Reduced Serum Levels of Neuron Specific Enolase (NSE) in Drug-Naïve Subjects with Major Depression and Bipolar Disorder

Several biological factors have been recently related with major depression and bipolar disorder. The aim of our paper was to investigate the peripheral levels of the protein neuronal specific enolase (NSE), a putative marker of neuronal damage, comparing patients with major depressive disorder and bipolar disorder to control subjects. This is a case–control study nested in a cross-sectional population-based survey. Psychopathology screen was performed using the Mini-International Neuropsychiatric Interview 5.0 and blood samples were collected from 108 young adults. Three groups were selected, 36 healthy controls, 36 subjects with major depression disorder and 36 subjects with bipolar disorder. Serum levels of NSE significantly decreased (p = 0.002) in major depression disorder (2.19 ± 1.78 ng/mL) and bipolar disorder subjects (2.53 ± 2.61 ng/mL) compared to the control group (3.55 ± 2.19 ng/mL). In conclusion, peripheral neuronal specific enolase may be a useful marker drug-naïve major depression disorder and bipolar disorder, but its pathophysiological significance and response to treatment should be further investigated.     

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ∼4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using ¹⁴C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of ¹⁴C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)''s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem.     

Phi Index: A New Metric to Test the Flush Early and Avoid the Rush Hypothesis

Optimal escape theory states that animals should counterbalance the costs and benefits of flight when escaping from a potential predator. However, in apparent contradiction with this well-established optimality model, birds and mammals generally initiate escape soon after beginning to monitor an approaching threat, a phenomena codified as the “Flush Early and Avoid the Rush” (FEAR) hypothesis. Typically, the FEAR hypothesis is tested using correlational statistics and is supported when there is a strong relationship between the distance at which an individual first responds behaviorally to an approaching predator (alert distance, AD), and its flight initiation distance (the distance at which it flees the approaching predator, FID). However, such correlational statistics are both inadequate to analyze relationships constrained by an envelope (such as that in the AD-FID relationship) and are sensitive to outliers with high leverage, which can lead one to erroneous conclusions. To overcome these statistical concerns we develop the phi index (Φ), a distribution-free metric to evaluate the goodness of fit of a 1∶1 relationship in a constraint envelope (the prediction of the FEAR hypothesis). Using both simulation and empirical data, we conclude that Φ is superior to traditional correlational analyses because it explicitly tests the FEAR prediction, is robust to outliers, and it controls for the disproportionate influence of observations from large predictor values (caused by the constrained envelope in AD-FID relationship). Importantly, by analyzing the empirical data we corroborate the strong effect that alertness has on flight as stated by the FEAR hypothesis.     

Structural design,synthesis and substituent effect of hydrazone-N-acylhydrazones reveal potent immunomodulatory agents

4-(Nitrophenyl)hydrazone derivatives of N-acylhydrazone were synthesized and screened for suppress lymphocyte proliferation and nitrite inhibition in macrophages. Compared to an unsubstituted N-acylhydrazone, active compounds were identified within initial series when hydroxyl, chloride and nitro substituents were employed. Structure-activity relationship was further developed by varying the position of these substituents as well as attaching structurally-related substituents. Changing substituent position revealed a more promising compound series of anti-inflammatory agents. In contrast, an N-methyl group appended to the 4-(nitrophenyl)hydrazone moiety reduced activity. Anti-inflammatory activity of compounds is achieved by modulating IL-1β secretion and prostaglandin E2 synthesis in macrophages and by inhibiting calcineurin phosphatase activity in lymphocytes. Compound SintMed65 was advanced into an acute model of peritonitis in mice, where it inhibited the neutrophil infiltration after being orally administered. In summary, we demonstrated in great details the structural requirements and the underlying mechanism for anti-inflammatory activity of a new family of hydrazone-N-acylhydrazone, which may represent a valuable medicinal chemistry direction for the anti-inflammatory drug development in general.     

Recurrent Circuitry for Balancing Sleep Need and Sleep

Download video (30MB)Help with mp4 files     

Ticks (Acari: Ixodidae) of the state of Amazonas,Brazil

The tick fauna of Brazil is currently composed by 72 species. The state of Amazonas is the largest of Brazil, with an area of ≈ 19% of the Brazilian land. Besides its vast geographic area, only 19 tick species have been reported for Amazonas. Herein, lots containing ticks from the state of Amazonas were examined in three major tick collections from Brazil. A total of 5933 tick specimens were examined and recorded, comprising 2693 males, 1247 females, 1509 nymphs, and 484 larvae. These ticks were identified into the following 22 species: Amblyomma cajennense sensu lato, Amblyomma calcaratum, Amblyomma coelebs, Amblyomma dissimile, Amblyomma dubitatum, Amblyomma geayi, Amblyomma goeldii, Amblyomma humerale, Amblyomma latepunctatun, Amblyomma longirostre, Amblyomma naponense, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma rotundatum, Amblyomma scalpturatum, Amblyomma varium, Dermacentor nitens, Haemaphysalis juxtakochi, Ixodes cf. Ixodes fuscipes, Ixodes luciae, Rhipicephalus microplus, Rhipicephalus sanguineus sensu lato. Ticks were collected from 17 (27.4%) out of the 62 municipalities that currently compose the state of Amazonas. The following four species are reported for the first time in the state of Amazonas: A. coelebs, A. dubitatum, H. juxtakochi, and Ixodes cf. I. fuscipes. The only tick species previously reported for Amazonas and not found in the present study is Amblyomma parvum. This study provides a great expansion of geographical and host records of ticks for the state of Amazonas, which is now considered to have a tick fauna composed by 23 species. It is noteworthy that we report 1391 Amblyomma nymphs that were identified to 13 different species.     

Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control

Background

Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profile and dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n?=?5) and (2) elite controllers (ECs; n?=?6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (V_E) and latest (V_L) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and flanking CTL epitopes.

Results

Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were?<?1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (<?1%); all VCs showed a high number of mutations, with significant frequency changes between V_E and V_L visits. A higher frequency of internal mutations was observed for gag epitopes, with significant changes across visits compared to Nef epitopes, indicating a pattern associated with differential genetic pressure.

Conclusions

The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants.

     

A quantitative analysis on the effects of critical factors limiting the effectiveness of species conservation in future time

The effectiveness of conservation plans depends on environmental, ecological, and socioeconomic factors. Global change makes conservation decisions even more challenging. Among others, the components of most concern in modern‐day conservation assessments are as follows: the magnitude of climate and land‐use changes; species dispersal abilities; competition with harmful socioeconomic activities for land use; the number of threatened species to consider; and, relatedly, the available budget to act. Here, we provide a unified framework that quantifies the relative effects of those factors on conservation. We conducted an area‐scheduling work plan in order to identify sets of areas along time in which the persistence expectancies of species are optimized. The approach was illustrated using data of potential distribution of ten nonvolant mammal species in Iberia Peninsula from current time up to 2080. Analyses were conducted considering possible setups among the factors that are likely to critically impact conservation success: three climate/land‐use scenarios; four species’ dispersal kernel curves; six land‐use layer types; and two planning designs, in which assessments were made independently for each species, or joining all species in a single plan. We identified areas for an array of investments levels capable to circumvent the spatial conflicts with socioeconomic activities. The effect of each factor on the estimated species persistence scores was assessed using linear mixed models. Our results evidence that conservation success is highly reliant on the resources available to abate land‐use conflicts. Nonetheless, under the same investment levels, planning design and climate change were the factors that most shaped species persistence scores. The persistence of five species was especially affected by the sole effect of planning design and consequently, larger conservation investments may retard climatic debts. For three species, the negative effects of a changing climate and of multiple‐species planning designs added up, making these species especially at risk. Integrated assessments of the factors most likely to limit species persistence are pivotal to achieve effectiveness.