yang Jean Y. H. , Rogers Natasha M. , Patrick Ellis
Published: June 2024

The pathogenesis of allograft (dys)function has been increasingly studied using ‘omics’-based technologies, but the focus on individual organs has created knowledge gaps that neither unify nor distinguish pathological mechanisms across allografts. Here we present a comprehensive study of human pan-organ allograft dysfunction, analyzing 150 datasets with more than 12,000 samples across four commonly transplanted solid organs (heart, lung, liver and kidney, n = 1,160, 1,241, 1,216 and 8,853 samples, respectively) that we leveraged to explore transcriptomic differences among allograft dysfunction (delayed graft function, acute rejection and fibrosis), tolerance and stable graft function. We identified genes that correlated robustly with allograft dysfunction across heart, lung, liver and kidney transplantation. Furthermore, we developed a transfer learning omics prediction framework that, by borrowing information across organs, demonstrated superior classifications compared to models trained on single organs. These findings were validated using a single-center prospective kidney transplant cohort study (a collective 329 samples across two timepoints), providing insights supporting the potential clinical utility of our approach. Our study establishes the capacity for machine learning models to learn across organs and presents a transcriptomic transplant resource that can be employed to develop pan-organ biomarkers of allograft dysfunction.
A hybrid ensemble learning merging approach for enhancing the super drought computation over Lake Victoria Basin
Authors: Das Priyanko , Zhang Zhenke , Ghosh Suravi , Hang Ren
Published: June 2024

This study introduces a novel Hybrid Ensemble Machine-Learning (HEML) algorithm to merge long-term satellite-based reanalysis precipitation products (SRPPs), enabling the estimation of super drought events in the Lake Victoria Basin (LVB) during the period of 1984 to 2019. This study considers three widely used Machine learning (ML) models, including RF (Random Forest), GBM (Gradient Boosting Machine), and KNN (k-nearest Neighbors), for the emerging HEML approach. The three SRPPs, including CHIRPS (Climate Hazards Group Infra-Red Precipitation with Station), ERA5-Land, and PERSIANN-CDR (Precipitation Estimation from Remotely Sensed Information using Artificial Neural Network-Climate Data Record), were used to merge for developing new precipitation estimates from HEML model. Additionally, classification and regression models were employed as base learners in developing this algorithm. The newly developed HEML datasets were compared with other ML and SRPP products for super-drought monitoring. The Standardized precipitation evapotranspiration index (SPEI) was used to estimate super drought characteristics, including Drought frequency (DF), Drought Duration (DD), and Drought Intensity (DI) from machine learning and SRPPs products in LVB and compared with RG observation. The results revealed that the HEML algorithm shows excellent performance (CC = 0.93) compared to the single ML merging method and SRPPs against observation. Furthermore, the HEML merging product adeptly captures the spatiotemporal patterns of super drought characteristics during both training (1984–2009) and testing (2010–2019) periods. This research offers crucial insights for near-real-time drought monitoring, water resource management, and informed policy decisions.
Bentonite-supplemented diets improved fish performance ammonia excretion haemato-biochemical analyses immunity antioxidants and histological characteristics of European seabass Dicentrarchus labrax
Authors: El-Dahhar Alaa A. , Elhetawy Ashraf. I. G. , Refaey Wael M. A. , El-Zaeem Samy Y. , Elebiary Elsayed H. , Lotfy Ayman M. , Abdel-Rahim Mohamed M.
Published: June 2024

The purpose of this research was to examine the potential effects of bentonite (BN) supplemented diets on growth, feed utilization, blood biochemistry, and histomorphology of Dicentrarchus labrax. Six treatments in triplicate were tested: B0, B0.5, B1.0, B1.5, B3.0, and B4.5, which represented fish groups fed diets supplemented with 0, 0.5, 1, 1.5, 3, and 4.5% BN, respectively. For 84 days, juveniles’ seabass (initial weight = 32.73 g) were fed diets containing 46% protein, three times daily at 3% of body weight. With a 5% daily water exchange, underground seawater (32 ppt) was used. Findings revealed significant improvements in water quality (TAN and NH3), growth (FW, WG and SGR) and feed utilization (FCR, PER and PPV) in fish fed BN-supplemented diets, with the best values in favor of the B1.5 group. Additional enhancements in kidney function indicators (urea and uric acid) and liver enzymes were observed in fish of the BN-treated groups along with a decrease in cholesterol level in the B1.5 group. Further improvements in fish innate immunity (hemoglobin, red blood cells, glucose, total protein, globulin, and immunoglobulin IgM), antioxidant activity (total antioxidative capacity and catalase), and decreased cortisol levels in fish of the BN-treated groups. Histological examinations of the anterior and posterior intestines and liver in groups B1.5 and B3 revealed the healthiest organs. This study recommends BN at a concentration of 1.5% as a feed additive in the Dicentrarchus labrax diet.
Fabrication and characterization of unique sustain modified chitosan nanoparticles for biomedical applications
Authors: Ahmed Marwa ElS. , Mohamed Mansoura I. , Ahmed Hanaa Y. , Elaasser Mahmoud M. , Kandile Nadia G.
Published: June 2024

Chitosan (CS) is a biopolymer that offers a wide range in biomedical applications due to its biocompatibility, biodegradability, low toxicity and antimicrobial activity. Syringaldehyde (1) is a naturally occurring organic compound characterized by its use in multiple fields such as pharmaceuticals, food, cosmetics, textiles and biological applications. Herein, development of chitosan derivative with physicochemical and anticancer properties via Schiff base formation from the reaction of chitosan with sustainable eco-friendly syringaldehyde yielded the (CS-1) derivative. Moreover, in the presence of polyethylene glycol diglycidyl ether (PEGDGE) or sodium tripolyphosphate (TPP) as crosslinkers gave chitosan derivatives (CS-2) and (CS-3NPs) respectively. The chemical structures of the new chitosan derivatives were confirmed using different tools. (CS-3NPs) nanoparticle showed improvement in crystallinity, and (CS-2) derivative revealed the highest thermal stability compared to virgin chitosan. The cytotoxicity activity of chitosan and its derivatives were evaluated against HeLa (human cervical carcinoma) and HEp-2 (Human Larynx carcinoma) cell lines. The highest cytotoxicity activity was exhibited by (CS-3NPs) compared to virgin chitosan against HeLa cell growth inhibition and apoptosis of 90.38 ± 1.46% and 30.3% respectively and IC50 of 108.01 ± 3.94 µg/ml. From the above results, it can be concluded that chitosan nanoparticle (CS-3NPs) has good therapeutic value as a potential antitumor agent against the HeLa cancer cell line.
Implantable photonic neural probes with out-of-plane focusing grating emitters
Authors: Xue Tianyuan , Stalmashonak Andrei , Chen Fu-Der , Ding Peisheng , Luo Xianshu , Chua Hongyao , Lo Guo-Qiang , Sacher Wesley D. , Poon Joyce K. S.
Published: June 2024

We have designed, fabricated, and characterized implantable silicon neural probes with nanophotonic grating emitters that focus the emitted light at a specified distance above the surface of the probe for spatially precise optogenetic targeting of neurons. Using the holographic principle, we designed gratings for wavelengths of 488 and 594 nm, targeting the excitation spectra of the optogenetic actuators Channelrhodopsin-2 and Chrimson, respectively. The measured optical emission pattern of these emitters in non-scattering medium and tissue matched well with simulations. To our knowledge, this is the first report of focused spots with the size scale of a neuron soma in brain tissue formed from implantable neural probes.
Mindfulness and self-regulation intervention for improved self-neglect and self-regulation in diabetic older adults
Authors: Motamed-Jahromi Mohadeseh , Kaveh Mohammad Hossein , Vitale Elsa
Published: June 2024

The current study aimed to assess the impact of combined interventions including mindfulness and self-regulation on self-neglect and self-regulation among Iranian older adults with type 2 diabetes. This was a three-arm cluster randomized controlled trial study conducted among 135 older diabetic patients in Shiraz, Iran. Three urban healthcare centers (clusters) were randomly assigned to three study groups. The intervention groups received either a Self-Regulation-based Intervention Program (SRIP) or a Combined Mindfulness and Self-Regulation Intervention Program (CMSRIP), while the control group received routine care and COVID-19 prevention training. These training programs, which consisted of text and video-based content, were conducted over 24 weeks using WhatsApp as a mobile-based communication platform. Outcomes were measured using the Elder Self-Neglect Scale and Short-Form Self-Regulation Questionnaire at baseline, week 4, and week 16 post-intervention, with data analysis conducted using SPSS 20 software. The CMSRIP led to significantly greater improvement in the score of self-regulation (χ2 = 73.23, P-Value =  < .001) and a reduction in the score of self-neglect (χ2 = 62.97, P-Value =  < .001) at both 4 weeks and 16 weeks after education compared to SRIP. In the control group, there was also a slight improvement. Improvement of self-regulation and reduction of self-neglect in all three groups were less in week 16 than in week 4. Nevertheless, the changes in the intervention groups were significantly better than the control group. This study confirmed a combination of mindfulness-based intervention and self-regulation intervention can effectively improve self-neglect and self-regulation behavior in older patients with type 2 diabetes.

Trial registration: This trial (ISRCTN77260130) was retrospectively registered on 28/09/2021.
Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest
Authors: Piel Sarah , McManus Meagan J. , Heye Kristina N. , Beaulieu Forrest , Fazelinia Hossein , Janowska Joanna I. , MacTurk Bryce , Starr Jonathan , Gaudio Hunter , Patel Nisha , Hefti Marco M. , Smalley Martin E. , Hook Jordan N. , Kohli Neha V. , Bruton James , Hallowell Thomas , Delso Nile , Roberts Anna , Lin Yuxi , Ehinger Johannes K. , Karlsson Michael , Berg Robert A. , Morgan Ryan W. , Kilbaugh Todd J.
Published: June 2024

Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.
RETRACTED ARTICLE: DNA encoding schemes herald a new age in cybersecurity for safeguarding digital assets
Authors: Aqeel Sehrish , Khan Sajid Ullah , Khan Adnan Shahid , Alharbi Meshal , Shah Sajid , Affendi Mohammed EL , Ahmad Naveed
Published: June 2024

With the urge to secure and protect digital assets, there is a need to emphasize the immediacy of taking measures to ensure robust security due to the enhancement of cyber security. Different advanced methods, like encryption schemes, are vulnerable to putting constraints on attacks. To encode the digital data and utilize the unique properties of DNA, like stability and durability, synthetic DNA sequences are offered as a promising alternative by DNA encoding schemes. This study enlightens the exploration of DNA’s potential for encoding in evolving cyber security. Based on the systematic literature review, this paper provides a discussion on the challenges, pros, and directions for future work. We analyzed the current trends and new innovations in methodology, security attacks, the implementation of tools, and different metrics to measure. Various tools, such as Mathematica, MATLAB, NIST test suite, and Coludsim, were employed to evaluate the performance of the proposed method and obtain results. By identifying the strengths and limitations of proposed methods, the study highlights research challenges and offers future scope for investigation.