Miracle-dz/UniFAR-FTUs huggingface dataset:
Live-cell invasive phenotyping uncovers the ALK2/BMP6 iron homeostasis pathway as a therapeutic vulnerability in LKB1-mutant lung cancer

The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that likely contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical discovery strategies designed to exploit invasive phenotypes are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early invasion phenotypes in the two most prominent molecular subtypes, TP53 and LKB1, of KRAS-driven lung adenocarcinoma (LUAD). By combining live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix with RNA transcriptome profiling, we identified the LKB1-specific upregulation of bone morphogenetic protein 6 (BMP6). Examination of early-stage lung cancer patients confirmed upregulation of BMP6 in LKB1-mutant lung tumors. At the molecular level, we find that the canonical iron regulatory hormone Hepcidin is induced via BMP6 signaling upon LKB1 loss, where intact LKB1 kinase activity is necessary to maintain signaling homeostasis. Furthermore, pre-clinical studies in a novel Kras/Lkb1-mutant syngeneic mouse model show that potent growth suppression was achieved by inhibiting the ALK2/BMP6 signaling axis with single agents that are currently in clinical trials. We show that alterations in the iron homeostasis pathway are accompanied by simultaneous upregulation of ferroptosis protection proteins. Thus, LKB1 is sufficient to regulate both the ‘gas’ and ‘breaks’ to finely tune iron-regulated tumor progression.
Evaluation of fMRI activation in post-stroke patients with movement disorders after repetitive transcranial magnetic stimulation: a scoping review

Background Movement disorders are one of the most common stroke residual effects, which cause a major stress on their families and society. Repetitive transcranial magnetic stimulation (rTMS) could change neuroplasticity, which has been suggested as an alternative rehabilitative treatment for enhancing stroke recovery. Functional magnetic resonance imaging (fMRI) is a promising tool to explore neural mechanisms underlying rTMS intervention. Object Our primary goal is to better understand the neuroplastic mechanisms of rTMS in stroke rehabilitation, this paper provides a scoping review of recent studies, which investigate the alteration of brain activity using fMRI after the application of rTMS over the primary motor area (M1) in movement disorders patients after stroke. Method The database PubMed, Embase, Web of Science, WanFang Chinese database, ZhiWang Chinese database from establishment of each database until December 2022 were included. Two researchers reviewed the study, collected the information and the relevant characteristic extracted to a summary table. Two researchers also assessed the quality of literature with the Downs and Black criteria. When the two researchers unable to reach an agreement, a third researcher would have been consulted. Results Seven hundred and eleven studies in all were discovered in the databases, and nine were finally enrolled. They were of good quality or fair quality. The literature mainly involved the therapeutic effect and imaging mechanisms of rTMS on improving movement disorders after stroke. In all of them, there was improvement of the motor function post-rTMS treatment. Both high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS) can induce increased functional connectivity, which may not directly correspond to the impact of rTMS on the activation of the stimulated brain areas. Comparing real rTMS with sham group, the neuroplastic effect of real rTMS can lead to better functional connectivity in the brain network in assisting stroke recovery. Conclusion rTMS allows the excitation and synchronization of neural activity, promotes the reorganization of brain function, and achieves the motor function recovery. fMRI can observe the influence of rTMS on brain networks and reveal the neuroplasticity mechanism of post-stroke rehabilitation. The scoping review helps us to put forward a series of recommendations that might guide future researchers exploring the effect of motor stroke treatments on brain connectivity.
Study of unripe and inferior banana flours pre-gelatinized by four different physical methods

This study aimed to prepare the pre-gelatinized banana flours and compare the effects of four physical treatment methods (autoclaving, microwave, ultrasound, and heat-moisture) on the digestive and structural characteristics of unripe and inferior banana flours. After the four physical treatments, the resistant starch (RS) content values of unripe and inferior banana flours were decreased from 96.85% (RS2) to 28.99–48.37% (RS2 + RS3), while C∞ and k values were increased from 5.90% and 0.039 min−1 to 56.22–74.58% and 0.040–0.059 min−1, respectively. The gelatinization enthalpy (ΔHg) and I1047/1022 ratio (short-range ordered crystalline structures) were decreased from 15.19 J/g and 1.0139 to 12.01–13.72 J/g, 0.9275–0.9811, respectively. The relative crystallinity decreased from 36.25% to 21.69–26.30%, and the XRD patterns of ultrasound (UT) and heat-moisture (HMT) treatment flours maintained the C-type, but those samples pre-gelatinized by autoclave (AT) and microwave (MT) treatment were changed to C + V-type, and heat-moisture (HMT) treatment was changed to A-type. The surface of pre-gelatinized samples was rough, and MT and HMT showed large amorphous holes. The above changes in structure further confirmed the results of digestibility. According to the experimental results, UT was more suitable for processing unripe and inferior banana flours as UT had a higher RS content and thermal gelatinization temperatures, a lower degree and rate of hydrolysis, and a more crystalline structure. The study can provide a theoretical basis for developing and utilizing unripe and inferior banana flours.
Restless leg syndrome in multiple sclerosis: a case–control study

Objectives This study assessed the prevalence of restless leg syndrome (RLS) among patients with multiple sclerosis (pwMS) and the association between RLS and MS disease duration, sleep disturbance, and daytime fatigue. Methods In this cross-sectional study, we interviewed 123 patients via phone calls using preset questionnaires containing the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) diagnostic criteria validated in both Arabic and English. The prevalence of RLS in MS was compared to a group of healthy controls. Results The prevalence of RLS in pwMS, defined by meeting all four requirements included in the IRLSSG diagnostic criteria, was 30.3% compared to 8.3% in the control group. About 27.3% had mild RLS, 36.4% presented with moderate, and the remaining had severe or very severe symptoms. Patients with MS who experience RLS had a 2.8 times higher risk of fatigue compared to pwMS without RLS. pwMS with RLS had worse sleep quality, with a mean difference of 0.64 in the global PSQI score. Sleep disturbance and latency had the most significant impact on sleep quality. Conclusion The prevalence of RLS among MS patients was significantly higher compared to the control group. We recommend educating neurologists and general physicians to increase their awareness of the increasing prevalence of RLS and its association with fatigue and sleep disturbance in patients with MS.
Knockout of angiotensin converting enzyme-2 receptor leads to morphological aberrations in rodent olfactory centers and dysfunctions associated with sense of smell

Neuronal morphological characterization and behavioral phenotyping in mouse models help dissecting neural mechanisms of brain disorders. Olfactory dysfunctions and other cognitive problems were widely reported in asymptomatic carriers and symptomatic patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This led us to generate the knockout mouse model for Angiotensin Converting Enzyme-2 (ACE2) receptor, one of the molecular factors mediating SARS-CoV-2 entry to the central nervous system, using CRISPR-Cas9 based genome editing tools. ACE2 receptors and Transmembrane Serine Protease-2 (TMPRSS2) are widely expressed in the supporting (sustentacular) cells of human and rodent olfactory epithelium, however, not in the olfactory sensory neurons (OSNs). Hence, acute inflammation induced changes due to viral infection in the olfactory epithelium may explain transient changes in olfactory detectabilities. As ACE2 receptors are expressed in different olfactory centers and higher brain areas, we studied the morphological changes in the olfactory epithelium (OE) and olfactory bulb (OB) of ACE2 KO mice in comparison with wild type animals. Our results showed reduced thickness of OSN layer in the OE, and a decrease in cross-sectional area of glomeruli in the OB. Aberrations in the olfactory circuits were revealed by lowered immunoreactivity toward microtubule associated protein 2 (MAP2) in the glomerular layer of ACE2 KO mice. Further, to understand if these morphological alterations lead to compromised sensory and cognitive abilities, we performed an array of behavioral assays probing their olfactory subsystems’ performances. ACE2 KO mice exhibited slower learning of odor discriminations at the threshold levels and novel odor identification impairments. Further, ACE2 KO mice failed to memorize the pheromonal locations while trained on a multimodal task implying the aberrations of neural circuits involved in higher cognitive functions. Our results thus provide the morphological basis for the sensory and cognitive disabilities caused by the deletion of ACE2 receptors and offer a potential experimental approach to study the neural circuit mechanisms of cognitive impairments observed in long COVID.
FINITARY ABSTRACT ELEMENTARY CLASSES

elementary classes Shelah suggested in [26] abstract elementary classes (AEC) as a platform to study model theoretic concepts in a more general setting. He studies a class K of structures in a fixed similarity type τ , but does not define any specific language. Instead he gives axioms for (K,4K) , where 4K is a relation between the models of the class. The class (K,4K) is for example assumed to be closed under isomorphisms, behave well with respect to 4K -increasing chains and have a downward LowenheimSkolem number LS(K) . If B is a subset of a structure A ∈ K , there is a 4K elementary substructure of A containing B of cardinality at most LS(K)+|B| . This context generalizes an elementary class (Mod(T ),4) , where 4 is the elementary substructure relation. In his Presentation Theorem Shelah showed that such a class can be presented as a class of reducts of models in an elementary class omitting a set of types. This
Dynamic distress calls: volatile info chemicals induce and regulate defense responses during herbivory

Plants are continuously threatened by a plethora of biotic stresses caused by microbes, pathogens, and pests, which often act as the major constraint in crop productivity. To overcome such attacks, plants have evolved with an array of constitutive and induced defense mechanisms— morphological, biochemical, and molecular. Volatile organic compounds (VOCs) are a class of specialized metabolites that are naturally emitted by plants and play an important role in plant communication and signaling. During herbivory and mechanical damage, plants also emit an exclusive blend of volatiles often referred to as herbivore-induced plant volatiles (HIPVs). The composition of this unique aroma bouquet is dependent upon the plant species, developmental stage, environment, and herbivore species. HIPVs emitted from infested and non-infested plant parts can prime plant defense responses by various mechanisms such as redox, systemic and jasmonate signaling, activation of mitogen-activated protein (MAP) kinases, and transcription factors; mediate histone modifications; and can also modulate the interactions with natural enemies via direct and indirect mechanisms. These specific volatile cues mediate allelopathic interactions leading to altered transcription of defense-related genes, viz., proteinase inhibitors, amylase inhibitors in neighboring plants, and enhanced levels of defense-related secondary metabolites like terpenoids and phenolic compounds. These factors act as deterrents to feeding insects, attract parasitoids, and provoke behavioral changes in plants and their neighboring species. This review presents an overview of the plasticity identified in HIPVs and their role as regulators of plant defense in Solanaceous plants. The selective emission of green leaf volatiles (GLVs) including hexanal and its derivatives, terpenes, methyl salicylate, and methyl jasmonate (MeJa) inducing direct and indirect defense responses during an attack from phloem-sucking and leaf-chewing pests is discussed. Furthermore, we also focus on the recent developments in the field of metabolic engineering focused on modulation of the volatile bouquet to improve plant defenses.
Peptidyl-prolyl cis/trans isomerase Pin1 interacts with hepatitis B virus core particle, but not with HBc protein, to promote HBV replication

Here, we demonstrate that the peptidyl-prolyl cis/trans isomerase Pin1 interacts noncovalently with the hepatitis B virus (HBV) core particle through phosphorylated serine/threonine-proline (pS/TP) motifs in the carboxyl-terminal domain (CTD) but not with particle-defective, dimer-positive mutants of HBc. This suggests that neither dimers nor monomers of HBc are Pin1-binding partners. The 162TP, 164SP, and 172SP motifs within the HBc CTD are important for the Pin1/core particle interaction. Although Pin1 dissociated from core particle upon heat treatment, it was detected as an opened-up core particle, demonstrating that Pin1 binds both to the outside and the inside of the core particle. Although the amino-terminal domain S/TP motifs of HBc are not involved in the interaction, 49SP contributes to core particle stability, and 128TP might be involved in core particle assembly, as shown by the decreased core particle level of S49A mutant through repeated freeze and thaw and low-level assembly of the T128A mutant, respectively. Overexpression of Pin1 increased core particle stability through their interactions, HBV DNA synthesis, and virion secretion without concomitant increases in HBV RNA levels, indicating that Pin1 may be involved in core particle assembly and maturation, thereby promoting the later stages of the HBV life cycle. By contrast, parvulin inhibitors and PIN1 knockdown reduced HBV replication. Since more Pin1 proteins bound to immature core particles than to mature core particles, the interaction appears to depend on the stage of virus replication. Taken together, the data suggest that physical association between Pin1 and phosphorylated core particles may induce structural alterations through isomerization by Pin1, induce dephosphorylation by unidentified host phosphatases, and promote completion of virus life cycle.
The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer’s disease and Parkinson’s disease

Alzheimer’s disease (AD) and Parkinson’s disease (PD) represent the most prevalent neurodegenerative disorders severely impacting life expectancy and quality of life of millions of people worldwide. AD and PD exhibit both a very distinct pathophysiological disease pattern. Intriguingly, recent researches, however, implicate that overlapping mechanisms may underlie AD and PD. In AD and PD, novel cell death mechanisms, encompassing parthanatos, netosis, lysosome-dependent cell death, senescence and ferroptosis, apparently rely on the production of reactive oxygen species, and seem to be modulated by the well-known, “old” second messenger cAMP. Signaling of cAMP via PKA and Epac promotes parthanatos and induces lysosomal cell death, while signaling of cAMP via PKA inhibits netosis and cellular senescence. Additionally, PKA protects against ferroptosis, whereas Epac1 promotes ferroptosis. Here we review the most recent insights into the overlapping mechanisms between AD and PD, with a special focus on cAMP signaling and the pharmacology of cAMP signaling pathways.
VertU: universal multilocus primer sets for eDNA metabarcoding of vertebrate diversity, evaluated by both artificial and natural cases

Environmental DNA (eDNA) metabarcoding is a powerful tool for monitoring biodiversity in natural ecosystems. The accuracy of eDNA metabarcoding relies heavily on the PCR primers that amplify target sequences. For vertebrates, most available primers are designed for particular groups. There have been inadequate attempts to design “universal” primers applicable to all vertebrates. Here, we developed three new universal primer sets (V12S-U, V16S-U, and VCOI-U) targeting mitochondrial 12S, 16S, and COI genes, respectively. They work for all vertebrate groups, with amplification length of 200-250 bp, facilitating the use of short-read sequencing platforms. We evaluated and compared the species detection ability of our primer sets and seven previously published ones through both in-silico PCR and experiment tests with mock DNA and zoo eDNA. The species detection success of the new primer sets is over 90%, showing better performance than previously published primer sets. We also tested our new primers with water eDNA samples of natural environments, and detected a total of 895 vertebrate OTUs (BLAST identity ≥ 0.95), comprising 182 species, 195 genera, and 94 families. Our results indicated that utilizing multiple markers can achieve better species detection than using only a single marker, which is especially important for monitoring large biological communities like vertebrates. The new primer sets enable researchers to detect the presence of species of different vertebrate groups in one eDNA metabarcoding survey, which simplifies the workflow and reduces the cost. It has the potential to serve as an alternative/complementary tool for future eDNA metabarcoding studies targeting vertebrates.
Field and in-silico analysis of harvest index variability in maize silage

Maize silage is a key component of feed rations in dairy systems due to its high forage and grain yield, water use efficiency, and energy content. However, maize silage nutritive value can be compromised by in-season changes during crop development due to changes in plant partitioning between grain and other biomass fractions. The partitioning to grain (harvest index, HI) is affected by the interactions between genotype (G) × environment (E) × management (M). Thus, modelling tools could assist in accurately predicting changes during the in-season crop partitioning and composition and, from these, the HI of maize silage. Our objectives were to (i) identify the main drivers of grain yield and HI variability, (ii) calibrate the Agricultural Production Systems Simulator (APSIM) to estimate crop growth, development, and plant partitioning using detailed experimental field data, and (iii) explore the main sources of HI variance in a wide range of G × E × M combinations. Nitrogen (N) rates, sowing date, harvest date, plant density, irrigation rates, and genotype data were used from four field experiments to assess the main drivers of HI variability and to calibrate the maize crop module in APSIM. Then, the model was run for a complete range of G × E × M combinations across 50 years. Experimental data demonstrated that the main drivers of observed HI variability were genotype and water status. The model accurately simulated phenology [leaf number and canopy green cover; Concordance Correlation Coefficient (CCC)=0.79-0.97, and Root Mean Square Percentage Error (RMSPE)=13%] and crop growth (total aboveground biomass, grain + cob, leaf, and stover weight; CCC=0.86-0.94 and RMSPE=23-39%). In addition, for HI, CCC was high (0.78) with an RMSPE of 12%. The long-term scenario analysis exercise showed that genotype and N rate contributed to 44% and 36% of the HI variance. Our study demonstrated that APSIM is a suitable tool to estimate maize HI as one potential proxy of silage quality. The calibrated APSIM model can now be used to compare the inter-annual variability of HI for maize forage crops based on G × E × M interactions. Therefore, the model provides new knowledge to (potentially) improve maize silage nutritive value and aid genotype selection and harvest timing decision-making.
Lumbar and pelvis movement comparison between cross-court and long-line topspin forehand in table tennis: based on musculoskeletal model

Introduction: Cross-court and the long-line topspin forehand is the common and basic stroke skill in table tennis. The purpose of this study was to investigate the differences in lumbar and pelvis movements between cross-court and long-line topspin forehand strokes in table tennis based on musculoskeletal demands using OpenSim. Materials and Methods: The eight-camera Vicon system and Kistler force platform were used to measure kinematics and kinetics in the lumbar and pelvis movement of sixteen participants (Weight: 69.89 ± 1.58 kg; Height: 1.73 ± 0.03 m; Age: 22.89 ± 2.03 years; BMI: 23.45 ± 0.69 kg/m2; Experience: 8.33 ± 0.71 years) during cross-court and long-line topspin forehand play. The data was imputed into OpenSim providing the establishment of the Giat2392 musculoskeletal model for simulation. One-dimensional statistical parametric mapping and independent samples t-test was performed in MATLAB and SPSS to analyze the kinematics and kinetics. Results: The results show that the range of motion, peak moment, and maximum angle of the lumbar and pelvis movement in cross-court play were significantly higher than in the long-line stroke play. The moment of long-line in the sagittal and frontal plane was significantly higher than cross-court play in the early stroke phase. Conclusion: The lumbar and pelvis embody greater weight transfer and greater energy production mechanisms when players performed cross-court compared to long-line topspin forehand. Beginners could enhance their motor control strategies in forehand topspin skills and master this skill more easily based on the results of this study.
Mental health in Canadian children and adolescents during COVID-19 pandemic: the role of personality and, coping and stress responses

In December 2019, the Coronavirus Disease (COVID-19) pandemic first emerged in China and quickly spread to other countries. Previous studies have shown that the COVID-19 pandemic and the consequences have negatively impacted the mental health of adults. Individual differences such as personality could contribute to mental health. Furthermore, coping and responses to stress may affect an individual’s response to the pandemic. In the past, studies have only investigated this relationship in adults. In the current study, we examine how personality traits (using the Five-Factor Model as our framework) and Coping and Response to COVID-19 stress are related to the mental health of Canadian children and adolescents during the pandemic. Using parent reports of 100 preschoolers and 607 6–18-year-old children, we performed multiple regression analysis to explore how personality traits predict the effects of COVID-19 on mental health. The results showed that personality traits are associated with the mental health of Canadian youth during the COVID-19 pandemic. In preschoolers, Neuroticism and Agreeableness predicted the most mental health problems, and in 6-18-year-old children, Extraversion negatively predicted the most mental health problems. Also, Openness to Experience was the weakest predictor of mental health status in Canadian youth. These findings could be useful in understanding children’s responses to the COVID-19 pandemic and could assist public health services delivering mental health services specifically tailored to children’s personalities during and after this pandemic.