PDK1 is a constitutively active master kinase that can phosphorylate and activate as many as 24 enzymes, all belonging to the AGC family of serine-threonine protein kinases. In this issue of
, ...Sacerdoti
. uncover how allosteric communication between different functional domains directs the selectivity of PDK1 toward particular subsets of substrates.
High nitrogen (N) concentration in bovine urine, which generally exceeds plant N uptake rates, results in the formation of hotspots of N loss when bovine urine is deposited on grazed pasture soils. ...High spatial variability in the distribution of urine patches in grazed pastures poses a major challenge to mitigate N losses. Some exudates from the roots of several tropical forage grasses were shown to inhibit the activity of soil nitrifiers; a process known as biological nitrification inhibition (BNI). We hypothesized that nitrate (NO3−) production and nitrous oxide (N2O) emissions from urine patches deposited on soils under forage grasses with high BNI capacity are lower than those with forage grasses with low BNI capacity. This hypothesis was tested using field plots of two tropical forage grass cultivars, Brachiaria humidicola cv. Tully (BT) and interspecific Brachiaria hybrid cv. Mulato (BM) which, correspondingly, have high and low BNI capacity. Nitrification rates and amoA gene copy numbers of ammonia oxidizing archaea (AOA) and bacteria (AOB) in soils under the two forage grasses were quantified before and after urine and water (control) application, as well, an additional experiment was conducted to quantify denitrification potential. Moreover, soil N2O emissions from simulated urine (0.123 kg N m−2) and water patches were monitored over a 29-day period. Results showed a greater suppression of nitrification, denitrification and AOA abundance in soils under BT than those under BM. Positive relationships (p < 0.05) existed between AOA and AOB abundance and NO3− contents in soils under BM. Bovine urine resulted in higher cumulative N2O fluxes from soils under BM (80 mg N2O-N m−2) compared to those under BT (32 mg N2O-N m−2). Consequently, N2O emission factors were higher for soils under BM (0.07%) than under BT (0.00002%). We conclude that tropical forage grasses with high BNI capacity play a key role in mitigating N2O emissions from bovine urine patches in archaea-dominated soils. This suggests that wide-spread adoption of tropical forage grasses with high BNI capacity may have a great potential to tighten N cycling in grazed pastures.
•Biological nitrification inhibition-BNI suppresses N2O emission from urine patches.•BNI: Brachiaria humidicola cv. Tully (BT) > Brachiaria hybrid cv. Mulato (BM).•Soil N2O emission was lower from urine patches in soils under BT than BM.•Ammonia oxidizing archaeal nitrifiers were particularly suppressed under BT.•High BNI of tropical forage grasses tightens N cycling in archaea-dominated soils.
Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a ...spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation. Along with the high associated economic burden, the high mortality rate among NAFLD patients raises interest, not only in the search for novel therapeutic approaches, but also in early diagnosis and prevention to reduce the incidence of NAFLD-related complications. In this line, an exhaustive characterization of the immune status of patients with NAFLD is mandatory. Herein, we attempted to gather and compare the current and relevant scientific evidence on this matter, mainly on human reports. We addressed the current knowledge related to circulating cellular and soluble mediators, particularly platelets, different leukocyte subsets and relevant inflammatory soluble mediators.
El culto a los «di Manes Arenas Gallego, Laura María
Cuadernos de arqueología de la Universidad de Navarra,
01/2023, Letnik:
31
Journal Article
Recenzirano
Odprti dostop
En la antigua Roma los antepasados, así como mantener vivo el recuerdo de los muer tos entre la familia, era realmente importante. Esto se expresaba a través de la religión privada, por un lado en el ...hogar, donde encontramos los retratos de los ancestros siempre presentes en la vida de los romanos, y por otro en las necrópolis convertidas en verdaderas ciudades donde las tumbas y las inscripciones que las acompañaban eran una forma de conmemoración a aquellos que permanecían sepultados allí. Lugares muy transitados donde rendir homenaje con ofrendas regulares a los muertos. Los difuntos se convertían en divinidades o espíritus familiares llamados Manes, que protegían a sus familias a cambio de no caer en el olvido. Así se instituyó un culto a los muertos repleto de ceremonias, fiestas, sacrificios rituales y ofrendas. Con este trabajo daremos una visión general de la muerte en la antigua Roma basándonos en el culto a los dioses Manes, intentando indagar en su origen y en la impor tancia que tenían dentro del mundo romano.
We studied species diversity and genetic variation among populations of Brevipalpus mites from four species of citrus host plants. We sampled mites on orange, lime, grapefruit and mandarin trees from ...orchards at six localities distributed in the five most important citrus producing states in Mexico. Genetic variation among citrus host plants and localities were assessed by analysis of nucleotide sequence data from fragments of the mitochondrial cytochrome oxidase subunit I (COI). Both Brevipalpus yothersi and B. californicus were found at these sites, and B. yothersi was the most abundant species found on all citrus species and in all localities sampled. B. californicus was found mainly on orange and mandarin and only in two of the states sampled. AMOVA and haplotype network analyses revealed no correlation between B. yothersi genetic population structure and geographical origin or citrus host plant species. Considering that a previous study reported greater genetic diversity in B. yothersi populations from Brazil than we observed in Mexico, we discuss the possibility that the Mexican populations may have originated in the southern region of America.
Abstract Background and Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the ...diagnostic accuracy in the post‐LT setting of patients transplanted for metabolic dysfunction‐associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings. Methods This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1‐year after LT. Results In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range IQR:16–46) and 26.0 (IQR: 16.8–41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0–5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients ( n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients ( n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa ( n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post‐LT hypertension (odds ratio OR: 12.0, 95% confidence interval CI: 1.8–80.4, p = .010) and post‐LT dyslipidaemia (OR: 7.9, 95% CI: 1.3–47.1, p = .024) with LSM (OR: 1.7, 95% CI: 1.1–2.8, p = .030) was independently associated with MASLD. Conclusions Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis.
Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after ...liver transplant(ation) (LT).
This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT.
We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates.
MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors.
Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.
Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for ...changing treatment in people with MS, especially in low prevalence populations, are unknown.
To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS.
We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality.
Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs.
A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.
Aim
The aim of this study was to determine whether a direct relationship existed between absolute telomere length (aTL), obesity and familial functionality in a group of Mexican children.
Methods
We ...recruited 134 children (52% boys) aged 8‐10 years during regular primary care check‐ups in 2016 and evaluated physical activity (PA), feeding practices, anthropometrics, body fat percentage (BF%) and family dysfunction. Optimised quantitative PCR determined aTL from genomic deoxyribonucleic acid isolated from saliva samples.
Results
Boys with a healthy BF% showed a higher aTL than their high BF% counterparts (P < .01). aTL was higher in children who performed PA than their sedentary counterparts (P < .05). Alarmingly, 90% of the children belonged to dysfunctional families and a dysfunctional family was correlated with a higher BF% (r = −.57). Negative correlations between the BF% and aTL (r = −.1765) and the BF% and time dedicated to PA (r = −.031) were observed in boys. On the contrary, we found a positive correlation between the aTL and weekly PA (r = .1938). These correlations were not observed in girls.
Conclusion
Telomere shortening was associated with a high BF% in boys, but not girls. Dysfunctional families were also a key factor. School PA programmes should be mandatory.
•Structural characterization of BtrK, a decarboxylase involved in the biosynthesis of butirosin, was performed.•BtrK has a structure similar to diaminopimelic acid decarboxylases (DAPDC), including ...the essential residues of the active site.•The molecular docking of a truncated version of the substrate indicates a hypothetical binding mode of the glutamate tethered to the Peptidyl Carrier Protein (PCP) BtrI.
Butirosin is an aminoglycoside that has an (S)-4-amino-2-hydroxybutyrate (AHBA) moiety capable of preventing the attack of several aminoglycoside modifying enzymes. The biosynthesis and the attachment of the AHBA to the 2-deoxystreptamine (2-DOS) involve seven enzymes that use glutamate as a precursor. BtrK is a pyridoxal-5-phosphate (PLP)-dependent enzyme and performs the decarboxylation of a glutamyl moiety tethered to the peptidyl carrier protein BtrI during the AHBA biosynthetic pathway. The structure of BtrK was solved at 1.4 Å resolution and indicated a conserved folding. The PLP is covalently linked through a Schiff base to Lys49 and performs intensive hydrogen bond interactions with active site residues that are also conserved in other members of type IV PLP-dependent enzymes. Additionally, a docking simulation indicates the possible anchoring of a substrate fragment constituted of O-S-γ-Lglutamylpantetheine-4′-phosphate. The glutamyl moiety forms a number of hydrogen bonds with the putative active site residues of BtrK. The pantetheine moiety seems to perform only a few interactions and should adopt a more flexible conformation. The description of BtrK structure contributes to the understanding of the large family of PLP-dependent enzymes and also in this crucial step during the butirosin biosynthesis.
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