Alcohol Use Disorder is Associated with Upregulation of MicroRNA-34a and MicroRNA-34c in Hippocampal Postmortem Tissue.

BACKGROUND: To investigate epigenetic mechanisms potentially involved in the cognitive decline associated with chronic alcohol intake, we evaluated the expressions of three micro-RNAs (miR-34a, -34b, and -34c) highly expressed in the hippocampus and involved in neuronal physiology and pathology. MiR-34a participates in functioning and survival of mature neurons; miR-34b is associated with Alzheimer-like disorders; and miR-34c is implicated in the memory impairment of Alzheimer disease in rodents and humans. METHODS: A total of 69 cases were selected from the Biobank for Aging Studies and categorized according to the absence (n = 50) or presence (n = 19) of alcohol use disorder (AUD). Cases presenting with neuropathological diagnoses of dementias were excluded. Total RNA was extracted from hippocampal paraffinized slices, complementary DNA was synthesized from miRs, and RT-qPCR was performed with TaqMan® assays. RESULTS: Higher expressions of miR-34a and miR-34c, but not of miR-34b, were found in the group with AUD in comparison with the group without AUD after adjustment for potential confounders (age, sex, body mass index, presence of hypertension, diabetes mellitus, smoking, and physical inactivity). CONCLUSIONS: Hippocampal upregulation of miR-34a and miR-34c may be involved in the cognitive decline associated with chronic alcohol consumption.

Beta-1,3-glucanase inhibitors in Brazilian brown seaweed.

Beta-1,3-glucanases are enzymes that hydrolyze beta-1,3-glucans, and they are essential for the metabolism of seaweed, plants and fungi. These enzymes also participate in the digestion of herbivore and fungivore animals. Because of the importance of these enzymes in insects, beta-1,3-glucanase inhibitors may be used for the development of new control strategies against agricultural pests and disease vectors. Beta-1,3-glucanase inhibitors have been described in the brown seaweed Laminaria cichorioides, but were never recorded in Brazilian seaweed species. We evaluated the presence of beta-1,3-glucanase inhibitors in samples of Padina gymnospora, Dictyota sp., Colpomenia sinuosa, and Lobophora sp., collected in Arraial d'Ajuda (Bahia). Ethanolic or buffer extracts were used in inhibition tests against the beta-1,3-glucanase of Trichoderma sp. Extracts in buffer showed no inhibition, but ethanolic extracts from all species showed different extents of inhibition. Samples from Dictyota sp. and P. gymnospora showed inhibitions above 75% (absolute ethanol) or 50% (ethanol 50%). In summary, extraction with absolute ethanol resulted in better inhibitions, and P. gymnospora showed the higher inhibitions. Brazilian seaweed may be good sources of beta-1,3-glucanase inhibitors for biochemical and physiological studies of these enzymes. Besides that, these molecules show potential for the development of new biotechnological tools for insect control.

Influence of Serratia marcescens and Rhodococcus rhodnii on the Humoral Immunity of Rhodnius prolixus.

Chagas disease is a human infectious disease caused by Trypanosoma cruzi and can be transmitted by triatomine vectors, such as Rhodnius prolixus. One limiting factor for T. cruzi development is the composition of the bacterial gut microbiota in the triatomine. Herein, we analyzed the humoral immune responses of R. prolixus nymphs treated with antibiotics and subsequently recolonized with either Serratia marcescens or Rhodococcus rhodnii. The treatment with antibiotics reduced the bacterial load in the digestive tract, and the recolonization with each bacterium was successfully detected seven days after treatment. The antibiotic-treated insects, recolonized with S. marcescens, presented reduced antibacterial activity against Staphylococcus aureus and phenoloxidase activity in hemolymph, and lower nitric oxide synthase (NOS) and higher defensin C gene (DefC) gene expression in the fat body. These insects also presented a higher expression of DefC, lower prolixicin (Prol), and lower NOS levels in the anterior midgut. However, the antibiotic-treated insects recolonized with R. rhodnii had increased antibacterial activity against Escherichia coli and lower activity against S. aureus, higher phenoloxidase activity in hemolymph, and lower NOS expression in the fat body. In the anterior midgut, these insects presented higher NOS, defensin A (DefA) and DefC expression, and lower Prol expression. The R. prolixus immune modulation by these two bacteria was observed not only in the midgut, but also systemically in the fat body, and may be crucial for the development and transmission of the parasites Trypanosoma cruzi and Trypanosoma rangeli.

Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes.

BACKGROUND AND AIMS: Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. METHODS AND RESULTS: Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4. CONCLUSION: In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.

Violence detection explanation via semantic roles embeddings.

BACKGROUND: Emergency room reports pose specific challenges to natural language processing techniques. In this setting, violence episodes on women, elderly and children are often under-reported. Categorizing textual descriptions as containing violence-related injuries (V) vs. non-violence-related injuries (NV) is thus a relevant task to the ends of devising alerting mechanisms to track (and prevent) violence episodes. METHODS: We present VIDES (so dubbed after VIOLENCE DETECTION SYSTEM), a system to detect episodes of violence from narrative texts in emergency room reports. It employs a deep neural network for categorizing textual ER reports data, and complements such output by making explicit which elements corroborate the interpretation of the record as reporting about violence-related injuries. To these ends we designed a novel hybrid technique for filling semantic frames that employs distributed representations of terms herein, along with syntactic and semantic information. The system has been validated on real data annotated with two sorts of information: about the presence vs. absence of violence-related injuries, and about some semantic roles that can be interpreted as major cues for violent episodes, such as the agent that committed violence, the victim, the body district involved, etc.. The employed dataset contains over 150K records annotated with class (V,NV) information, and 200 records with finer-grained information on the aforementioned semantic roles. RESULTS: We used data coming from an Italian branch of the EU-Injury Database (EU-IDB) project, compiled by hospital staff. Categorization figures approach full precision and recall for negative cases and.97 precision and.94 recall on positive cases. As regards as the recognition of semantic roles, we recorded an accuracy varying from.28 to.90 according to the semantic roles involved. Moreover, the system allowed unveiling annotation errors committed by hospital staff. CONCLUSIONS: Explaining systems' results, so to make their output more comprehensible and convincing, is today necessary for AI systems. Our proposal is to combine distributed and symbolic (frame-like) representations as a possible answer to such pressing request for interpretability. Although presently focused on the medical domain, the proposed methodology is general and, in principle, it can be extended to further application areas and categorization tasks.

Public space, socio-environmental responsibility and citizenship: a case study on a Brazilian borough.

Some researchers point out the decline in contemporary cities of the use of public spaces, whether free or restricted access. In this sense, the present essay proposes a reflection on a "public sphere of organized presence", according to Habermas classification, as a rescue of the importance of this space for the exercise of citizenship and social-environmental responsibility. The reflection was based on the results obtained from a study in the district of Riacho Grande, São Bernardo do Campo, São Paulo, Brazil, in which the environmental perception of the participants of the meetings about the region was known by documentary analysis, direct observation and interviews with questionnaires. It was possible to verify that this public space can facilitate a greater integration between the public administrators and citizens, helping even in the defense to the environment.

Propargylglycine decreases neuro-immune interaction inducing pain response in temporomandibular joint inflammation model.

The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1ß in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.

An outbreak of poisoning by Kalanchoe blossfeldiana in cattle in northeastern Brazil.

In the world, Kalanchoe species are primarily ornamentals and houseplants, but some have escaped cultivation and can be found in the field. In Latin America, there are no reports of spontaneous poisoning by Kalanchoe species in animals. This study aimed to describe the epidemiological, clinical, and pathological aspects of an outbreak of poisoning by Kalanchoe blossfeldiana in cattle in the semiarid region of Pernambuco, Brazil. Epidemiological and clinical data were obtained from the owner and veterinarian during technical visits. Prunings of this plant were disposed of in a pasture with a shortness of forage. Seventeen cattle had clinical signs, and thirteen died 4-5 days after the first clinical signs were observed. Clinical signs and gross and histological lesions include gastrointestinal, cardiovascular, and neuromuscular disorders. Kalanchoe spp. contain cardiotoxic glycosides, and the clinical signs and lesions in cattle of this outbreak were consistent with poisoning by plants that contain these toxins.

A sea urchin in vivo model to evaluate Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is an evolutionarily conserved cellular program, which is a prerequisite for the metastatic cascade in carcinoma progression. Here, we evaluate the EMT process using the sea urchin Paracentrotus lividus embryo. In sea urchin embryos, the earliest EMT event is related to the acquisition of a mesenchymal phenotype by the spiculogenetic primary mesenchyme cells (PMCs) and their migration into the blastocoel. We investigated the effect of inhibiting the epidermal growth factor (EGF) signaling pathway on this process, and we observed that mesenchyme cell differentiation was blocked. In order to extend and validate our studies, we investigated the migratory capability and the level of potential epidermal growth factor receptor (EGFr) targets in a breast cancer cell line after EGF modulation. Altogether, our data highlight the sensitivity of the sea urchin embryo to anti-EMT drugs and pinpoint the sea urchin embryo as a valuable in vivo model system for studying EMT and the screening of anti-EMT candidates.

Impact of Rhg1 copy number, type, and interaction with Rhg4 on resistance to Heterodera glycines in soybean.

KEY MESSAGE: Evaluations of soybean populations showed that both Rhg1 copy number and type were important in determining soybean cyst nematode resistance with higher copy number within Rhg1 type conferring greater resistance. Rhg1 and Rhg4 are important loci conferring resistance to soybean cyst nematode (SCN; Heterodera glycines). Alleles at Rhg1 have been shown to vary for copy number and type and the importance of this variation in conferring resistance is not well defined. The repeat number ranges from one to 10 and there are three variant repeat sequence types [plant introduction (PI) 88788-'Fayette' type (F), 'Peking' type (P) and Williams 82 type (W)] across diverse soybean germplasm. We developed populations segregating for Rhg1 copy number and type and Rhg4 allele type to investigate the effect of these factors and their interaction on SCN resistance. F2 plants from each cross were evaluated for the segregation of Rhg1 and Rhg4 alleles and for SCN reproduction after infesting plants with HG type 2.5.7 and HG type 7 populations. Within repeat types, an increase in repeat number was associated with greater resistance. The P type Rhg1 showed an advantage over F + W type for SCN population HG type 2.5.7 but this was not observed for SCN HG type 7. While plants with P type Rhg1 required Rhg4 to achieve full resistance, Rhg4 did not increase resistance in the background of F + W type Rhg1 repeat. This study demonstrates the importance of both Rhg1 copy number and type in determining resistance and can assist soybean breeders in determining what alleles would best fit their breeding goals.

Assessing the formation of weak sodium complexes with negatively charged ligands.

The stability of sodium complexes with poly-carboxylic and polyamino-carboxylic acids is investigated with ion-selective electrode-Na(+) potentiometry, working at strictly constant ionic strength. It is observed that the formation constants of the Na(+) complexes with monoligand stoichiometry (ML) increase with the number of charges on the ligand. For example, in poly-carboxylic acids this dependency is linear and is well captured by an experimental equation. A different behaviour is observed for the poly-amino carboxylic acids, which show higher complexation capabilities reaching a plateau of the binding energy past a specific ligand size. The experimental results are discussed qualitatively using ab initio calculations based on DFT B3LYP, and the principal electronic characteristics of the ligands under investigation are identified. As a result of the flexibility imparted by the long chains of polyamino-carboxylic ligands, both experimental and theoretical models demonstrate that nitrogen atoms in proximity of Na(+) ions can participate in the metal coordination, thus providing further stabilization for the complexes. Moreover, by increasing the ligand size the stabilization gained in terms of ΔG reached a plateau for EDTA, in agreement with experimental observations.

Beyond flood hazard. Mapping the loss probability of pedestrians to improve risk estimation and communication.

The effective communication of flood hazard and risk is a necessary step to foster preparedness and resilience, hence reducing the detrimental impacts of flooding events. Classical flood maps, which show flow depth and velocity, have often proved to be incomprehensible to the majority of people. Some recent studies used color maps to convey the spatial distribution of diverse hazard indexes that, accounting for both water depth and velocity, are intended to communicate the hazard degree in a more intelligible way. It is first shown that these hazard indexes have some inherent limitations, as for example the implicit assumption of a linear relationship between flood hazard and flow velocity. As an alternative, we propose to map the loss probability (LP) of pedestrians exposed to floodwaters, which is a physics-based and data-consistent risk index accounting for both hazard and vulnerability. LP can be easily computed and allows for a sounder estimation and a more effective communication of flood risk to the general public.

All You Need Is Music: Supporting Medical Students' Emotional Development With a Music-Based Pedagogy.

PROBLEM: Although the practice of medicine is often emotionally challenging, medical curricula seldom systematically address the emotional development of medical students. To fill this gap, the authors developed and evaluated an innovative pedagogical activity based on music to nurture medical students' emotional development. The authors believe that the metaphoric nature of music offers an efficient venue for exploring emotion perception, expression, and regulation. APPROACH: The pedagogical activity Emotions in Medicine was carried out throughout 2020 and 2021 and consisted of 4 encounters to explore: (1) emotion perception, (2) emotion expression, (3) emotion regulation, and (4) the role of emotions in medical practice. During all encounters, the authors used music to evoke students' emotions and focused the discussions on the relevance of emotions for meaningful medical practice. Emotional intelligence before and after the workshop was tested using the Schutte Self-Report Emotional Intelligence Test (SSEIT), a validated psychometric scale. OUTCOMES: The workshop facilitated emotional connection among students and created a safe space to explore the role of emotions in medical practice. The mean total pretest SSEIT score was 110 (SD = 14.2); it increased to 116.8 (SD = 16.1) in the posttest ( P < .001). This increase was true across its 4 dimensions: (1) perception of emotions, (2) management of own emotions (3) management of others' emotions, and (4) use of emotions. NEXT STEPS: Music can be an active tool to explore the role of emotions in medical practice. It fosters students' capacity to identify and reflect on emotions while exploring their role in patient care. Further (qualitative) research is needed to explore the mechanisms by which music facilitates learning emotion perception, expression, and regulation.

Alix protein is substrate of Ozz-E3 ligase and modulates actin remodeling in skeletal muscle.

Alix/AIP1 is a multifunctional adaptor protein that participates in basic cellular processes, including membrane trafficking and actin cytoskeleton assembly, by binding selectively to a variety of partner proteins. However, the mechanisms regulating Alix turnover, subcellular distribution, and function in muscle cells are unknown. We now report that Alix is expressed in skeletal muscle throughout myogenic differentiation. In myotubes, a specific pool of Alix colocalizes with Ozz, the substrate-binding component of the muscle-specific ubiquitin ligase complex Ozz-E3. We found that interaction of the two endogenous proteins in the differentiated muscle fibers changes Alix conformation and promotes its ubiquitination. This in turn regulates the levels of the protein in specific subcompartments, in particular the one containing the actin polymerization factor cortactin. In Ozz(-/-) myotubes, the levels of filamentous (F)-actin is perturbed, and Alix accumulates in large puncta positive for cortactin. In line with this observation, we show that the knockdown of Alix expression in C2C12 muscle cells affects the amount and distribution of F-actin, which consequently leads to changes in cell morphology, impaired formation of sarcolemmal protrusions, and defective cell motility. These findings suggest that the Ozz-E3 ligase regulates Alix at sites where the actin cytoskeleton undergoes remodeling.

Identification and characterization of PlAlix, the Alix homologue from the Mediterranean sea urchin Paracentrotus lividus.

The sea urchin provides a relatively simple and tractable system for analyzing the early stages of embryo development. Here, we use the sea urchin species, Paracentrotus lividus, to investigate the role of Alix in key stages of embryogenesis, namely the egg fertilization and the first cleavage division. Alix is a multifunctional protein involved in different cellular processes including endocytic membrane trafficking, filamentous (F)-actin remodeling, and cytokinesis. Alix homologues have been identified in different metazoans; in these organisms, Alix is involved in oogenesis and in determination/differentiation events during embryo development. Herein, we describe the identification of the sea urchin homologue of Alix, PlAlix. The deduced amino acid sequence shows that Alix is highly conserved in sea urchins. Accordingly, we detect the PlAlix protein cross-reacting with monoclonal Alix antibodies in extracts from P. lividus, at different developmental stages. Focusing on the role of PlAlix during early embryogenesis we found that PlAlix is a maternal protein that is expressed at increasingly higher levels from fertilization to the 2-cell stage embryo. In sea urchin eggs, PlAlix localizes throughout the cytoplasm with a punctuated pattern and, soon after fertilization, accumulates in larger puncta in the cytosol, and in microvilli-like protrusions. Together our data show that PlAlix is structurally conserved from sea urchin to mammals and may open new lines of inquiry into the role of Alix during the early stages of embryo development.

Optical penalization with contact lenses for children with unilateral aphakia: an alternative to patching.

OBJECTIVES: To evaluate the efficacy of high-plus contact lenses as a form of optical penalization in children with unilateral aphakia. METHODS: An internal database review was used to identify 10 patients with unilateral aphakia after congenital cataract extraction who underwent treatment with a high-plus contact lens in their sound eye after a period of failure with traditional occlusive patching. The details surrounding the switch from patching to optical penalization with contact lens were recorded along with related changes in compliance and any demonstrable effect suggestive of an improvement in visual ability. RESULTS: After an average 15-month delay between the end of occlusive patching and the start of optical penalization with high-plus contact lenses, 6 of 10 patients achieved good compliance with high-plus contact lens therapy and most families were able to successfully administer the lenses according to the prescribed regimen. Three patients showed evidence of a fixation switch to the contact-lens-corrected aphakic eye during optical penalization of the sound eye. No safety issues were reported. CONCLUSION: Using a high-plus contact lens to optically penalize the sound eye of a unilaterally aphakic child seems to have the potential as an effective alternative to occlusive patching for those with compliance issues. A prospective study is warranted to assess long-term safety, and above all, efficacy in visual outcome.

Semantic Coherence Dataset: Speech transcripts.

The Semantic Coherence Dataset has been designed to experiment with semantic coherence metrics. More specifically, the dataset has been built to the ends of testing whether probabilistic measures, such as perplexity, provide stable scores to analyze spoken language. Perplexity, which was originally conceived as an information-theoretic measure to assess the probabilistic inference properties of language models, has recently been proven to be an appropriate tool to categorize speech transcripts based on semantic coherence accounts. More specifically, perplexity has been successfully employed to discriminate subjects suffering from Alzheimer Disease and healthy controls. Collected data include speech transcripts, intended to investigate semantic coherence at different levels: data are thus arranged into two classes, to investigate intra-subject semantic coherence, and inter-subject semantic coherence. In the former case transcripts from a single speaker can be employed to train and test language models and to explore whether the perplexity metric provides stable scores in assessing talks from that speaker, while allowing to distinguish between two different forms of speech, political rallies and interviews. In the latter case, models can be trained by employing transcripts from a given speaker, and then used to measure how stable the perplexity metric is when computed using the model from that user and transcripts from different users. Transcripts were extracted from talks lasting almost 13 hours (overall 12:45:17 and 120,326 tokens) for the former class; and almost 30 hours (29:47:34 and 252,270 tokens) for the latter one. Data herein can be reused to perform analyses on measures built on top of language models, and more in general on measures that are aimed at exploring the linguistic features of text documents.

A Simple, Semi-Quantitative Acyl Biotin Exchange-Based Method to Detect Protein S-Palmitoylation Levels.

Protein S-palmitoylation is a reversible post-translational lipidation in which palmitic acid (16:0) is added to protein cysteine residue by a covalent thioester bond. This modification plays an active role in membrane targeting of soluble proteins, protein-protein interaction, protein trafficking, and subcellular localization. Moreover, palmitoylation is related to different diseases, such as neurodegenerative pathologies, cancer, and developmental defects. The aim of this research is to provide a straightforward and sensitive procedure to detect protein palmitoylation based on Acyl Biotin Exchange (ABE) chemistry. Our protocol setup consists of co-immunoprecipitation of native proteins (i.e., CD63), followed by the direct detection of palmitoylation on proteins immobilized on polyvinylidene difluoride (PVDF) membranes. With respect to the conventional ABE-based protocol, we optimized and validated a rapid semi-quantitative assay that is shown to be significantly more sensitive and highly reproducible.

Effect of tissue fixation on the optical properties of structural components assessed by non-linear microscopy imaging.

Fixation methods such as formalin are commonly used for the preservation of tissue with the aim of keeping their structure as close as possible to the native condition. However, fixatives chemically interact with tissue molecules, such as collagen in the extracellular matrix (ECM) or myosin, and may thus modify their structure. Taking advantage of the second- and third-harmonic generation (SHG and THG) emission capabilities of such components, we used nonlinear two-photon microscopy (NL2PM) to evaluate the effect that preservation methods, such as chemical fixatives, have on the nonlinear capabilities of protein components within mouse tissues. Our results show that depending on the preservation technique used, the nonlinear capabilities of collagen, lipid droplets and myosin microarchitecture are strongly affected. Parameters of collagen fibers, such as density and branch points, especially in collagen-sparse regions, e.g., in kidneys, were found to be altered upon formalin fixation. Moreover, cryo-freezing drastically reduced SHG signals from myosin. Our findings provide valuable information to select the best tissue fixation method for visualization and quantification of structural proteins, such as collagen and myosin by advanced NL2PM imaging techniques. This may advance the interpretation of the role these proteins play in disease.