bluuebunny/crossref_metadata_2025 huggingface dataset:
DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer
Authors: Mei Jie , Pan Liuliu , Huang Min , Bao Dandan , Gao Hui , Wang Danhan
Published: March 2024

Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.
Investigation of media for wheat (Triticum aestivum L.) immature embryo culture
Authors: Mohammed Abdullah Hassn , Baldwin Brian S.
Published: March 2024

Immature embryos of F1 progeny resulting from taxonomically wide hybridizations require tissue culture using complex media to mature, grow and develop into normal and healthy plants. To gain insight as to how progeny of wide-crosses between wild and domestic Triticum species, 12 domestic varieties (Al-Eiz, Babel, Bedhaa, Entisar, Hadbaa, IPA 99, Latifia, Nour, Rabia, Sally, Sham 6, Tamoz 2) were used to determine the genotype response to culture media type. Immature embryos the aforementioned wheat varieties were screened on four media (Murashige and Skoog; MS full strength, ½ strength MS, Gamborg B-5; B-5 full strength, and ½ strength B-5) to determine performance when used as a female in a cross with wild species. The experiment used a completely randomized design with six replications. Traits recorded were final germinations percentage (FGP), shoot length (SL), root length (RL), and root number (RN). Results indicated significant variety x media interaction for all traits studied. Despite the interaction, in a practical sense, all varieties performed adequately on ½ B-5 and varieties Al-Eiz, Entisar, Hadbaa, and Latifia performed well on any of the four media. Tamoz 2 behaved recalcitrantly on all media tested. Data from this study indicated genetic variability among these wheat varieties caused substantial differences in response to each type of media.
Enhancing Steel Wheel Ventilation Efficiency Through Multi-Objective Optimization
Authors: Bogrekci I. , Demircioglu P. , Sasmaz M. E. , Unal C.
Published: March 2024

This study focuses on the optimization of ventilation hole design in steel wheels used for heavy commercial vehicles. The primary objective is to reduce the weight of the wheel while ensuring compliance with radial fatigue and cornering fatigue test requirements. Four distinct ventilation types were parametrized using ANSYS Mechanical, with the von Mises stress on the disk, number of ventilations, and wheel weight serving as design parameters. Stress analysis and weight comparisons were performed between wheels featuring different ventilation types and an ellipse ventilation wheel. Incorporating the design of experiment (DoE) and response surface optimization (RSO) module in ANSYS Workbench 2022 R1 was employed to compare and evaluate the obtained values. Subsequently, the multi-objective genetic algorithm (MOGA-II) method was employed for optimization, aiming to identify the optimal design. The optimization process, utilizing a maximum of 20 iterations, a convergence stability percentage of 2%, and a maximum allowable Pareto percentage of 70%, yielded 1, 3, 3, and 3 candidate design points for round, slot, trapezoid, and halfmoon-type ventilation holes, respectively. Among the various ventilation types considered, the halfmoon-type ventilation hole exhibited the most promising results. Compared to the current design, the optimized wheel achieved a weight reduction of 0.9 kg (2.05%). This outcome demonstrates the effectiveness of the proposed methodology. Although lighter designs were not attainable while maintaining the same stress values for the other three ventilation types, the halfmoon-type ventilation hole was ultimately selected as the preferred design.
Unlocking the power of motor imagery: a comprehensive review on its application in alleviating foot pain
Authors: Tedeschi Roberto
Published: March 2024

Background

Motor imagery is a cognitive process that involves mentally simulating movements without physical execution. It has been studied in the context of foot pain to understand the role of motor cortical reorganization and its impact on motor imagery abilities. However, further research is needed to establish consistent evidence regarding the relationship between motor imagery and foot pain.

Methods

This review analyzed five relevant articles that investigated motor imagery in the context of foot pain. The studies involved participants with various conditions, including leg amputation, chronic leg pain, complex regional pain syndrome, and Achilles tendinopathy. Different methodologies were employed, including motor cortical mapping, foot laterality recognition tasks, EEG recordings, and treatment interventions incorporating motor imagery.

Results

The findings indicated that individuals with leg amputation exhibited functional reorganization in upper limb motor cortical maps, with a breakdown in the inhibitory relationship between foot and hand representations. Participants with chronic leg pain demonstrated slower and less accurate performance on foot laterality recognition tasks compared to healthy controls. Complex regional pain syndrome patients displayed distinct motor imagery strategies and responded differently to first-person and third-person perspectives. EEG studies revealed differences in brain activity during motor imagery tasks under pain-free and pain conditions. Treatment interventions incorporating motor imagery showed promising outcomes in improving functional outcomes and reducing pain levels.

Conclusions

Motor imagery plays a significant role in foot pain conditions, although the evidence is still emerging. The findings suggest that motor imagery abilities may be affected by leg amputation, chronic pain, and complex regional pain syndrome. Further research is needed to establish standardized protocols for assessing motor imagery, identify specific patient populations that may benefit most from motor imagery interventions, and explore long-term effects. Integrating motor imagery into clinical practice has the potential to enhance rehabilitation approaches and improve outcomes in foot pain management.
Development and Validation of the Adolescent and Children Risk of Abuse and Maltreatment Unaccompanied Scale (ACRAM-US)
Authors: Samper Paula , García-Mollá Adrián , Tomás José M. , Marco-Arocas Elisabet
Published: March 2024

Independent migration of children and adolescents is becoming a political and social issue in recent years. Literature documents that the migration process of young people without an adult referent entail serious psychological problems. Moreover, the lack of coherence in the assessment and care processes aggravates the damage suffered by minors, which requires a greater investment of institutional resources. The aim of this research is to describe the development and provide psychometric properties of Adolescent and Children Risk of Abuse and Maltreatment Unaccompanied Scale (ACRAM-US), a 9-items scale for the assessment of risks factors of child abuse and neglect in the specific population of unaccompanied asylum-seeking children and adolescents. Structural validity, reliability and convergent-related validity were studied for this measure in a sample of 128 unaccompanied children and adolescents. The sample included cases of 14 different nationalities. Children’s mean age was 16.94 (SD = 1.84), and 96.9% were male and 3.1% were female. Cases were informed by child welfare workers from different protective services in the XXXX Community (XXXX). The results of Exploratory Factor Analyses (EFA) indicate performance better solution with 2-dimensions which was also in line with theoretical formulation (χ2 = 31.55, df = 19, p = .035, CFI = 0.991, SRMR = 0.081, RMSEA = 0.072, [90% CI: 0.019 − 0.115]). Results of convergent validity showed significant correlation with the Children Trauma Questionnaire-Short Form (CTQ-SF). Therefore, this study provides data of the first scale that assess risks factors of maltreatment for the unaccompanied asylum-seeking children and adolescents.
Byrd Ice Core Debris Constrains the Sediment Provenance Signature of Central West Antarctica
Authors: Marschalek J. W. , Blard P.‐H. , Sarigulyan E. , Ehrmann W. , Hemming S. R. , Thomson S. N. , Hillenbrand C.‐D. , Licht K. , Tison J.‐L. , Ardoin L. , Fripiat F. , Allen C. S. , Marrocchi Y. , Siegert M. J. , van de Flierdt T.
Published: March 2024

Provenance records from sediments deposited offshore of the West Antarctic Ice Sheet (WAIS) can help identify past major ice retreat, thus constraining ice‐sheet models projecting future sea‐level rise. Interpretations from such records are, however, hampered by the ice obscuring Antarctica's geology. Here, we explore central West Antarctica's subglacial geology using basal debris from within the Byrd ice core, drilled to the bed in 1968. Sand grain microtextures and a high kaolinite content (∼38–42%) reveal the debris consists predominantly of eroded sedimentary detritus, likely deposited initially in a warm, pre‐Oligocene, subaerial environment. Detrital hornblende 40Ar/39Ar ages suggest proximal late Cenozoic subglacial volcanism. The debris has a distinct provenance signature, with: common Permian‐Early Jurassic mineral grains; absent early Ross Orogeny grains; a high kaolinite content; and high 143Nd/144Nd and low 87Sr/86Sr ratios. Detecting this “fingerprint” in Antarctic sedimentary records could imply major WAIS retreat, revealing the WAIS's sensitivity to future warming.
CS2 Cycling in Seawater: Dark Production and UV Light Driven Consumption
Authors: Lennartz S. T. , Simon H. , Booge D. , Zhou L. , Marandino C.
Published: March 2024

Carbon disulfide (CS2) has recently gained attention as an important precursor for the atmospheric trace gas carbonyl sulfide (OCS), which delivers sulfur to the stratospheric sulfur layer and impacts the radiative budget of the Earth. CS2 is naturally produced in the ocean and emitted to the atmosphere. However, the magnitude of its marine emissions is only poorly constrained due to lacking understanding of its production and consumption processes. Here, we present incubation experiments with and without UV light treatment and provide evidence for a previously not considered UV‐light‐driven degradation process of CS2 in seawater, following first‐order kinetics. In addition to its already known photochemical production process, CS2 production is found in the dark, depending on the amount of dissolved organic sulfur present in seawater. We provide novel production and consumption rates of CS2 in seawater that pave the way toward mechanistically quantifying marine emissions of this important trace gas.
Particulate Nitrate Photolysis as a Possible Driver of Rising Tropospheric Ozone
Authors: Shah Viral , Keller Christoph A. , Knowland K. Emma , Christiansen Amy , Hu Lu , Wang Haolin , Lu Xiao , Alexander Becky , Jacob Daniel J.
Published: March 2024

Tropospheric ozone is an air pollutant and a greenhouse gas whose anthropogenic production is limited principally by the supply of nitrogen oxides (NOx) from combustion. Tropospheric ozone in the northern hemisphere has been rising despite the flattening of NOx emissions in recent decades. Here we propose that this sustained increase could result from the photolysis of nitrate particles (pNO3−) to regenerate NOx. Including pNO3− photolysis in the GEOS‐Chem atmospheric chemistry model improves the consistency with ozone observations. Our simulations show that pNO3− concentrations have increased since the 1960s because of rising ammonia and falling SO2 emissions, augmenting the increase in ozone in the northern extratropics by about 50% to better match the observed ozone trend. pNO3− will likely continue to increase through 2050, which would drive a continued increase in ozone even as NOx emissions decrease. More work is needed to better understand the mechanism and rates of pNO3− photolysis.
Surface Heat Fluxes Drive a Two‐Phase Response in Southern Ocean Mode Water Stratification
Authors: Pimm Ciara , Williams Richard G. , Jones Dani , Meijers Andrew J. S.
Published: March 2024

Subantarctic mode waters have low stratification and are formed through subduction from thick winter mixed layers in the Southern Ocean. To investigate how surface forcing affects the stratification in mode water formation regions in the Southern Ocean, a set of adjoint sensitivity experiments are conducted. The objective function is the annual‐average stratification over the mode water formation region, which is evaluated from potential temperature and salinity adjoint sensitivity experiments. The analysis of impacts, from the product of sensitivities and forcing variability, identifies the separate effects of the wind stress, heat flux, and freshwater flux, revealing that the dominant control on stratification is from surface heat fluxes, as well as a smaller effect from zonal wind stress. The adjoint sensitivities of stratification to surface heat flux reveal a surprising change in sign over 2 years lead time: surface cooling leads to the expected initial local decrease in stratification, but there is a delayed response leading to an increase in stratification. This delayed response in stratification involves effective atmospheric damping of the surface thermal contribution, so that eventually the oppositely‐signed advective haline contribution dominates. This two‐phase response of stratification is found to hold over mode water formation regions in the South Indian and Southeast Pacific sectors of the Southern Ocean, where there are strong advective flows linked to the Antarctic Circumpolar Current.
Surface Rupturing Earthquakes of the Greater Caucasus Frontal Thrusts, Azerbaijan
Authors: Pierce Ian , Guliyev Ibrahim , Yetirmishli Gurban , Muradov Rauf , Kazimova Sabina , Javanshir Rashid , De Pascale Gregory P. , Johnson Ben , Marshall Neill , Walker Richard , Wordsworth Paul
Published: March 2024

Here we present the results of the first paleoseismic study of the Kura fold‐thrust belt in Azerbaijan based on field mapping, fault trenching, and Quaternary dating. Convergence at rates of ∼10 mm/yr between the Arabian and Eurasian Plates is largely accommodated by the Kura fold‐thrust belt which stretches between central Azerbaijan and Georgia along the southern front of the Greater Caucasus (45–48°E). Although destructive historic earthquakes are known here, little is known about the active faults responsible for these earthquakes. A paleoseismic trench was excavated across a 2‐m‐high fault scarp near Agsu revealing evidence of two surface rupturing earthquakes. Radiocarbon dating of the faulted sediments limits the earthquake timing to AD 1713–1895 and AD 1872–2003. Allowing for uncertainties in dating, the two events likely correspond to historical destructive M ∼ 7 earthquakes near Shamakhi, Azerbaijan in AD 1668 and 1902. A second trench 60 km west of Agsu was excavated near Goychay also revealing evidence of at least one event that occurred 334–118 BC. Holocene shortening and dip‐slip rates for the Kura fold‐thrust belt are ∼8.0 and 8.5 mm/yr, respectively, based on an uplifted strath terrace west of Agsu. The only known historical devastating (M > ∼7) earthquakes in the Kura region, west of Shamakhi, occurred in 1139 and possibly 1668. The lack of reported historical ruptures from the past 4–8 centuries in the Kura, in contrast with the numerous recorded destructive earthquakes in Shamakhi, suggests that the Kura fold‐thrust belt may have accumulated sufficient strain to produce a M > 7.7 earthquake.
Evidence for a Constant Slip Rate Over the Last ∼40 ka Along the Mt. Morrone Fault System in Central Apennines
Authors: Puliti I. , Benedetti L. , Pizzi A. , Fleury J. , Francescone M. , Guillou V. , Team Aster
Published: March 2024

Located in the easternmost portion of the Central Apennines, the Mt. Morrone normal fault system is one of the highest seismic hazards in Italy. Previous geological and geomorphological observations revealed the presence of a ∼22 km‐long NW‐SE right‐lateral en echelon fault system made of two parallel faults affecting Quaternary deposits. Our analysis focused on the westernmost fault, which bounds the Sulmona Basin. Cumulative offsets were identified and quantified using high‐resolution Digital Elevation Models derived from LiDAR, Satellite Pleiades images, and drone acquisition at the three sites. Morphological markers displaced from a few to tens of meters were dated using 36Cl exposure dating. The results would be suggesting a fault slip rate of 0.2–0.4 mm/a. The deformed markers that dated at 36–44 ka consist of alluvial terraces emplaced by the main streams flowing down from Mt. Morrone to the Sulmona Basin, subsequently incised, and preserved when the fluvial base level dropped because of the former Sulmona lake fluctuations. The yielded ages for these markers fit well with the last major aggradational event associated with the 35–40 ka Heinrich event described and dated to other fluvial basins in the Apennines. Furthermore, the estimated rate agrees with the values obtained in previous studies over shorter and longer periods (105−6 years) and within similar uncertainties. This might then suggest that the period recovered by this study encompasses the entire seismic cycle.
Hiroshima Fallout May Offer a Glimpse of the Early Solar System
Authors: Scharping Nathaniel
Published: March 2024

Bits of glass called Hiroshimaites may have formed by processes similar to those that formed the Sun and the planets.
Inland Waters Are a Blind Spot in Greenhouse Gas Emissions
Authors: Sidik Saima
Published: March 2024

Researchers call for an extensive monitoring network to quantify carbon dioxide and methane released by China’s rivers, lakes, reservoirs, and ponds.
Redefining high risk multiple myeloma with an APOBEC/Inflammation-based classifier
Authors: Grasedieck Sarah , Panahi Afsaneh , Jarvis Matthew C. , Borzooee Faezeh , Harris Reuben S. , Larijani Mani , Avet-Loiseau Hervé , Samur Mehmet , Munshi Nikhil , Song Kevin , Rouhi Arefeh , Kuchenbauer Florian
Published: March 2024

Graphical Abstract
Childbirth rates in women with myeloproliferative neoplasms
Authors: Landtblom Anna Ravn , Andersson Therese M-L , Johansson Anna L. V. , Lundberg Frida E. , Samuelsson Jan , Björkholm Magnus , Hultcrantz Malin
Published: March 2024

Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15–44 years with an MPN diagnosis 1973–2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68–0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86–1.22) while the HR was 0.50 (0.33–0.76) in PV and 0.45 (0.28–0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.
Effect of serum concentrations of IL-6 and TNF-α on brain structure in anorexia nervosa: a combined cross-sectional and longitudinal study
Authors: Bernardoni Fabio , Tam Friederike , Poitz David M. , Hellerhoff Inger , Arold Dominic , Geisler Daniel , Lemme Frances , Keeler Johanna , Weidner Kerstin , Pariante Carmine , Roessner Veit , King Joseph A. , Ehrlich Stefan
Published: March 2024

Previous studies of brain structure in anorexia nervosa (AN) have reported reduced gray matter in underweight patients, which largely normalizes upon weight gain. One underlying biological mechanism may be glial cell alterations related to low-grade inflammation. Here, we investigated relationships between brain structure as measured by magnetic resonance imaging and serum concentrations of two pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) cross-sectionally in 82 underweight adolescent and young adult female patients (mean age 16.8 years; 59 of whom were observed longitudinally after short-term weight restoration; mean duration 2.8 months), 20 individuals long-term weight-recovered from AN (mean age 22.7 years) and 105 healthy control (HC) participants (mean age 17.2 years). We measured cortical thickness, subcortical volumes and local gyrification index, a measure of cortical folding. In contrast to most previous studies of cytokine concentrations in AN, we found no cross-sectional group differences (interleukin-6: p = 0.193, tumor necrosis factor alpha: p = 0.057) or longitudinal changes following weight restoration (interleukin-6: p = 0.201, tumor necrosis factor alpha: p = 0.772). As expected, widespread gray matter reductions (cortical thickness, subcortical volumes, cortical folding) were observed in underweight patients with AN compared to HC. However, we found no evidence of associations between cytokine concentrations and structural brain measures in any participant group. Furthermore, longitudinal changes in cytokine concentrations were unrelated to changes in gray matter. In conclusion, we did not identify any association between (sub-)inflammatory processes and structural brain changes in AN. Future studies are needed to elucidate which other factors besides nutritional status may contribute to brain morphological alterations.
Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer
Authors: Zhang Jian , Zhao Kejia , Zhou Wenjing , Kang Ran , Wei Shiyou , Shu Yueli , Yu Cheng , Ku Yin , Mao Yonghong , Luo Hao , Yang Juqin , Mei Jiandong , Pu Qiang , Deng Senyi , Zha Zhengyu , Yuan Gang , Shen Shensi , Chen Yaohui , Liu Lunxu
Published: March 2024

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.
Machine learning and the prediction of suicide in psychiatric populations: a systematic review
Authors: Pigoni Alessandro , Delvecchio Giuseppe , Turtulici Nunzio , Madonna Domenico , Pietrini Pietro , Cecchetti Luca , Brambilla Paolo
Published: March 2024

Machine learning (ML) has emerged as a promising tool to enhance suicidal prediction. However, as many large-sample studies mixed psychiatric and non-psychiatric populations, a formal psychiatric diagnosis emerged as a strong predictor of suicidal risk, overshadowing more subtle risk factors specific to distinct populations. To overcome this limitation, we conducted a systematic review of ML studies evaluating suicidal behaviors exclusively in psychiatric clinical populations. A systematic literature search was performed from inception through November 17, 2022 on PubMed, EMBASE, and Scopus following the PRISMA guidelines. Original research using ML techniques to assess the risk of suicide or predict suicide attempts in the psychiatric population were included. An assessment for bias risk was performed using the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines. About 1032 studies were retrieved, and 81 satisfied the inclusion criteria and were included for qualitative synthesis. Clinical and demographic features were the most frequently employed and random forest, support vector machine, and convolutional neural network performed better in terms of accuracy than other algorithms when directly compared. Despite heterogeneity in procedures, most studies reported an accuracy of 70% or greater based on features such as previous attempts, severity of the disorder, and pharmacological treatments. Although the evidence reported is promising, ML algorithms for suicidal prediction still present limitations, including the lack of neurobiological and imaging data and the lack of external validation samples. Overcoming these issues may lead to the development of models to adopt in clinical practice. Further research is warranted to boost a field that holds the potential to critically impact suicide mortality.
Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions
Authors: Medrano M. , Contreras M. , Caballero-Velázquez T. , Martínez L. , Bejarano-García J. A. , Calderón-Ruiz R. , García-Calderón C. B. , Rosado I. V. , Pérez-Simón J. A.
Published: March 2024

Background

Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB.

Methods

Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo.

Results

We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition.

Conclusions

WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.
Deficiency of skeletal muscle Agrin contributes to the pathogenesis of age-related sarcopenia in mice
Authors: Chen Jie , Chen Hong , Dong Xia , Hui Tiankun , Yan Min , Ren Dongyan , Zou Suqi , Wang Shunqi , Fei Erkang , Zhang Wenhua , Lai Xinsheng
Published: March 2024

Sarcopenia, a progressive and prevalent neuromuscular disorder, is characterized by age-related muscle wasting and weakening. Despite its widespread occurrence, the molecular underpinnings of this disease remain poorly understood. Herein, we report that levels of Agrin, an extracellular matrix (ECM) protein critical for neuromuscular formation, were decreased with age in the skeletal muscles of mice. The conditional loss of Agrin in myogenic progenitors and satellite cells (SCs) (Pax7 Cre:: Agrin flox/flox) causes premature muscle aging, manifesting a distinct sarcopenic phenotype in mice. Conversely, the elevation of a miniaturized form of Agrin in skeletal muscle through adenovirus-mediated gene transfer induces enhanced muscle capacity in aged mice. Mechanistic investigations suggest that Agrin-mediated improvement in muscle function occurs through the stimulation of Yap signaling and the concurrent upregulation of dystroglycan expression. Collectively, our findings underscore the pivotal role of Agrin in the aging process of skeletal muscles and propose Agrin as a potential therapeutic target for addressing sarcopenia.
Identification of the growth cone as a probe and driver of neuronal migration in the injured brain
Authors: Nakajima Chikako , Sawada Masato , Umeda Erika , Takagi Yuma , Nakashima Norihiko , Kuboyama Kazuya , Kaneko Naoko , Yamamoto Satoaki , Nakamura Haruno , Shimada Naoki , Nakamura Koichiro , Matsuno Kumiko , Uesugi Shoji , Vepřek Nynke A. , Küllmer Florian , Nasufović Veselin , Uchiyama Hironobu , Nakada Masaru , Otsuka Yuji , Ito Yasuyuki , Herranz-Pérez Vicente , García-Verdugo José Manuel , Ohno Nobuhiko , Arndt Hans-Dieter , Trauner Dirk , Tabata Yasuhiko , Igarashi Michihiro , Sawamoto Kazunobu
Published: March 2024

Axonal growth cones mediate axonal guidance and growth regulation. We show that migrating neurons in mice possess a growth cone at the tip of their leading process, similar to that of axons, in terms of the cytoskeletal dynamics and functional responsivity through protein tyrosine phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin sulfate (CS) through PTPσ and collapse, which leads to inhibition of neuronal migration. In the presence of CS, the growth cones can revert to their extended morphology when their leading filopodia interact with heparan sulfate (HS), thus re-enabling neuronal migration. Implantation of an HS-containing biomaterial in the CS-rich injured cortex promotes the extension of the growth cone and improve the migration and regeneration of neurons, thereby enabling functional recovery. Thus, the growth cone of migrating neurons is responsive to extracellular environments and acts as a primary regulator of neuronal migration.
FUS unveiled in mitochondrial DNA repair and targeted ligase-1 expression rescues repair-defects in FUS-linked motor neuron disease
Authors: Kodavati Manohar , Wang Haibo , Guo Wenting , Mitra Joy , Hegde Pavana M. , Provasek Vincent , Rao Vikas H. Maloji , Vedula Indira , Zhang Aijun , Mitra Sankar , Tomkinson Alan E. , Hamilton Dale J. , Van Den Bosch Ludo , Hegde Muralidhar L.
Published: March 2024

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3’s repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS’s critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.
Temporally organized representations of reward and risk in the human brain
Authors: Man Vincent , Cockburn Jeffrey , Flouty Oliver , Gander Phillip E. , Sawada Masahiro , Kovach Christopher K. , Kawasaki Hiroto , Oya Hiroyuki , Howard III Matthew A. , O’Doherty John P.
Published: March 2024

The value and uncertainty associated with choice alternatives constitute critical features relevant for decisions. However, the manner in which reward and risk representations are temporally organized in the brain remains elusive. Here we leverage the spatiotemporal precision of intracranial electroencephalography, along with a simple card game designed to elicit the unfolding computation of a set of reward and risk variables, to uncover this temporal organization. Reward outcome representations across wide-spread regions follow a sequential order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We further highlight the role of the anterior insula in generalizing between reward prediction error and risk prediction error codes. Together our results emphasize the importance of neural dynamics for understanding value-based decisions under uncertainty.
Drivers and impact of the early silent invasion of SARS-CoV-2 Alpha
Authors: Faucher Benjamin , Sabbatini Chiara E. , Czuppon Peter , Kraemer Moritz U. G. , Lemey Philippe , Colizza Vittoria , Blanquart François , Boëlle Pierre-Yves , Poletto Chiara
Published: March 2024

SARS-CoV-2 variants of concern (VOCs) circulated cryptically before being identified as a threat, delaying interventions. Here we studied the drivers of such silent spread and its epidemic impact to inform future response planning. We focused on Alpha spread out of the UK. We integrated spatio-temporal records of international mobility, local epidemic growth and genomic surveillance into a Bayesian framework to reconstruct the first three months after Alpha emergence. We found that silent circulation lasted from days to months and decreased with the logarithm of sequencing coverage. Social restrictions in some countries likely delayed the establishment of local transmission, mitigating the negative consequences of late detection. Revisiting the initial spread of Alpha supports local mitigation at the destination in case of emerging events.
Spatially selective delivery of living magnetic microrobots through torque-focusing
Authors: Mirkhani Nima , Christiansen Michael G. , Gwisai Tinotenda , Menghini Stefano , Schuerle Simone
Published: March 2024

Rotating magnetic fields enable biomedical microrobots to overcome physiological barriers and promote extravasation and accumulation in tumors. Nevertheless, targeting deeply situated tumors requires suppression of off-target actuation in healthy tissue. Here, we investigate a control strategy for applying spatially selective torque density to microrobots by combining rotating fields with magnetostatic selection fields. Taking magnetotactic bacteria as diffuse torque-based actuators, we numerically model off-target torque suppression, indicating the feasibility of centimeter to millimeter resolution for human applications. We study focal torque application in vitro, observing off-target suppression of actuation-dependent effects such as colonization of bacteria in tumor spheroids. We then design and construct a mouse-scale torque-focusing apparatus capable of maneuvering the focal point. Applying this system to a mouse tumor model increased accumulation of intravenously injected bacteria within tumors receiving focused actuation compared to non-actuated or globally actuated groups. This control scheme combines the advantages of torque-based actuation with spatial targeting.
Deciphering the contributing motifs of reconstructed cobalt (II) sulfides catalysts in Li-CO2 batteries
Authors: Liu Yingqi , Zhang Zhiyuan , Tan Junyang , Chen Biao , Lu Bingyi , Mao Rui , Liu Bilu , Wang Dashuai , Zhou Guangmin , Cheng Hui-Ming
Published: March 2024

Developing highly efficient catalysts is significant for Li-CO2 batteries. However, understanding the exact structure of catalysts during battery operation remains a challenge, which hampers knowledge-driven optimization. Here we use X-ray absorption spectroscopy to probe the reconstruction of CoSx (x = 8/9, 1.097, and 2) pre-catalysts and identify the local geometric ligand environment of cobalt during cycling in the Li-CO2 batteries. We find that different oxidized states after reconstruction are decisive to battery performance. Specifically, complete oxidation on CoS1.097 and Co9S8 leads to electrochemical performance deterioration, while oxidation on CoS2 terminates with Co-S4-O2 motifs, leading to improved activity. Density functional theory calculations show that partial oxidation contributes to charge redistributions on cobalt and thus facilitates the catalytic ability. Together, the spectroscopic and electrochemical results provide valuable insight into the structural evolution during cycling and the structure-activity relationship in the electrocatalyst study of Li-CO2 batteries.
Molecular near-infrared triplet-triplet annihilation upconversion with eigen oxygen immunity
Authors: Wang Xinyu , Ding Fangwei , Jia Tao , Li Feng , Ding Xiping , Deng Ruibin , Lin Kaifeng , Yang Yulin , Wu Wenzhi , Xia Debin , Chen Guanying
Published: March 2024

Molecular triplet-triplet annihilation upconversion often experiences drastic luminescence quenching in the presence of oxygen molecules, posing a significant constraint on practical use in aerated conditions. We present an oxygen-immune near-infrared triplet-triplet annihilation upconversion system utilizing non-organometallic cyanine sensitizers (λex = 808 nm) and chemically synthesized benzo[4,5]thieno[2,3-b][1,2,5]thiadiazolo[3,4-g]quinoxaline dyes with a defined dimer structure as annihilators (λem = 650 nm). This system exhibits ultrastable upconversion under continuous laser irradiance (>480 mins) or extended storage (>7 days) in aerated solutions. Mechanistic investigations reveal rapid triplet-triplet energy transfer from sensitizer to annihilators, accompanied by remarkably low triplet oxygen quenching efficiencies ($${\eta }_{{{{\mbox{O}}}}_{2}}$$

η

O

2

 < 13% for the sensitizer, <3.7% for the annihilator), endowing the bicomponent triplet-triplet annihilation system with inherent oxygen immunity. Our findings unlock the direct and potent utilization of triplet-triplet annihilation upconversion systems in real-world applications, demonstrated by the extended and sensitive nanosensing of peroxynitrite radicals in the liver under in vivo nitrosative stress.
Field-controlled multicritical behavior and emergent universality in fully frustrated quantum magnets
Authors: Fan Yuchen , Xi Ning , Liu Changle , Normand Bruce , Yu Rong
Published: March 2024

Phase transitions in condensed matter are a source of exotic emergent properties. We study the fully frustrated bilayer Heisenberg antiferromagnet to demonstrate that an applied magnetic field creates a previously unknown emergent criticality. The quantum phase diagram contains four states with distinctly different symmetries, all but one pair separated by first-order transitions. We show by quantum Monte Carlo simulations that the thermal phase diagram is dominated by a wall of discontinuities extending between the dimer-triplet phases and the singlet-containing phases. This wall is terminated at finite temperatures by a critical line, which becomes multicritical where the Berezinskii-Kosterlitz-Thouless (BKT) transition of the dimer-triplet antiferromagnet and the thermal Ising transition of the singlet-triplet crystal phase also terminate. The combination of merging symmetries leads to a 4-state Potts universality not contained in the microscopic Hamiltonian, which we interpret within the Ashkin-Teller model. Our results represent a systematic step in understanding emergent phenomena in quantum magnetic materials, including the “Shastry-Sutherland compound” SrCu2(BO3)2.
Bio-economic potential of ethno-entomophagy and its therapeutics in India
Authors: Devi Wahengbam Deepanita , Bonysana Rajkumari , Singh Kabrambam Dasanta , Koijam Arunkumar Singh , Mukherjee Pulok Kumar , Rajashekar Yallappa
Published: March 2024

Insects are the largest group of arthropods with the highest faunal diversity of over a million species. Apart from many other roles in the environment, the aspect of several insects being used for human consumption (entomophagy) and as traditional medicine (entomotherapy) by different communities of the world holds special significance for countering global food crisis. The enormous insect resources contribute a reasonable share in improving the livelihoods of many entomophagy practicing communities. Considering this significance, the present review emphasizes the bio-economic potential of insect resources. An overview of entomophagy practices in India; benefits towards the environment, humans and animals; insect species used in entomophagy along with therapeutic importance, nutritional, physical, chemical, and microbiological hazards; farming and mass production technologies; legal status and socio-economic implications in Indian scenario have been presented. Traditionally tested and accepted therapeutic use of edible insects have been reported to cure various disease conditions and calls for scientific exploration and validation to rediscover promising medical products of modern medicine. Edible insects as an alternative food need to be popularized in India with a new policy or regulation to harvest and sell insect-derived food products with proper safe consumption demonstrations. Considering the facts that insects reproduce in large numbers at a faster rate, require less land, water and other resources for farming, and economically and ecologically sustainable harvesting can be done in a short time, insect farming can offer revenue and rural job opportunities in developing countries, especially in India. Therefore, the traditional use of insects as food and medicine has tremendous potential to enhance the economy and living standards.
Re-analysis of an outbreak of Shiga toxin-producing Escherichia coli O157:H7 associated with raw drinking milk using Nanopore sequencing
Authors: Greig David R. , Do Nascimento Vivienne , Gally David L. , Gharbia Saheer E. , Dallman Timothy J. , Jenkins Claire
Published: March 2024

The aim of this study was to compare Illumina and Oxford Nanopore Technology (ONT) sequencing data to quantify genetic variation to assess within-outbreak strain relatedness and characterise microevolutionary events in the accessory genomes of a cluster of 23 genetically and epidemiologically linked isolates related to an outbreak of Shiga toxin-producing Escherichia coli O157:H7 caused by the consumption of raw drinking milk. There were seven discrepant variants called between the two technologies, five were false-negative or false-positive variants in the Illumina data and two were false-negative calls in ONT data. After masking horizontally acquired sequences such as prophages, analysis of both short and long-read sequences revealed the 20 isolates linked to the outbreak in 2017 had a maximum SNP distance of one SNP between each other, and a maximum of five SNPs when including three additional strains identified in 2019. Analysis of the ONT data revealed a 47 kbp deletion event in a terminal compound prophage within one sample relative to the remaining samples, and a 0.65 Mbp large chromosomal rearrangement (inversion), within one sample relative to the remaining samples. Furthermore, we detected two bacteriophages encoding the highly pathogenic Shiga toxin (Stx) subtype, Stx2a. One was typical of Stx2a-phage in this sub-lineage (Ic), the other was atypical and inserted into a site usually occupied by Stx2c-encoding phage. Finally, we observed an increase in the size of the pO157 IncFIB plasmid (1.6 kbp) in isolates from 2019 compared to those from 2017, due to the duplication of insertion elements within the plasmids from the more recently isolated strains. The ability to characterize the accessory genome in this way is the first step to understanding the significance of these microevolutionary events and their impact on the genome plasticity and virulence between strains of this zoonotic, foodborne pathogen.
Efficacy of memory protocols in 9- to 89-year-olds’ memory for prior contacts
Authors: Goldfarb Deborah , Chae Hana , Dawson Haley R. , Evans Jacqueline R. , Fisher Ronald P. , Daneshbodi Ariana , Meissner Christian A.
Published: March 2024

Memory for prior contacts has several important applied implications, including contact tracing (for communicable diseases). Incomplete episodic memory reports, which occur across the developmental lifespan but are particularly relevant for children and older adults, may hamper such efforts. Prior research has shown that cognitively informed memory techniques may bolster recall of contacts in adults, but that work has not addressed the developmental efficacy of these techniques. Here we evaluated the effectiveness of such techniques for familiar and unfamiliar contacts within a sample of 9- to 89-year-olds in the context of an ongoing pandemic. The tested memory techniques bolstered recall across the lifespan, irrespective of whether the interview was conducted live with an interviewer or via a self-led interview. Children, emerging adults, and adults did not reveal any differences in memory productivity, however, older adults recalled fewer contacts. Implications for theory and application are discussed.
Neural asymmetry in aligning with generous versus selfish descriptive norms in a charitable donation task
Authors: Díaz-Gutiérrez Paloma , Boone Christophe , Vyas Harshil , Declerck Carolyn H.
Published: March 2024

Social alignment is supported by the brain’s reward system (ventral striatum), presumably because attaining synchrony generates feelings of connectedness. However, this may hold only for aligning with generous others, while aligning with selfishness might threaten social connectedness. We investigated this postulated asymmetry in an incentivized fMRI charitable donation task. Participants decided how much of their endowment to donate to real charities, and how much to keep for themselves. Compared to a baseline condition, donations significantly increased or decreased in function of the presence of descriptive norms. The fMRI data reveal that processing selfish norms (more than generous ones) recruited the amygdala and anterior insula. Aligning with selfish norms correlated on average with reduced activity in the lateral prefrontal cortex (LPFC) and, at the individual level, with decreasing activity in the ventral striatum (VS). Conversely, as participants aligned more with generous norms, they showed increasing activity in the LPFC and, on average, increased activity in the VS. This increase occurred beyond the increased VS activity which was also observed in the baseline condition. Taken together, this suggests that aligning with generosity, while effortful, provides a “warm glow of herding” associated with collective giving, but that aligning with selfishness does not.