Miracle-dz/UniFAR-FTUs huggingface dataset:
Laterodorsal tegmentum–ventral tegmental area projections encode positive reinforcement signals

The laterodorsal tegmentum (LDT) is a brainstem nucleus classically involved in REM sleep and attention, and that has recently been associated with reward‐related behaviors, as it controls the activity of ventral tegmental area (VTA) dopaminergic neurons, modulating dopamine release in the nucleus accumbens. To further understand the role of LDT–VTA inputs in reinforcement, we optogenetically manipulated these inputs during different behavioral paradigms in male rats. We found that in a two‐choice instrumental task, optical activation of LDT–VTA projections shifts and amplifies preference to the laser‐paired reward in comparison to an otherwise equal reward; the opposite was observed with inhibition experiments. In a progressive ratio task, LDT–VTA activation boosts motivation, that is, enhances the willingness to work to get the reward associated with LDT–VTA stimulation; and the reverse occurs when inhibiting these inputs. Animals abolished preference if the reward was omitted, suggesting that LDT–VTA stimulation adds/decreases value to the stimulation‐paired reward. In addition, we show that LDT–VTA optical activation induces robust preference in the conditioned and real‐time place preference tests, while optical inhibition induces aversion. The behavioral findings are supported by electrophysiological recordings and c‐fos immunofluorescence correlates in downstream target regions. In LDT–VTA ChR2 animals, we observed an increase in the recruitment of lateral VTA dopamine neurons and D1 neurons from nucleus accumbens core and shell; whereas in LDT–VTA NpHR animals, D2 neurons appear to be preferentially recruited. Collectively, these data show that the LDT–VTA inputs encode positive reinforcement signals and are important for different dimensions of reward‐related behaviors.
Recurrent Vulvovaginal Candidiasis: a Dynamic Interkingdom Biofilm Disease of Candida and Lactobacillus

RVVC is a significant burden, both economically and for women's health, but its prevalence is poorly documented globally due to the levels of self-treatment. Identifying triggers for development and recurrence of VVC and the pathogenesis of the microbes involved could considerably improve prevention and treatment options for women with recurrent, azole-resistant cases. ABSTRACT Despite the strikingly high worldwide prevalence of vulvovaginal candidiasis (VVC), treatment options for recurrent VVC (RVVC) remain limited, with many women experiencing failed clinical treatment with frontline azoles. Further, the cause of onset and recurrence of disease is largely unknown, with few studies identifying potential mechanisms of treatment failure. This study aimed to assess a panel of clinical samples from healthy women and those with RVVC to investigate the influence of Candida, the vaginal microbiome, and how their interaction influences disease pathology. 16S rRNA sequencing characterized disease by a reduction in specific health-associated Lactobacillus species, such as Lactobacillus crispatus, coupled with an increase in Lactobacillus iners. In vitro analysis showed that Candida albicans clinical isolates are capable of heterogeneous biofilm formation, and we found the presence of hyphae and C. albicans aggregates in vaginal lavage fluid. Additionally, the ability of Lactobacillus to inhibit C. albicans biofilm formation and biofilm-related gene expression was demonstrated. Using RNA sequencing technology, we were able to identify a possible mechanism by which L. crispatus may contribute to re-establishing a healthy vaginal environment through amino acid acquisition from C. albicans. This study highlights the potential formation and impact of Candida biofilms in RVVC. Additionally, it suggests that RVVC is not entirely due to an arbitrary switch in C. albicans from commensal to pathogen and that understanding interactions between this yeast and vaginal Lactobacillus species may be crucial to elucidating the cause of RVVC and developing appropriate therapies. IMPORTANCE RVVC is a significant burden, both economically and for women's health, but its prevalence is poorly documented globally due to the levels of self-treatment. Identifying triggers for development and recurrence of VVC and the pathogenesis of the microbes involved could considerably improve prevention and treatment options for women with recurrent, azole-resistant cases. This study therefore aimed to examine the interkingdom dynamics from healthy women and those with RVVC using next-generation sequencing techniques and to further investigate the molecular interactions between C. albicans and L. crispatus in a relevant biofilm coculture system.
The integrated production of ultrathin g-C3N4 and membrane assisted by edible syrup for the sustained photocatalytic treatment of Cr(VI) and tetracycline

The exfoliation of bulk raw graphitic carbon nitride (g-C3N4) by edible glucose syrup to produce ultrathin g-C3N4 nanosheets in concentrations of up to 0.2 mg ml−1 was achieved. Detailed characterization through TEM, AFM, FT-IR, XRD, Raman and TGA confirmed the formation of ultrathin structure and improved properties. Compared to raw g-C3N4, the prepared thin g-C3N4 layers exhibited a 18-fold enhancement in Cr(VI) reduction and a 3-fold enhancement in tetracycline hydrochloride degradation, which is ascribed to their larger specific surface area and more exposed active sites. The layered g-C3N4 membrane was constructed via direct vacuum filtration. The layer-stacked g-C3N4 nanosheet membrane exhibited an excellent and sustained photocatalytic performance as the prepared thin g-C3N4 layers could maintain a layered lamella after stacking in filtration process. The recyclable synthesis of ultrathin g-C3N4 layers and layer-stacked g-C3N4 membrane by our method provides a sustainable strategy to pollution treatment by 2D materials.
Superior galvanostatic electrochemical deposition of platinum nanograss provides high performance planar microelectrodes for in vitro neural recording

Objective. Platinum nanograss (Ptng) has been demonstrated as an excellent coating to increase the electrode roughness and reduce the impedance of microelectrodes for neural recording. However, the optimisation of the original potentiostatic electrochemical deposition (PSED) method has been performed by the original group only and no in vitro validation of functionality was reported. Approach. This study firstly reinvestigates the use of the PSED method for Ptng coating at different charge densities which highlights non-uniformities in the edges of the microelectrodes for increasing deposition charge densities, leading to a decreased impedance which is in fact an artefact. We then introduce a novel Ptng fabrication method of galvanostatic electrochemical deposition (GSED). Main results. We demonstrate that the GSED deposition method also significantly reduces the electrode impedance, raises the charge storage capacity and provides a significantly more planar electrode surface in comparison to the PSED method with negligible edge effects. In addition, we demonstrate how high-quality neural recordings were performed, for the first time, using the Ptng GSED deposition microelectrodes from human hNT neurons and how spiking and bursting were observed. Significance. Thus, the GSED Ptng deposition method presented here provides an alternative method of microelectrode fabrication for neural applications with excellent impedance and planarity of surface.
Labelling of human Wharton's jelly‐derived mesenchymal stem cells with gold nanorods by biomimicry method

Mesenchymal stem cell (MSC)‐based cell therapy can provide opportunities for the treatment of various diseases. However, when used in vivo, these cells should be labelled and monitored by a non‐invasive method during delivery to the desired locations within the body. This study describes a biomimicry method that effectively labels human Wharton's jelly‐derived MSCs (hWJ‐MSCs) with a photoacoustics (PA) contrast agent, gold nanorods (GNRs), without the need for transfection agents (TAs). In this method for cell labelling, the hWJ‐MSCs were co‐incubated with non‐adherent cells isolated from fresh umbilical cord for 2 days immediately before incubation with GNRs. Next, hWJ‐MSCs were labelled with the GNRs at a concentration of approximately 1010 nanorads/mL (NR/mL) followed by transmission electron microscopy (TEM) and inductively coupled plasma mass spectroscopy (ICP‐MS) to verify their labelling effectiveness. The GNRs‐labelled MSCs prepared by this method had an intracellular gold (Au) concentration of 3.4 ± 0.4 pg/cell, which is an acceptable amount for cell labelling.
Identification of lectin receptors for conserved SARS‐CoV‐2 glycosylation sites

New SARS‐CoV‐2 variants are continuously emerging with critical implications for therapies or vaccinations. The 22 N‐glycan sites of Spike remain highly conserved among SARS‐CoV‐2 variants, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate‐binding proteins (lectins) to probe critical sugar residues on the full‐length trimeric Spike and the receptor binding domain (RBD) of SARS‐CoV‐2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single‐molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD‐ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS‐CoV‐2 infections. These data report the first extensive map and 3D structural modelling of lectin‐Spike interactions and uncovers candidate receptors involved in Spike binding and SARS‐CoV‐2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS‐CoV‐2 viral entry holds promise for pan‐variant therapeutic interventions.
Development and Cross-National Validation of a French Version of the Jefferson Scale of Empathy for Students

Empathy is a multifaceted personal ability combining emotional and cognitive features modulated by cultural specificities. It is widely recognized as a key clinical competence that should be valued during professional training. The Jefferson Scale of Empathy for medical students (JSE-S) has been developed for this purpose and validated in several languages, but not in French. The aims of this study were to gather validity evidence for a newly developed version of the JSE-S and compare it between two French-speaking contexts. In total, 1,433 undergraduate medical students from the universities of Lyon (UL), France and Geneva (UG), Switzerland participated in the study completing the JSE-S in French. Total and partial scores of the three subscales (“perspective taking,” “compassionate care” and “walking in patient’s shoes”) were calculated for each site. Construct validity of the JSE-S was analyzed considering three sources of evidence: content, internal structure and relations to other variables. A first-order Confirmatory Factor Analysis using structural equation modeling examined the three latent variables of the JSE-S subscales. Cronbach’s α coefficients were 0.75 (UG) and 0.81 (UL). The items’ discrimination power ranged between 0.29 and 1.60 (median effect size of 1.24). The overall correlations between items and total or partial scores derived from the latent JSE-S subscales were consistently similar in both study sites. Findings of this study confirm the latent structure of the JSE-S in French and its cross-national reproducibility. The comparable underlying structure of the questionnaire tested in two distinct French-speaking contexts endorses the generalizability of its measure.
A mathematical comparison of non‐negative matrix factorization related methods with practical implications for the analysis of mass spectrometry imaging data

Rationale Non‐negative matrix factorization (NMF) has been used extensively for the analysis of mass spectrometry imaging (MSI) data, visualizing simultaneously the spatial and spectral distributions present in a slice of tissue. The statistical framework offers two related NMF methods: probabilistic latent semantic analysis (PLSA) and latent Dirichlet allocation (LDA), which is a generative model. This work offers a mathematical comparison between NMF, PLSA, and LDA, and includes a detailed evaluation of Kullback–Leibler NMF (KL‐NMF) for MSI for the first time. We will inspect the results for MSI data analysis as these different mathematical approaches impose different characteristics on the data and the resulting decomposition. Methods The four methods (NMF, KL‐NMF, PLSA, and LDA) are compared on seven different samples: three originated from mice pancreas and four from human‐lymph‐node tissues, all obtained using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). Results Where matrix factorization methods are often used for the analysis of MSI data, we find that each method has different implications on the exactness and interpretability of the results. We have discovered promising results using KL‐NMF, which has only rarely been used for MSI so far, improving both NMF and PLSA, and have shown that the hitherto stated equivalent KL‐NMF and PLSA algorithms do differ in the case of MSI data analysis. LDA, assumed to be the better method in the field of text mining, is shown to be outperformed by PLSA in the setting of MALDI‐MSI. Additionally, the molecular results of the human‐lymph‐node data have been thoroughly analyzed for better assessment of the methods under investigation. Conclusions We present an in‐depth comparison of multiple NMF‐related factorization methods for MSI. We aim to provide fellow researchers in the field of MSI a clear understanding of the mathematical implications using each of these analytical techniques, which might affect the exactness and interpretation of the results.
Decoding the intricacies of the mast cell compartment

Historically, understanding of the human mast cell (MC) compartment has lagged behind the appreciation of other cell lineages. MCs exist in vascularised tissues but do not under normal circumstances circulate in blood, and there has been no pharmacological agent identified that totally and selectively inhibits human MC function. There are no substantiated accounts of an apparently healthy individual who is severely lacking in MCs. Thus, some of the approaches employed to understand the function of a specific immune cell are not available to the MC biologist. The disease categories that have provided the greatest insight into MC biology have been monoclonal and IgE‐mediated MC disorders. This has led to the categorisation of MC diseases as intrinsic or extrinsic to the MC compartment and to the recognition of the role of mediators in MC activation disorders. Mastocytosis as a clonal disorder not only impacts the MC compartment through changes intrinsic to the MC, but also by the effects of episodes of significant release of MC mediators. The availability of newer therapeutic approaches developed to treat monoclonal MC disorders offer insights into how to more selectively approach management of MC centric diseases.
iPSC-Derived Natural Killer Cells for Cancer Immunotherapy

The discovery of human pluripotent stem cells (PSCs) at the turn of the century opened the door to a new generation of regenerative medicine research. Among PSCs, the donors available for induced pluripotent stem cells (iPSCs) are greatest, providing a potentially universal cell source for all types of cell therapies including cancer immunotherapies using natural killer (NK cells). Unlike primary NK cells, those prepared from iPSCs can be prepared with a homogeneous quality and are easily modified to exert a desired response to tumor cells. There already exist several protocols to genetically modify and differentiate iPSCs into NK cells, and each has its own advantages with regards to immunotherapies. In this short review, we detail the benefits of using iPSCs in NK cell immunotherapies and discuss the challenges that must be overcome before this approach becomes mainstream in the clinic.
Profiling and Validation of Live‐Cell Protein Methylation with Engineered Enzymes and Methionine Analogues

Protein methyltransferases (PMTs) regulate many aspects of normal and disease processes through substrate methylation, with S‐adenosyl‐L‐methionine (SAM) as a cofactor. It has been challenging to elucidate cellular protein lysine and arginine methylation because these modifications barely alter physical properties of target proteins and often are context dependent, transient, and substoichiometric. To reveal bona fide methylation events associated with specific PMT activities in native contexts, we developed the live‐cell Bioorthogonal Profiling of Protein Methylation (lcBPPM) technology, in which the substrates of specific PMTs are labeled by engineered PMTs inside living cells, with in situ–synthesized SAM analogues as cofactors. The biorthogonality of this technology is achieved because these SAM analogue cofactors can only be processed by the engineered PMTs—and not native PMTs—to modify the substrates with distinct chemical groups. Here, we describe the latest lcBPPM protocol and its application to reveal proteome‐wide methylation and validate specific methylation events. © 2021 Wiley Periodicals LLC.
Basophil activation test in food allergy: is it ready for real-time?

Purpose of review Utilization of basophil activation in the diagnosis and monitoring of food allergy has gained increasing recognition. An ex-vivo functional assay, basophil activation reflects clinical reactivity, thereby providing clinically relevant insights. Moreover, as a biomarker of reactivity and tolerance, basophil activation testing (BAT) may provide a useful tool for management of food allergies. Despite its utility, significant limitations of BAT have prevented widespread use. Addressing these limitations will increase the future application and adoption of BAT in food allergy. Recent findings A number of clinical trials in the past few years have demonstrated the use of BAT in the diagnosis and treatment of food allergy. Specifically, BAT has been found to be a biomarker of tolerance. Summary Basophil activation testing is an effective biomarker for diagnosis and monitoring of food allergy.
Bio-inspired graphene-based nano-systems for biomedical applications

The increasing demands of environmentally sustainable, affordable, and scalable materials have inspired researchers to explore greener nanosystems of unique properties which can enhance the performance of existing systems. Such nanosystems, extracted from nature, are state-of-art high-performance nanostructures due to intrinsic hierarchical micro/nanoscale architecture and generous interfacial interactions in natural resources. Among several, bio-inspired nanosystems graphene nanosystems have emerged as an essential nano-platform wherein a highly electroactive, scalable, functional, flexible, and adaptable to a living being is a key factor. Preliminary investigation project bio-inspired graphene nanosystems as a multi-functional nano-platform suitable for electronic devices, energy storage, sensors, and medical sciences application. However, a broad understanding of bio-inspired graphene nanosystems and their projection towards applied application is not well-explored yet. Considering this as a motivation, this mini-review highlights the following; the emergence of bio-inspired graphene nanosystems, over time development to make them more efficient, state-of-art technology, and potential applications, mainly biomedical including biosensors, drug delivery, imaging, and biomedical systems. The outcomes of this review will certainly serve as a guideline to motivate scholars to design and develop novel bio-inspired graphene nanosystems to develop greener, affordable, and scalable next-generation biomedical systems.
Audiological and vestibular evaluations in vitiligo patients

The aim of this paper was to investigate audiological abnormalities and potential vestibular injury in a sample of vitiligo subjects. Thirty-five patients with non-segmental vitiligo (NSV) were enrolled in the study. They underwent pure tonal audiometry (PTA), vestibular Fitzgerald-Hallpike caloric test, C-VEM, and ocular VEMP (O-VEMP) testing. The χ2 test and multiple regression analysis were performed. At PTA, 69% of patients presented with bilateral hearing loss, 8% monaural hearing loss, and 23% normal values. Bilateral caloric stimulations were performed and demonstrated that 14% of patients had a monolateral and 9% had a bilateral pathological response. VEMPs analysis showed that 20% of patients had no O-VEMPs response and 3% had no cervical VEMPS (C-VEMPs) response. Comparison between the normal values of healthy subjects and NSV patients showed an alteration of VEMPs in 44%. Multiple regressions showed no statistical differences. We propose a specific diagnostic protocol employing PTA, bithermal caloric tests, C-VEMP, and O-VEMP testing to evaluate audio-vestibular damage. Our data were concordant with the anatomic-physiological melanocytic distribution and their possible degeneration linked with NSV.
Combined Experimental and Computational Study of the Role of Promoters in Selective Hydrogenation

This thesis provides a systematic insight into the observed catalytic performance of the Pd promoted Ag nanoparticles on SiO2 support for α,β-unsaturated aldehyde hydrogenation to allyl alcohol, and of V promoted Rh surfaces for CO hydrogenation to C2+ oxygenates. It addresses a fundamentally important and interesting problems of regioselectivity with respect to selective hydrogenation of C=O bond vs. C=C bond in unsaturated aldehydes, and metal-oxide interface mediated H-assisted vs. Direct CO dissociation mechanism. Multiple critical properties affecting the activity and selectivity of heterogeneous catalyst were investigated. Heterogeneity is usually present due to a broad size distribution of the supported metal particles with irregular morphology, various alloy phases in bimetallic alloys, and multiple types of active sites. As such, elucidation of reaction mechanisms is rarely straightforward. Experimental study of a well-dispersed, single atom alloyed Pd-Ag/SiO2 catalysts on a selective hydrogenation of acrolein to allyl alcohol, showed that the activity of the catalyst is a function of particle size, with minimal dependence on the amount of Pd. The selectivity to allyl alcohol of the Ag/SiO2 catalyst cannot be improved on, as it appears to be limited by the intrinsic property of the silver on a silica support. The performance of these catalysts appears to be a delicate balance between the surface morphology and alloying effect. The origin of this morphology-dependence might be related to the activation energy for the formation of the reaction intermediates on silver surface planes. Varying Pd to Ag ratio causes a change to H2 reaction order corresponding to the observed change in the rate-determining step in the reaction mechanism In the computational study of vanadium promoted Rh surfaces, metallic V promotion induced a charge transferred from each adjacent Rh to V in the RhV structure, creating a more reactive Rh site necessary for C-O bond breaking reactions. Promotion via surface oxide clusters (V6O12) was shown to be an example of a bifunctional catalyst, where the presence of both elements (V and Rh) is necessary for the proposed V3+/V4+ oxidation/reduction cycle. Metal-oxide interface can provide oxygen “vacancy” sites for CO adsorption and highly favorable C-O bond dissociation.