Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain ...transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG.
Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL- 6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors.
Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor TNFR subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling.
Conclusions: Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.
Carbapenemase-producing Klebsiella pneumoniae (CRKP) are increasingly reported worldwide being necessary the local epidemiological monitoring. Our aim was to characterize the hypermucoviscous CRKP ...isolates collected in our hospital during a 6 months period. Carriage of the carbapenemase genes (blaKPC, blaNDM, blaVIM and blaOXA-48), extended spectrum β-lactamases (blaSHV-2, blaCTX-M) and the virulence genes (magA, k2A, rmpA, wabG, uge, allS, entB, ycfM, kpn, wcaG, fimH, mrkD, iutA, iroN, hly and cnf-1) were determined by multiplex-PCR. Genetic relationship among the isolates was performed by PFGE and MLST. A total of 35 isolates were recovered, being the urinary and respiratory tract the most common infection sites (34.2%). The blaKPC-2 gene was present in all the isolates, coexisting with blaCTX-M-2 (45.7%), blaSHV-2 (28.6%), and blaCTX-M-2/blaSHV-2 (14.3%). The capsular serotype K2 corresponded with 68.6% of the isolates. Virulence factors frequency were variable adhesins (97.1%), siderophores (94.3%) and phagocytosis resistance (wabG 48.5%, uge 80% and ycfM 57.1%). A total of 10 STs were identified although 40% of them clustered on ST25-CC65, and 17% to ST17. The incidence of KPC-2-producing K. pneumoniae reported by the hospital was 0.290 per 1000 admissions. In summary we described an epidemic scenario of multidrug resistant hypermucoviscous KPC-2 producing ST25 K. pneumoniae in our institution.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:Sedentary behavior may be an independent risk factor for cardiovascular events. This study aimed to clarify the effects of extended sedentary time in patients with diabetic kidney disease ...(DKD) on the risk of all-cause death and new events.Methods and Results:A prospective cohort study was performed over 39 months. The study included 173 patients with DKD who completed the International Physical Activity Questionnaire (IPAQ) (101 men; mean age, 71±11 years); 37 patients (21.4%) were diagnosed with cardiovascular disease (CVD). New events were defined as all-cause death, cerebral stroke, or CVD requiring hospitalization or commencing hemodialysis (HD). Data were analyzed using a multivariate Cox proportional hazard regression model with variables, including sedentary time. There were 34 cases of new events during the observation period, including 4 cases of stroke, 20 cases of CVD, 4 cases of HD implementation, and 6 cases of death. Hazard ratio (HR) calculations for the new event onset group identified sedentary time as a significant independent variable. The independent variable that was identified as a significant predictor of new events was the sedentary time (60 min/day; HR: 1.23, 95% CI: 1.05–1.45, P=0.012).Conclusions:Extended sedentary time increased the risk of new cardiovascular or renal events and/or all-cause death in patients with DKD.
Large errors in Quantitative Precipitation Estimates (QPE) tied to remote-sensing retrieval algorithms remain a challenge especially in complex terrain with fast hydrologic response. We propose a new ...framework to derive dynamic hydrologic corrections of rainfall in headwater basins that enforces water budget closure, and distributes transient rainfall corrections by Lagrangian backtracking along runoff trajectories constrained by realistic time-of-travel distributions. Downscaled QPE products (250 m resolution) are applied first as input to a distributed hydrologic model to predict runoff trajectories and the event hydrograph at the basin's outlet. Second, time-varying rainfall corrections are derived from the residuals between predicted and observed discharge at the outlet. Finally, the corrections are spatially distributed following the runoff trajectories backward (i.e. trajectories are used as streaklines originating at the basin's outlet). Because nonlinear interactions between rainfall, runoff and storage are transient, the corrections are applied recursively until the shape and volume of the predicted hydrograph are stable. The framework is applied to ground-based (e.g. Stage IV) and satellite-based remote-sensing QPEs (e.g. IMERG) associated with the 49 largest floods 2008–2018 in the Southern Appalachian Mountains, USA. The results show improvements in hydrograph prediction efficiency skill at 15 min timescale from −0.5 to 0.6 on average and up to 0.9 for warm season events, bounding event runoff volume errors with a mean of 3%, and reducing time to peak errors by half an hour on average. Corrected QPEs exhibit nearly perfect correlation and no bias at high elevation gauge locations. Uncertainty in the water budget closure at the event scale is less than the uncertainty in streamflow measurements. Error attribution shows strong organization of QPE corrections according to seasonal weather and rainfall regime, thus providing a path to generalization to ungauged mountain basins.
•Hydrograph analysis and travel time theory guide QPE correction in gauged basins.•Lagrangian backtracking of discharge residuals enables space-time QPE correction.•Improved hydrologic performance is robust independently of QPE product.•Corrected QPE leads to water budget closure at event scale.•QPE corrections exhibit coherent dependence on seasonal weather and rainfall type.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many GTPases have been shown to utilize ATP too as the phosphoryl donor. Both GTP and ATP are important molecules in the cellular environments and play multiple and discrete functional role within ...the cells. In our present study, we showed that one of the purine metabolic enzymes Adenylosuccinate synthetase from Leishmania donovani (LdAdSS) which belongs to the BioD-superfamily of GTPases can also carry out the catalysis by hydrolysing ATP instead of its cognate substrate GTP albeit with less efficiency. Biochemical and biophysical studies indicated its ability to bind to ATP too but at a higher concentration of ATP compared to that of GTP. Sequence analysis and molecular dynamic simulations suggested that residues of the switch loop and the G4-G5 (593SAXD596) connected motif of LdAdSS plays a role in determining the nucleotide specificity. Though the crucial interaction between Asp596 and the nucleotide is broken when ATP is bound, interactions between the Ala594 and the adenine ring of ATP could still hold ATP in the GTP binding site. The results of the present study suggested that though LdAdSS is GTP specific, it still shows ATP hydrolysing activity.
•Leishmania donovani Adenylosuccinate synthetase (LdAdSS), a GTPase can also utilize ATP for phosphoryl transfer onto IMP instead of GTP.•The binding affinity of LdAdSS with GTP is stronger than with ATP.•LdAdSS switch loop assumes a closed catalytically active conformation on GDP binding compared to the partially open conformation on ADP binding.•Residues belonging to the connected G4-G5 motif in LdAdSS may be a determinant of its purine base selectivity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Grazing is one of the principal drivers triggering woody invasion in grasslands and savannas worldwide, but evidence is opposing. Cattle can promote or limit woody establishment by direct and ...indirect mechanisms, like consumption, trampling or relaxing grass competition. Despite its increasing relevance, it is unknown if intensively managed cattle grazing can curb woody establishment. We evaluated the effect of cattle grazing with short cycles of high stocking rate and resting periods on
Gleditsia triacanthos
establishment, an invasive tree in grasslands. By two field experiments in pastures, we manipulated cattle grazing (with or without) and: Exp. (1) initial age-related size of
G. triacanthos
(small plants: 3 mo.; or large plants: 9 mo.), and Exp. (2) neighbouring vegetation (clipped or intact). Overall, grazing had a negative effect due to tree consumption and a positive effect by relaxing grass competition on tree establishment, but the first effect outweighed the second. Grazing reduced by 25%
G. triacanthos
survival and by 40% its biomass. Consumption was independent of plant size and neighbouring vegetation, but large plants had more resprouting capacity than small plants. Regardless of grazing, small plants had higher mortality than large plants. Intact neighbouring vegetation did not modify survival but decreased tree biomass which may affect middle or long-term tolerance and survival. Intensively managed rotational grazing with resting periods for pasture recovery may limit woody establishment, but this management strategy should be applied immediately after tree germination. The increasing intensification of production systems requires to evaluate the impact of management on invasion processes.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Questions
How does the grass layer affect seedlings across large environmental gradients in savannas?
Location
Savanna sites in Argentina, Tanzania, and South Africa.
Methods
We carried out a joint ...analysis of three grass removal experiments in which seedlings of various Fabaceae species were transplanted into plots with native grass and companion plots where grass had been removed. First, we estimated the effect of grasses on tree seedling mortality and seedling growth rate at each site. Then, we used the resulting coefficient estimates from site‐level models to examine the impact of two climate (monthly precipitation and aridity index) and two soil (soil organic carbon content and clay content) variables on the direction and magnitude of the grass effects.
Results
Grasses increased the risk of mortality, but there was no evidence for a global effect of grasses on tree seedling rate of height growth. The best model fit indicated a high mortality risk of tree seedlings in response to grasses at intermediate aridity index values. No other climate or soil variable influenced tree seedling survival or growth (monthly precipitation, soil organic carbon content and clay content).
Conclusions
Our results support the notion that the grass layer consistently creates a bottleneck to tree seedling establishment in African and South American savannas beyond climate and soil conditions, mainly by affecting tree seedling survival. The negative effect of grasses on seedling survival was lower in dry conditions compared to intermediate aridity levels. These results suggest that grass–seedling interaction is less intense in drier conditions, possibly due to reduced total grass biomass, which leads to decreased site evapotranspiration and improved soil water retention capacity.
This study presents a joint analysis of field research in African and South American savannas. We assessed the effect of grasses on tree seedling survival and growth across a gradient of climate and soil variables. Grasses reduced tree seedling survival with no consistent global effects on growth. The influence of grass on seedling mortality was higher at moderately arid sites.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The aim of this study was to evaluate the stability of prosthetic screws after applying cyclic loadings in an "all-on-four" rehabilitation model with the OT Bridge system. The model was tested both ...with and without anterior screws. Four implant analogues following the "all-on-four" concept were inserted in an edentulous mandibular resin model. An OT Bridge system with a Cr-Co prosthetic framework was fabricated. Depending on the presence or absence of one or two anterior screws on the implant analogues, three groups were created, i.e., Gr.1: three tightening screws, Gr.2: two tightening screws, Control Group: four tightening screws. Each single group underwent subsequent 400,000 cyclic loads, simulating approximately a year of chewing by using a dynamometer machine. This cycle was repeated five times for each group, and preload loss values were evaluated on each prosthetic screw after each cycle. All the data obtained were analyzed by one-way ANOVA and Student's
-test. No statistically significant differences after intragroup analysis were found. A statistically significant difference within the Gr.1 between the screws in positions 33 and 36, equal to 15.2% (
-value = 0.0176), was found. The OT Bridge seems a useful system to maintain the retention of a prosthesis during mechanical stress conditions even in the absence of one screw in an "all-on-four" rehabilitation. This could represent a good solution to solve the esthetic problem of the screw buccal access hole for fixed solutions.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We ...present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal’s position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal’s position and orientation. Custom software tracks the 3D position of the animal’s head in real time and two feedback loops adjust a motorized stage and objective to keep the animal’s head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal’s behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
PDF
