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Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

The irreversible Bruton tyrosine kinase (BTK) inhibitor ibrutinib has changed the therapeutic landscape of patients affected by chronic lymphocytic leukemia (CLL), leading to high clinical response...

During 2018, Heartland virus RNA was detected in an Amblyomma americanum tick removed from a resident of Suffolk County, New York, USA. The persons showed seroconversion. Tick surveillance and white-tailed deer (Odocoileus virginianus) serosurveys showed widespread distribution in Suffolk County, emphasizing a need for disease surveillance anywhere A. americanum ticks are established or emerging.

MDFRC item.Morphological (growth, Fulton's condition factor), physiological (per cent dry mass, total lipid content) and behavioural (activity levels) response patterns of carp gudgeon Hypseleotris spp. were examined in response to food deprivation during a 56 day experiment. Considerable variability in the nature and magnitude of these response patterns was observed, suggesting that caution should be taken when interpreting changes in the health of small-bodied fishes based on individual response variables.

A decrease in brain-derived neurotrophic factor (BDNF), a neurotrophin essential for synaptic function, plasticity and neuronal survival, is evident early in the progression of Alzheimer’s disease (AD), being apparent in subjects with mild cognitive impairment or mild AD, and both proBDNF and mature BDNF levels are positively correlated with cognitive measures. BDNF delivery is, therefore, considered of great interest as a potentially useful therapeutic strategy to contrast AD. Invasive BDNF administration has indeed been recently used in animal models of AD with promising results in rescuing memory deficits, synaptic density and cell loss. Here, we tested whether non-invasive intranasal administration of different BDNF concentrations after the onset of cognitive and anatomical deficits (6 months of age) could rescue neuropathological and memory deficits in AD11 mice, a model of NGF deprivation-induced neurodegeneration. In addition to AD hallmarks, we investigated BDNF effects on microglia presence in the brain of AD11 mice, since alterations in microglia activation have been associated with ageing-related cognitive decline and with the progression of neurodegenerative diseases, including AD. We found that intranasal delivery of 42 pmol BDNF (1 μM), but not PBS, was sufficient to completely rescue performance of AD11 mice both in the object recognition test and in the object context test. No further improvement was obtained with 420 pmol (10 μM) BDNF dose. The strong improvement in memory performance in BDNF-treated mice was not accompanied by an amelioration of AD-like pathology, Aβ burden, tau hyperphosphorylation and cholinergic deficit, but there was a dramatic decrease of CD11b immunoreactive brain microglia. These results reinforce the potential therapeutic uses of BDNF in AD and the non-invasive intranasal route as an effective delivery strategy of BDNF to the brain. They also strengthen the connection between neuroinflammation and neurodegenerative dementia and suggest microglia as a possible mediator of BDNF therapeutic actions in the brain.

AIMS To gather data on agricultural practices in organic farms in Sao Paulo, Brazil, and evaluate their relationship with the microbiological characteristics of samples collected along the production chain. METHODS AND RESULTS Practices data were based on field observations and interviews with farmers in 10 selected organic lettuce producing farms. Counts of Enterobacteriaceae and surveys for Salmonella were performed in samples of lettuce (before and after washing), fertilizers, irrigation and washing water, all collected in the same farm. Water samples were also tested for total coliforms and generic Escherichia coli. Isolated Enterobacteriaceae were identified by MALDI-TOF MS. Contamination of lettuce was influenced by some agricultural practices: chicken manure-based fertilization resulted in higher Enterobacteriaceae counts in lettuce when compared to other types of manure, whereas pre-washed lettuces presented lower microbial counts than non-pre-washed samples. Salmonella was detected in one lettuce sample by qPCR. Escherichia coli was detected in all irrigation water samples. All sample types contained Enterobacteriaceae species commonly reported as opportunistic human pathogens. CONCLUSIONS The data highlight the need for improvement in the good agricultural practices in the studied farms. SIGNIFICANCE AND IMPACT OF THE STUDY This study provides information on agricultural practices and microbiological characteristics of organic lettuce, contributing to the development of more accurate risk assessments.

Burnout syndrome has a multidimensional characteristic, and there are feelings inherent to this syndrome, and it has different response due to characteristic of the athletes and their sport. The purpose of the present study was to identify burnout levels and its relationship between sex, age and type of sport. The Athletes Burnout Questionnaire (ABQ) was used to assess the prevalence of burnout in athletes and whether burnout is influenced by sex, age group, and type of sport (individual versus team sports). The ABQ was administered to 223 athletes (50 females (15,4± 4,17 years old) and 173 males (17,8±4,34 years old)) in 4 different sports modalities (swimming, gymnastics, basketball, and soccer). The results showed that between 1% and 9% of the athletes showed elevated burnout scores on these four subscales, and the hypothesis of higher prevalence of burnout in individual sports was supported someway, by athletes who had higher levels of Emotional and Physical Exhaustion when compared to those of team sports. It was also found that age did not influence burnout levels. Furthermore, only a no correlation between sex and burnout scores was found. These findings suggest that factors other than sex, and age must be considered when athletes at risk for burnout are investigated.

Leptin, produced and secreted by white adipose tissue in tight relationship with adipose mass, informs the brain about the status of the energy stores serving as the main peripheral signal for energy balance regulation through interaction with a multitude of highly interconnected neuronal populations. Most obese patients display resistance to the anorectic effect of the hormone. The present review unravels the multiple levels of complexity that trigger hypothalamic response to leptin with the objective of highlighting those critical hubs that, mainly in the hypothalamic arcuate nucleus, may undergo obesity-induced alterations and create an obstacle to leptin action. Several mechanisms underlying leptin resistance have been proposed, possibly representing useful targets to empower leptin effects. Among these, a special focus is herein dedicated to detail how leptin gains access into the brain and how neuronal plasticity may interfere with leptin function.

Sera from white-tailed deer (WTD, Odocoileus virginianus) hunter-harvested throughout New York State (NYS), 2007–2015, were tested by plaque reduction neutralization for antibodies against nine mosquito-borne viruses from the families Peribunyaviridae, Flaviviridae, and Togaviridae. Overall, 76.1% (373/490) of sampled WTD were seropositive against at least one virus, and 38.8% were exposed to multiple viruses. The seropositivity rate in adult WTD (78.0%) was significantly greater (P < 0.0001) than that in fawns (47.7%). Neutralizing antibodies against California serogroup viruses were most common in WTD sampled across all regions (67.1%), followed by the Bunyamwera serogroup (BUN) (37.6%). Jamestown Canyon and Cache Valley orthobunyaviruses were responsible for most California and BUN infections, respectively. Seroprevalence rates to West Nile virus were higher in samples originating from Long Island (LI) (19.0%) than in those originating from the central (7.3%), western (5.0%), and Hudson Valley (4.4%) regions of NYS. Antibodies to Eastern equine encephalitis virus were seen primarily in WTD from central NYS (5.1%), where annual enzootic activity occurs, but low rates were documented in western NYS (1.4%) and LI (1.7%). Low rates of Potosi and LaCrosse orthobunyavirus, and Highlands J virus antibodies were detected over the course of this investigation. St. Louis encephalitis virus (or a closely related virus) antibodies were detected in samples collected from central and western NYS, suggesting local virus transmission despite a lack of evidence from routine mosquito surveillance. Serologic results demonstrate the value of WTD in NYS as an indicator of arbovirus distribution and recent transmission on a relatively fine spatial scale.

Proteasome inhibition represents an important anticancer strategy. Here, we studied the mechanisms at the basis of the pro-apoptotic activity of the standardized decoction of Hemidesmus indicus, a plant evoking a complex anticancer activity, and explored its inhibition of proteasome activity in human leukemia cells. Additionally, we preliminary tested the cytotoxicity of some H. indicus’s phytochemicals on leukemia cells and their intestinal absorption on a human intestinal epithelium model consisting of a monolayer of differentiated Caco2 cells. We observed a potent antileukemic effect for H. indicus, imputable to the modulation of different critical targets at protein and mRNA levels and the reduction of the 26S proteasome expression. We found that some phytomarkers of H. indicus decoction passed through the enterocyte monolayer. Overall, our study supports the pharmacological potential of H. indicus, which can represent an interesting botanical drug in the oncological area.

Maculinea (=Phengaris) are endangered butterflies that are characterized by a very complex biological cycle. Maculinea larvae behave as obligate parasites whose survival is strictly dependent on both particular food plants and species-specific Myrmica ants. In this interaction, Maculinea caterpillars induce Myrmica workers to retrieve and rear them in the nest by chemical and acoustic deception. Social insect symbiotic microorganisms play a key role in intraspecific and interspecific communication; therefore, it is possible that the Maculinea caterpillar microbiome might be involved in the chemical cross-talk by producing deceptive semiochemicals for host ants. To address this point, the microbiota of Maculinea alcon at different larval stages (phytophagous early larvae, intermediate larvae, carnivorous late larvae) was analyzed by using 16S rRNA-guided metabarcoding approach and compared to that of the host ant Myrmica scabrinodis. Structural and deduced functional profiles of the microbial communities were recorded, which were used to identify specific groups of microorganisms that may be involved in the chemical cross-talk. One of the most notable features was the presence in all larval stages and in the ants of two bacteria, Serratia marcescens and S. entomophila, which are involved in the chemical cross-talk between the microbes and their hosts.

The genus Pistacia (Anacardiaceae family) is represented by several species, of which only P. vera L. produces edible seeds (pistachio). Despite the different flavor and taste, a correct identification of pistachio varieties based on the sole phenotypic character is sometimes hard to achieve. Here we used a combination of chemical partitioning and molecular fingerprinting for the unequivocal identification of commercial pistachio seed varieties (Bronte, Kern, Kerman, Larnaka, Mateur and Mawardi) of different geographical origin. The total phenolic content was higher in the variety Bronte followed by Larnaka and Mawardi cultivars. The total anthocyanin content was higher in Bronte and Larnaka varieties, whereas the total proanthocyanidin content was higher in Bronte, followed by Mawardi and Larnaka varieties. HPLC-DAD-ESI-MS/MS analyses revealed significant (P < 0.05) higher amounts of cyanidin-3-glucoside, idein, eryodictol-7-galactoside, quercetin-3-glucoside, luteolin-glucoside and marein in the variety Bronte, whereas higher amounts of peonidin-3-glucoside, okanin 4′-galactoside, hyperoside and quercetin-4′-glucoside were found in the variety Larnaka. The highest content of catechin was found in the Mawardi variety. A significantly (P < 0.05) higher total amount of fatty acids was found in the varieties Mateur, Kern and Bronte, followed by the varieties Larnaka and Mawardi, whereas the variety Kerman showed the lowest total fatty acid content. GC-FID and GC-MS analyses revealed the presence of several polyunsaturated fatty acids. Kern and Mateur varieties showed a significantly (P < 0.05) higher amount of linoleic acid, whereas the variety Bronte showed the highest amount of oleic acid. Molecular fingerprinting was achieved by ITS DNA PCR-RFLP analysis. Three different restriction enzymes (RsaI, TaqαI and PstI) were used to selectively cleave the resulting amplicons. A TaqαI site could be selectively found in the varieties Kerman, Larnaka and Mateur, whereas the digestion of the PCR products by RsaI gave specific patters exclusively on Bronte and Mawardi. Digestion by PstI gave specific patters exclusively on the Kern variety. The results showed that the Mediterranean varieties (Mateur, Bronte and Larnaka) show similar chemical patterns and (particularly for Mateur and Larnaka) a close phylogenetic relationship, allowing a chemical and molecular partitioning with respect to the other varieties.

Introduction The purpose of the present study was to compare the immunomodulatory effect of azithromycin (AZM), ampicillin (AMP), amoxicillin (AMX), and clindamycin (CLI) in vitro and AZM on preexisting periapical lesions compared with AMP. Methods The susceptibility of 4 common human endodontic pathogens (Parvimonas micra, Streptococcus intermedius, Prevotella intermedia, and Fusobacterium nucleatum) to AZM, AMP, AMX, and CLI was confirmed by agar disk diffusion assay. Preexisting periapical lesions in C57BL/6J mice were treated with AZM, AMP, or phosphate-buffered saline (PBS). Periapical bone healing and the pattern of inflammatory cell infiltration were evaluated after a 10-day treatment by micro–computed tomographic and histology, respectively. Besides, the effect of antibiotics in pathogen-stimulated nuclear factor kappa B activation and the production of interleukin 1 alpha and tumor necrosis factor alpha was assessed in vitro by luciferase assay and enzyme-linked immunosorbent assay. Results All examined endodontic pathogens were susceptible to AZM, AMP, AMX, and CLI. AZM significantly attenuated periapical bone loss versus PBS. PBS resulted in widely diffused infiltration of mixed inflammatory cells. By contrast, AZM brought about localized infiltration of neutrophils and M2 macrophages and advanced fibrosis. Although the effect of AMP on bone was uncertain, inflammatory cell infiltration was considerably milder than PBS. However, most macrophages observed seemed to be M1 macrophages. AZM suppressed pathogen-stimulated nuclear factor kappa B activation and cytokine production, whereas AMP, AMX, and CLI reduced only cytokine production moderately. Conclusions This study showed that AZM led to the resolution of preexisting experimental periapical inflammation. Our data provide a perspective on host response in antibiotic selection for endodontic treatment. However, well-designed clinical trials are necessary to better elucidate the benefits of AZM as an adjunctive therapy for endodontic treatment when antibiotic therapy is recommended. Although both AZM and AMP were effective on preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect.

On December 30th 2019, some patients with pneumonia of unknown etiology were reported in the Program for Monitoring Emerging Diseases (ProMED), a program run by the International Society for Infectious Diseases (ISID), hypothesized to be related to subjects who had had contact with the seafood market in Wuhan, China. Chinese authorities instituted an emergency agency aimed at identifying the source of infection and potential biological pathogens. It was subsequently named by the World Committee on Virus Classification as 2019-nCoV (2019-novel coronavirus) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of studies have demonstrated that 2019-nCoV and the SARS-CoV shared the same cell entry receptor named angiotensin-converting enzyme 2 (ACE2). This is expressed in human tissues, not only in the respiratory epithelia, but also in the small intestines, heart, liver, and kidneys. Here, we examine the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, mainly acute kidney injury, and the potential role of the chemokine network.

The present study shows the results of the microbiological quality and safety of minimally processed vegetables sold in supermarkets and grocery stores located in the city of Piracicaba, SP, Brazil. A total of 100 samples were collected and submitted to enumeration of total coliforms, coliforms at 45°C and generic Escherichia coli using the standard most probable number (MPN) method, in addition to enumeration of total Enterobacteriaceae by plating on MacConkey agar. Moreover, colonies of Enterobacteriaceae were randomly selected and submitted to identification on a MALDI-TOF MS Biotyper™. Samples were also tested for Salmonella spp. according to the ISO 6579:2002 method. The mean count of total coliforms was 2·9 ± 0·5 log MPN per g. For coliforms at 45°C, 20 samples were positive (mean 1·5 ± 1·0 log MPN per g). Generic E. coli was detected in 16 samples (mean 1·4 ± 0·9 log MPN per g) and only one was positive for Salmonella. The mean count of total Enterobacteriaceae was 6·5 ± 1·2 log CFU per g and the most frequent genera identified by MALDI-TOF were Enterobacter (25·9%), Pantoea (9·6%) and Rahnella (9·0%). Overall, results point to poor microbiological quality of a few samples, indicating hygiene failure during their processing. This can pose health risks to consumers, mainly because these products were labelled as sanitized and marketed as ready-to-eat. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, the microbiological quality and safety of minimally processed vegetables sold in the city of Piracicaba, SP, Brazil, were evaluated through the detection of Salmonella spp., generic Escherichia coli and other Enterobacteriaceae. The results obtained point to poor microbiological quality and safety of a few samples, as generic E. coli was detected in 16 out of 100 samples and Salmonella was isolated from one of them. This indicates hygiene failures during their processing and health risk to consumers, since these products are usually sold as ready-to-eat and typically require no further heat treatment before consumption.

Background Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell – WBC – count, C-reactive protein — CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. Methods Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. Results Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers Conclusions Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage–host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications., This study presents the BASEL collection of phages that infect the model bacterium Escherichia coli; this resource for the community is representative of natural E. coli phage diversity and has been extensively characterized phenotypically and genomically.

Background: Hemoglobin A (Hb A) (α2β2) in the normal adult subject constitutes 96–98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A2 (Hb A2) (α2δ2), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene defects in order to correctly diagnose the β-thalassemia carrier. Methods: The most used methods for the quantification of Hb A2 are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols. Results: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A2 variants that were found with an estimated frequency of about 1–2% during the screening tests in our laboratories. Conclusions: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis.

BACKGROUND: Abnormal sulcation of the brain is frequently associated with severe malformations, but the prenatal diagnosis is challenging, especially in early pregnancy. OBJECTIVE: Our study aimed to investigate the value of Sylvian fossa sonographic biometry in the diagnosis of cerebral malformation in the second trimester of gestation. STUDY DESIGN: We prospectively established the normal values of the Sylvian fossa depth in a cohort of nonconsecutive patients, with singleton pregnancies and normal fetuses between 18+0 and 23+0 weeks’ gestation. For each patient, a coronal view of the fetal brain, with a clear visualization of the anterior complex and the Sylvian fissure, was acquired by 1 sonologist, who also measured the depth of the fossa. Reproducibility for each parameter was assessed by a second sonologist using stored images. We also retrospectively acquired the same measurements in second trimester fetuses with central nervous system anomalies. RESULTS: In 103 fetuses with a normal sonogram, the mean depth of the Sylvian fossa was 3.9±0.8 mm Interobserver reproducibility analysis demonstrated good results. Notably, 11 of 31 fetuses with cerebral malformations had a Sylvian fossa depth of

Background: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)—can induce both polyclonal and specific IgE responses. Objective: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). Methods: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1kU/L and >0.35kU/L, respectively) were used to assess serum SEsIgE. Results: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. Conclusions: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma.

In humans and experimental animals, the administration of ciliary neurotrophic factor (CNTF) reduces food intake and body weight. To gain further insights into the mechanism(s) underlying its satiety effect, we: (i) evaluated the CNTF-dependent activation of the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) pathway in mouse models where neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) neurons can be identified by green fluorescent protein (GFP); and (ii) assessed whether CNTF promotes leptin signaling in hypothalamic feeding centers. Immunohistochemical experiments enabled us to establish that intraperitoneal injection of mouse recombinant CNTF activated the JAK2-STAT3 pathway in a substantial proportion of arcuate nucleus (ARC) NPY neurons (18.68% ± 0.60 in 24-h fasted mice and 25.50% ± 1.17 in fed mice) but exerted a limited effect on POMC neurons (4.15% ± 0.33 in 24-h fasted mice and 2.84% ± 0.45 in fed mice). CNTF-responsive NPY neurons resided in the ventromedial ARC, facing the median eminence (ME), and were surrounded by albumin immunoreactivity, suggesting that they are located outside the blood-brain barrier (BBB). In both normally fed and high-fat diet (HFD) obese animals, CNTF activated extracellular signal-regulated kinase signaling in ME β1- and β2-tanycytes, an effect that has been linked to the promotion of leptin entry into the brain. Accordingly, compared to the animals treated with leptin, mice treated with leptin/CNTF showed: (i) a significantly greater leptin content in hypothalamic protein extracts; (ii) a significant increase in phospho-STAT3 (P-STAT3)-positive neurons in the ARC and the ventromedial hypothalamic nucleus of normally fed mice; and (iii) a significantly increased number of P-STAT3-positive neurons in the ARC and dorsomedial hypothalamic nucleus of HFD obese mice. Collectively, these data suggest that exogenously administered CNTF reduces food intake by exerting a leptin-like action on distinctive NPY ARC neurons and by promoting leptin signaling in hypothalamic feeding centers.

GABAergic interneurons are highly diverse, and their synaptic outputs express various forms of plasticity. Compelling evidence indicates that activity-dependent changes of inhibitory synaptic transmission play a significant role in regulating neural circuits critically involved in learning and memory and circuit refinement. Here, we provide an updated overview of inhibitory synaptic plasticity with a focus on the hippocampus and neocortex. To illustrate the diversity of inhibitory interneurons, we discuss the case of two highly divergent interneuron types, parvalbumin-expressing basket cells and neurogliaform cells, which support unique roles on circuit dynamics. We also present recent progress on the molecular mechanisms underlying long-term, activity-dependent plasticity of fast inhibitory transmission. Lastly, we discuss the role of inhibitory synaptic plasticity in neuronal circuits' function. The emerging picture is that inhibitory synaptic transmission in the CNS is extremely diverse, undergoes various mechanistically distinct forms of plasticity and contributes to a much more refined computational role than initially thought. Both the remarkable diversity of inhibitory interneurons and the various forms of plasticity expressed by GABAergic synapses provide an amazingly rich inhibitory repertoire that is central to a variety of complex neural circuit functions, including memory.

COVID-19 is a highly infectious disease caused by a newly emerged coronavirus (SARS-CoV-2) that has rapidly progressed into a pandemic. This unprecedent emergency has stressed the significance of developing effective therapeutics to fight current and future outbreaks. The receptor-binding domain (RBD) of the SARS-CoV-2 surface Spike protein is the main target for vaccines and represents a helpful “tool” to produce neutralizing antibodies or diagnostic kits. In this work, we provide a detailed characterization of the native RBD produced in three major model systems: Escherichia coli, insect and HEK-293 cells. Circular dichroism, gel filtration chromatography and thermal denaturation experiments indicated that recombinant SARS-CoV-2 RBD proteins are stable and correctly folded. In addition, their functionality and receptor-binding ability were further evaluated through ELISA, flow cytometry assays and bio-layer interferometry.

Myrciaria dubia (Kunth) McVaugh is a fruit tree native to the Amazon with great potential due to its nutraceutical properties; thus, ex situ adaptation technologies should be developed. The objective of this study was to determine the evapotranspiration (ETc) and crop coefficient (Kc) of Myrciaria dubia for domestication and conservation on uplands. Two Myrciaria dubia plants of 2, 4, and 6 years old with similar morphological characteristics of height, number of branches (basal and terminal), and diameter (stem and canopy) were transplanted into drainage lysimeters. Residue of organic mulching composed of a native grass (Trachypogon plumosus) was applied once to one plant of each age category. The mean ETc values for 2-, 4-, and 6-year-old plants in the presence and absence of mulch were 2- and 2.7-mm∙day-1, 3.2- and 3.9-mm∙day-1, and 6.1- and 7.2-mm∙day-1, respectively. The mean Kc values in the EI, EII, and EIII phenological stages with and without mulch were 0.4 and 0.6, 0.6 and 0.8, and 1.1 and 1.3, respectively. The ETc and Kc values for Myrciaria dubia plants with organic mulching can be used in irrigation planning for cultivation, domestication, conservation, and efficient use of water resources in tropical savannas of Roraima, Brazil.

Mikania micrantha is native to Central and South America and exhibits morphological and cytological polymorphism, and evidence of a non-monophyletic origin. In Brazil, the species is widely distributed in the Atlantic Forest, one of the most threatened biomes in the world. AFLP, ITS, ETS and rps16 markers were employed to estimate the genetic diversity and the existence of independent evolutionary lineages in the species, and chromosomes were counted to determine ploidy of 11 populations of M. micrantha. Molecular markers showed relatively high genetic diversity and absence of genetic structure, and chromosome counts revealed pure diploid and tetraploid populations and mixed-cytotype populations in M. micrantha. There was no significant genetic difference between cytotypes, suggesting an autopolyploid origin for tetraploids. However, analyses of species delimitation showed that two highly divergent genetic clusters, constituted of samples from different populations, consisted of two independent evolutionary lineages, demonstrating putative cryptic species in M. micrantha. Our data highlight the need for more genetic studies in M. micrantha to ensure effective conservation actions in its natural area of occurrence and the correct management of the species in introduced areas, where it causes severe damage to forests and plantations.

The aim of this research activity was based on the revalorization of Amplodesmos mauritanicus (Diss), an African grass largely presented in the Algerian territory. Diss stems were selected as native botanic material for the extraction of cellulose nanocrystals (CNC). Two different pretreatment steps were carried out to extract CNC from Amplodesmos mauritanicus stems and the following acidic hydrolysis procedure allowed to extract/obtain cellulose nanocrystals in aqueous suspension. The effect of the two different pretreatments, based essentially on chemical or enzymatic treatments, were deeply investigated and the properties compared. Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were considered for the characterization of raw material, chemical or enzymatic treated Diss stems and CNC extracted from both chemical and enzymatic pretreated cellulose.

The COVID-19 pandemic caused by the β-coronavirus SARS-CoV-2 has made the development of safe and effective vaccines a critical global priority. To date, four vaccines have already been approved by European and American authorities for preventing COVID-19 but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle, a technology previously utilized for cancer vaccines. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 Spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax – a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein RBD – induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function and significantly lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started in Italy.

Made available in DSpace on 2022-04-29T08:30:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 The matamatas (Chelus fimbriata and the recently described Chelus orinocensis) are the largest species in the family Chelidae, easily identified by their distinct morphological characteristics. The matamatas have a wide distribution in South America, occurring in Bolivia, Brazil, Colombia, Ecuador, Guyana, French Guiana, Peru, and Venezuela, as well as Trinidad and Tobago. However, there are many gaps in the knowledge of its distribution. The objective of this study was to present new records of occurrence for the C. fimbriata species complex and describe the area of distribution. We compiled data from published papers, databases in museums and other scientific collections, and research institutes and conservation organizations. From these data we mapped the species distribution, considering 3 types of river drainages based on water color in the Amazon Basin. We added 182 new records in Brazil, Venezuela, Colombia, Bolivia, and Peru, demonstrating that the C. fimbriata species complex has a wide distribution, totaling 6,907,551 kmacross all 3 river types. Most records were concentrated in areas lower than 200 m above sea level. Centro de Estudos de Quelônios da Amazônia/CEQUA Instituto Nacional de Pesquisa da Amazônia/INPA, AM Wildlife Conservation Society Brazil Program, AM Programa de Capacitação Institucional (PCI) Museu Paraense Emílio Goeldi/Instituto Nacional de Pesquisas Do Pantanal/MPEG/INPP, MT Coordenação de Biodiversidade Instituto Nacional de Pesquisa da Amazônia/INPA, AM Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências de Bauru Departamento de Ciências Biológicas, SP Núcleo de Altos Estudos Amazônicos/NAEA Universidade Federal Do Pará/UFPA, PA Museo de Historia Natural la Salle Fundación la Salle de Ciencias Naturales, Apartado Postal 1930 Instituto de Investigación de Recursos Biológicos Alexander von Humboldt Programa de Pós-Graduação em Bioprospecção Molecular Universidade Regional Do Cariri/URCA, CE Instituto de Desenvolvimento Sustentável Mamirauá, AM Centro Nacional de Pesquisa e Conservação de Répteis e Anfíbios/RAN Instituto Chico Mendes de Conservação da Biodiversidade/ICMBio, GO Universidade Federal Do Tocantins, Quadra 109 Norte, TO Programa de Pós-Graduação em Ecologia Aquática e Pesca/PPGEAP Universidade Federal Do Pará/UFPA, PA Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Ciências de Bauru Departamento de Ciências Biológicas, SP

The elongator complex is a highly conserved macromolecular assembly composed by 6 individual proteins (Elp 1–6) and it is essential for many cellular functions such as transcription elongation, histone acetylation and tRNA modification. ELP2 is the second major subunit and with Elp1 and Elp3 it shapes the catalytic core of this essential complex. ELP2 gene pathogenic variants have been reported to be associated with several neurodevelopmental disorders, such as intellectual disability, severe motor development delay with truncal hypotonia, spastic diplegia, choreoathetosis, short stature and neuropsychiatric problems. Here we report a case with heterozygous variants of the ELP2 gene associated with unpublished electro-clinical and neuroimaging features, such as abnormal eye movements, focal epilepsy, cortico-cerebellar atrophy and nodular cortical heterotopia on brain MRI. A possible phenotype-genotype correlation and the electro-clinical and neuroimaging phenotype expansion of ELP2 mutations are here discussed, together with considerations on involved cortico-cerebellar networks and a detailed review of the literature.

Hypothalamic proopiomelanocortin (POMC) neurons are important players in the regulation of energy homeostasis; we previously demonstrated that environmental stimulation excites arcuate nucleus circuits to undergo plastic remodeling, leading to altered ratio between excitatory and inhibitory synaptic contacts on these neurons. The widely used selective serotonin reuptake inhibitor fluoxetine (FLX) is known to affect body weight. On the other hand, FLX administration mimics the effects of environmental stimulation on synaptic plasticity in the hippocampus and cortex. The mammalian target of rapamycin (mTOR) pathway is instrumental in these phenomena. Thus, we aimed at investigating whether and how FLX affects POMC neurons activity and hypothalamic mTOR function. Adult mice expressing green fluorescent protein (GFP) under the POMC promoter were treated with FLX for 3 weeks resulting in diminished body weight. Patch clamp recordings performed on POMC neurons indicate that FLX increases their firing rate and the excitatory AMPA-mediated transmission, and reduces the inhibitory GABAergic currents at presynaptic level. Immunofluorescence studies indicate that FLX increases the ratio between excitatory and inhibitory synaptic contacts on POMC neurons. These changes are associated with an increased activity of the hypothalamic mTOR pathway. Use of the mTOR inhibitor rapamycin blunts the effects of FLX on body weight and on functional and structural plasticity of POMC neurons. Our findings indicate that FLX is able to remodel POMC neurons, and that this may be partly mediated by the mTOR signaling pathway.

The geomagnetic field (GMF) is one of the environmental stimuli that plants experience continuously on Earth; however, the actions of the GMF on plants are poorly understood. Here, we carried out a time-course microarray experiment to identify genes that are differentially regulated by the GMF in shoot and roots. We also used qPCR to validate the activity of some genes selected from the microarray analysis in a dose-dependent magnetic field experiment. We found that the GMF regulated genes in both shoot and roots, suggesting that both organs can sense the GMF. However, 49% of the genes were regulated in a reverse direction in these organs, meaning that the resident signaling networks define the up- or downregulation of specific genes. The set of GMF-regulated genes strongly overlapped with various stress-responsive genes, implicating the involvement of one or more common signals, such as reactive oxygen species, in these responses. The biphasic dose response of GMF-responsive genes indicates a hormetic response of plants to the GMF. At present, no evidence exists to indicate any evolutionary advantage of plant adaptation to the GMF; however, plants can sense and respond to the GMF using the signaling networks involved in stress responses.

Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of molecular mechanisms underlying phage-host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage-host interactions by composing a well-assorted library of 66 newly isolated phages infecting the model organismEscherichia colithat we share with the community as the BASEL collection (BActeriophage SElection for your Laboratory). This collection is largely representative of naturalE. coliphage diversity and was intensively characterized phenotypically and genomically alongside ten well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to eleven defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Our results reveal clear patterns in the distribution of phage phenotypes and genomic features that highlight systematic differences in the potency of different immunity systems and point towards the molecular basis of receptor specificity in several phage groups. Strong trade-offs were detected between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .).

The Zika virus (ZIKV) attracted attention due to one striking characteristic: the ability to cross the placental barrier and infect the fetus, possibly causing severe neurodevelopmental disruptions included in the Congenital Zika Syndrome (CZS). Few years after the epidemic, the CZS incidence has begun to decline. However, how ZIKV causes a diversity of outcomes is far from being understood. This is probably driven by a chain of complex events that relies on the interaction between ZIKV and environmental and physiological variables. In this review, we address open questions that might lead to an ill-defined diagnosis of CZS. This inaccuracy underestimates a large spectrum of apparent normocephalic cases that remain underdiagnosed, comprising several subtle brain abnormalities frequently masked by a normal head circumference. Therefore, new models using neuroimaging and artificial intelligence are needed to improve our understanding of the neurobiology of ZIKV and its true impact in neurodevelopment.

Aims This study evaluated the microbiological quality and safety of minimally processed parsley sold in southeastern Brazilian food markets. Methods and results One hundred samples were submitted to the enumeration of Enterobacteriaceae by plating on MacConkey agar. Colonies of Enterobacteriaceae were randomly selected and identified by MALDI-TOF MS. Samples were also tested for Listeria monocytogenes and Salmonella spp. The mean count of Enterobacteriaceae was 6.0±1.0 log CFU g-1 , while 18 genera (including 30 species) of bacteria belonging to this family were identified. Salmonella and L. monocytogenes were not detected, while L. innocua was found in two samples and L. fleischmannii was found in one sample. Moreover, generic Escherichia coli was found in three samples, all from different brands of minimally processed parsley. Conclusions Even though microbial pathogens were not isolated, a variety of indicator microorganisms were identified, including vegetable spoilers and species capable of causing human opportunistic infections. These results suggest hygienic failures and/or lack of temperature control during processing and storage of these ready-to-eat products. Significance and impact of study This study highlights the need for control measures during the production chain of minimally processed parsley in order to reduce microbial contamination and the risks of foodborne diseases.

Bacterial persisters are difficult to eradicate because of their ability to survive prolonged exposure to a range of different antibiotics. Because they often represent small subpopulations of otherwise drug-sensitive bacterial populations, studying their physiological state and antibiotic stress response remains challenging. Sorting and enrichment procedures of persister fractions introduce experimental biases limiting the significance of follow-up molecular analyses. In contrast, proteome analysis of entire bacterial populations is highly sensitive and reproducible and can be employed to explore the persistence potential of a given strain or isolate. Here, we summarize methodology to generate proteomic signatures of persistent Pseudomonas aeruginosa isolates with variable fractions of persisters. This includes proteome sample preparation, mass spectrometry analysis, and an adaptable machine learning regression pipeline. We show that this generic method can determine a common proteomic signature of persistence among different P. aeruginosa hyper-persister mutants. We propose that this approach can be used as diagnostic tool to gauge antimicrobial persistence of clinical isolates.

Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus. It is responsible for a serious hemorrhagic disease, for which specific and effective treatment and preventive systems are missing. Bioactive compounds derived from several natural products may provide a natural source of broad-spectrum antiviral agents, characterized by good tolerability and minimal side effects. Previous in vitro studies have shown that a cranberry (Vaccinium macrocarpon Ait.) extract containing a high content of A-type proanthocyanidins (PAC-A) inhibits the replication of herpes simplex and influenza viruses by hampering their attachment to target cells. Given the broad-spectrum antimicrobial activity of polyphenols and the urgency to develop therapies for the treatment of CCHF, we investigated the antiviral activity of cranberry extract against HAZV, a surrogate nairovirus model of CCHFV that can be handled in Level 2 Biosafety Laboratories (BSL-2). The results indicate that the cranberry extract exerts an antiviral activity against HAZV by targeting early stages of the viral replication cycle, including the initial adsorption to target cells. Although the details of the molecular mechanism of action remain to be clarified, the cranberry extract exerts a virucidal effect through a direct interaction with HAZV particles that leads to the subsequent impairment of virus attachment to cell-surface receptors. Finally, the antiviral activity of the cranberry extract was also confirmed for CCHFV. As a whole, the evidence obtained suggests that cranberry extract is a valuable candidate to be considered for the development of therapeutic strategies for CCHFV infections.

This chapter examines the development, structure, and function of the central and peripheral nervous systems within the context of caring for critically ill children. The development of the nervous system begins with the establishment of the neuroectoderm and continues through neurogenesis, neuronal migration, synaptogenesis, and programmed cell death. This chapter describes these processes using both normal and pathologic consequences of various developmental stages. An illustrated overview of the structures and function of the nervous system is then provided using clinical correlates to emphasize key concepts.

Antibiotic tolerance and persistence allow bacteria to survive lethal doses of antibiotic drugs in the absence of genetic resistance. Despite the urgent need to address these phenomena as a cause of clinical antibiotic treatment failure, studies on antibiotic tolerance and persistence are notorious for contradictory and inconsistent findings. Many of these problems are likely caused by differences in the methodology used to study antibiotic tolerance and persistence in the laboratory. Standardized experimental procedures would therefore greatly promote research in this field by facilitating the integrated analysis of results obtained by different research groups. Here, we present a robust and adaptable methodology to study antibiotic tolerance/persistence in broth cultures of Escherichia coli and Pseudomonas aeruginosa . The hallmark of this methodology is that the formation and disappearance of antibiotic-tolerant cells is recorded throughout all bacterial growth phases from lag after inoculation over exponential growth into early and then late stationary phase. In addition, all relevant experimental conditions are rigorously controlled to obtain highly reproducible results. We anticipate that this methodology will promote research on antibiotic tolerance and persistence by enabling a deeper view at the growth-dependent dynamics of this phenomenon and by contributing to the standardization or at least comparability of experimental procedures used in the field.

The cuticular hydrocarbon (CHC) profile reflects the insects’ physiological states. These include age, sex, reproductive stage, and gravidity. Environmental factors such as diet, relative humidity or exposure to insecticides also affect the CHC composition in mosquitoes. In this work, the CHC profile was analyzed in two Anopheles albimanus phenotypes with different degrees of susceptibility to Plasmodium, the susceptible-White and resistant-Brown phenotypes, in response to the two dietary regimes of mosquitoes: a carbon-rich diet (sugar) and a protein-rich diet (blood) alone or containing Plasmodium ookinetes. The CHCs were analyzed by gas chromatography coupled to mass spectrometry or flame ionization detection, identifying 19 CHCs with chain lengths ranging from 20 to 37 carbons. Qualitative and quantitative changes in CHCs composition were dependent on diet, a parasite challenge, and, to a lesser extent, the phenotype. Blood-feeding caused up to a 40% reduction in the total CHC content compared to sugar-feeding. If blood contained ookinetes, further changes in the CHC profile were observed depending on the Plasmodium susceptibility of the phenotypes. Higher infection prevalence caused greater changes in the CHC profile. These dietary and infection-associated modifications in the CHCs could have multiple effects on mosquito fitness, impacts on disease transmission, and tolerance to insecticides.

Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

A novel, pleasant taste stimulus becomes aversive if associated with gastric malaise, a form of learning known as conditioned taste aversion (CTA). CTA is common to vertebrates and invertebrates and is an important survival response: eating the wrong food may be deadly. CTA depends on the gustatory portion of the insular cortex (GC) and the basolateral nucleus of the amygdala (BLA) however, its synaptic underpinnings are unknown. Here we report that CTA was associated with decreased expression of immediate early genes in rat GC of both sexes, and with reduced amplitude of BLA-GC synaptic responses, pointing to long term depression (LTD) as a mechanism for learning. Indeed, association of a novel tastant with induction of LTD at the BLA-GC input in vivo was sufficient to change the hedonic value of a taste stimulus. Our results demonstrate a direct role for amygdalocortical LTD in taste aversion learning.

As the novel coronavirus disease sweeps across the world, there is growing speculation on the role that atmospheric factors may have played on the different distribution of SARS-CoV-2, and on the epidemiological characteristics of COVID-19. Knowing the role that environmental factors play in influenza virus outbreaks, environmental pollution and, in particular, atmospheric airborne (particulate matter, PM) has been considered as a potential key factor in the spread and mortality of COVID-19. A possible role of the PM as the virus carrier has also been debated. The role of PM in exacerbating respiratory and cardiovascular disease has been well recognized. Accumulating evidence support the hypothesis that PM can trigger inflammatory response at molecular, cellular and organ levels. On this basis, we developed the hypothesis that PM may play a role as a booster of COVID-19 rather than as a carrier of SARS-CoV-2. To support our hypothesis, we analyzed the molecular signatures detected in cells exposed to PM samples collected in one of the most affected areas by the COVID-19 outbreak, in Italy. T47D human breast adenocarcinoma cells were chosen to explore the global gene expression changes induced by the treatment with organic extracts of PM 2.5. The analysis of the KEGG's pathways showed modulation of several gene networks related to the leucocyte transendothelial migration, cytoskeleton and adhesion system. Three major biological process were identified, including coagulation, growth control and immune response. The analysis of the modulated genes gave evidence for the involvement of PM in the endothelial disease, coagulation disorders, diabetes and reproductive toxicity, supporting the hypothesis that PM, directly or through molecular interplay, affects the same molecular targets as so far known for SARS-COV-2, contributing to the cytokines storm and to the aggravation of the symptoms triggered by COVID-19. We provide evidence for a plausible cooperation of receptors and transmembrane proteins, targeted by PM and involved in COVID-19, together with new insights into the molecular interplay of chemicals and pathogens that could be of importance for sustaining public health policies and developing new therapeutic approaches.

The widespread use of antibiotics promotes the evolution and dissemination of resistance and tolerance mechanisms. To assess the relevance of tolerance and its implications for resistance development, we used in vitro evolution and analyzed inpatient microevolution of Pseudomonas aeruginosa, an important human pathogen causing acute and chronic infections. We show that the development of tolerance precedes and promotes the acquisition of resistance in vitro and we present evidence that similar processes shape antibiotic exposure in human patients. Our data suggest that during chronic infections, P. aeruginosa first acquires moderate drug tolerance before following distinct evolutionary trajectories that lead to high-level multi-drug tolerance or to antibiotic resistance. Our studies propose that the development of antibiotic tolerance predisposes bacteria for the acquisition of resistance at early stages of infection and that both mechanisms independently promote bacterial survival during antibiotic treatment at later stages of chronic infections.

This study focused on bioglea in thermal material sampled at Saturnia spa (Tuscany, Italy). Bioglea is the term used to define the thermal plankton consisting of biogenic substances that have been investigated little from the chemical and biological points of view. Bioglea is mainly formed of cyanobacteria, particularly from the Oscillatoriales subsection, and it seems to have an important role in the maturation of thermal mud for the development of organic matter. This cyanobacteria-dominated community develops in a large outdoor pool at the spa, where the spring water is collected, over the sediments, with matter floating at the surface. Throughout the year, the cyanobacterial species of bioglea were the same, but their relative abundance changed significantly. For chemical characterization an extractive method and several analytical techniques (HPLC, GC-MS, SPME) were used. We also studied the radical scavenging activity using in vitro tests (DPPH, ORAC, ABTS). We found various groups of compounds: saturated and unsaturated fatty acids, hydroxyl acids, alcohols, phenols, amino acids. Many of the compounds have already been identified in the mud, particularly the lipid component. SPME indicated several hydrocarbons (C11&ndash, C17) and long-chain alcohols (C12&ndash, C16). The qualitative composition of volatile substances identified in bioglea was very similar to that of the mud previously analysed. These results contribute to our knowledge on thermal photosynthetic community and its possible exploitation.

(E)-&beta, caryophyllene (BCP) is a natural sesquiterpene hydrocarbon present in hundreds of plant species. BCP possesses several important pharmacological activities, ranging from pain treatment to neurological and metabolic disorders. These are mainly due to its ability to interact with the cannabinoid receptor 2 (CB2) and the complete lack of interaction with the brain CB1. A systematic analysis of plant species with essential oils containing a BCP percentage &gt, 10% provided almost 300 entries with species belonging to 51 families. The essential oils were found to be extracted from 13 plant parts and samples originated from 56 countries worldwide. Statistical analyses included the evaluation of variability in BCP% and yield% as well as the statistical linkage between families, plant parts and countries of origin by cluster analysis. Identified species were also grouped according to their presence in the Belfrit list. The survey evidences the importance of essential oil yield evaluation in support of the chemical analysis. The results provide a comprehensive picture of the species with the highest BCP and yield percentages.