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Sclerotherapy is the treatment of choice for telangiectasias and reticular veins. The most common side effects of this procedure are hyperpigmentation and matting, which are feared owing to their aesthetic damage and difficulty of treatment. Combined treatments with laser and hypertonic glucose sclerotherapy have been described with excellent results, but limited to treatment of veins of ≤2 mm in diameter. Cryo laser after foam sclerotherapy is a procedure to treat reticular veins in the lower extremities that utilizes first foam sclerotherapy with polidocanol than immediately followed by transdermal Nd:YAG 1064 laser treatment and we can treat veins ≤5 mm. This report presents a successful case of varicose vein treatment using combined transdermal laser and sclerotherapy with foam sclerotherapy with polidocanol to treat veins >2.5 mm in diameter.

ABSTRACTGonorrhea, caused by the bacterium Neisseria gonorrhoeae (Gc), is characterized by neutrophilic influx to infection sites. Gc has developed mechanisms to resist killing by neutrophils that include modifications to its surface lipooligosaccharide (LOS). One such LOS modification is sialylation: Gc sialylates its terminal LOS sugars with cytidine-5′-monophosphate-N-acetylneuraminic acid, which is scavenged from the host using LOS sialyltransferase (Lst) since Gc cannot make its sialic acid. Sialylation enables sensitive strains of Gc to resist complement-mediated killing in a serum-dependent manner. However, little is known about the contribution of sialylation to complement-independent, direct Gc-neutrophil interactions. In the absence of complement, we found sialylated Gc expressing opacity-associated (Opa) proteins decreased the oxidative burst and granule exocytosis from primary human neutrophils. In addition, sialylated Opa+ Gc survived better than vehicle treated or Δlst Gc when challenged with neutrophils. However, Gc sialylation did not significantly affect Opa-dependent association with or internalization of Gc by neutrophils. Previous studies have implicated sialic acid-binding immunoglobulin-type lectins (Siglecs) in modulating neutrophil interactions with sialylated Gc. Blocking neutrophil Siglecs with antibodies that bind to their extracellular domains eliminated the ability of sialylated Opa+ Gc to suppress the oxidative burst and resist neutrophil killing. These findings highlight a new role for sialylation in Gc evasion of human innate immunity, with implications for the development of vaccines and therapeutics for gonorrhea.IMPORTANCENeisseria gonorrhoeae, the bacterium that causes gonorrhea, is an urgent global health concern due to increasing infection rates, widespread antibiotic resistance, and its ability to thwart protective immune responses. The mechanisms by which Gc subverts protective immune responses remain poorly characterized. One way N. gonorrhoeae evades human immunity is by adding sialic acid that is scavenged from the host onto its lipooligosaccharide, using the sialyltransferase Lst. Here, we found that sialylation enhances N. gonorrhoeae survival from neutrophil assault and inhibits neutrophil activation, independently of the complement system. Our results implicate bacterial binding of sialic acid-binding lectins (Siglecs) on the neutrophil surface, which dampens neutrophil antimicrobial responses. This work identifies a new role for sialylation in protecting N. gonorrhoeae from cellular innate immunity, which can be targeted to enhance the human immune response in gonorrhea.

Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan side-chains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics, altered spatial localization of new peptidoglycan and increased NOD-1 expression in macrophages. In cell culture experiments, training of a human monocyte cell line with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, which is expected to unmask the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.

Most modern large-scale multi-agent systems operate by taking actions based on local data and cooperate by exchanging information over communication networks. Due to the abundance of sensors, each agent is capable of generating more data than what could be supported by communication channels in near real-time. Thus, not every piece of information can be transmitted perfectly over the network. Such communication constraints lead to a large number of challenging research problems, some of which have been solved, and many more that remain open. The focus of this paper is to present a comprehensive treatment of this new class of fundamental problems in information dissemination over networks, which is based on the notion of extremum information. The unifying theme herein is that the strategic communication, i.e., when the agents decide on what to transmit based on their observed data (or state), leads to the optimality of extremum (or outlier) information. In other words, when a random information source deviates from the average by a certain amount, that realization should be prioritized for transmission. This creates a natural ranking of the data points based on their magnitude such that if an agent has access to more than one piece of information, the ones that display the largest deviation from the average are transmitted and the rest is discarded. We show that the problem of finding the top-K largest measurements over a network can be cast and efficiently implemented as a distributed inference problem. Curiously, the same principle holds for the framework of distributed optimization, leading to a class of state-dependent protocols known as max-dissent. While still a heuristic, max-dissent can considerably accelerate the convergence to an optimal solution in distributed convex optimization. We provide open problems and present several directions for future work including questions related to cyber-security and robustness of such networks as well as new architectures for distributed learning and optimization.

Cytotoxic T lymphocytes are the primary effector immune cells responsible for protection against cancer, as they target peptide neoantigens presented through the major histocompatibility complex (MHC) on cancer cells, leading to cell death. Targeting peptide-MHC (pMHC) complex offers a promising strategy for immunotherapy due to their specificity and effectiveness against cancer. In this work, we exploit the acidic tumor micro-environment to selectively deliver antigenic peptides to cancer using pH(low) insertion peptides (pHLIP). We demonstrated the delivery of MHC binding peptides directly to the cytoplasm of melanoma cells resulted in the presentation of antigenic peptides on MHC, and activation of T cells. This work highlights the potential of pHLIP as a vehicle for the targeted delivery of antigenic peptides and its presentation via MHC-bound complexes on cancer cell surface for activation of T cells with implications for enhancing anti-cancer immunotherapy.

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Dragonflies are insects that act as predators and prey, both in freshwater and associated terrestrial ecosystems, which makes the understanding of trophic relationships established by these insects important. In this sense, the present study aimed to report the predation of Odonata by Araneae in areas of seasonal semideciduous forest, phytophysiognomy of the Atlantic Forest at the Iguaçu National Park (PARNA Iguaçu), and in the Bela Vista Biological Refuge (RBBV). The records occurred at random in 2021 from December 13 to 21, and in 2022 from January 4 to April 22. Five individuals of three species and two morphospecies of Odonata preyed upon by three morphospecies of spiders were recorded. Predation of Odonata by spiders seems to be frequent in different ecosystems, but further studies are required to understand the impact of this predation on the size of dragonfly communities in the Brazilian Atlantic Forest biome.

Social wasps can feed on a wide variety of animal and plant resources, however, there is little information available in the literature on the use of extra-floral nectaries (EFNs) as a food resource. In this regard, the present study aims to record the occurrence of visitation by social wasps in NEFs of Sapium obovatum Klotzsch ex Müll.Arg. in southeastern Brazil. The record took place on January 1 and 11, 2023, in a swampy area of ​​a pasture in the urban area of ​​the municipality of Ritápolis, Minas Gerais. Three species of social wasps were recorded: Polybia fastidiosuscula Saussure, 1854, Polybia scutellaris (White, 1841) and Protopolybia sedula (Saussure, 1854) visiting the NEFs of Sapium obovatum. Our results point to a generalist nature of foraging by social wasps, however further studies are suggested to understand this interaction.

IntroductionMycobacteria assemble a complex cell wall with cross-linked peptidoglycan (PG) which plays an essential role in maintenance of cell wall integrity and tolerance to osmotic pressure. We previously demonstrated that various hydrolytic enzymes are required to remodel PG during essential processes such as cell elongation and septal hydrolysis. Here, we explore the chemistry associated with PG cross-linking, specifically the requirement for amidation of the D-glutamate residue found in PG precursors.MethodsSynthetic fluorescent probes were used to assess PG remodelling dynamics in live bacteria. Fluorescence microscopy was used to assess protein localization in live bacteria and CRISPR-interference was used to construct targeted gene knockdown strains. Time-lapse microscopy was used to assess bacterial growth. Western blotting was used to assess protein phosphorylation.Results and discussionIn Mycobacterium smegmatis, we confirmed the essentiality for D-glutamate amidation in PG biosynthesis by labelling cells with synthetic fluorescent PG probes carrying amidation modifications. We also used CRISPRi targeted knockdown of genes encoding the MurT-GatD complex, previously implicated in D-glutamate amidation, and demonstrated that these genes are essential for mycobacterial growth. We show that MurT-rseGFP co-localizes with mRFP-GatD at the cell poles and septum, which are the sites of cell wall synthesis in mycobacteria. Furthermore, time-lapse microscopic analysis of MurT-rseGFP localization, in fluorescent D-amino acid (FDAA)-labelled mycobacterial cells during growth, demonstrated co-localization with maturing PG, suggestive of a role for PG amidation during PG remodelling and repair. Depletion of MurT and GatD caused reduced PG cross-linking and increased sensitivity to lysozyme and β-lactam antibiotics. Cell growth inhibition was found to be the result of a shutdown of PG biosynthesis mediated by the serine/threonine protein kinase B (PknB) which senses uncross-linked PG. Collectively, these data demonstrate the essentiality of D-glutamate amidation in mycobacterial PG precursors and highlight the MurT-GatD complex as a novel drug target.

Objective: Population-level monitoring of body composition requires accurate, biologically-relevant, yet feasible methods for estimating percent body fat (%BF). The aim of this study was to develop and cross-validate an equation for %BF from Body Mass Index (BMI), age, and sex among children with intellectual disability (ID). This study further aimed to examine the performance of an existing BMI-based equation (Deurenberg equation) for %BF in children with ID. Method: Participants were 107 children (63 boys; aged 6-15 years) with ID randomly allocated to development (n = 81) and cross-validation (n = 26) samples. Dual-Energy X-Ray Absorptiometry provided the criterion %BF. Results: The model including BMI, age, and sex (0 = male; 1 = female) had a significant goodness-of-fit in determining %BF (p

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

Flat sheet membranes offer many advantages over other membrane configurations, (e.g. ease of maintenance and low pressure drops) that make them a strong candidate for post-combustion carbon capture. A performance model for a stacked flat sheet membrane module is reported in this work. The model is based on the reported specifications for the Gen 2 Polaris™ module developed by Membrane Technology & Research (MTR) and predicts performance based on solution of the governing momentum and mass balance equations. The model accounts for variability in flow channel heights within the module that can arise during module manufacturing. The model is first verified against similar membrane models. Simulations are then performed over a wide range of conditions to demonstrate how much performance declines as channel height variability increases. As per the performance metrics, the dimensionless feed flow rate processed per unit membrane area (f-curve) shows the greatest decline. The changes in performance are comparable to those that occur with hollow fiber membrane modules that possess similar fiber size variations. Together, the results of this study indicate that flow channel height variation in flat sheet membrane modules can hurt CO2 separation performance, but the impact is minor except at low CO2 retentate compositions with large channel height variation (e.g. a 10% decline in stage cut performance for a mixture with 94% CO2 in the permeate stream and 30% channel height variation). However, high variation has a significant impact on overall membrane area with a 30% increase at 30% variation.

Abstract Bacteriophages are highly abundant molecular machines that have evolved proteins to target the surface of host bacterial cells. Given the ubiquity of lipopolysaccharides (LPS) on the outer membrane of Gram-negative bacteria, we reasoned that targeting proteins from bacteriophages could be leveraged to target the surface of Gram-negative pathogens for biotechnological applications. To this end, a short tail fiber (GP12) from the T4 bacteriophage, which infects Escherichia coli (E. coli), was isolated and tested for the ability to adhere to whole bacterial cells. We found that, surprisingly, GP12 effectively bound the surface of Pseudomonas aeruginosa cells despite the established preferred host of T4 for E. coli. In efforts to elucidate why this binding pattern was observed, it was determined that the absence of the O-antigen region of LPS on E. coli improved cell surface tagging. This indicated that O-antigens play a significant role in controlling cell adhesion by T4. Probing GP12 and LPS interactions further using deletions of the enzymes involved in the biosynthetic pathway of LPS revealed the inner core oligosaccharide as a possible main target of GP12. Finally, we demonstrated the potential utility of GP12 for biomedical applications by showing that GP12-modified agarose beads resulted in the depletion of pathogenic bacteria from solution.

Harvestmen are relevant in the food chains of different terrestrial ecosystems, including agricultural systems. In this sense, this work presents new information about the use of social wasps, Polistes simillimus Zikán, 1951 in the diet of Gonyleptes atrus Mello-Leitão, 1923. The recording was carried out at random, on May 31, 2022 in a semideciduous seasonal forest, phytophysiognomy of the Atlantic Forest, in the Parque Nacional do Iguaçu, municipality of Foz do Iguaçu, Paraná, southern Brazil. This record incorporates new information about the diet of Gonyleptes atrus.

During the Mexican Colonial period, masonry made of stone and lime mortar was the main building material used to build churches, convents, and government buildings. After the Axochiapan earthquake (September 19, 2017, Mw 7.1), many of these buildings were seriously damaged, and an important quantity of debris was generated. Due to the limited information on the mechanical properties of such materials, a recollection campaign was carried out with the main objective of obtaining masonry samples from the debris produced from the damaged churches. Nine damaged churches built during the Colonial period were selected, seven of which were located in the “Route of convents”, a World Heritage site, in Morelos, Mexico. The masonry samples are composed mainly of tezontle, a light igneous stone and lime mortar. Some cases contain stone-like “boleos” and lime-mortar combined with clay or topsoil. The samples collected were transported to the laboratory with the main objective of obtaining their compressive strength, Young’s modulus and Poisson’s ratio through uniaxial compression tests. According to the results, the mechanical properties computed had a high coefficient of variation due to the heterogeneity of the masonry, which is a typical characteristic of this type of material. Despite this heterogeneity, the results are an important contribution to the state of the art, which will allow more reliable numerical models to make more precise structural evaluations.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69–/– mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69–/– mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

Summary: Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support ‘normal life’ following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.’s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Summary: Public goods are biomolecules that benefit cellular populations, such as by providing access to previously unutilized resources. Public good production is energetically costly. To reduce this cost, populations control public good biosynthesis, for example using density-dependent regulation accomplished by quorum sensing. Fitness costs and benefits of public good production must be balanced, similar to optimal investment decisions used in economics. We explore the regulation of a public good that increases the carrying capacity, through experimental measurements of growth in Escherichia coli and analysis using a modified logistic growth model. The timing of public good production showed a sharply peaked optimum in population fitness. The cell density associated with maximum public good benefits was determined by the trade-off between the cost of public good production, in terms of reduced growth rate, and benefits received from public goods, in the form of increased carrying capacity.

We propose a model of the Universe (dubbed η CDM) featuring a controlled stochastic evolution of the cosmological quantities that is meant to render the effects of small deviations from homogeneity/isotropy on scales of 30–50 h ^−1 Mpc at late cosmic times associated with the emergence of the cosmic web. Specifically, we prescribe that the behavior of the matter/radiation energy densities in different patches of the Universe with such a size can be effectively described by a stochastic version of the mass–energy evolution equation. The latter includes, besides the usual dilution due to cosmic expansion, an appropriate noise term that statistically accounts for local fluctuations due to inhomogeneities, anisotropic stresses, and matter flows induced by complex gravitational processes. The evolution of the different patches as a function of cosmic time is rendered via the diverse realizations of the noise term; meanwhile, at any given cosmic time, sampling the ensemble of patches will create a nontrivial spatial distribution of the various cosmological quantities. Finally, the overall behavior of the Universe will be obtained by averaging over the patch ensemble. We assume a simple and physically reasonable parameterization of the noise term, gauging it against a wealth of cosmological data sets in the local and high-redshift Universe. We find that, with respect to standard ΛCDM, the ensemble-averaged cosmic dynamics in the η CDM model is substantially altered by the stochasticity in three main respects: (i) an accelerated expansion is enforced at late cosmic times without the need for any additional exotic component (e.g., dark energy), (ii) the spatial curvature can stay small even in a low-density Universe constituted solely by matter and radiation, (iii) matter can acquire an effective negative pressure at late times. The η CDM model is Hubble tension–free, meaning that the estimates of the Hubble constant from early- and late-time measurements do not show marked disagreement as in ΛCDM. We also provide specific predictions for the variance of the cosmological quantities among the different patches of the Universe at late cosmic times. Finally, the fate of the Universe in the η CDM model is investigated to show that the cosmic coincidence problem is relieved without invoking the anthropic principle.

The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson’s disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic β-sitosterol β-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.

The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

ABSTRACT: Great part of the veterinary care in wild carnivores is intended to treat the dental disorders, and oral cavity disorders may generally affect the animal health as a whole. It is factual that knowing the location of the mandibular foramen is vital for local anesthetic block of the inferior alveolar nerve, however, there is still no data on the morphometry of the hoary fox mandibular foramen. The aim was describing morphometry of the mandibular foramen of this species and associating its position with anatomic reference points in the mandible, thus providing support for more effective local anesthetic block of the inferior alveolar nerve in such species. Four adult jaws of Lycalopex vetulus were used. Radiography and biometrics of the hemimandibulas were performed. The rostral third of the jaw body in a lateral view presented three mental foramens, being a rostral, a medium and a caudal. Each hemimandibula presented I3/C1/PM4/M3. The angle of the mandible was marked by the masseteric fossa, the angular incisure, the angular process and the mandibular foramen, and this last one located perpendicularly to the dorsal edge of the angular incisures in medial view. In this view, the crevice to the milohyoid nerve, projected in the caudodorso rostral direction, was also evidenced. The ramus of the mandible was characterized by the presence of the condylar and coronoid processes, and by the dorsal and ventral mandibular incisions. Statistical analyzes did not present significant differences between the antimeres of the studied animals, and the penetration of the needle perpendicularly to the dorsal end of the angular incision on average 8.79mm, overlapped to the medial face of the angle of the mandible could be indicated. Alternatively, the access may also be achieved by inserting the needle in an average of 17.69mm perpendicular to the dorsal end of the angular process, in contact with the medial aspect of the angle of the mandible, and in caudo-rostral projection, also allowing a better anesthetic blockade of the inferior alveolar nerve in L. vetulus. It can also be concluded that the masseteric fossa, the dorsal and ventral mandibular angles, the crevice to the milohyoid nerve, the ramus of the mandible and the mandibular foramen presented differences in their topographic descriptions when compared to the other canids.

Abstract Background The most common infusion in southern Latin-American countries is prepared with dried leaves of Ilex paraguariensis A. St.-Hil., an aboriginal ancestral beverage known for its high polyphenols concentration currently consumed in > 90% of homes in Argentina, in Paraguay and Uruguay. The economy of entire provinces heavily relies on the production, collection and manufacture of Ilex paraguariensis, the fifth plant species with highest antioxidant activity. Polyphenols are associated to relevant health benefits including strong antioxidant properties. Despite its regional relevance and potential biotechnological applications, little is known about functional genomics and genetics underlying phenotypic variation of relevant traits. By generating tissue specific transcriptomic profiles, we aimed to comprehensively annotate genes in the Ilex paraguariensis phenylpropanoid pathway and to evaluate differential expression profiles. Results In this study we generated a reliable transcriptome assembly based on a collection of 15 RNA-Seq libraries from different tissues of Ilex paraguariensis. A total of 554 million RNA-Seq reads were assembled into 193,897 transcripts, where 24,612 annotated full-length transcripts had complete ORF. We assessed the transcriptome assembly quality, completeness and accuracy using BUSCO and TransRate; consistency was also evaluated by experimentally validating 11 predicted genes by PCR and sequencing. Functional annotation against KEGG Pathway database identified 1395 unigenes involved in biosynthesis of secondary metabolites, 531 annotated transcripts corresponded to the phenylpropanoid pathway. The top 30 differentially expressed genes among tissue revealed genes involved in photosynthesis and stress response. These significant differences were then validated by qRT-PCR. Conclusions Our study is the first to provide data from whole genome gene expression profiles in different Ilex paraguariensis tissues, experimentally validating in-silico predicted genes key to the phenylpropanoid (antioxidant) pathway. Our results provide essential genomic data of potential use in breeding programs for polyphenol content. Further studies are necessary to assess if the observed expression variation in the phenylpropanoid pathway annotated genes is related to variations in leaves’ polyphenol content at the population scale. These results set the current reference for Ilex paraguariensis genomic studies and provide a substantial contribution to research and biotechnological applications of phenylpropanoid secondary metabolites.

Se realizó un estudio de mercado de los minerales presentes en las presas de colas niquelíferas del municipio de Moa, basándose en el modelo diseñado por Philip Kotler para realizar estas investigaciones utilizando técnicas estadísticas de pronósticos para el análisis de sus precios en el mercado, que permita plantear estrategias bien fundamentadas sobre la posibilidad de su explotación e iniciar nuevas inversiones en Cuba. En los resultados obtenidos del estudio se evidencia que el cromo es uno de los minerales presentes en los residuales con amplias posibilidades de explotación, lo que permite contribuir a sustituir importaciones y proporcionar el ahorro de algunas empresas en inversión en materias primas.

Pulmonary arterial hypertension impairs exercise tolerance and daily physical activity. Aside from the hemodynamic limitations, physical, cognitive, and emotional factors may play a relevant and as yet unexplored role. We investigated whether there is an association between the physical activity level and psychological disorders, health-related quality of life, and daily activities. We also searched for an association of the physical activity level with clinical factors and functional capacity. This was an analytical, cross-sectional, observational study conducted in a Brazilian University Hospital. Twenty stable pulmonary arterial hypertension subjects wore an accelerometer for a week and completed an activity diary. They answered the quality of life questionnaire (SF-36), as well as the Hospital Anxiety and Depression scale, and the Manchester Respiratory Activities of Daily Living questionnaire. Transthoracic echocardiography, the six-minute walk test, the one-minute sit-to-stand test, and spirometry were performed. For statistical analysis, we used Chi-square tests or Fisher’s test as appropriate and the Mann–Whitney test to compare numerical values between two groups. The relationship between the parameters was assessed using the Spearman correlation test. The mean age was 44.3 years, 80% were women, 80% had idiopathic pulmonary arterial hypertension, and 20% had connective tissue disease. The mean daily step count was 4280 ± 2351, and the mean activity time was 41.6 ± 19.3 min. The distance covered (six-minute walk test) was 451.5 m, and the number of movements (one-minute sit-to-stand test) was 23.8. Thirty percent scored positive for anxiety, and 15% for depression (Hospital Anxiety and Depression scale). There was a significant correlation between accelerometer data and walking distance (six-minute walk test), number of movements (one-minute sit-to-stand test), level of daily physical activity (Manchester Respiratory Activities of Daily Living questionnaire), and depression symptoms. Our findings support the hypothesis that other aspects beyond physical and hemodynamic ones might impact the daily physical activity of patients with pulmonary arterial hypertension.

Neste artigo apresentamos um sistema para aquisição de intervalos de tempo e estimativas da velocidade a partir de sensores de luz infravermelha acoplados à placa Arduíno. Devido à precisão das medidas de tempo, que apresentam incertezas da ordem de 10−4s, somos capazes de determinar a taxa de amortecimento para o pêndulo devido à resistência do ar em um regime de pequenos ângulos. Estudamos o sistema físico formado por um pequeno frasco de vidro suspenso por um fio. Este sistema foi modelado por diferentes pêndulos, como o pêndulo físico, o pêndulo simples e o pêndulo amortecido, onde discutimos sobre os limites de validade destes modelos.

Abstract Biological and abiotic processes influence ecosystem structure and species distribution. For bryozoan assemblages, depth, substratum and habitat structure are among the main factors influencing their distribution. Ecological studies on bryozoan fauna from Brazil are scarce and factors affecting the distribution and/or diversity of this common group are obscure. Here we attempted to verify the influence of bathymetry on bryozoan richness on the north shore of Bahia State, north-eastern Brazil. We identified 57 bryozoan taxa, comprising 35 families and 50 genera, all belonging to the Cheilostomata. Retevirgula multipunctata Winston, Vieira & Woollacott, 2014 and Tetraplaria dichotoma (Osburn, 1914) and the genus Aimulosia Jullien, 1888 were recorded for the first time from Bahia State. Species growing as encrusting sheets were dominant at all depths. There was a significant difference in richness among samples at different depths, with highest values of richness at 40 meters (Kruskal-Wallis Test). Analysis of similarities revealed a significant difference among the bryozoan assemblages, mainly when comparing assemblages from 10 and 20 meters with deeper ones. Also, shallower assemblages composition varied much than assemblages from 30 and 40 meters. Since depth is a proxy for several environmental parameters, further studies are needed to identify other factors influencing bryozoan distribution.

Five new disubstituted 2,6-thioaryl-BODIPY dyes were synthesized via selective aromatic electrophilic substitution from commercially available thiophenols. The analysis of the photophysical properties via absorption and emission spectroscopy showed unusually large Stokes shifts for BODIPY fluorophores (70–100 nm), which makes them suitable probes for bioimaging. Selected compounds were evaluated for labelling primary immune cells as well as different cancer cell lines using confocal fluorescence microscopy.

El Virus Epstein Barr (EBV) está relacionado como agente oncogénico en el desarrollo del cáncer gástrico, atribuyéndosele el 10 % de los casos de esta neoplasia a nivel mundial. No existen estudios previos que identifiquen la presencia EBV en los pacientes con cáncer gástrico en Guatemala, por lo que en este estudio se evaluó por hibridación in situ la presencia del micro ARN EBER (Epstein Barr-encoded RNAs) de EBV en 71 pacientes con cáncer gástrico que asistieron al Instituto de Cancerología (Incan). Se determinó una prevalencia de 21.1 % (IC 95 % [10.9, 31.3] ) (15 pacientes), mayor que la reportada en otros estudios latinoamericanos. Se determinó asociación significativa entre la expresión del EBER del EBV, y el género masculino OR = 4.9 (IC 95 % [1.4, 17.5]) p < .05. Los factores asociados fueron, el padecer diarrea OR 5.7 IC 95 % [1.5, 12.6] p = .008, y la detección del anticuerpos de Helicobacter pylori séricos, OR 7.2 (IC 95 % [1.1, 18.9]) p = .03. Aun cuando la mayoría de los pacientes que expresan el EBER de EBV desarrollaron cáncer gástrico del tipo difuso 66.67 % no existe asociación significativa p = 0.13 OR = 2.5 (IC 95 % [1.1, 8.2]).

Aspergillus tamarii grows abundantly in naturally composting waste fibers of the textile industry and has a great potential in biomass decomposition. Amongst the key (hemi)cellulose-active enzymes in the secretomes of biomass-degrading fungi are the lytic polysaccharide monooxygenases (LPMOs). By catalyzing oxidative cleavage of glycoside bonds, LPMOs promote the activity of other lignocellulose-degrading enzymes. Here, we analyzed the catalytic potential of two of the seven AA9-type LPMOs that were detected in recently published transcriptome data for A. tamarii, namely AtAA9A and AtAA9B. Analysis of products generated from cellulose revealed that AtAA9A is a C4-oxidizing enzyme, whereas AtAA9B yielded a mixture of C1- and C4-oxidized products. AtAA9A was also active on cellopentaose and cellohexaose. Both enzymes also cleaved the β-(1→4)-glucan backbone of tamarind xyloglucan, but with different cleavage patterns. AtAA9A cleaved the xyloglucan backbone only next to unsubstituted glucosyl units, whereas AtAA9B yielded product profiles indicating that it can cleave the xyloglucan backbone irrespective of substitutions. Building on these new results and on the expanding catalog of xyloglucan- and oligosaccharide-active AA9 LPMOs, we discuss possible structural properties that could underlie the observed functional differences. The results corroborate evidence that filamentous fungi have evolved AA9 LPMOs with distinct substrate specificities and regioselectivities, which likely have complementary functions during biomass degradation.

ObjectiveTo evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated.Materials and methodsThirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (pResultsTest group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens.ConclusionImmunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP.Clinical relevanceB. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.

Abstract Background Patients with ischemic cardiomyopathy and severe left ventricular dysfunction have a worse survival prognosis than patients with preserved ventricular function. The role of diabetes in the long-term prognosis of this patient group is unknown. This study investigated whether the presence of diabetes has a long-term impact on left ventricular function. Methods Patients with coronary artery disease who underwent coronary artery bypass graft surgery, percutaneous coronary intervention, or medical therapy alone were included. All patients had multivessel disease and left ventricular ejection fraction measurements. Overall mortality, nonfatal myocardial infarction, stroke, and additional interventions were investigated. Results From January 2009 to January 2010, 918 consecutive patients were selected and followed until May 2015. They were separated into 4 groups: G1, 266 patients with diabetes and ventricular dysfunction; G2, 213 patients with diabetes without ventricular dysfunction; G3, 213 patients without diabetes and ventricular dysfunction; and G4, 226 patients without diabetes but with ventricular dysfunction. Groups 1, 2, 3, and 4, respectively, had a mortality rate of 21.6, 6.1, 4.2, and 10.6% (P

Abstract Background Bovine leukemia virus (BLV) infection is omnipresent in dairy herds causing direct economic losses due to trade restrictions and lymphosarcoma-related deaths. Milk production drops and increase in the culling rate are also relevant and usually neglected. The BLV provirus persists throughout a lifetime and an inter-individual variation is observed in the level of infection (LI) in vivo. High LI is strongly correlated with disease progression and BLV transmission among herd mates. In a context of high prevalence, classical control strategies are economically prohibitive. Alternatively, host genomics studies aiming to dissect loci associated with LI are potentially useful tools for genetic selection programs tending to abrogate the viral spreading. The LI was measured through the proviral load (PVL) set–point and white blood cells (WBC) counts. The goals of this work were to gain insight into the contribution of SNPs (bovine 50KSNP panel) on LI variability and to identify genomics regions underlying this trait. Results We quantified anti–p24 response and total leukocytes count in peripheral blood from 1800 cows and used these to select 800 individuals with extreme phenotypes in WBCs and PVL. Two case-control genomic association studies using linear mixed models (LMMs) considering population stratification were performed. The proportion of the variance captured by all QC-passed SNPs represented 0.63 (SE ± 0.14) of the phenotypic variance for PVL and 0.56 (SE ± 0.15) for WBCs. Overall, significant associations (Bonferroni’s corrected -log10p > 5.94) were shared for both phenotypes by 24 SNPs within the Bovine MHC. Founder haplotypes were used to measure the linkage disequilibrium (LD) extent (r2 = 0.22 ± 0.27 at inter-SNP distance of 25−50 kb). The SNPs and LD blocks indicated genes potentially associated with LI in infected cows: i.e. relevant immune response related genes (DQA1, DRB3, BOLA-A, LTA, LTB, TNF, IER3, GRP111, CRISP1), several genes involved in cell cytoskeletal reorganization (CD2AP, PKHD1, FLOT1, TUBB5) and modelling of the extracellular matrix (TRAM2, TNXB). Host transcription factors (TFs) were also highlighted (TFAP2D; ABT1, GCM1, PRRC2A). Conclusions Data obtained represent a step forward to understand the biology of BLV–bovine interaction, and provide genetic information potentially applicable to selective breeding programs.

The waste generated by single-use plastics is often non-recyclable and non-biodegradable, inevitably ending up in our landfills, ecosystems, and food chain. Through the introduction of biodegradable polymers as substitutes for common plastics, we can decrease our impact on the planet. In this study, we evaluate the changes in mechanical and thermal properties of polyhydroxybutyrate-based composites with various additives: Microspheres, carbon fibers or polyethylene glycol (2000, 10,000, and 20,000 MW). The mixtures were injection molded using an in-house mold attached to a commercial extruder. The resulting samples were characterized using microscopy and a series of spectroscopic, thermal, and mechanical techniques. We have shown that the addition of carbon fibers and microspheres had minimal impact on thermal stability, whereas polyethylene glycol showed slight improvements at higher molecular weights. All of the composite samples showed a decrease in hardness and compressibility. The findings described in this study will improve our understanding of polyhydroxybutyrate-based composites prepared by injection molding, enabling advancements in integrating biodegradable plastics into everyday products.