Abstract
Agaves are major biotic resources in arid and semi-arid ecosystems. Despite their ecological, economical and cultural relevance, many aspects of the microbial communities associated with ...agaves are still unknown. Here, we investigated the bacterial communities associated with two Agave species by 16S rRNA- Denaturing gradient gel electrophoresis fingerprinting and sequencing. We also evaluated the effects of biotic and abiotic factors in the structure of the bacterial communities. In parallel, we isolated and characterized diazotrophic bacteria associated with agaves, as Agave soils are characterized by their low nitrogen content. Our results demonstrate that in Agave, the structure of prokaryotic assemblages was mostly influenced by the community group, where the soil, episphere, and endosphere were clearly distinct. Proteobacteria (γ and α), Actinobacteria, and Acidobacteria were the dominant phyla. Bacterial communities in the episphere of agaves were mainly influenced by the host species, whereas in the endosphere were affected by the season. Fifteen bacterial taxa were common and abundant in the endosphere of both Agave species during the dry season. Notably, some of the confirmed diazotrophic strains belonged to this group, suggesting a possible beneficial role in planta.
The structure of bacterial communities associated with Agave species is distinct among soil, episphere and endosphere, where diazotrophic bacteria may facilitate adaption of these crassulacean acid metabolism-plants to low-nutrient environments.
The structure of bacterial communities associated with Agave species is distinct among soil, episphere and endosphere, where diazotrophic bacteria may facilitate adaption of these crassulacean acid metabolism-plants to low-nutrient environments.
Objective
We aimed (1) to analyze salivary calcitonin gene‐related peptide (CGRP) levels in patients with migraine, (2) to predict erenumab response from baseline CGRP levels, and (3) to evaluate ...CGRP change post‐treatment.
Methods
This is a prospective observational study that measured salivary CGRP levels in healthy controls (HCs), patients with episodic migraine (EM) and patients with chronic migraine (CM). Participants collected saliva samples at baseline and, the patients who were candidates to receive erenumab, also collected saliva after 3 doses of treatment. We quantified CGRP‐like immunoreactivity (CGRP‐LI) by enzyme‐linked immunosorbent assay (ELISA) and we performed an analysis at baseline and post‐treatment through generalized linear mixed models.
Results
At baseline, a higher headache frequency was associated with higher CGRP levels, those being even higher in the presence of depressive symptoms. A cutoff point (mean, 95% confidence interval CI) of 103.93 (95% CI = 103.35–104.51) pg/ml was estimated to differentiate migraine from controls with an area under the receiver operating characteristic (ROC) curve (AUC, 95% CI) of 0.801 (95% CI = 0.798–0.804). We also found that higher pretreatment salivary CGRP levels were statistically significantly associated to a higher probability of having 50% or greater reduction in headache frequency in patients with EM, but not in patients with CM. After 12 weeks of treatment with erenumab, salivary CGRP levels from patients within all spectrum of migraine frequency converged to similar CGRP values. In contrast, in patients with concomitant depressive symptoms, this convergence did not happen.
Interpretation
Patients with migraine not only have higher CGRP levels compared with HCs, but also the presence of depressive symptoms seems to increase salivary CGRP levels and we have evidence, for the first time, that baseline salivary CGRP concentration is associated with treatment response to erenumab. ANN NEUROL 2022;92:846–859
There are few studies of careful examination of wildlife casualties in Wildlife Rehabilitation Centers. These studies are essential for detecting menaces to wild species and providing objective ...criteria about cost-benefit of treatments in those centers. The release rate is considered the main outcome indicator, but other parameters such as length of stay at the center and a cost-benefit index expressed as number of released animals per euro and day, could be used as reliable estimators of the rehabilitation costs.
A retrospective study based on 54772 admissions recorded from 1995-2013 in the database of the Wildlife Rehabilitation Center of Torreferrussa (Catalonia, NW Spain) assessed the morbidity, outcomes and cost-benefits of the rehabilitation practices.
Three hundred and two species were included: 232 birds (n = 48633), 37 mammals (n = 3293), 20 reptiles (n = 2705) and 13 amphibians (n = 141). The most frequent causes of admission were: 39.8% confiscation of protected species (89.4% passerines), 31.8% orphaned young animals (35.3% swifts, 21.7% diurnal raptors and owls) and 17.4% trauma casualties (46.7% raptors and owls). The highest proportion of releases was found in the captivity confiscation category 87.4% passerines (median time of stay: 12 days), followed by the orphaned category 78% owls (66 days), 76.5% diurnal birds of prey (43 days), 75.6% hedgehogs (49 days), 52.7% swifts (19 days) and 52% bats (55 days). For the trauma group, 46.8% of releases were hedgehogs (44 days) and 25.6% owls (103 days). As regards the cost-benefit index, the trauma casualties and infectious diseases had the worse values with 1.3 and 1.4 released animals/euro/day respectively, and were particularly low in raptors, waders, marine birds and chiroptera. On the contrary, captivity (4.6) and misplacement (4.1) had the best index, particulary in amphibian, reptiles and passerines.
Cost-benefit studies including the release rate, the time of stay at the center and the cost-benefit index should be implemented for improving management efficiency of the Wildlife Rehabilitation Centers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
CGRP plays a key role in the transmission and modulation of nociceptive signals and is a critical component in the pathogenesis of migraine.
Objective
To assess saliva as a substrate to ...measure CGRP by comparing interictal levels in patients with episodic migraine and controls; and to evaluate CGRP’s temporal profile during migraine attacks.
Methods
This prospective observational pilot study included young women with episodic migraine and healthy controls. We monitored salivary CGRP-like immunoreactivity (CGRP-LI) during 30 consecutive days and during migraine attacks. We considered six timepoints for the analysis: interictal (72h headache free), preictal (PRE-24h before the attack), ictal (headache onset, after 2h, after 8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA.
Results
44 women (22 with episodic migraine, 22 healthy controls) were recruited. Differences in interictal salivary levels of CGRP between patients and controls (Me IQR: 98.0 80.3 (95% CI 56.6, 124.0) vs. 54.3 44.0 (95% CI 42.2, 70.1) pg/mL, p = 0.034) were found. An increase in CGRP levels during migraine attacks was detected (pre:169.0 95% CI 104.2–234.0; headache onset: 247.0 181.9–312.0; after 2h: 143.0 77.6–208.0; after 8h: 169.0 103.5–234.0, post: 173.0 107.8–238.0). Patients were classified as having CGRP-dependent (79.6%) and non-CGRP dependent migraine attacks (20.4%) according to the magnitude of change between preictal and ictal phase. Accompanying symptoms such as photophobia and phonophobia were significantly associated to the first group.
Conclusions
Salivary CGRP-LI levels, which interictally are elevated in episodic migraine patients, usually increase during a migraine attack in the majority of patients. However, not every attack is CGRP-dependent, which in turn, might explain different underlying pathophysiology and response to treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The advent of multidrug-resistant bacteria has hampered the development of new antibiotics, exacerbating their morbidity and mortality. In this context, the gastrointestinal tract reveals a valuable ...source of novel antimicrobials. Microcins are bacteriocins produced by members of the family
which are endowed with a wide diversity of structures and mechanisms of action, and exert potent antibacterial activity against closely related bacteria. In this study, we investigated the antibacterial activities of four microcins against 54
isolates from three species (Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The selected microcins, microcin C (McC, nucleotide peptide), microcin J25 (MccJ25, lasso peptide), microcin B17 (MccB17, linear azol(in)e-containing peptide), and microcin E492 (MccE492, siderophore peptide) carry different post-translational modifications and have distinct mechanisms of action. MICs and minimal bactericidal concentrations (MBC) of the microcins were measured and the efficacy of combinations of the microcins together or with antibiotics was assessed to identify potential synergies. Every isolate showed sensitivity to at least one microcin with MIC values ranging between 0.02 μM and 42.5 μM. Among the microcins tested, McC exhibited the broadest spectrum of inhibition with 46 strains inhibited, closely followed by MccE492 with 38 strains inhibited, while MccJ25 showed the highest activity. In general, microcin activity was observed to be independent of antibiotic resistance profile and strain genus. Of the 42 tested combinations, 20 provided enhanced activity (18 out of 20 being microcin-antibiotic combinations), with two being synergetic.
With their wide range of structures and mechanisms of action, microcins are shown to exert antibacterial activities against
resistant to antibiotics together with synergies with antibiotics and in particular colistin.
Background
Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a ...key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables.
Methods
A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2 h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype.
Results
A total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. SE: 19.4 5.8,
p
= 0.001) and quadratic terms of time (-19.1 6.0,
p
= 0.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 6.2,
p
= 0.005; quadratic-term: 19.2 6.8,
p
= 0.005) was also found. Molecular phenotyping revealed that 72.7% (32/44) of patients presented only CGRP-dependent attacks, while 27.3% (12/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (
p
< 0.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks.
Conclusions
Our study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.
l-Arginine metabolism through arginase 1 (Arg-1) and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of leishmaniasis. Infection with
can cause ...two distinct clinical manifestations: localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). In this work, we analyzed in an
model the capacity of two
isolates, one obtained from a patient with LCL and the other from a patient with DCL, to regulate the metabolism of l-arginine through Arg-1 and NOS2. Susceptible BALB/c mice were infected with
isolates from both clinical manifestations, and the evolution of the infection as well as protein presence and activity of Arg-1 and NOS2 were evaluated. The lesions of mice infected with the DCL isolate were bigger, had higher parasite loads, and showed greater protein presence and enzymatic activity of Arg-1 than the lesions of mice infected with the LCL isolate. In contrast, NOS2 protein synthesis was poorly or not induced in the lesions of mice infected with the LCL or DCL isolate. The immunochemistry analysis of the lesions allowed the identification of highly parasitized macrophages positive for Arg-1, while no staining for NOS2 was found. In addition, we observed in lesions of patients with DCL macrophages with higher parasite loads and stronger Arg-1 staining than those in lesions of patients with LCL. Our results suggest that
isolates obtained from patients with LCL or DCL exhibit different virulence or pathogenicity degrees and differentially regulate l-arginine metabolism through Arg-1.
Iron chelation therapy (ICT) is the mainstay of treatment in patients with thalassemia requiring blood transfusions. This phase 2 JUPITER study evaluated patient preference between film-coated tablet ...(FCT) and dispersible tablet (DT) in transfusion-dependent thalassemia (TDT) or non-TDT (NTDT) patients treated with both formulations in a sequential manner. The primary endpoint was patient-reported preference for FCT over DT, while secondary outcomes included patient reported outcomes (PROs) evaluated by overall preference, and by age, thalassemia transfusion status, and previous ICT status. Out of 183 patients screened, 140 and 136 patients completed the treatment periods 1 and 2 of the core study, respectively. At week 48, the majority of patients preferred FCT over DT (90.3 vs. 7.5%; difference of percentage: 0.83 95% confidence interval (CI), 0.75–0.89;
P
< 0.0001). FCT scored better on secondary PROs and showed less severe gastrointestinal symptoms than DT, except in the change of modified Satisfaction with Iron Chelation Therapy (mSICT) preference scores, which were similar for both the formulations. Patients with TDT had stable ferritin levels, while it showed a downward trend up to week 48 in patients with NTDT on deferasirox treatment. Overall, 89.9% of patients reported ≥ 1 adverse event (AE), of which 20.3% experienced ≥ 1 serious AE. The most common treatment-emergent AEs were proteinuria, pyrexia, urine protein/creatinine ratio increase, diarrhea, upper respiratory tract infections, transaminase increase, and pharyngitis. Overall, this study reinforced the observations from the previous study by showing a distinct patient preference for FCT over DT formulation and further supported the potential benefits of life-long compliance with ICT.
Necrotic enteritis (NE) caused by
is one of the most common diseases of poultry and results in a huge economic loss to the poultry industry, with resistant clostridial strains being a serious concern ...and making the treatment difficult. Whole-genome sequencing approaches represent a good tool to determine resistance profiles and also shed light for a better understanding of the pathogen. The aim of this study was to characterize, at the genomic level, a collection of 20
isolates from poultry affected by NE, giving special emphasis to resistance mechanisms and production of bacteriocins. Antimicrobial resistance genes were found, with the
genes (associated with tetracycline resistance) being the most prevalent. Interestingly, two isolates carried the
gene associated with erythromycin resistance, which has only been reported in other Gram-positive bacteria. Twelve of the isolates were toxinotyped as type A and seven as type G. Other virulence factors encoding hyaluronases and sialidases were frequently detected, as well as different plasmids. Sequence types (ST) revealed a high variability of the isolates, finding new allelic combinations. Among the isolates,
MLG7307 showed unique characteristics; it presented a toxin combination that made it impossible to toxinotype, and, despite being identified as
, it lacked the housekeeping gene
. Genes encoding bacteriocin BCN5 were found in five isolates even though no antimicrobial activity could be detected in those isolates. The
gene of three of our isolates was similar to one previously reported, showing two polymorphisms. Concluding, this study provides insights into the genomic characteristics of
and a better understanding of this avian pathogen.
Summary
Citrus canker is an important disease of citrus, whose causal agent is the bacterium Xanthomonas citri ssp. citri (Xcc). In previous studies, we found a group of Xcc mutants, generated by the ...insertion of the Tn5 transposon, which showed impaired ability to attach to an abiotic substrate. One of these mutants carries the Tn5 insertion in hupB, a gene encoding a bacterial histone‐like protein, homologue to the β‐subunit of the Heat‐Unstable (HU) nucleoid protein of Escherichia coli. These types of protein are necessary to maintain the bacterial nucleoid organization and the global regulation of gene expression. Here, we characterized the influence of the mutation in hupB regarding Xcc biofilm formation and virulence. The mutant strain hupB was incapable of swimming in soft agar, whereas its complemented strain partially recovered this phenotype. Electron microscope imaging revealed that impaired motility of hupB was a consequence of the absence of the flagellum. Comparison of the expression of flagellar genes between the wild‐type strain and hupB showed that the mutant exhibited decreased expression of fliC (encoding flagellin). The hupB mutant also displayed reduced virulence compared with the wild‐type strain when they were used to infect Citrus lemon plants using different infection methods. Our results therefore show that the histone‐like protein HupB plays an essential role in the pathogenesis of Xcc through the regulation of biofilm formation and biosynthesis of the flagellum.
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