Periodontitis is an inflammatory disease induced by a dysbiotic oral microbiome. Probiotics of the genus
Bifidobacterium
may restore the symbiotic microbiome and modulate the immune response, leading ...to periodontitis control. We evaluated the effect of two strains of
Bifidobacterium
able to inhibit
Porphyromonas gingivalis
interaction with host cells and biofilm formation, but with distinct immunomodulatory properties, in a mice periodontitis model. Experimental periodontitis (P+) was induced in C57Bl/6 mice by a microbial consortium of human oral organisms.
B. bifidum
162
2A
B+ (1622) and
B. breve
110
1A
B+ (1101) were orally inoculated for 45 days. Alveolar bone loss and inflammatory response in gingival tissues were determined. The microbial consortium induced alveolar bone loss in positive control (P + B-), as demonstrated by microtomography analysis, although
P. gingivalis
was undetected in oral biofilms at the end of the experimental period. TNF-α and IL-10 serum levels, and Treg and Th17 populations in gingiva of SHAM and P + B- groups did not differ.
B. bifidum
162
2A
, but not
B. breve
110
1A
, controlled bone destruction in P+ mice.
B. breve
110
1A
upregulated transcription of
Il-1β
,
Tnf-α
,
Tlr2
,
Tlr4
, and
Nlrp3
in P-B+(1101), which was attenuated by the microbial consortium P + B+(1101). All treatments downregulated transcription of
Il-17
, although treatment with
B. breve
110
1A
did not yield such low levels of transcripts as seen for the other groups.
B. breve
110
1A
increased Th17 population in gingival tissues P-B+ (1101) and P + B+ (1101) compared to SHAM and P + B-. Administration of both bifidobacteria resulted in serum IL-10 decreased levels. Our data indicated that the beneficial effect of
Bifidobacterium
is not a common trait of this genus, since
B. breve
110
1A
induced an inflammatory profile in gingival tissues and did not prevent alveolar bone loss. However, the properties of
B. bifidum
162
2A
suggest its potential to control periodontitis.
Phosphorus (P) is the fifth most abundant element in living cells. This element is acquired mainly as inorganic phosphate (Pi, PO
). In enteric bacteria, P starvation activates a two-component signal ...transduction system which is composed of the membrane sensor protein PhoR and its cognate transcription regulator PhoB. PhoB, in turn, promotes the transcription of genes that help maintain Pi homeostasis. Here, we characterize the P starvation response of the bacterium
. We determine the PhoB-dependent and independent transcriptional changes promoted by P starvation and identify proteins enabling the utilization of a range of organic substrates as sole P sources. We show that transcription and activity of a subset of these proteins are independent of PhoB and Pi availability. These results establish that
can maintain Pi homeostasis and repress PhoB/PhoR activation even when cells are grown in medium lacking Pi.
Pre-operative 5-fluoracil-based chemoradiotherapy (nCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC). Patients with pathological complete response (pCR-0% of ...tumor cells in the surgical specimen after nCRT) have better overall survival and lower risk of recurrence in comparison with incomplete responders (pIR). Predictive biomarkers to be used for new therapeutic strategies and capable of stratifying patients to avoid overtreatment are needed. We evaluated the genomic profiles of 33 pre-treatment LARC biopsies using SNP array and targeted-next generation sequencing (tNGS). Based on the large number of identified genomic alterations, we calculated the genomic instability index (GII) and three homologous recombination deficiency (HRD) scores, which have been reported as impaired DNA repair markers. We observed high GII in our LARC cases, which was confirmed in 165 rectal cancer cases from TCGA. Patients with pCR presented higher GII compared with pIR. Moreover, a negative correlation between GII and the fraction of tumor cells remaining after surgery was observed (ρ = -0.382,
= 0.02). High HRD scores were detected in 61% of LARC, of which 70% were incomplete responders. Using tNGS (105 cancer-related genes, 13 involved in HR and 5 in mismatch repair pathways), we identified 23% of cases with mutations in HR genes, mostly in pIR cases (86% of mutated cases). In agreement, the analysis of the TCGA dataset (
= 145) revealed 21% of tumors with mutations in HR genes. The HRD scores were shown to be predictive of better response to PARP-inhibitors and platinum-based chemotherapy in breast and ovarian cancer. Our results suggest that the same strategy could be applied in a set of LARC patients with HRD. In conclusion, we identified high genomic instability in LARC, which was related to alterations in the HR pathway, especially in pIR. These findings suggest that patients with impaired HRD would clinically benefit from PARP-inhibitors and platinum-based therapy.
We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to ...zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well.S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol.
COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. ...Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress.
Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects.
Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e' ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors.
Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.
Biofuels have been seen as potential sources to meet future energy demand as a renewable and sustainable energy source. Despite the fact that the production technology of first-generation biofuels is ...consolidated, these biofuels are produced from foods crops such as grains, sugar cane, and vegetable oils competing with food for crop use and agricultural land. In recent years, it was found that microalgae have the potential to provide a viable alternative to fossil fuels as source of biofuels without compromising food supplies or arable land. On this scenario, this paper aims to demonstrate the energetic potential to produce bio-oil and chemicals from microalgae
Chlorella vulgaris
and
Arthrospira platensis
. The potential of these biomasses was evaluated in terms of physical-chemical characterization, thermogravimetric analysis, and analytical pyrolysis interfaced with gas chromatograph (Py-GC/MS). The results show that
C. vulgaris
and
A. platensis
are biomasses with a high heating value (24.60 and 22.43 MJ/kg) and low ash content, showing a high percentage of volatile matter (72.49 and 79.42%). These characteristics confirm their energetic potential for conversion process through pyrolysis, whereby some important aromatic compounds such as toluene, styrene, and phenol were identified as pyrolysis products, which could turn these microalgae a potential for biofuels and bioproduct production through the pyrolysis.
The observation of tumor-derived cell-free DNA (ctDNA) in plasma brought new expectations to monitor treatment response in cancer patients.
In an exploratory case of a 57-year-old man diagnosed with ...metastatic sigmoid adenocarcinoma, we used a hotspot panel of cancer-associated gene mutations to identify tumor-specific mutations in the primary tumor and metastasis.
Five mutations were detected (
, p.Gly12Val;
, p.Arg175His;
, p.Ile680Thr;
, p.Gly1184Glu; and
, p.Lys860Lys), of which three were detected in both tissue types (primary tumor and metastasis). All five mutations were monitored in the ctDNA of six serial plasma samples. Only
and
mutations were detected at a high frequency in the first plasma sample. After 1 month of chemotherapy the allele frequencies of both mutations fell below the detection limit. From the third month of systemic treatment onward, the allele frequencies of both mutations were detectable in plasma, displaying a continual increase thereafter. The remaining three mutations were not detected in plasma samples. Signs of disease progression in ctDNA during the treatment period were evident while computed tomography (CT) measurements suggested stable metastatic lesions throughout the treatment.
Liquid biopsies revealed tumor heterogeneity and predicted tumor progression, demonstrating the potential of ctDNA analysis to be a sensitive and specific tool for monitoring treatment responsivity and for early identification of treatment resistance.
The use of insoles, which is increasingly widespread, can promote changes in biomechanics during running.
Can the use of insoles with various patterns of infracapital support influence factors ...related to the dynamic stability of the lower limbs during running on a treadmill in recreational runners?
This is controlled single-blind repeated measures. Static baropodometric data were collected, as well as kinematic data for the lower limbs and electromyographic data for the gluteus maximus and gluteus medius muscles, for twelve recreational runners on a treadmill using four models of insoles (neutral and with forefoot elements - infracapital bar).
Neutral insoles were able to reduce laterolateral displacement, increase the displacement of the mass to the posterior, and increase the lateral rotation of the left knee and medial rotation of the right hip. Insoles with a 2 mm total infracapital bar were able to move the mass to the posterior, increase laterolateral displacement and activate the gluteus medius. Insoles with a 2 mm medial infracapital bar were able to increase the displacement of the mass to the posterior, increase the adduction of left hip and the medial rotation of right hip, and activate the gluteus medius. Insoles with a 4 mm medial infracapital element were able to move the body mass to the posterior and to the left, increase laterolateral displacement, increase the adduction of left hip, the medial rotation of right hip and the abduction of right knee.
The insoles evaluated in the present study were able to modify biomechanical variables of recreational runners related to dynamic stability during running on a treadmill and static baropodometric variables.
•Insoles with forefoot elements can promote changes in static and dynamic variables.•Neutral insoles can improve static balance.•Insoles can increase the activation of the gluteus medius during the run.
•Female zebrafish display higher baseline anxiety-like behavior.•Females demonstrated greater individual variability in locomotor activity.•Acute scopolamine exposure causes anxiogenic-like effect in ...males.•Acute scopolamine exposure caused anxiolytic-like effect in females.•These findings support overt sex and individual differences in zebrafish behavior.
Sex differences influence human and animal behavioral and pharmacological responses. The zebrafish (Danio rerio) is a powerful, popular model system in neuroscience and drug screening. However, the impact of zebrafish sex differences on their behavior and drug responses remains poorly understood. Here, we evaluate baseline anxiety-like behavior in adult male and female zebrafish, and its changes following an acute 30-min exposure to 800-μM scopolamine, a common psychoactive anticholinergic drug. Overall, we report high baseline anxiety-like behavior and more individual variability in locomotion in female zebrafish, as well as distinct, sex-specific (anxiolytic-like in females and anxiogenic-like in males) effects of scopolamine. Collectively, these findings reinforce the growing importance of zebrafish models for studying how both individual and sex differences shape behavioral and pharmacological responses.
•Colors are an important biological factor affecting human and animal behavior and physiology.•The zebrafish is rapidly emerging as a novel model species in neuroscience research.•Colors potently ...affect zebrafish affective, social and cognitive behaviors.•Color is a key factor in zebrafish neurophenomics and CNS disease modeling.
Color is an important environmental factor that in multiple ways affects human and animal behavior and physiology. Widely used in neuroscience research, various experimental (animal) models may help improve our understanding of how different colors impact brain and behavioral processes. Complementing laboratory rodents, the zebrafish (Danio rerio) is rapidly emerging as an important novel model species to explore complex neurobehavioral processes. The growing utility of zebrafish in biomedicine makes it timely to consider the role of colors in their behavioral and physiological responses. Here, we summarize mounting evidence implicating colors as a critical variable in zebrafish models and neurobehavioral traits, with a particular relevance to CNS disease modeling, genetic and pharmacological modulation, as well as environmental enrichment and animal welfare. We also discuss the growing value of zebrafish models to study color neurobiology and color-related neurobehavioral phenomics, and outline future directions of research in this field.
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