RNA-seq – Revealing Biological Insights in Bacteria

New technologies are constantly being released and the improvements therein bring advances not only to transcriptome, the focus of this chapter, but also to diverse areas of biological research. Since the announcement and application of the RNA-seq approach, discoveries are being made in this field, but when we consider bacterial species, this progress proceeded a few years behind. However, with the application of RNA-seq derivative approaches, we can gain biological insights into the bacterial world and aspire to uncover the mysteries involving gene expression, organization and other functional genomic features

In silico characterization of microRNAs-like sequences in the genome of Paracoccidioides brasiliensis

Eukaryotic cells have different mechanisms of post-transcriptional regulation. Among these mechanisms, microRNAs promote regulation of targets by cleavage or degradation of the mRNA. Fungi of the Paracoccidioides complex are the etiological agents of the main systemic mycosis of Latin America. These fungi present a plasticity to adapt and survive in different conditions, and the presence of microRNAs-like molecules could be part of the mechanisms that provide such plasticity. MicroRNAs produced by the host influence the progression of this mycosis in the lungs besides regulating targets involved in apoptosis in macrophage, activation of T and B cells and the production of cytokines. Therefore, this work analyzed the presence of regions in the genome of this fungus with a potential to encode microRNAs-like molecules. Here we show by analysis of sequence similarity the presence of 18 regions, putatively coding for microRNAs-like molecules in the Paracoccidioides brasiliensis genome. We also described the conservation of dicer and argonaut proteins and the cognate transcripts induced in the yeast parasitic phase. This work represents a starting point for the analysis of the presence of those molecules in the morphological stages of the fungus and their role in fungal development

Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury.

BACKGROUND: The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury. METHOD: To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitin(G76V)-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology. RESULTS AND CONCLUSIONS: Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy

Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence

Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (“metabolic disorder group”) and (2) without any of these features (“non-metabolic-disorder group”). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1–17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The “metabolic disorder group” (n = 52) had a median survival of 15.5 months (95% CI 10.9–33.9) vs. 11.5 months (95% CI 8.4–16.5) in the “non-metabolic-disorder group” (n = 70) (HR: 1.10; 95% CI 0.62–1.94). Patients with resectable disease in the “metabolic group” had longer survival than patients in the “non-metabolic group” (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6–26.9); HR = 0.12, 95% CI 0.03–0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background

Impact of the timing of hepatitis B virus identification and antiâ hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138209/1/cncr30729_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138209/2/cncr30729.pd

Key epidemiological indicators and spatial autocorrelation patterns across five waves of COVID-19 in Catalonia

This research studies the evolution of COVID-19 crude incident rates, effective reproduction number R(t) and their relationship with incidence spatial autocorrelation patterns in the 19 months following the disease outbreak in Catalonia (Spain). A cross-sectional ecological panel design based on n = 371 health-care geographical units is used. Five general outbreaks are described, systematically preceded by generalized values of R(t) &gt; 1 in the two previous weeks. No clear regularities concerning possible initial focus appear when comparing waves. As for autocorrelation, we identify a wave’s baseline pattern in which global Moran’s I increases rapidly in the first weeks of the outbreak to descend later. However, some waves significantly depart from the baseline. In the simulations, both baseline pattern and departures can be reproduced when measures aimed at reducing mobility and virus transmissibility are introduced. Spatial autocorrelation is inherently contingent on the outbreak phase and is also substantially modified by external interventions affecting human behavior

World squid fisheries

Peer reviewedPublisher PD

Maternal Protein Restriction in Two Successive Generations Impairs Mitochondrial Electron Coupling in the Progeny’s Brainstem of Wistar Rats From Both Sexes

Maternal protein deficiency during the critical development period of the progeny disturbs mitochondrial metabolism in the brainstem, which increases the risk of developing cardiovascular diseases in the first-generation (F1) offspring, but is unknown if this effect persists in the second-generation (F2) offspring. The study tested whether mitochondrial health and oxidative balance will be restored in F2 rats. Male and female rats were divided into six groups according to the diet fed to their mothers throughout gestation and lactation periods. These groups were: (1) normoprotein (NP) and (2) low-protein (LP) rats of the first filial generation (F1-NP and F1-LP, respectively) and (3) NP and (4) LP rats of the second filial generation (F2-NP and F2-LP, respectively). After weaning, all groups received commercial chow and a portion of each group was sacrificed on the 30th day of life for determination of mitochondrial and oxidative parameters. The remaining portion of the F1 group was mated at adulthood and fed an NP or LP diet during the periods of gestation and lactation, to produce progeny belonging to (5) F2R-NP and (6) F2R-LP group, respectively. Our results demonstrated that male F1-LP rats suffered mitochondrial impairment associated with an 89% higher production of reactive species (RS) and 137% higher oxidative stress biomarkers, but that the oxidative stress was blunted in female F1-LP animals despite the antioxidant impairment. In the second generation following F0 malnutrition, brainstem antioxidant defenses were restored in the F2-LP group of both sexes. However, F2R-LP offspring, exposed to LP in the diets of the two preceding generations displayed a RS overproduction with a concomitant decrease in mitochondrial bioenergetics. Our findings demonstrate that nutritional stress during the reproductive life of the mother can negatively affect mitochondrial metabolism and oxidative balance in the brainstem of F1 progeny, but that restoration of a normal diet during the reproductive life of those individuals leads toward a mitochondrial recovery in their own (F2) progeny. Otherwise, if protein deprivation is continued from the F0 generation and into the F1 generation, the F2 progeny will exhibit no recovery, but instead will remain vulnerable to further oxidative damage