Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcending time in the brain: How event memories are constructed from experience

Our daily lives unfold continuously, yet when we reflect on the past, we remember those experiences as distinct and cohesive events. To understand this phenomenon, early investigations focused on how and when individuals perceive natural breakpoints, or boundaries, in ongoing experience. More recent research has examined how these boundaries modulate brain mechanisms that support long‐term episodic memory. This work has revealed that a complex interplay between hippocampus and prefrontal cortex promotes the integration and separation of sequential information to help organize our experiences into mnemonic events. Here, we discuss how both temporal stability and change in one's thoughts, goals, and surroundings may provide scaffolding for these neural processes to link and separate memories across time. When learning novel or familiar sequences of information, dynamic hippocampal processes may work both independently from and in concert with other brain regions to bind sequential representations together in memory. The formation and storage of discrete episodic memories may occur both proactively as an experience unfolds. They may also occur retroactively, either during a context shift or when reactivation mechanisms bring the past into the present to allow integration. We also describe conditions and factors that shape the construction and integration of event memories across different timescales. Together these findings shed new light on how the brain transcends time to transform everyday experiences into meaningful memory representations.
Is a combination of progesterone and chloroquine more effective than either alone in the treatment of cerebral ischemic injury?

BACKGROUND In this proof-of-concept paper, we investigated whether combination treatment with progesterone (P4) and chloroquine (CQ) would reduce ischemic injury more effectively than either agent alone in a transient middle cerebral artery occlusion (tMCAO) model in male rats. METHODS P4 (8 mg/kg) and CQ (25 mg/kg) were given alone or in combination beginning at different times during surgery and for 3 days post-occlusion. Locomotor activity and grip strength were evaluated as measures of impairment and recovery. Infarct size was assessed by TTC staining. Markers of autophagy (LC3 and SQSTM1/p62) and apoptosis (Bcl-2 and Bax) were evaluated with western blotting. RESULTS At the doses we employed, the combination was not more effective than either drug given separately on measures of grip strength or locomotor activity. However, combination therapy substantially reduced infarct size, and significantly increased Bcl-2 protein levels and suppressed Bax expression. Progesterone decreased the expression of LC3-II 24 h and SQSTM1/p62 after ischemia. CONCLUSIONS Our findings suggest that combination therapy with P4 and CQ is not detrimental and has a small-to-moderate additive neuroprotective effect on ischemic injury in rats without substantively affecting behavioral outcomes. CQ and P4 may help to regulate the expression of both autophagy-related and apoptosis-related proteins.
Development and Biological Analysis of a Novel Orthotopic Peritoneal Dissemination Mouse Model Generated Using a Pancreatic Ductal Adenocarcinoma Cell Line

Objectives Peritoneal dissemination (PD) is an important cause of morbidity and mortality among patients with pancreatic ductal adenocarcinoma (PDAC). We sought to develop and characterized a novel PD mouse model by using a previously established PDAC cell line TCC-Pan2. Methods TCC-Pan2 cell line was characterized for growth rate, tumor markers, histology, and somatic mutations. TCC-Pan2 cells were implanted orthotopically to produce PD. TCC-Pan2 cells from these metastatic foci were expanded in vitro and then implanted orthotopically in mice. This PD model was used for comparing the antitumor effect of paclitaxel and NK105. Results Orthotopically implanted TCC-Pan2 cells caused tumor formation and PD with high frequency in mice. A potent metastatic subline—Pan2M—was obtained. NK105 exerted a stronger antitumor effect than paclitaxel against Pan2M cells harboring a luciferase gene (Pan2MmLuc). Notably, the survival rate on day 80 in the Pan2MmLuc mouse model was 100% for the NK105 group and 0% for the paclitaxel group. Conclusion TCC-Pan2 cell line and Pan2MmLuc PD model can serve as useful tools for monitoring the responses to antineoplastic agents and for studying PDAC biology.
Suboptimal osteoporosis evaluation and treatment in older men with and without additional high-risk factors for fractures

We compared osteoporosis case-finding, evaluation and treatment in groups of Older Men and Older Women with age alone as a significant risk for fracture and Older Men with Higher Risk (older men additionally having previous hip fracture, corticosteroid use or androgen deprivation therapy). We studied 13,704 older men and women (≥70 years old) receiving care at a Veterans Affairs medical center from January 2000 to August 2010 whose 10-year hip fracture risk was assessed by limited FRAX score. The main outcome measures were the proportion of patients who had bone mineral density (by dual-energy X-ray absorptiometry [DXA]) and serum 25-hydroxy vitamin D (25-OH D) measurements performed, and calcium/vitamin D or bisphosphonates prescribed. The proportion of men with a 10-year hip fracture risk ≥3% with age alone as a risk was 48% and 88% in men aged 75–79 and ≥80 years, respectively. Compared with Older Women, fewer Older Men underwent DXA (12% vs 63%, respectively) and 25-OH D measurements (18% vs 39%), and fewer received calcium/vitamin D (20% vs 63%) and bisphosphonate (5% vs 44%) prescriptions. In Older Men with Higher Risk category, the proportion of men with 10-year hip fracture risk ≥3% ranged from 69% to 95%. Despite a higher risk and expectation that this group would have greater case detection and screening, few Older Men with Higher risk underwent DXA screening (27%–36%) and 25-OH D measurements (23%–28%), and received fewer calcium/vitamin D (40%–50%) and bisphosphonate (13%–24%) prescriptions. Considering the known morbidity and mortality, our findings underscore the need for improved evaluation and management of osteoporosis in older men at high risk for fracture.
Concentration of exopolysaccharides produced by Fusarium fujikuroi and application of bioproduct as an effective bioherbicide

ABSTRACT Exopolysaccharides are secondary metabolites produced by microorganisms and are a subject of research in many fields of science and industry due to some of their confirmed properties, especially in the pharmaceutical and agrochemical areas. In this context, the objectives of this work were to evaluate the potential of Fusarium fujikuroi for producing exopolysaccharides and to concentrate such compounds in order to increase the herbicidal activity. Exopolysaccharides were produced by submerged fermentation and different concentration methods (membranes, lyophilization, and evaporation) were evaluated. The phytotoxic effects were assessed through absorption assays in detached leaves of Cucumis sativus and evaluated on the seventh day after application. The surface tension was evaluated for each concentration method. The production of exopolysaccharides in the crude broth without concentration was 5.94 g/L. When using the lyophilization method, a maximum yield of exopolysaccharides of 10.64 g/L was obtained. The membranes also presented satisfactory results of exopolysaccharides: 9.60 g/L. The increase of bioherbicidal activity and the lower surface tension are proportionally related to the increase of the concentration of exopolysaccharides. GRAPHICAL ABSTRACT
Phosphatases in Mitosis: Roles and Regulation

Mitosis requires extensive rearrangement of cellular architecture and of subcellular structures so that replicated chromosomes can bind correctly to spindle microtubules and segregate towards opposite poles. This process originates two new daughter nuclei with equal genetic content and relies on highly-dynamic and tightly regulated phosphorylation of numerous cell cycle proteins. A burst in protein phosphorylation orchestrated by several conserved kinases occurs as cells go into and progress through mitosis. The opposing dephosphorylation events are catalyzed by a small set of protein phosphatases, whose importance for the accuracy of mitosis is becoming increasingly appreciated. This review will focus on the established and emerging roles of mitotic phosphatases, describe their structural and biochemical properties, and discuss recent advances in understanding the regulation of phosphatase activity and function.
Investigating the real role of HIF-1 and HIF-2 in iron recycling by macrophages

Most of the iron required for erythropoiesis is acquired by heme iron recycling of senescent erythrocytes by tissue macrophages (mainly spleen, bone marrow and liver macrophages). This process, called erythrophagocytosis (EP), is essential for mammalian iron homeostasis. Perturbations in EP occur in
Relationship Between Spasticity and Upper-Limb Movement Disorders in Individuals With Subacute Stroke Using Stochastic Spatiotemporal Modeling

Background. Spasticity is common in patients with stroke, yet current quantification methods are insufficient for determining the relationship between spasticity and voluntary movement deficits. This is partly a result of the effects of spasticity on spatiotemporal characteristics of movement and the variability of voluntary movement. These can be captured by Gaussian mixture models (GMMs). Objectives. To determine the influence of spasticity on upper-limb voluntary motion, as assessed by the bidirectional Kullback-Liebler divergence (BKLD) between motion GMMs. Methods. A total of 16 individuals with subacute stroke and 13 healthy aged-equivalent controls reached to grasp 4 targets (near-center, contralateral, far-center, and ipsilateral). Two-dimensional GMMs (angle and time) were estimated for elbow extension motion. BKLD was computed for each individual and target, within the control group and between the control and stroke groups. Movement time, final elbow angle, average elbow velocity, and velocity smoothness were computed. Results. Between-group BKLDs were much larger than within control-group BKLDs. Between-group BKLDs for the near-center target were lower than those for the far-center and contralateral targets, but similar to that for the ipsilateral target. For those with stroke, the final angle was lower for the near-center target, and the average velocity was higher. Velocity smoothness was lower for the near-center than for the ipsilateral target. Elbow flexor and extensor passive muscle resistance (Modified Ashworth Scale) strongly explained BKLD values. Conclusions. Results support the view that individuals with poststroke spasticity have a velocity-dependent reduction in active elbow joint range and that BKLD can be used as an objective measure of the effects of spasticity on reaching kinematics.
Magnetic body alignment in migratory songbirds: a computer vision approach

ABSTRACT Several invertebrate and vertebrate species have been shown to align their body relative to the geomagnetic field. Many hypotheses have been proposed to explain the adaptive significance of magnetic body alignment outside the context of navigation. However, experimental evidence to investigate alternative hypotheses is still limited. We present a new setup to track the preferential body alignment relative to the geomagnetic field in captive animals using computer vision. We tested our method on three species of migratory songbirds and provide evidence that they align their body with the geomagnetic field. We suggest that this behaviour is involved in the underlying mechanism for compass orientation and calibration, which may occur near to sunrise and sunset periods. Our method could easily be extended to other species and used to test a large set of hypotheses to explain the mechanisms behind the magnetic body alignment and the magnetic sense in general. Summary: Spontaneous alignment with the magnetic field in resting migratory songbirds revealed by computer vision suggests behaviour associated with magnetic field perception and compass calibration.
Risk of Atrial Fibrillation in Black Versus White Medicare Beneficiaries With Implanted Cardiac Devices

Background Black individuals in the United States experience higher rates of ischemic stroke than other racial groups but have lower rates of clinically apparent atrial fibrillation (AF). It is unclear whether blacks truly have less AF or simply more undiagnosed AF. Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims from 2009 to 2015 for a 5% nationally representative sample of Medicare beneficiaries. We included patients aged ≥66 years with at least 1 documented Current Procedural Terminology code for interrogation of an implantable pacemaker, cardioverter‐defibrillator, or loop recorder and no documented history of AF, atrial flutter, or stroke before their first device interrogation. Kaplan–Meier statistics and Cox proportional hazards models were used to examine the association between black race and the composite outcome of AF or atrial flutter while adjusting for age, sex, and vascular risk factors. Among 47 417 eligible patients, the annual incidence of AF/atrial flutter was 12.2 (95% CI, 11.5–13.1) per 100 person‐years among blacks and 17.6 (95% CI, 17.4–17.9) per 100 person‐years among non‐black beneficiaries. After adjustment for confounders, black beneficiaries faced a lower hazard of AF/atrial flutter than non‐black beneficiaries (hazard ratio, 0.75; 95% CI, 0.70–0.80). Despite the lower risk of AF, black patients faced a higher hazard of ischemic stroke (hazard ratio, 1.37; 95% CI, 1.22–1.53). Conclusions Among Medicare beneficiaries with implanted cardiac devices capable of detecting atrial rhythm, black patients had a lower incidence of AF despite a higher burden of vascular risk factors and a higher risk of stroke.
Diagnosis in a Preclinical Model of Bladder Pain Syndrome Using a Au/ZnO Nanorod-based SERS Substrate

To evaluate the feasibility of ZnO nanorod-based surface enhanced Raman scattering (SERS) diagnostics for disease models, particularly for interstitial cystitis/bladder pain syndrome (IC/BPS), ZnO-based SERS sensing chips were developed and applied to an animal disease model. ZnO nanorods were grown to form nano-sized porous structures and coated with gold to facilitate size-selective biomarker detection. Raman spectra were acquired on a surface enhanced Raman substrate from the urine in a rat model of IC/BPS and analyzed using a statistical analysis method called principal component analysis (PCA). The nanorods grown after the ZnO seed deposition were 30 to 50 nm in diameter and 500 to 600 nm in length. A volume of gold corresponding to a thin film thickness of 100 nm was deposited on the grown nanorod structure. Raman spectroscopic signals were measured in the scattered region for nanometer biomarker detection to indicate IC/BPS. The Raman peaks for the control group and IC/BPS group are observed at 641, 683, 723, 873, 1002, 1030, and 1355 cm−1, which corresponded to various bonding types and compounds. The PCA results are plotted in 2D and 3D. The Raman signals and statistical analyses obtained from the nano-sized biomarkers of intractable inflammatory diseases demonstrate the possibility of an early diagnosis.
Application of the Multi-Process Action Control Framework to Understand Parental Support of Child and Youth Physical Activity, Sleep, and Screen Time Behaviours.

BACKGROUND The purpose of this paper was to apply a framework designed to evaluate the intention-behaviour gap, known as multi-process action control (M-PAC), to understand parental support for the Canadian 24-Hour Movement Guidelines for Children and Youth. METHOD Parents (N = 1,208) of children 5-17 years of age, completed measures of reflective (attitudes, perceived control), regulatory (planning), and reflexive (identity, habit) processes as well as intention and support behaviours. RESULTS Parents had significantly (p < .01) higher intentions in descending order to support sleep (86%), reduce screen time (62%), or support physical activity (65% to 61%). Translation of these intentions into behaviour was also significantly (p < .01) higher in a descending pattern for sleep support (80%), screen time reduction (68%), and physical activity support (56% to 31%). Congruent with M-PAC, a discriminant function analysis of the results showed that the translation of parental support intentions into behaviour was associated with a combination of reflective, regulatory, and reflexive antecedents but these varied by the behaviours. CONCLUSION The majority of parents have positive intentions to support child and youth health behaviours, yet many fail to enact this support. Translation of intention into action was associated with attitudinal aspects, control over support, self-regulation skills, and parental habits and identity.
The effects of adipose‐derived stem cells on CD133‐expressing bladder cancer cells

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. They are also considered as a preferred cell source for urinary tract reconstruction. However, as MSCs exhibit affinity to tumor microenvironment, possible activation of tumor‐initiating cells remains a major concern in the application of stem cell‐based therapies for patients with a bladder cancer history. To analyze the influence of adipose‐derived stem cells (ASCs) on bladder cancer cells with stem cell‐like properties, we isolated CD133‐positive bladder cancer cells and cultured them in conditioned medium from ASCs (ASC‐CM). Our results showed that parental 5637 and HB‐CLS‐1 cells showed induced clonogenic potential when cultured in ASC‐CM. Soluble mediators secreted by ASCs increased proliferation and viability of unsorted cells as well as CD133+ and CD133− subpopulations. Furthermore, incubation with ASC‐CM modulated activation of intracellular signaling pathways. Soluble mediators secreted by ASCs increased phosphorylation of AKT1/2/3 (1.4‐fold, P < 0.05), ERK1/2 (1.6‐fold, P < 0.02), and p70 S6K (1.4‐fold) in CD133+ cells isolated from 5637 cell line. In turn, decreased phosphorylation of those three proteins involved in PI3K/Akt and MAPK signaling was observed in CD133+ cells isolated from HB‐CLS‐1 cell line. Our results revealed that bladder cancer stem‐like cells are responsive to signals from ASCs. Paracrine factors secreted by locally‐delivered ASCs may, therefore, contribute to the modulation of signaling pathways involved in cancer progression, metastasis, and drug resistance.
Stem Cell Therapy Is Proarrhythmic

Stem cell therapy appears to be a promising modality for myocardial repair of both hearts that are post myocardial infarction (MI) and those with other forms of structural cardiac disease (eg, congestive heart failure). In fact, recent experimental and clinical work has suggested that stem cell therapy contributes to cardiac regeneration. Unfortunately at this time, we contend that stem cell therapy is proarrhythmic. Accordingly, in this review we will approach this subject by restating this potential in the framework of traditional mechanisms of arrhythmias (automaticity and reentry). Lastly, we will address recent clinical work with stem cells, commenting on the proarrhythmic outcomes. Before assessing the proarrhythmic potential of stem cells, we think it important to first address the nature of the players. After all, these “players” are the cells selected for use in trials. ### Embryonic Stem Cells Obviously, because this cell population has the capacity to develop into differentiated cardiac cells, these cells have been phenotyped in terms of ionic current makeup, intracellular Ca2+ handling, and connexin expression.1 Embryonic Stem Cells (ESCs) have been shown to have at least fast sodium current, L-type Ca2+ current, If, IK1,2,3 and immature excitation-contraction (EC) coupling.4 Thus, implanting them into damaged myocardium would mean implanting areas of additional excitable cells that presumably would form gap junctions not only with fellow ESCs but also with surviving myocytes of the damaged substrate. Evidence for resident cardiac stem cells5,6 has surfaced, and these excitable cells could show promise for use in stem cell therapy. For example, c-Kit+ cardiac-derived cells isolated from a normal rat heart when delivered via the aortic root seem to invade the infarcted myocardium and regenerate muscle to improve left ventricular (LV) function.7 Unfortunately, no mention was made of rhythm instability (or stability) of the injected …
The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

Plants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.