Seasonal Dynamics of Nutrient Loading and Chlorophyll A in a Northern Prairies Reservoir, Saskatchewan, Canada

Harmful algae blooms have become an increasing concern in context with the safety of water resources around the globe;however, little is known about the dynamics and specific causes of such blooms in the prairie ecozone in North America. The aim of this study was to research the nitrogen (N) and phosphorous (P) content and nutrient limitation (defined as N and P limitation) of growth of cyanobacteria in a northern prairies reservoir (Lake Diefenbaker [LD], SK, Canada). A combination of concentration balance analysis for N and P, controlled bioassays with the natural consortium of phytoplankton or defined monocultures of cyanobacteria, and satellite imagery was applied to address this aim. The current trophic status of Lake Diefenbaker is one of moderate eutrophication. Primary production in the lake is P-limited, and N did not represent a limiting factor for algal production. There was no significant increase in TP con- centrations between the upper and lower portions of the reservoir, indicating that most of the phosphorus in LD comes from upstream sites in Alberta. Anabaena circinalis, a species that has the potential to seriously degrade lake ecosys- tems, was identified as the predominant cyanobacteria in LD. Together with the fact that TP influxes into the reservoir primarily originate from upstream sources, these results suggest the need for remedial measures in the upstream reach of the South Saskatchewan River. Satellite imaging represented a promising approach in support of monitoring for po- tential algal blooms in LD;however, due to limited sensitivity and issues associated with atmosphere interference this methodology should only be used in combination with in situ water quality monitoring. In summary, while this study indicated that Lake Diefenbaker is potentially at risk with cyanobacteria blooms (some of which such as Anabena sp. that can produce toxins) during late summer and fall, development of clear causal relationships and risk assessment strategies is currently limited due to lack of monitoring data and programs.

Emerging role of galectin 3 in neuroinflammation and neurodegeneration

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases.However,the mechanisms modulating these processes in different diseases remain incompletely understood.Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases.While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s disease.In this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases.We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

Response of Soybean and Lentil to a Seed-Row Placed Starter Nitrogen-Phosphorus Fertilizer Blend in a Brown Chernozem in South-Central Saskatchewan

Soybean and lentil are important legume crops in southern Saskatchewan (SK) that can supply the majority of their nitrogen (N) requirement through biological N fixation (BNF). However, the onset of BNF can be slow in cold;dry prairie soils and a small amount of seed-row placed fertilizer containing both N and phosphorus (P) may benefit the crop. Nevertheless, high rates of fertilizer in close proximity to the seed can also cause injury. This study was conducted to determine the response of lentil and soybean to a starter N-P fertilizer blend applied in the seed-row. A farm field located at the boundary of the Brown and Dark Brown soil zones in south-central Saskatchewan was selected to evaluate the effect of seed-row placed N-P fertilizer blend: 50% Urea + 50% mono-ammonium phosphate (MAP) applied at 0, 10, 20 and 30 kg N and P2O5 ha-1 on emergence, yield, and nutrient uptake. The proportion of nitrogen derived from fixation (ndff) was determined in the soybean using N-15 dilution technique. The rate of 10 kg N and P2O5 ha-1 was found to be the rate that did not significantly reduce emergence, stand count or proportion of N derived from fixation, and was sufficient to maximize yield, N and P uptake for both soybean and lentil under field conditions. Rates higher than 10 kg N ha-1 in the seed row as starter 28-26-0 blend reduced emergence and decreased the proportion of ndff.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Landscape spatial structure for predicting suitable habitat: The case of <i>Dalea villosa</i>in Saskatchewan

Prediction of potentially suitable habitat is important for the recovery of species protected by federal laws. Therefore, the objective of this research was to study the relationship between habitat configuration and hairy prairie-clover occurrence in order to predict suitable and unsuitable bare sand habitat across the study site. Bare sand patches were extracted from a land cover classification of the study site and several patch scaled metrics were calculated to characterize habitat spatial structure. Binary logistic regression was used to determine which metrics were significantly correlated with hairy prairie-clover occurrences. The logistic regression equation was subsequently used to predict suitable and unsuitable bare sand habitat for hairy prairie-clover based on the probability of occupancy. Results showed that about 29% of the variation in bare sand patch occupancy could be explained by the size, shape, and degree of isolation of a sand patch as well as the amount of vegetation on a sand patch in the early growing season. Based on these variables, 18.8% of bare sand patches in the study site were predicted to be unsuitable hairy prairie-clover habitat, 45.7% were predicted to be marginally unsuitable, 32.7% were predicted to be suitable, and 2.8% were predicted to be marginally suitable.

Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to disability.Inducing efficient and effective repair programs following demyelination is a major goal and challenge in MS.Conventional MS therapies focus largely on modulating the immune aspects of the disease contributing to lesions.While this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

Effects of vacuum magnetic field region on the compact torus trajectory in a tokamak plasma

The trajectory of the compact torus(CT)within a tokamak discharge is crucial to fueling.In this study,we developed a penetration model with a vacuum magnetic field region to accurately determine CT trajectories in tokamak discharges.This model was used to calculate the trajectory and penetration parameters of CT injections by applying both perpendicular and tangential injection schemes in both HL-2A and ITER tokamaks.For perpendicular injection along the tokamak's major radius direction from the outboard,CTs with the same injection parameters exhibited a 0.08 reduction in relative penetration depth when injected into HL-2A and a 0.13reduction when injected into ITER geometry when considering the vacuum magnetic field region compared with cases where this region was not considered.In addition,we proposed an optimization method for determining the CT's initial injection velocity to accurately calculate the initial injection velocity of CTs for central fueling in tokamaks.Furthermore,this paper discusses schemes for the tangential injection of CT into tokamak discharges.The optimal injection angle and CT magnetic moment direction for injection into both HL-2A and ITER were determined through numerical simulations.Finally,the kinetic energy loss occurring when the CT penetrated the vacuum magnetic field region in ITER was reduced byΔEk=975.08 J by optimizing the injection angle for the CT injected into ITER.These results provide valuable insights for optimizing injection angles in fusion experiments.Our model closely represents actual experimental scenarios and can assist the design of CT parameters.

The changes of Trp-deficient linusorb during the oxidation and the influence of γ-tocopherol on their oxidative stability

Linusorbs(LOs),particularly the Methionine(Met)-containing yet Tryptophan(Trp)-free LO(CLB and CLP),play a significant role in shaping the quality and sensory attributes of flaxseed oil.To investigate the stability of these LOs and their oxidized forms during accelerated oxidation,the polar fractions of crude flaxseed oil were selectively removed using silica absorption and then reintroduced separately into the oil matrix along with LOs andγ-tocopherol(γ-T).Through comprehensive analysis of oxidative stability indexes,LOs content changes,oxidation kinetics,and the correlation between LOs and oxidative stability indexes,we observed that the LOs fraction alone exhibited a moderate antioxidant effect on the peroxide value(PV)but a weaker effect on the panisidine value(p-AV)of flaxseed oil.However,upon addition ofγ-T,we observed a weak synergistic effect betweenγ-T and LOs in suppressing PV,while a stronger effect in suppressing p-AV.Additionally,a comparison of the oxidation kinetics of different LOs indicated thatγ-T preferentially protected the oxidation of CLP over CLB.Similar protective trends ofγ-T towards the methionine sulfoxide(MetO)and methionine sulfoxide(MetO2)form of LOs were also observed,albeit to a lesser extent.Correlation analysis revealed that changes in Metcontaining LOs,particularly CLP,showed a high correlation with PV in the tested matrices,while MetOcontaining LOs better depicted changes in p-AV.Importantly,CLP demonstrated higher susceptibility to the influence of antioxidants,making it more suitable for evaluating the peroxide value in flaxseed oil samples.

The global,prevalence,and risk factors of postoperative fever after percutaneous nephrolithotomy:A systematic review and meta-analysis

Objective:This study aimed to explore the global,prevalence,and risk factors of fever after percutaneous nephrolithotomy(PCNL)by conducting a systematic review and meta-analysis.Methods:The high-sensitivity searching was conducted without time limitation until December 30,2020 in Web of Sciences,Scopus,and PubMed based on inclusion and exclusion criteria.Results:The prevalence rates of fever and sepsis among patient undergoing PCNL were estimated 9.5%(95%confidence interval[CI]:9.3%-9.7%),and 4.5%(95%CI:4.2%-4.8%),respectively.Nephrostomy tube was used in 9.96%(95%CI:9.94%-9.97%)of patients.The mean preoperative white blood cells of patients were 6.401×109/L;18.3%and 4.55%of patients were considered as the positive urinary culture and pyuria,respectively.About 20.4%of patients suffered from residual stones.The odds ratios(ORs)of fever in patients who suffering from diabetes mellitus,hydronephrosis,staghorn stones,and blood transfusion were 4.62(95%CI:2.95-7.26),1.04(95%CI:0.81-1.34),2.57(95%CI:0.93-7.11),and 2.65(95%CI:1.62-4.35),respectively.Patients who underwent PCNL in prone position were more likely to develop fever(OR:1.23;95%CI:0.75-2.00)than patients in supine position.Conclusion:The current study showed that patients who suffer from diabetes mellitus,hydronephrosis,staghorn stones,nephrostomy tube or double-J stent,blood transfusion,and also patients who underwent PCNL in prone position surgery are more likely to develop a postoperative fever after PCNL.

Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes

BACKGROUND Hypothermic machine perfusion(HMP)has demonstrated benefits in terms of early kidney transplant function compared to static cold storage.While longer preservation times have shown detrimental effects,a previous paired study indicated that longer pump times(the second kidney in a pair)might lead to improved outcomes.AIM To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.METHODS A total of 61 pairs of transplant recipients who received kidneys from the same donor(2012-2021)were analyzed.Patients were divided into two groups depending on whether they were transplanted first(K1)or second(K2).Therefore,the patients in each pair had identical donor characteristics,except for time on the pump.Statistical analyses included Kaplan-Meyer analysis and paired tests,including McNemar's test,student's paired t-test,or Wilcoxon's test,as appropriate.RESULTS The two groups of recipients had similar demographics(age,body mass index,diabetes,time on dialysis,sensit-ization and retransplants).Cold ischemic times for K1 and K2 were 8.9(95%CI:7.9,9.8)and 14.7 hours(13.7,15.8)(P<0.0001),respectively.Overall,K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year(P=0.015).Delayed graft function was less common in K2,12/61(20%)than in K1,20/61(33%)(P=0.046).Finally,K2 showed a higher graft survival than K1(P=0.023).CONCLUSION Our results agree with a previous study that suggested possible advantages to longer pump times.Both studies should encourage further research into HMP's potential anti-inflammatory effect.

DFT Studies of Electronic Properties and Effect of He and Xe Incorporation in Selected Ceramics

The electronic properties of several prospective nuclear fuels are not yet well known. We used Quantum Espresso and EPW codes to evaluate the electron density of states, the electronic heat capacity coefficient, the electron-phonon coupling strength, the number of mobility electrons, and the electronic heat conductivity. The electronic properties for ThN, ThC and UN using a slightly different approach that were previously evaluated are discussed and the results are compared. We confirmed that while the electronic heat capacity coefficient is linearly dependent on the electron density of states at Fermi energy, such a simple relation could not be used to determine the difference in the electronic heat conductivity of investigated materials. The highest heat conductivity was registered in ThN. These metallic fuels also have high U/Th density, therefore are more economical since enrichment is expensive. Furthermore, it is important to examine swelling in these high-density fuels. We evaluated that UN had 42% more U atoms per unit volume than UO2 and a 55% higher volume increase when accommodating one Xe atom in one interstitial of a (2 × 2 × 2) supercell. However, for He, the volume increase was 27% lower in UN. Interestingly, even though the Th atom’s density in ThN and ThC was lower than that of U atoms in the UN compound, a similar trend of volume changes was found. We concluded, therefore, that when we consider swelling, the local structural symmetry (tetrahedral versus octahedral sites) is more important than the density of atoms. The 37 % greater of absolute value of the total energy increase due to incorporation of Xe in ThC versus ThN cannot be explained by the crystal structure since a ThC-Xe supercell has a higher lattice constant than a ThN-Xe corresponding supercell. Such results can only be explained by investigating electronic structure.

Predicting Standardized Precipitation Evapotranspiration Index for Fada N’Gourma by 2050 Using CMPI-6 Outputs under SSPs Scenarios

Extreme weather events,such as floods and droughts,are expected to rise significantly worldwide as a result of climate change.Investigating future drought patterns is therefore a key approach for elaborating anticipatory water resources management responses to climate change.In this paper,future meteorological drought conditions are investigated based on the SPEI(Standardised Precipitation Evapotranspiration Index).This study makes use of observed and projected data.The simulated data were retrieved from the CMIP6(Coupled Model Intercomparison Project Phase 6)over the period 2025-2050,and the Delta change method was adopted to remove the bias in the dataset.Then SPEI at various scales has been estimated under four future scenarios(SSP1-2.6,SSP2-4.5,SSP3-7.0 and SSP5-8.5).The trend analysis of the projected SPEI was performed at p<0.05 using the MMK(Modified Mann-Kendall)test in order to detect the statistically significant trend of the drought against the null hypothesis of no trend.Results show large variability in the magnitude of drought in the past and future.Based on SPEI at 24 months accumulation,the result shows that under SSP1-2.6,the basin will experience a wet period during the first decade(SPEI=0.60),the second decade will be dry(SPEI24=-0.43).The remaining years will be also dry(SPEI=-0.34).Under SSP2-4.5,SSP3-7.0 and SSP5-8.5 scenarios,the district will experience a wet period during the first two decades with SPEI ranging from 0.38 to 0.59.This wet period will be followed by a dry period under these scenarios ranging from-0.14 to-0.06.Overall,under SSPs scenarios,two main periods characterized by a rainfall recovery spanning from followed by a moderately prolonged drought are identified within the study area.The findings of this study may provide valuable information for developing proactive measures to reduce water insecurity in Fada N’Gourma through effective drought mitigation.

Effects of intermittent fasting on health markers in those with type 2 diabetes:A pilot study

AIMTo determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM).METHODSWe describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase.RESULTSAt baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m2]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P < 0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82 ± 1.18). The increased fasting duration improved at-goal (< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours).CONCLUSIONThe results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.

Patterns of lymph node metastasis are different in colon and rectal carcinomas

AIM:To describe patterns of lymph node metastasis in invasive colon and rectal carcinomas.METHODS:Clinical data of 2340 patients with colorectal carcinoma(stageⅠ to Ⅲ) who received radical resection,was retrospectively reviewed.Of the 2340 patients,1314 patients suffered from rectal carcinoma and 1026 from colon carcinoma.Patients with rectal cancer who received neoadjuvant chemoradiation therapy were excluded.Statistical analysis was performed using MannWhitney,χ 2 and Cochran's and Mantel-Haenszel tests(SPSS 15.0).A two-tailed P < 0.05 was considered statistically significant.RESULTS:Lymph node retrieval in the rectal carcinoma group was significantly lower than that in the colon carcinoma group(P < 0.001),while positive lymph node retrieval in the rectal carcinoma group was significantly higher than that in the colon carcinoma group(P < 0.001).The proportion of lymph node positive(N+) cases was higher(patients with one or more positive lymph nodes) in the rectal carcinoma group(P = 0.004).The number of N+ cases was compared at different T stages(T1-T4) to eliminate background bias and the results were confirmed(P < 0.001).In addition,the lymph node ratio(the ratio of number of positive lymph nodes over the number of lymph nodes examined) of stage Ⅲ cases in the rectal carcinoma group was significantly higher than that in the colon carcinoma group(P < 0.001).CONCLUSION:Rectal carcinomas seem more prone to metastasize to the lymph nodes than colon carcinomas,which may be of potential clinical significance.

Eastern Dharwar Craton,India:Continental lithosphere growth by accretion of diverse plume and arc terranes

Abstract Greenstone belts of the eastern Dharwar Craton, India are reinterpreted as composite tecto- nostratigraphic terranes of accreted plume-derived and convergent margin-derived magmatic sequences based on new high-precision elemental data. The former are dominated by a komatiite plus Mg-tholeiitic basalt volcanic association, with deep water siliciclastic and banded iron formation （BIF） sedimentary rocks. Plumes melted at 〈90 km under thin rifted continental lithosphere to preserve intrao- ceanic and continental margin aspects. Associated alkaline basalts record subduction-recycling of Me- soarchean oceanic crust, incubated in the asthenosphere, and erupted coevally with Mg basalts from a heterogeneous mantle plume. Together, komatiites-Mg basalts-alkaline basalts plot along the Phanero- zoic mantle array in Th/Yb versus Nb/Yb coordinate space, representing zoned plumes, establishing that these reservoirs were present in the Neoarchean mantle. Convergent margin magmatic associations are dominated by tholeiitic to calc-alkaline basalts compo- sitionally similar to recent intraoceanic arcs. As well, boninitic flows sourced in extremely depleted mantle are present, and the association of arc basalts with Mg-andesites-Nb enriched basalts-adakites documented from Cenozoic arcs characterized by subduction of young （〈20 Ma）, hot, oceanic litho- sphere. Consequently, Cenozoic style ＂hot＂ subduction was operating in the Neoarchean. These diverse volcanic associations were assembled to give composite terranes in a subduction-accretion orogen at -2.7 Ga, coevally with a global accretionary orogen at -2.7 Ga, and associated orogenic gold mineralization.

Conversion of Malaysian low-rank coal to mesoporous activated carbon:Structure characterization and adsorption properties

Malaysian Selantik low-rank coal(SC)was used as a precursor to prepare a form of mesoporous activated carbon(SC-AC)with greater surface area(SA)via a microwave induced KOH-activation method.The characteristics of the SC and SC-AC were evaluated by the iodine number,ash content,bulk density,and moisture content The structure and surface characterization was carried out using pore structure analysis(BET),scanning electron microscopy with energy dispersive X-ray spectroscopy(SEM-EDX),X-ray diffraction(XRD),Fourier Transform Infrared(FTIR),elemental analysis(CHNS),thermogravimetric analysis(TGA),and determination of the point of zero charge(pH(PZC)).These results signify a mesoporous structure of SC-AC with an increase of ca.1160 times(BET SA=1094.3 m^2·g^-1)as compared with raw SC without activation(BET SA=1.23 m^2·g^-1).The adsorptive properties of the SC-AC with methylene blue(MB)was carried out at variable adsorbent dose(0.2-1.6 g·L^-1),solution pH(2-12),initial MB concentrations(25-400 mg·L^-1),and contact time(0-290 min)using batch mode operation.The kinetic profiles follow pseudo-second order kinetics and the equilibrium uptake of MB conforms to the Langmuir model with a maximum monolayer adsorption capacity of 491.7 mg g^-1 at 303 K.Thermodynamic functions revealed a spontaneous endothermic adsorption process.The mechanism of adsorption included mainly electrostatic attractions,hydrogen bonding interaction,andπ-πstacking interaction.This work shows that Malaysian Selantik low-rank coal is a promising precursor for the production of low-cost and efficient mesoporous activated carbon with substantive surface area.

Direct conversion of natural gas to higher hydrocarbons:A review

Direct conversion of methane to higher hydrocarbons is an effective process to solve the problem of natural gas utilization. Although remarkable progress has been achieved on the dehydro-aromatization of methane （DAM）, low conversion caused by severe thermodynamic limitations, coke formation, and catalysis deactivation remain important drawbacks to the direct conversion process. Molybdenum catalysts supported on HZSM-5 type zeolite support are among the most promising catalysts. This review focuses on the aspects of direct methane conversion, in terms of catalysts containing metal and support, reaction conditions, and conversion in different types of reactors. The reaction mechanism for this catalytic process is also discussed.

Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

In addition to well-defined DNA repair pathways, all living organisms have evolved mechanisms to avoid cell death caused by replication fork collapse at a site where replication is blocked due to disruptive covalent modifications of DNA. The term DNA damage tolerance （DDT） has been employed loosely to include a collection of mechanisms by which cells survive replication-blocking lesions with or without associated genomic instability. Recent genetic analyses indicate that DDT in eukaryotes, from yeast to human, consists of two parallel pathways with one being error-free and another highly mutagenic. Interestingly, in budding yeast, these two pathways are mediated by sequential modifications of the proliferating cell nuclear antigen （PCNA） by two ubiquitination complexes Rad6-Rad18 and Mms2-Ubc13-Rad5. Damage-induced monoubiquitination of PCNA by Rad6-Rad18 promotes translesion synthesis （TLS） with increased mutagenesis, while subsequent polyubiquitination of PCNA at the same K164 residue by Mms2-Ubc13-Rad5 promotes error-free lesion bypass. Data obtained from recent studies suggest that the above mechanisms are conserved in higher eukaryotes. In particular, mammals contain multiple specialized TLS polymerases. Defects in one of the TLS polymerases have been linked to genomic instability and cancer.

Brief electrical nerve stimulation enhances intrinsic repair capacity of the focally demyelinated central nervous system

Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair phenotype.Whether this same potential exists in the central nervous system is not known.Thus,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated axons.Data reveal a robust focal demyelination at 7 days post-LPC injection.Delivery of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of Ranvier.ES also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon protection.Collectively these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple sclerosis.All animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).

Synthesis and in-vitro characterization of biodegradable porous magnesium-based scaffolds containing silver for bone tissue engineering

Infection is a major potential complication in the clinical treatment of bone injuries. Magnesium (Mg)-based composites are biodegradable and antibacterial biomaterials that have been employed to reduce infection following surgical implants. The aim of present study was to synthesize and in-vitro characterize Mg-based scaffolds containing silver for bone tissue engineering. Porous Mg-based scaffolds with four silver concentrations (i.e., 0, 0.5 wt.%, 1 wt.%, and 2 wt.%), denoted by Mg?Ca?Mn-Zn-xAg (MCMZ?xAg)(where x is the silver concentration), were fabricated by the space holder technique. The effects of silver concentration on pore architecture, mechanical properties, bioactivity, and zone of bacterial inhibition were investigated in-vitro. X-ray diffractometry (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and fluorescence microscopy were utilized to characterize the obtained scaffolds. In-vitro corrosion test results indicated that the MCMZ scaffolds with lower silver content were more resistant to corrosion than those enriched with higher amounts of silver. Examination of the antibacterial activity showed that the MCMZ?Ag scaffolds exhibited superb potential with respect to suppressing the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), in the inhibition zone around the MCMZ?Ag scaffolds, with increasing in the amount of incorporated silver;however, higher amounts of silver increased the cytotoxicity. Taken together, the results of this study demonstrate that the porous 0.5 wt.% Ag-containing scaffolds with interconnected pores, adequate mechanical properties, antibacterial activity, and cell adhesion are promising with respect to the repair and substitution of damaged and diseased bones.