Miracle-dz/UniFAR-FTUs huggingface dataset:
CA1 pyramidal cell diversity is rooted in the time of neurogenesis

Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morpho-physiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of age-matched principal neurons: pioneer, early-and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is significantly predetermined at the earliest steps of development.
Chromatin accessibility and microRNA expression in nephron progenitor cells during kidney development

Mammalian nephrons originate from a population of nephron progenitor cells (NPCs), and it is known that NPCs’ transcriptomes change throughout nephrogenesis during healthy kidney development. To characterize chromatin accessibility and microRNA (miRNA) expression throughout this process, we collected NPCs from mouse kidneys at embryonic day 14.5 (E14.5) and postnatal day zero (P0) and assayed cells for transposase-accessible chromatin and small RNA expression. We observe 46,374 genomic regions of accessible chromatin, with 2,103 showing significant changes in accessibility between E14.5 and P0. In addition, we detect 1,104 known microRNAs, with 114 showing significant changes in expression. Genome-wide, changes in DNA accessibility and microRNA expression highlight biological processes like cellular differentiation, cell migration, extracellular matrix interactions, and developmental signaling pathways such as Notch. Furthermore, our data identify novel candidate cis-regulatory elements for Eya1 and Pax8, both genes with a role in NPC differentiation; we also associate expression-changing microRNAs, including let-7-5p, miR-125b-5p, miR-181a-2-3p, and miR-9-3p, with candidate cis-regulatory elements. Overall, our data characterize NPCs during kidney development and point out new candidate regulatory elements for genes and microRNA with key roles in nephrogenesis.
Re-bordering Europe? Collective action barriers to ‘Fortress Europe’

ABSTRACT This article discusses the collective action problems associated with different kinds of joint external bordering and highlights specific aspects of the European Union which I argue make it particularly ineffective at supplying (many) forms of external bordering. Applying this framework to the EU’s Common Security and Defence Policy, European Immigration Policy, and European Neighbourhood Policy, I explain why each of these areas is subject to chronic under-provision. I conclude that a ‘Fortress Europe’ is unlikely to materialize, giving rise instead to national re-bordering as a reaction to growing pressures on the Union’s internal and external borders.
Rebordering Europe: external boundaries and integration in the European Union

ABSTRACT The crises of the European Union and the geopolitical shifts in its international environment have generated a backlash against the post-Cold War ‘debordering’ of European integration. Whereas integration theories focus almost exclusively on the EU’s internal boundaries and developments, this framework paper conceptualizes and theorizes integration as a process of internal debordering and external rebordering. It sketches the history of European integration in a bordering perspective and proposes general assumptions about the EU’s bordering process. Accordingly, rebordering pressures result from widening boundary gaps at the EU’s external borders, exogenous shocks to cross-border transactions, growing community deficits of debordering, and their politicization. Whether external rebordering succeeds and how it interacts with internal boundary formation, depends on EU-level boundary negotiations and the relative costs and benefits of external vs. internal rebordering.
Friction stir welding in corrosion resistant alloys

Components of the offshore industry have to withstand high mechanical loads under extreme conditions. Thus, noble metals have been used for manufacturing of pipes, with materials as corrosion resistant alloys (CRA). Nevertheless, fusion welding for CRA still lacks of reproducibility, looking for more effective processes. In this context, friction stir welding is suitable for CRA. Therefore, this study focuses on mechanical and corrosion properties of friction stir welds in UNS N06625 and UNS S32760. At first, the weld microstructure and its corresponding heat input were analysed. Besides, microhardness measurements were performed. Moreover, the pitting resistance was studied according ASTM G48A. The results showed that friction-stir-welded alloy 625 had greater pitting resistance than friction-stir-welded super duplex.
Emerging diagnostic and therapeutic strategies for urothelial carcinoma

Urothelial carcinomas (UCs) represent the fourth most frequent tumours in developed countries [1]; among these, bladder cancer (BCa) is the 10th most common form of cancer worldwide, with 549 000 new cases and 200 000 deaths estimated in 2018 [2], while upper urinary tract UC (UTUC) accounts for 5–10% of UCs [1]. Recently, the European Association of Urology (EAU) and the European Society of Medical Oncology (ESMO) selected a panel of experts to define ‘hot topics’ in the BCa field, in order to improve current management and to propose new solutions [3,4]. In >50 years of BCa care a limited amount of improvement has been verified in terms of cancer-specific survival and quality of life for patients harbouring the disease. Just recently, comprehensive understanding of BCa biology has changed the status of tumour treatment and today we have not only improved our approach to localised disease, but we are providing effective treatment for more advance stages. In this regard, it is important to continue the efforts in Urological Oncology to improve survival and quality of life of patients with BCa even in these difficult times with the entirety of humanity challenged by the wellknown coronavirus disease 2019 (COVID-19) pandemic. Therefore, we are grateful to the Arab Journal of Urology and to the Editor-in-Chief, Professor Shokeir, for giving us this unique opportunity and challenge to keep on supporting thoughtful BCa research. In this Special Issue on BCa and UTUC, we collected a series of articles treating some of the most important and innovative topics on the subject. First, the use of biomarkers in the form of inflammation markers or questionnaires (such as the Frailty Score) to individuate prognostic outcomes and to select the optimal treatment in patients with BCa, even in the postoperative management. Second, new imaging techniques are being implemented in this field to improve substratification and offer the optimal treatment to our patients. In this issue, we will evaluate the role of multiparametric MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) as emerging tools in the diagnosis of BCa. Third, novel treatments have been recently developed in the field of non-muscleinvasive BCa, especially the role of programmed deathligand 1 (PD-L1) and the effect of electro-motive drug administration (EMDA) in a subgroup of patients. Fourth, we also give some space to UTUC, reporting about optimal surgical technique and the need for lymph node dissection. The readers will find interesting clinical information that can be readily taken to the patient’s side and ideally included into prospective trial assessment. The UC path as we know today could elegantly be challenged with novel medical tools and information with the objective of improving patient’s outcomes. We would like to thank once again the editorial team, the Editor-in-Chief, authors, reviewers and all the readers for their efforts in putting together robust work to further improve research and care of patients with UC.
A simple and rapid method for high-resolution visualization of single-ion tracks

Prompt determination of spatial points of single-ion tracks plays a key role in high-energy particle induced-cancer therapy and gene/plant mutations. In this study, a simple method for the high-resolution visualization of single-ion tracks without etching was developed through the use of polyacrylic acid (PAA)-N, N’-methylene bisacrylamide (MBAAm) blend films. One of the steps of the proposed method includes exposure of the irradiated films to water vapor for several minutes. Water vapor was found to promote the cross-linking reaction of PAA and MBAAm to form a bulky cross-linked structure; the ion-track scars were detectable at a nanometer scale by atomic force microscopy. This study demonstrated that each scar is easily distinguishable, and the amount of generated radicals of the ion tracks can be estimated by measuring the height of the scars, even in highly dense ion tracks. This method is suitable for the visualization of the penumbra region in a single-ion track with a high spatial resolution of 50 nm, which is sufficiently small to confirm that a single ion hits a cell nucleus with a size ranging between 5 and 20 μm.
Psychometric Properties of the German Version of the Self-Regulation of Eating Behavior Questionnaire

Background: The Self-Regulation of Eating Behavior Questionnaire (SREBQ) is an economical way of assessing an individual's self-regulatory abilities regarding eating behavior. Such scales are needed in the German population; therefore, the purpose of the present study was the translation and validation of a German version of the SREBQ. Method: First, we conducted a pilot study (Study 1; N = 371) after the translation procedure. Second, we assessed the final scale in a representative sample of the German population (Sample 2; N = 2,483) and its underlying factor structure. Further, we tested for measurement invariance and evaluated the SREBQ's associations with related scales to explore convergent and discriminant validity. Finally, we considered differences in SREBQ based on sociodemographic variables and provided derived reference scores (norm values). Results: Factor analysis revealed deficiencies in the original model. Thus, we shortened the scale based on statistical considerations and the adapted version showed improved fit in Confirmatory Factor Analysis and reliability. We also found evidence for partial strict invariance, which means the measure is equivalent for the tested groups of age and gender. Item and scale psychometric properties of the shortened version were satisfactory. In terms of diagnostic validity, it was shown that individuals with higher body mass index (kg/m2) have worse self-regulation of eating behavior than those with lower. Conclusion: In sum, the SREBQ evidenced good validity and reliability and is suitable for application in medical, psychological, and nutritional research.
Inhibition of 14-3-3 Proteins Alters Neural Oscillations in Mice

Accumulating evidence suggests that schizophrenia is a disorder of the brain’s communication, a result of functional and structural dysconnectivities. Patients with schizophrenia exhibit irregular neuronal circuit and network activity, but the causes and consequences of such activity remain largely unknown. Inhibition of 14-3-3 proteins in the mouse brain leads to the expression of multiple schizophrenia endophenotypes. Here we investigated how 14-3-3 inhibition alters neuronal network activity in the mouse hippocampus (HPC) and prefrontal cortex (PFC), key brain regions implicated in schizophrenia pathophysiology. We implanted monopolar recording electrodes in these two regions to record local field potentials both at rest and during a cognitive task. Through our assessment of band power, coherence, and phase-amplitude coupling, we found that neural oscillations in the theta and gamma frequency ranges were altered as a result of 14-3-3 dysfunction. Utilizing transgenic and viral mouse models to assess the effects of chronic and acute 14-3-3 inhibition on oscillatory activities, respectively, we observed several fundamental similarities and differences between the two models. We localized viral mediated 14-3-3 protein inhibition to either the HPC or PFC, allowing us to assess the individual contributions of each region to the observed changes in neural oscillations. These findings identify a novel role of 14-3-3 proteins in neural oscillations that may have implications for our understanding of schizophrenia neurobiology.
Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss

Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways was inhibited by JZL184 and deletion of MAGL. Our in vivo study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
Affective Face Processing Modified by Different Tastes

Facial emotional recognition is something used often in our daily lives. How does the brain process the face search? Can taste modify such a process? This study employed two tastes (sweet and acidic) to investigate the cross-modal interaction between taste and emotional face recognition. The behavior responses (reaction time and correct response ratios) and the event-related potential (ERP) were applied to analyze the interaction between taste and face processing. Behavior data showed that when detecting a negative target face with a positive face as a distractor, the participants perform the task faster with an acidic taste than with sweet. No interaction effect was observed with correct response ratio analysis. The early (P1, N170) and mid-stage [early posterior negativity (EPN)] components have shown that sweet and acidic tastes modified the ERP components with the affective face search process in the ERP results. No interaction effect was observed in the late-stage (LPP) component. Our data have extended the understanding of the cross-modal mechanism and provided electrophysiological evidence that affective facial processing could be influenced by sweet and acidic tastes.
TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; P < 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37–0.61; P < 0.001) and 0.48 (95% CI, 0.36–0.64; P < 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with FLT3-ITD positive AML.
Modeling and Reconstruction of State Variables for Low-Level Control of Soft Pneumatic Actuators

To further advance closed-loop control for soft robotics, suitable sensor and modeling strategies have to be investigated. Although there are many flexible and soft sensors available, the integration into the actuator and the use in a control loop is still challenging. Therefore, a state-space model for closed-loop low-level control of a fiber-reinforced actuator using pressure and orientation measurement is investigated. To do so, the integration of an inertial measurement unit and geometric modeling of actuator is presented. The piecewise constant curvature approach is used to describe the actuator’s shape and deformation variables. For low-level control, the chamber’s lengths are reconstructed from bending angles with a geometrical model and the identified material characteristics. For parameter identification and model validation, data from a camera tracking system is analyzed. Then, a closed-loop control of pressure and chambers’ length of the actuator is investigated. It will be shown, that the reconstruction model is suitable for estimating the state variables of the actuator. In addition, the use of the inertial measurement unit will demonstrate a cost-effective and compact sensor for soft pneumatic actuators.
Prospects for the Use of Cannabinoids in Psychiatric Disorders

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.
Mechanism of Resistance to S-metolachlor in Palmer amaranth

Herbicides are major tools for effective weed management. The evolution of resistance to herbicides in weedy species, especially contributed by non-target-site-based resistance (NTSR) is a worrisome issue in crop production globally. Glyphosate-resistant Palmer amaranth (Amaranthus palmeri) is one of the extremely difficult weeds in southern US crop production. In this study, we present the level and molecular basis of resistance to the chloroacetamide herbicide, S-metolachlor, in six field-evolved A. palmeri populations that had survivors at the recommended field-dose (1.1 kg ai ha−1). These samples were collected in 2014 and 2015. The level of resistance was determined in dose-response assays. The effective dose for 50% control (ED50) of the susceptible population was 27 g ai ha−1, whereas the ED50 of the resistant populations ranged from 88 to 785 g ai ha−1. Therefore, A. palmeri resistance to S-metolachlor evolved in Arkansas as early as 2014. Metabolic-inhibitor and molecular assays indicated NTSR in these populations, mainly driven by GSTs. To understand the mechanism of resistance, selected candidate genes were analyzed in leaves and roots of survivors (with 1 × S-metolachlor). Expression analysis of the candidate genes showed that the primary site of S-metolachlor detoxification in A. palmeri is in the roots. Two GST genes, ApGSTU19 and ApGSTF8 were constitutively highly expressed in roots of all plants across all resistant populations tested. The expression of both GSTs increased further in survivors after treatment with S-metolachlor. The induction level of ApGSTF2 and ApGSTF2like by S-metolachlor differed among resistant populations. Overall, higher expression of ApGSTU19, ApGSTF8, ApGSTF2, and ApGSTF2like, which would lead to higher GST activity in roots, was strongly associated with the resistant phenotype. Phylogenetic relationship and analysis of substrate binding site of candidate genes suggested functional similarities with known metolachlor-detoxifying GSTs, effecting metabolic resistance to S-metolachlor in A. palmeri. Resistance is achieved by elevated baseline expression of these genes and further induction by S-metolachlor in resistant plants.