Explore the vast range of titles available.

Real-world memories are formed in a particular context and are often not acquired or recalled in isolation 1 – 5 . Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not 1 – 4 . How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12–24 h) increase in the expression of C-C chemokine receptor type 5 (CCR5)—an immune receptor that is well known as a co-receptor for HIV infection 6 , 7 —after the formation of a contextual memory determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed expression of CCR5 in mouse dorsal CA1 neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and therefore closes the temporal window for memory linking. Our findings also show that an age-related increase in the neuronal expression of CCR5 and its ligand CCL5 leads to impairments in memory linking in aged mice, which could be reversed with a Cc r5 knockout and a drug approved by the US Food and Drug Administration (FDA) that inhibits this receptor, a result with clinical implications. Altogether, the findings reported here provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking. A molecular mechanism involving CCR5 and CCL5 determines the temporal window in which a memory can be linked with subsequent memories, and in aged mice an increase in CCR5 is associated with defects in memory linking.

The neural circuits underlying memory change over prolonged periods after learning, in a process known as systems consolidation. Postlearning spontaneous reactivation of memory-related neural ensembles is thought to mediate this process, although a causal link has not been established. Here we test this hypothesis in mice by using optogenetics to selectively reactivate neural ensembles representing a contextual fear memory (sometimes referred to as engram neurons). High-frequency stimulation of these ensembles in the retrosplenial cortex 1 day after learning produced a recent memory with features normally observed in consolidated remote memories, including higher engagement of neocortical areas during retrieval, contextual generalization, and decreased hippocampal dependence. Moreover, this effect was only present if memory ensembles were reactivated during sleep or light anesthesia. These results provide direct support for postlearning memory ensemble reactivation as a mechanism of systems consolidation, and show that this process can be accelerated by ensemble reactivation in an unconscious state.

The nature and distribution of the synaptic changes that underlie memory are not well understood. Here we examine the synaptic plasticity behind context fear conditioning in male and female mice and find that new learning produces synaptic potentiation specifically onto engram neurons in the basolateral amygdala. This potentiation lasts at least 7 days, is reversed by extinction, and its disruption impairs memory recall. High frequency optogenetic stimulation of the CS and US-activated ensembles, or biochemical induction of synaptic potentiation in US-responsive neurons alone, is sufficient to produce a context fear association without prior associative training. These results suggest that plasticity of CS inputs onto US-responsive amygdala neurons underlies memory formation and is necessary and sufficient to establish context fear associations.

The nature and distribution of the synaptic changes that underlie memory are not well understood. We examined the synaptic plasticity behind context fear conditioning and found that learning produced synaptic potentiation specifically onto engram neurons in the basolateral amygdala. This potentiation lasted at least 7 days, was reversed by extinction, and its disruption impaired memory recall. High frequency optogenetic stimulation of the CS and US-activated ensembles, or biochemical induction of synaptic potentiation in US-responsive neurons alone, was sufficient to produce a context fear association without prior associative training. These results suggest that plasticity of CS inputs onto US-responsive amygdala neurons underlies memory formation and is necessary and sufficient to establish context fear associations.

Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers. In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18-55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing-including determination of maximal oxygen uptake (VO2max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O2 pulse). Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO2max and O2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group. The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD patients are needed in order to confirm the utility of short-term aerobic exercise as an alternative therapeutic approach in MDD. ClinicalTrials.gov NCT02427789.

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in β-cyclodextrin (β-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:β-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:β-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:β-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:β-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with a wide variety of infections in humans. The ability of MRSA to infect companion animals has gained increasing attention in the scientific literature. In this study, 334 dogs were screened for MRSA in two cities located in Rio de Janeiro State. The prevalence of MRSA in dogs was 2.7%. Genotyping revealed isolates from sequence types (ST) 1, 5, 30, and 239 either colonizing or infecting dogs. The genome of the canine ST5 MRSA (strain SA112) was compared with ST5 MRSA from humans—the main lineage found in Rio de Janeiro hospitals—to gain insights in the origin of this dog isolate. Phylogenetic analysis situated the canine genome and human strain CR14-035 in the same clade. Comparative genomics revealed similar virulence profiles for SA112 and CR14-035. Both genomes carry S. aureus genomic islands νSAα, νSAβ, and νSAγ. The virulence potential of the canine and human strains was similar in a Caenorhabditis elegans model. Together, these results suggest a potential of canine MRSA to infect humans and vice versa. The circulation in community settings of a MRSA lineage commonly found in hospitals is an additional challenge for public health surveillance authorities.

Although Global Navigation Satellite Systems (GNSS) receivers currently achieve high accuracy when processing their geographic location under line of sight (LOS), multipath interference and noise degrades the accuracy considerably. In order to mitigate multipath interference, receivers based on multiple antennas became the focus of research and technological development. In this context, tensor-based approaches based on Parallel Factor Analysis (PARAFAC) models have been proposed in the literature, providing optimum performance. State-of-the-art techniques for antenna array based GNSS receivers compute singular value decomposition (SVD) for each new sample, implying into a high computational complexity, being, therefore, prohibitive for real-time applications. Therefore, in order to reduce the computational complexity of the parameter estimates, subspace tracking algorithms are essential. In this work, we propose a tensor-based subspace tracking framework to reduce the overall computational complexity of the highly accurate tensor-based time-delay estimation process.

IntroductionNeurological soft signs (NSS) have long been described in schizophrenic patients. However, recent studies focusing on first-episode psychosis and at-risk mental states have brought up some aspects that may point to a neurodevelopmental underpinning of the disease.ObjectivesWe aimed to review the published literature concerning NSS and psychosis and critically analyze it in regard to how it may constitute a body of evidence favouring the neurodevelopmental hypothesis of schizophrenia.MethodsWe conducted a Pubmed ® research using the following terms “neurological soft signs”, “psychosis”, “psychotic” and “first-episode”.ResultsThe studies that have been carried out found a gradation of NSS scores that had its minimum values in healthy controls, intermediate scores in at-risk mental state individuals, and highest scores in first-episode psychosis. NSS correlate with various brain imaging anomalies, which indicates abnormal neurological function. Its scores also correlate with poorer cognitive performance and more prominent negative symptoms in the short- and long-term. Interestingly, patients who have psychotic episodes associated with cannabis use have lower NSS scores than all the other psychotic-illness diagnostic groups.ConclusionsNSS might thus translate a neurological dysfunction that exists previous to the psychotic break and is a measure of one’s vulnerability to psychosis. These results point to the existence of two distinct groups: one that has high NSS scores and therefore a high genetic vulnerability, needing little contribution of environmental factors to manifest a psychotic episode; and another one with low NSS scores, a smaller genetic vulnerability and a greater role played by environmental influences.Disclosure of InterestNone Declared

A superabsorbent hydrogel composite based on a starch-grafted-poly(sodium acrylate) matrix filled with husk rice ash (RHA) was synthesized and tested as a soil conditioner to enhance the melon seedling growth. The incorporation of 20 wt% of RHA in the hydrogel matrix endowed the composite with an outstanding liquid uptake capacity (42,000%). Field experiments were performed to investigate the effect of the amount of hydrogel, type o subtract (sandy soil and coconut fibers) and type of soil (sandy soil and clay soil) on several parameters related to the plants' growth process. Overall, the plants cultivated in coconuts fibers exhibited the highest plant growth (5.60 cm) as compared to the plants cultivated in sandy soil (4.12 cm); however, the conditioning effect was limited in this case. Also, in this experiment, the amount of hydrogel used only affected the plant roots size. Additional analyses showed that the plant growth process is enhanced in clay soil as compared to sandy soil. Here, a synergistic beneficial effect was noticed between the type of soil and the amount of hydrogel used as conditioners. A small amount of hydrogel (≤ 0.75 wt%) had an apparent positive effect on the plants' growth process when they are cultivated in clay soils. In summary, the results presented here allow inferring that these composite hydrogels can be ranked as promising materials for use as soil conditioners.