Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Electrochemical Sensor Based on Electropolymerized Ion Imprinted PoPD/ERGO Composite for Trace Cd(II) Determination in Water

A novel electrochemical sensor based on electropolymerized ion imprinted poly (o-phenylenediamine) PoPD/electrochemical reduced graphene (ERGO) composite on glass carbon electrode (GCE) was fabricated for selective and sensitive determination of trace Cd(II) in water. ERGO was first deposited on the surface of GCE by electrochemical cyclic voltammetry (CV) scanning to enhance the electron transport activity at electrode surface. The ion imprinted polymer (IIP) of imprinted PoPD was then in situ electropolymerized on ERGO via CV scanning with oPD as functional monomer and Cd(II) ions as template, following removal of the template using electrochemical peroxidation method. The obtained imprinted PoPD/RERGO composites were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray energy spectroscopy (EDS) for the observation of their morphologies and components. The electrochemical behavior of the imprinted PoPD/ERGO/GCE was performed by CV and SWASV. The fabricated sensor of the imprinted PoPD/ERGO/GCE showed a good selectivity toward target Cd(II) ions in the presence of other heavy metal ions. Under the optimized experimental conditions, the sensor exhibited a good linear relationship between SWASV stripping peak values and Cd(II) concentration in the range of 1 to 50 ng/mL, with the limit of detection as 0.13 ng/mL (S/N = 3). The proposed electrochemical sensor of imprinted PoPD/ERGO/GCE was successfully applied for trace Cd(II) determination in real water samples.
Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases

Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the BLM gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is still not completely understood.
Assessment of intima-media thickness of the carotid artery and intraluminal diameter of the brachial artery as cardiovascular risk markers in Brazilian adolescents with overweight or obesity

Abstract Background The intima-media thickness of the carotid artery (cIMT) and endothelial dysfunction are associated with cardiovascular (CV) disease. Objectives To evaluate the correlation between cIMT, brachial intraluminal diameter and flow-mediated vasodilation on the reactive hyperemia phase in adolescents with obesity with predictors of CV risk. Methods Seventy-three pubertal patients with overweight or obesity were evaluated (45 girls) with a mean (standard deviation [SD]) age of 12.9 (2.5) years. Patients underwent anthropometric measurements and had the lipid profile, oral glucose tolerance test (oGTT) and serum intercellular adhesion molecule-1 (sICAM-1) levels analyzed. The ratios of the waist circumference (WC)/height (WHtR) and triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C), homeostatic model assessment of insulin resistance (HOMA-IR), the Matsuda index and insulin area under the curve (AUC) were calculated. All patients were evaluated for cIMT and arterial blood flow velocity of the brachial artery. Results 75.3% of the patients had high cIMT values. We found a positive correlation between WHtR and cIMT (r = 0.233; p = 0.050). There was a positive correlation between sICAM-1 and insulin AUC (r = 0.323; p = 0.012) and WHtR (r = 0.258; p = 0.047). Patients with abnormal arterial dilation had higher sICAM-1 values (p = 0.02) despite having smaller WHtR (p = 0.046). Conclusions These adolescents with obesity had high cIMT values. Insulin resistance was associated with sICAM-1. Endothelial dysfunction was positively correlated with sICAM-1. There is no consensus about what the best laboratorial approach to evaluate insulin resistance in adolescents is, and the cutoff values of each method are arbitrary. So, as we saw earlier, the association between anthropometric data (WHtR) and ultrasound findings could be useful to evaluate the CV risk of these adolescents with obesity, because of its practical, direct and low-cost value.
New neuromodulation techniques for treatment resistant depression

Abstract In the treatment of depression, when pharmacotherapy, psychotherapy and the oldest brain stimulation techniques are deadlocked, the emergence of new therapies is a necessary development. The field of neuromodulation is very broad and controversial. This article provides an overview of current progress in the technological advances in neuromodulation and neurostimulation treatments for treatment-resistant depression: magnetic seizure therapy; focal electrically administered seizure therapy; low field magnetic stimulation; transcranial pulsed electromagnetic fields; transcranial direct current stimulation; epidural cortical stimulation; trigeminal nerve stimulation; transcutaneous vagus nerve stimulation; transcranial focussed ultrasound; near infra-red transcranial radiation; closed loop stimulation. The role of new interventions is expanding, probably with more efficacy. Nowadays, still under experimentation, neuromodulation will probably revolutionise the field of neuroscience. At present, major efforts are still necessary before that these therapies are likely to become widespread. Key points There is a critical need for new therapies for treatment resistant depression. Newer therapies are expanding. In the future, these therapies, as an evidence-based adjunctive treatments, could offer a good therapeutic choice for the patients with a TRD. The current trend in the new neuromodulation therapies is to apply a personalised treatment. These news therapies can be complementary. That treatment approaches can provide clinically significant benefits.
Temperament in preadolescence is associated with weight and eating pathology in young adulthood

Abstract Objective Few longitudinal studies have investigated the role of temperament traits on weight and eating problems thus far. We investigated whether temperament in preadolescence influences body weight and the development of eating pathology in adolescence and young adulthood. Method This study used data from TRAILS (Tracking Adolescents' Individual Lives Survey), a Dutch community cohort study (N = 2,230) from preadolescence into adulthood. At age 11, the temperament dimensions negative affectivity and effortful control were measured with the Early Adolescent Temperament Questionnaire‐Revised. Body mass index (BMI) was measured at all assessment waves. At age 19, the prevalence of eating disorders was investigated by two‐stage screening including interviews by eating disorder experts. At age 22 and 26, the Eating Disorder Diagnostic Scale was used to assess the level of eating pathology. Results Higher negative affectivity in preadolescence was associated with higher BMI and eating pathology in young adulthood. Lower effortful control in preadolescence was found to be a risk factor for the development of obesity in young adulthood. No association was found between effortful control in preadolescence and eating pathology in later life. Discussion Both negative affectivity and effortful control play a role in the development of weight or eating problems during adolescence.
Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1

Understanding the sequence of events leading to cancer relies in large part upon identifying the tumour cell of origin. Glioblastoma is the most malignant brain cancer but the early stages of disease progression remain elusive. Neural lineages have been implicated as cells of origin, as have glia. Interestingly, high levels of the neural stem cell regulator TLX correlate with poor patient prognosis. Here we show that high levels of the Drosophila TLX homologue, Tailless, initiate tumourigenesis by reverting intermediate neural progenitors to a stem cell state. Strikingly, we could block tumour formation completely by re-expressing Asense (homologue of human ASCL1), which we show is a direct target of Tailless. Our results predict that expression of TLX and ASCL1 should be mutually exclusive in glioblastoma, which was verified in single-cell RNA-seq of human glioblastoma samples. Counteracting high TLX is a potential therapeutic strategy for suppressing tumours originating from intermediate progenitor cells.
Fluoride exposure alters Ca2+ signaling and mitochondrial function in enamel cells

The mechanisms by which excessive fluoride causes defects in tooth enamel mineralization are revealed. How too much fluoride derails dentition Excessive fluoride ingestion during childhood results in defective tooth enamel mineralization, which can lead to dental problems later in life. Aulestia et al. investigated the molecular mechanisms underlying fluorosis in enamel-forming cells isolated from rats and in an enamel cell line. Exposure of enamel cells to fluoride resulted in decreases in ER Ca2+ content and store-operated Ca2+ entry into the ER, reduced the expression of genes encoding ER stress–response proteins, and resulted in mitochondrial dysfunction. These effects were not seen in HEK-293 cells (which are derived from kidney epithelium). These data may explain how fluorosis affects Ca2+ homeostasis in enamel-forming cells and highlight cell type–specific stress responses. Fluoride ions are highly reactive, and their incorporation in forming dental enamel at low concentrations promotes mineralization. In contrast, excessive fluoride intake causes dental fluorosis, visually recognizable enamel defects that can increase the risk of caries. To investigate the molecular bases of dental fluorosis, we analyzed the effects of fluoride exposure in enamel cells to assess its impact on Ca2+ signaling. Primary enamel cells and an enamel cell line (LS8) exposed to fluoride showed decreased internal Ca2+ stores and store-operated Ca2+ entry (SOCE). RNA-sequencing analysis revealed changes in gene expression suggestive of endoplasmic reticulum (ER) stress in fluoride-treated LS8 cells. Fluoride exposure did not alter Ca2+ homeostasis or increase the expression of ER stress–associated genes in HEK-293 cells. In enamel cells, fluoride exposure affected the functioning of the ER-localized Ca2+ channel IP3R and the activity of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) pump during Ca2+ refilling of the ER. Fluoride negatively affected mitochondrial respiration, elicited mitochondrial membrane depolarization, and disrupted mitochondrial morphology. Together, these data provide a potential mechanism underlying dental fluorosis.
Not Seeing the Forest for the Trees: The Impact of Multiple Labelling on Consumer Choices for Olive Oil

Multiple quality labels that signal whether a particular food has special characteristics relating to geographical origin or production method have become standard within European food policy. The aim of this paper was to investigate how two of these labels in particular influence consumers’ food choices. We assessed consumers’ preferences for an extra virgin olive oil (EVOO) displaying EU quality labels and focus on whether they are complements or substitutes. In order to do so, we used a discrete choice experiment (DCE) to estimate main and two-way interactions effects with data from a self-administrated survey in a Spanish region. Results indicate that while consumers positively value both the Protected Designation of Origin (PDO) and the organic labels, the valuation for PDO is almost double that of the valuation of the organic label. Furthermore, the findings show that for a majority of consumers considered both labels substitutes, while a small group considered them complements. These findings can help producers identify an optimal labelling strategy to maximize returns on certification investments.
SLX4IP and telomere dynamics dictate breast cancer metastasis and therapeutic responsiveness

An unbiased genetic screen established SLX4IP as an essential driver of telomere maintenance mechanism identity, metastatic progression, and therapeutic response of breast cancers. Metastasis is the leading cause of breast cancer-related death and poses a substantial clinical burden owing to a paucity of targeted treatment options. The clinical manifestations of metastasis occur years-to-decades after initial diagnosis and treatment because disseminated tumor cells readily evade detection and resist therapy, ultimately giving rise to recurrent disease. Using an unbiased genetic screen, we identified SLX4-interacting protein (SLX4IP) as a regulator of metastatic recurrence and established its relationship in governing telomere maintenance mechanisms (TMMs). Inactivation of SLX4IP suppressed alternative lengthening of telomeres (ALT), coinciding with activation of telomerase. Importantly, TMM selection dramatically influenced metastatic progression and survival of patients with genetically distinct breast cancer subtypes. Notably, pharmacologic and genetic modulation of TMMs elicited telomere-dependent cell death and prevented disease recurrence by disseminated tumor cells. This study illuminates SLX4IP as a potential predictive biomarker for breast cancer progression and metastatic relapse. SLX4IP expression correlates with TMM identity, which also carries prognostic value and informs treatment selection, thereby revealing new inroads into combating metastatic breast cancers.
Older mothers produce more successful daughters

Significance There is substantial variation in aging patterns across individuals. Even more interesting is that these patterns may depend not only on an individual’s own age but also on that of its parents. However, little is known about such transgenerational effects of parent age, especially regarding offspring reproduction and senescence during adulthood. Capitalizing on a long-term study of free-living yellow-bellied marmots in which individuals’ fates were followed throughout their lives, we show that daughters born to older mothers had greater annual and lifetime reproductive success, but also senesced faster or tended to have shorter lifespans, depending on environmental harshness. Thus, parental age may have longer-lasting effects on offspring performance and should be considered in future studies of aging in wild populations. Annual reproductive success and senescence patterns vary substantially among individuals in the wild. However, it is still seldom considered that senescence may not only affect an individual but also affect age-specific reproductive success in its offspring, generating transgenerational reproductive senescence. We used long-term data from wild yellow-bellied marmots (Marmota flaviventer) living in two different elevational environments to quantify age-specific reproductive success of daughters born to mothers differing in age. Contrary to prediction, daughters born to older mothers had greater annual reproductive success on average than daughters born to younger mothers, and this translated into greater lifetime reproductive success. However, in the favorable lower elevation environment, daughters born to older mothers also had greater age-specific decreases in annual reproductive success. In the harsher higher elevation environment on the other hand, daughters born to older mothers tended to die before reaching ages at which such senescent decreases could be observed. Our study highlights the importance of incorporating environment-specific transgenerational parent age effects on adult offspring age-specific life-history traits to fully understand the substantial variation observed in senescence patterns in wild populations.
Phage liquid crystalline droplets form occlusive sheaths that encapsulate and protect infectious rod-shaped bacteria

Significance In this study, we investigate how phage molecules secreted by pathogenic Pseudomonas aeruginosa bacteria drive antibiotic tolerance by forming phase-separated liquid crystalline compartments around bacterial cells. This study spans across spatial scales, combining atomic structure determination using electron cryomicroscopy with cellular electron cryotomography, optical microscopy, and biochemical reconstitution. We show that encapsulation of rod-shaped bacteria by spindle-shaped liquid crystalline droplets made of phage molecules is a process profoundly influenced by shape and size complementarity. The opportunistic pathogen Pseudomonas aeruginosa is a major cause of antibiotic-tolerant infections in humans. P. aeruginosa evades antibiotics in bacterial biofilms by up-regulating expression of a symbiotic filamentous inoviral prophage, Pf4. We investigated the mechanism of phage-mediated antibiotic tolerance using biochemical reconstitution combined with structural biology and high-resolution cellular imaging. We resolved electron cryomicroscopy atomic structures of Pf4 with and without its linear single-stranded DNA genome, and studied Pf4 assembly into liquid crystalline droplets using optical microscopy and electron cryotomography. By biochemically replicating conditions necessary for antibiotic protection, we found that phage liquid crystalline droplets form phase-separated occlusive compartments around rod-shaped bacteria leading to increased bacterial survival. Encapsulation by these compartments was observed even when inanimate colloidal rods were used to mimic rod-shaped bacteria, suggesting that shape and size complementarity profoundly influences the process. Filamentous inoviruses are pervasive across prokaryotes, and in particular, several Gram-negative bacterial pathogens including Neisseria meningitidis, Vibrio cholerae, and Salmonella enterica harbor these prophages. We propose that biophysical occlusion mediated by secreted filamentous molecules such as Pf4 may be a general strategy of bacterial survival in harsh environments.
Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre

Abstract Systemic amyloidosis is a serious disease which is caused when normal circulating proteins misfold and aggregate extracellularly as insoluble fibrillary deposits throughout the body. This commonly results in cardiac, renal and neurological damage. The tissue target, progression and outcome of the disease depends on the type of protein forming the fibril deposit, and its correct identification is central to determining therapy. Proteomics is now used routinely in our centre to type amyloid; over the past 7 years we have examined over 2000 clinical samples. Proteomics results are linked directly to our patient database using a simple algorithm to automatically highlight the most likely amyloidogenic protein. Whilst the approach has proved very successful, we have encountered a number of challenges, including poor sample recovery, limited enzymatic digestion, the presence of multiple amyloidogenic proteins and the identification of pathogenic variants. Our proteomics procedures and approaches to resolving difficult issues are outlined.
A Detailed Review Study on Potential Effects of Microplastics and Additives of Concern on Human Health

The distribution and abundance of microplastics into the world are so extensive that many scientists use them as key indicators of the recent and contemporary period defining a new historical epoch: The Plasticene. However, the implications of microplastics are not yet thoroughly understood. There is considerable complexity involved to understand their impact due to different physical–chemical properties that make microplastics multifaceted stressors. If, on the one hand, microplastics carry toxic chemicals in the ecosystems, thus serving as vectors of transport, they are themselves, on the other hand, a cocktail of hazardous chemicals that are added voluntarily during their production as additives to increase polymer properties and prolong their life. To date, there is a considerable lack of knowledge on the major additives of concern that are used in the plastic industry, on their fate once microplastics dispose into the environment, and on their consequent effects on human health when associated with micro and nanoplastics. The present study emphasizes the most toxic and dangerous chemical substances that are contained in all plastic products to describe the effects and implications of these hazardous chemicals on human health, providing a detailed overview of studies that have investigated their abundance on microplastics. In the present work, we conducted a capillary review of the literature on micro and nanoplastic exposure pathways and their potential risk to human health to summarize current knowledge with the intention of better focus future research in this area and fill knowledge gaps.
Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding

Many bacteria use type IV secretion systems (T4SSs) to translocate proteins and nucleic acids into target cells, which promotes DNA transfer and host infection. The Dot/Icm T4SS in Legionella pneumophila is a multiprotein nanomachine that is known to translocate over 300 different protein effectors into eukaryotic host cells. Here, advanced cryoelectron tomography and subtomogram analysis were used to visualize the Dot/Icm machine assembly and distribution in a single L. pneumophila cell. Extensive classification and averaging revealed five distinct intermediates of the Dot/Icm machine at high resolution. Comparative analysis of the Dot/Icm machine and subassemblies derived from wild-type cells and several mutants provided a structural basis for understanding mechanisms that underlie the assembly and activation of the Dot/Icm machine. ABSTRACT Type IV secretion systems (T4SSs) are sophisticated nanomachines used by many bacterial pathogens to translocate protein and DNA substrates across a host cell membrane. Although T4SSs have important roles in promoting bacterial infections, little is known about the biogenesis of the apparatus and the mechanism of substrate transfer. Here, high-throughput cryoelectron tomography (cryo-ET) was used to visualize Legionella pneumophila T4SSs (also known as Dot/Icm secretion machines) in both the whole-cell context and at the cell pole. These data revealed the distribution patterns of individual Dot/Icm machines in the bacterial cell and identified five distinct subassembled intermediates. High-resolution in situ structures of the Dot/Icm machine derived from subtomogram averaging revealed that docking of the cytoplasmic DotB (VirB11-related) ATPase complex onto the DotO (VirB4-related) ATPase complex promotes a conformational change in the secretion system that results in the opening of a channel in the bacterial inner membrane. A model is presented for how the Dot/Icm apparatus is assembled and for how this machine may initiate the transport of cytoplasmic substrates across the inner membrane. IMPORTANCE Many bacteria use type IV secretion systems (T4SSs) to translocate proteins and nucleic acids into target cells, which promotes DNA transfer and host infection. The Dot/Icm T4SS in Legionella pneumophila is a multiprotein nanomachine that is known to translocate over 300 different protein effectors into eukaryotic host cells. Here, advanced cryoelectron tomography and subtomogram analysis were used to visualize the Dot/Icm machine assembly and distribution in a single L. pneumophila cell. Extensive classification and averaging revealed five distinct intermediates of the Dot/Icm machine at high resolution. Comparative analysis of the Dot/Icm machine and subassemblies derived from wild-type cells and several mutants provided a structural basis for understanding mechanisms that underlie the assembly and activation of the Dot/Icm machine.