Regrowth Patterns Research Articles

Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition.

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities. The majority of pLGGs have an underlying activation of the RAS/MAPK pathway due to mutational events, leading to the use of molecularly targeted therapies in clinical trials, with recent regulatory approval for the combination of BRAF and MEK inhibition for BRAFV600E mutated pLGG. Despite encouraging activity, tumor regrowth can occur during therapy due to drug resistance, off treatment as tumor recurrence, or as reported in some patients as a rapid rebound growth within 3 months of discontinuing targeted therapy. Definitions of these patterns of regrowth have not been well described in pLGG. For this reason, the International Pediatric Low-Grade Glioma Coalition, a global group of physicians and scientists, formed the Resistance, Rebound, and Recurrence (R3) working group to study resistance, rebound, and recurrence. A modified Delphi approach was undertaken to produce consensus-based definitions and recommendations for regrowth patterns in pLGG with specific reference to targeted therapies.

Multiple-Criteria Decision Analysis for Effect of Shoot Growth at Difference Combination Nutrient Fertiliser NPK for Harumanis Mango

It is vital to have the correct fertiliser arrangement for effective tree development, fruit yield, and essential fruit quality. The amount of fertiliser suggested with adequate nutrition will be maintained in the soil to supply the needs of the trees as they grow throughout the various growth stages. This study evaluated the effect of different combinations of Nitrogen(N), Phosphorus(P), and Potassium(K) on the vegetative flush physiology of Harumanis mango (Mangifera Indica. L). Single and combinations of N (511g), P(511g), and K(255g) fertilisers were used, which were N, P, NP, and NPK throughout May 2021. The results revealed that the minimum number of mature green leaves and a higher number of healthy panicles were observed in the NPK-treated plants. Moreover, NPK treatment showed the lowest malformation intensity percentage compared to other fertiliser treatments. The data were analysed to obtain the best regrowth pattern of shoots using Multiple-Criteria Decision Analysis (MCDA) techniques. The results on the pattern of regrowth after pruning when federalised with NPK fertiliser showed that the maximum percentage of total vegetative flush was 87.5% and the remaining 12.5% did not reach a satisfactory level according to the MCDA analysis.

Effect of Mowing on Wheat Growth at Seeding Stage.

Winter wheat is used as forage at the tillering stage in many countries; however, the regrowth pattern of wheat after mowing remains unclear. In this study, the growth patterns of wheat were revealed through cytological and physiological assessments as well as transcriptome sequencing. The results of agronomic traits and paraffin sections showed that the shoot growth rate increased, but root growth was inhibited after mowing. The submicroscopic structure revealed a decrease in heterochromatin in the tillering node cell and a change in mitochondrial shape in the tillering node and secondary root. Analysis of the transcriptome showed the number of differentially expressed genes (DEGs) involved in biological processes, cellular components, and molecular functions; 2492 upregulated DEGs and 1534 downregulated DEGs were identified. The results of the experimental study showed that mowing induced expression of DEGs in the phenylpropanoid biosynthesis pathway and increased the activity of PAL and 4CL. The upregulated DEGs in the starch and sucrose metabolism pathways and related enzyme activity alterations indicated that the sugar degradation rate increased. The DEGs in the nitrogen metabolism pathway biosynthesis of the amino acids, phenylpropanoid biosynthesis metabolism, and in the TCA pathway also changed after mowing. Hormone content and related gene expression was also altered in the tillering and secondary roots after mowing. When jasmonic acid and ethylene were used to treat the wheat after mowing, the regeneration rate increased, whereas abscisic acid inhibited regrowth. This study revealed the wheat growth patterns after mowing, which could lead to a better understanding of the development of dual-purpose wheat.

When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials.

Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations. To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups. The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported. Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss. These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.

Monolithic integrated all-GaN-based µLED display by selective area regrowth.

This work demonstrates an all-GaN-based µLED display with monolithic integrated HEMT and µLED pixels using the selective area regrowth method. The monochrome µLED-HEMT display has a resolution of 20 × 20 and a pixel pitch of 80 µm. With the optimized regrowth pattern, the µLED-HEMT achieves a maximum light output power of 36.2 W/cm2 and a peak EQE of 3.36%, mainly due to the improved crystal quality of regrown µLED. TMAH treatment and Al2O3 surface passivation are also performed to minimize the impact of nonradiative recombination caused by the dry etching damage. With a custom-designed driving circuit board, images of "HKUST" are successfully shown on the µLED-HEMT display.

Different regrowth patterns after repeated clipping in two Mongolian pasture species

Different regrowth patterns after repeated clipping in two Mongolian pasture species

The effect of rainfall amount and timing on annual transpiration in a grazed savanna grassland

Abstract. The role of precipitation (P) variability with respect to evapotranspiration (ET) and its two components, transpiration (T) and evaporation (E), from savannas continues to draw significant research interest given its relevance to a number of ecohydrological applications. Our study reports on 6 years of measured ET and estimated T and E from a grazed savanna grassland at Welgegund, South Africa. Annual P varied significantly with respect to amount (508 to 672 mm yr−1), with dry years characterized by infrequent early-season rainfall. T was determined using annual water-use efficiency and gross primary production estimates derived from eddy-covariance measurements of latent heat flux and net ecosystem CO2 exchange rates. The computed annual T for the 4 wet years with frequent early wet-season rainfall was nearly constant, 326±19 mm yr−1 (T/ET=0.51), but was lower and more variable between the 2 dry years (255 and 154 mm yr−1, respectively). Annual T and T/ET were linearly related to the early wet-season storm frequency. The constancy of annual T during wet years is explained by the moderate water stress of C4 grasses as well as trees' ability to use water from deeper layers. During extreme drought, grasses respond to water availability with a dieback–regrowth pattern, reducing leaf area and transpiration and, thus, increasing the proportion of transpiration contributed by trees. The works suggest that the early-season P distribution explains the interannual variability in T, which should be considered when managing grazing and fodder production in these grasslands.

MODL-14. MODELING THE INTRATUMORAL HETEROGENEITY OF AGGRESSIVE GLIOBLASTOMA ON ORGANOTYPIC BRAIN SLICES TO OPTIMIZE TUMOR-HOMING TUMORICIDAL INSC TREATMENT

Abstract BACKGROUND Tumor-homing tumoricidal neural stem cell (tNSC) therapy is a promising new strategy that recently entered human patient testing for glioblastoma (GBM). Developing strategies for tNSC therapy to overcome intratumoral heterogeneity, variable cancer cell invasiveness, and differential drug response of GBM will be essential for efficacious treatment response in the clinical setting. We sought to create novel hybrid tumor models and investigate the impact of GBM heterogeneity on tNSC tumor response and treatment durability. METHODS We utilized organotypic brain slice explants and human cells with varied properties to generate heterogeneous GBM models ex vivo and in vivo. We first investigated the treatment response and durability of mono- and combination therapy with primary NSCs and fibroblast-derived human induced neural stem cells (iNSCs) engineered with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or enzyme-prodrug therapy. Next, we utilized the ex vivo models and molecular assays to explore mechanisms driving tumor adaption and escape. RESULTS Non-invasive imaging, molecular assays, and immunohistochemistry showed the new hybrid GBM models recapitulated key aspects of the clinical disease. Testing in multiple in vivo models showed that tNSC-TRAIL therapy induced robust initial inhibitions in tumor growth and significantly increased survival. However, tumors rebounded in multiple models and patterns of tumor regrowth varied with therapeutic, dose, and route of administration. We found that adjusting iNSC delivery strategies increased spatiotemporal TRAIL coverage and significantly decreased GBM volume throughout the brain, reducing tumor burden 100-fold as quantified in live ex vivo brain slices and resulting in varied impact on treatment durability and median survival across models of both solid and invasive tumors. CONCLUSIONS These studies report new hybrid models that accurately capture key aspects of GBM heterogeneity which markedly impact treatment response while demonstrating the ability of tNSC mono- and combination therapy to overcome certain aspects of heterogeneity for robust tumor kill.

Relationship of Hair Regrowth Pattern in Alopecia Areata Patches According to DIMT Classification with Treatment Modalities and Patch Size: A Retrospective Cross-Sectional Analysis.

BackgroundThe morphology of hair regrowth in alopecia areata (AA) patches could be classified into four types, namely diffuse, irregular, marginal, and targetoid patterns, according to the DIMT classification. However, factors affecting hair regrowth patterns have not been investigated.ObjectiveWe investigated whether the DIMT-classified hair regrowth patterns of AA patches are associated with treatment modality and patch size.MethodsWe conducted a retrospective, cross-sectional study of 152 AA patches with hair regrowth.ResultsThe associations between the diffuse pattern and patch size >2 cm (p=0.006; odds ratio [OR]: 0.36, 95% confidence interval [CI]: 0.17~0.74), between the irregular pattern and triamcinolone acetonide intralesional injection (p<0.001; OR: 274.87, 95% CI: 25.75~2,933.56), between the marginal pattern and systemic and topical corticosteroid (p=0.018; OR: 4.89, 95% CI: 1.31~18.27), and between the targetoid pattern and patch size >2 cm (p=0.028; OR: 2.50, 95% CI: 1.10~5.68) were statistically significant.ConclusionTreatment modalities and patch size are the factors affecting hair regrowth patterns in AA patches.

Tracking the Rates and Mechanisms of Canopy Damage and Recovery Following Hurricane Maria Using Multitemporal Lidar Data

Hurricane Maria, a Category 4 storm, snapped and uprooted canopy trees, removed large branches, and defoliated vegetation across Puerto Rico. The magnitude of forest damages and the rates and mechanisms of forest recovery following Maria provide important benchmarks for understanding the ecology of extreme events. We used airborne Lidar data acquired before (2017) and after Maria (2018, 2020) to quantify landscape-scale changes in forest structure along a 439-ha elevational gradient (100–800 m) in the Luquillo Experimental Forest. Damages from Maria were widespread, with 73% of the study area losing ≥ 1 m in canopy height (mean = −7.1 m). Taller forests at lower elevations suffered more damage than shorter forests above 600 m. Yet only 13.5% of the study area had canopy heights ≤ 2 m in 2018, a typical threshold for forest gaps, highlighting the importance of damaged trees and advanced regeneration on post-storm forest structure. Heterogeneous patterns of regrowth and recruitment yielded shorter and more open forests by 2020. Nearly 45% of forests experienced initial height loss > 1 m (2017–2018) followed by rapid height gain > 1 m (2018–2020), whereas 21.6% of forests with initial height losses showed little or no height gain, and 17.8% of forests exhibited no height changes larger than ± 1 m in either period. Canopy layers < 10 m tall accounted for most increases in canopy height and fractional cover between 2018 and 2020, with gains split evenly between height growth and lateral crown expansion by surviving individuals. These findings benchmark rates of gap formation, crown expansion, and canopy closure following hurricane damage and highlight the diversity of ecosystem impacts from heterogeneous spatial patterns and vertical stratification of forest regrowth following a major disturbance event.

Hydrological soil properties control tree regrowth after forest disturbance in the forest steppe of central Mongolia

Abstract. The central Mongolian forest steppe forms a transition between different ecozones and is as such particularly sensitive to environmental changes. It is commonly affected by disturbances such as logging and forest fires. Intensified drought events aggravate stress on the trees that are anyway at their drier limit in the forest steppe. Climate change increases evapotranspiration and reduces the distribution of discontinuous permafrost, which leads to drier soil conditions. The motivation for this study came about through our previous observation that forest stands show great differences with respect to their recovery after disturbance by fire or logging. Sometimes, no regrowth of trees takes place at all. As water availability is the main limiting factor of forest growth in this region, we hypothesised that differences in soil hydrology control the forest recovery pattern. To test this hypothesis, we analysed soil properties under forests, predominantly consisting of Siberian larch (Larix sibirica Ledeb.), in the forest steppe of the northern Khangai Mountains, central Mongolia. We distinguished the following four vegetation categories: (1) near-natural forest (FOR), (2) steppe close to the forest (STE), (3) disturbed forest with regrowth of trees (DWIR), and (4) disturbed forest showing no regrowth of trees (DNOR). A total of 54 soil profiles were described in the field and sampled for soil chemical, physical, and hydrological analysis. We found a significant difference in soil texture between soils under DWIR and DNOR. Sand generally dominated the soil texture, but soils under DWIR had more silt and clay compared to soils under DNOR. Soil pF curves showed that soils under DWIR had higher plant-available field capacity in their uppermost parts than soils under DNOR. In addition, hydraulic conductivity tended to be higher in the uppermost horizons of soils under DWIR compared to their counterparts under DNOR. Chemical properties of the soils under DWIR and DNOR showed no significant differences. We conclude that the differences in post-disturbance tree regrowth are mainly caused by different soil hydrology. High plant-available field capacity is the key factor for forest recovery under semi-arid conditions. High hydraulic conductivity in the uppermost soil horizons can further support tree regrowth because it reduces the evaporation loss and the competition of larch saplings with grasses and herbs for water. Another important factor is human impact, particularly grazing livestock on cleared forest sites, which often keeps seedlings from growing and, thus, inhibits forest recovery. None of the disturbed sites (DWIR and DNOR) had permafrost. We, thus, conclude that permafrost is no major factor for the post-disturbance tree regrowth pattern, although it generally supports tree growth in the forest steppe by preventing meltwater from seasonal ice from seeping below the root zone, thus increasing the water supply in summer.

Effect of Culture Medium Incorporated with Ocimum sanctum Extract in Enhancing Anti-MRSA activity of Endophytic Fungus, Lasiodiplodia pseudotheobromae

The effect of incorporating plant extract in the culture medium on anti-MRSA activity of Lasiodiplodia pseudotheobromae IBRL OS-64, was investigated in the present study. On disk diffusion assay, the ethyl acetate fungal extract from culture medium supplemented with host plant extract (HPE) of Ocimum sanctum leaves demonstrated good anti-MRSA activity with a diameter inhibition zone of 22.6±0.6 mm. Meanwhile, the minimal inhibition concentration (MIC) values of the extract from YES broth and YES broth incorporated with HPE were 1000 µg/mL and 250 µg/mL, respectively. The MBC values were 8000 µg/mL and 500 µg/mL, respectively. The YES + HPE extracts exerted bactericidal effect against the test bacteria since the MBC/MIC ratio was less than or equal to 4. The time-kill study revealed a 90% of growth reduction of MRSA ATCC 33591 after 16 h exposure to the fungal extract cultured in YES + HPE. Ironically, for fungal extract grown in YES broth, time-kill curve showed a regrowth pattern of bacterial cells after 24 h exposed to the extract. Therefore, the present study suggested that the addition of HPE in the culture medium could enhance the anti-MRSA activity of endophytic fungus, L. pseudotheobromae IBRL OS-64 against MRSA ATCC 33591.

Large carbon sink potential of secondary forests in the Brazilian Amazon to mitigate climate change

Tropical secondary forests sequester carbon up to 20 times faster than old-growth forests. This rate does not capture spatial regrowth patterns due to environmental and disturbance drivers. Here we quantify the influence of such drivers on the rate and spatial patterns of regrowth in the Brazilian Amazon using satellite data. Carbon sequestration rates of young secondary forests (<20 years) in the west are ~60% higher (3.0 ± 1.0 Mg C ha−1 yr−1) compared to those in the east (1.3 ± 0.3 Mg C ha−1 yr−1). Disturbances reduce regrowth rates by 8–55%. The 2017 secondary forest carbon stock, of 294 Tg C, could be 8% higher by avoiding fires and repeated deforestation. Maintaining the 2017 secondary forest area has the potential to accumulate ~19.0 Tg C yr−1 until 2030, contributing ~5.5% to Brazil’s 2030 net emissions reduction target. Implementing legal mechanisms to protect and expand secondary forests whilst supporting old-growth conservation is, therefore, key to realising their potential as a nature-based climate solution.

Containment effort reduction and regrowth patterns of the Covid-19 spreading.

In all countries the political decisions aim to achieve an almost stable configuration with a small number of new infected individuals per day due to Covid-19. When such a condition is reached, the containment effort is usually reduced in favor of a gradual reopening of the social life and of the various economical sectors. However, in this new phase, the infection spread restarts and, moreover, possible mutations of the virus give rise to a large specific growth rate of the infected people. Therefore, a quantitative analysis of the regrowth pattern is very useful. We discuss a macroscopic approach which, on the basis of the collected data in the first lockdown, after few days from the beginning of the new phase, outlines different scenarios of the Covid-19 diffusion for longer time. The purpose of this paper is a demonstration-of-concept: one takes simple growth models, considers the available data and shows how the future trend of the spread can be obtained. The method applies a time dependent carrying capacity, analogously to many macroscopic growth laws in biology, economics and population dynamics. The illustrative cases of France, Italy and United Kingdom are analyzed.

Urban Fire Severity and Vegetation Dynamics in Southern California

A combination of satellite image indices and in-field observations was used to investigate the impact of fuel conditions, fire behavior, and vegetation regrowth patterns, altered by invasive riparian vegetation. Satellite image metrics, differenced normalized burn severity (dNBR) and differenced normalized difference vegetation index (dNDVI), were approximated for non-native, riparian, or upland vegetation for traditional timeframes (0-, 1-, and 3-years) after eleven urban fires across a spectrum of invasive vegetation cover. Larger burn severity and loss of green canopy (NDVI) was detected for riparian areas compared to the uplands. The presence of invasive vegetation affected the distribution of burn severity and canopy loss detected within each fire. Fires with native vegetation cover had a higher severity and resulted in larger immediate loss of canopy than fires with substantial amounts of non-native vegetation. The lower burn severity observed 1–3 years after the fires with non-native vegetation suggests a rapid regrowth of non-native grasses, resulting in a smaller measured canopy loss relative to native vegetation immediately after fire. This observed fire pattern favors the life cycle and perpetuation of many opportunistic grasses within urban riparian areas. This research builds upon our current knowledge of wildfire recovery processes and highlights the unique challenges of remotely assessing vegetation biophysical status within urban Mediterranean riverine systems.

Landsat near-infrared (NIR) band and ELM-FATES sensitivity to forest disturbances and regrowth in the Central Amazon

Abstract. Forest disturbance and regrowth are key processes in forest dynamics, but detailed information on these processes is difficult to obtain in remote forests such as the Amazon. We used chronosequences of Landsat satellite imagery (Landsat 5 Thematic Mapper and Landsat 7 Enhanced Thematic Mapper Plus) to determine the sensitivity of surface reflectance from all spectral bands to windthrow, clear-cut, and clear-cut and burned (cut + burn) and their successional pathways of forest regrowth in the Central Amazon. We also assessed whether the forest demography model Functionally Assembled Terrestrial Ecosystem Simulator (FATES) implemented in the Energy Exascale Earth System Model (E3SM) Land Model (ELM), ELM-FATES, accurately represents the changes for windthrow and clear-cut. The results show that all spectral bands from the Landsat satellites were sensitive to the disturbances but after 3 to 6 years only the near-infrared (NIR) band had significant changes associated with the successional pathways of forest regrowth for all the disturbances considered. In general, the NIR values decreased immediately after disturbance, increased to maximum values with the establishment of pioneers and early successional tree species, and then decreased slowly and almost linearly to pre-disturbance conditions with the dynamics of forest succession. Statistical methods predict that NIR values will return to pre-disturbance values in about 39, 36, and 56 years for windthrow, clear-cut, and cut + burn disturbances, respectively. The NIR band captured the observed, and different, successional pathways of forest regrowth after windthrow, clear-cut, and cut + burn. Consistent with inferences from the NIR observations, ELM-FATES predicted higher peaks of biomass and stem density after clear-cuts than after windthrows. ELM-FATES also predicted recovery of forest structure and canopy coverage back to pre-disturbance conditions in 38 years after windthrows and 41 years after clear-cut. The similarity of ELM-FATES predictions of regrowth patterns after windthrow and clear-cut to those of the NIR results suggests the NIR band can be used to benchmark forest regrowth in ecosystem models. Our results show the potential of Landsat imagery data for mapping forest regrowth from different types of disturbances, benchmarking, and the improvement of forest regrowth models.

Regional moose (Alces alces) responses to forestry cutblocks are driven by landscape-scale patterns of vegetation composition and regrowth

Forestry activities are globally widespread and can have a large positive or negative influence on wildlife. Wildlife responses to forestry cutblocks (defined areas where trees were harvested) vary as a function of forest succession, which differs across systems. Across their distribution, moose (Alces alces) and forestry are often closely associated. Moose are predicted to select for cutblocks because of greater browse quantity in early successional vegetation, but moose responses to cutblocks are inconsistent across studies. Our objective was to compare moose spatial responses to cutblocks as a function of year since cut between study areas (Prince George South [PGS] and Bonaparte [BP]) while considering differences in vegetation composition and regrowth to better inform forestry planning in British Columbia, Canada. We characterized cutblocks by dominant tree species as a proxy for vegetation composition and estimated the normalized burn ratio (NBR) from multispectral satellite imagery as an index of vegetation regrowth (i.e., structure). We then examined the use of cutblocks by moose dependent upon vegetation composition and NBR using generalized additive mixed effects models. Next, we used locations of collared moose and nearby available locations to examine moose responses as a function of year since cut and used those responses to group cutblocks into age classes, which were incorporated into resource selection functions (RSF) to compare moose responses between study areas. Vegetation composition differed between study areas, and although cutblocks in both study areas followed similar regrowth trajectories, NBRs for cutblocks > 13 years post-logging in PGS exceeded those in BP. Moose demonstrated greater use of locations within cutblocks with intermediate NBRs and dominanted by spruce (Picea engelmannii × glauca) versus Douglas fir (Pseudotsuga menziesii var. glauca). Moose responses as a function of year since cut varied seasonally, but across seasons, moose tended to avoid new cutblocks (1–8 years), select for regenerating cutblocks (9–24 years), and avoid older cutblocks (25–40 years). In both study areas, RSFs revealed that moose avoided new cutblocks, but moose in PGS were more likely to select for regenerating cutblocks in comparison to BP. Our analyses suggest that the use of cutblocks by moose is a function of year since cut, vegetation composition, and vegetation regrowth, likely resulting from differences in browse quantity and lateral cover. To maintain stable moose populations, managers should consider vegetation composition and regrowth during forestry planning, and future research should focus on identifying region-specific forestry thresholds for moose.

3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments

For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0–20 Gy), and hyperthermia at 47 °C (0–780 CEM43) has been evaluated. Response was analysed in terms of spheroid growth, cell viability and the distribution of live/dead cells. Time-lapse imaging was used to evaluate mechanisms of cell death and cell detachment. It was found that sensitivity to heat in spheroids was significantly less than that seen in monolayer cultures. Spheroids showed different patterns of shrinkage and regrowth when exposed to heat or radiation: heated spheroids shed dead cells within four days of heating and displayed faster growth post-exposure than samples that received radiation or no treatment. Irradiated spheroids maintained a dense structure and exhibited a longer growth delay than spheroids receiving hyperthermia or combination treatment at (thermal) doses that yielded equivalent levels of clonogenic cell survival. We suggest that, unlike radiation, which kills dividing cells, hyperthermia-induced cell death affects cells independent of their proliferation status. This induces microenvironmental changes that promote spheroid growth. In conclusion, 3D tumour spheroid growth studies reveal differences in response to heat and/or radiation that were not apparent in 2D clonogenic assays but that may significantly influence treatment efficacy.

A comparative study of liquid holding restitution of viability after oxidative stress in Ustilago maydis and Saccharomyces cerevisiae cell populations

The ability of Saccharomyces cerevisiae to reconstitute viability after strong peroxide-induced oxidative stress during liquid holding (LH) in non-nutrient medium has been compared with that of Ustilago maydis. It was found that like U. maydis, S. cerevisiae was capable of reconstituting viability through multiplication of the survivors. However, differences were observed in the pattern of their response: (i) the reconstitution of viability was slower in S. cerevisiae; (ii) before the viability was progressively increasing the treated samples of this fungus reproducibly passed through a phase of additional decrease of the surviving fraction and (iii) the final yields of viable cells attained in S. cerevisiae were below those achieved by U. maydis. The reason for the relative superiority of U. maydis is twofold: (1) early initiated and faster degradation and leakage of the intracellular biomolecules and (2) greater ability of U. maydis cells to recycle damaged and released intracellular compounds. Conceptually similar studies extended to another oxidative-stress-inducing condition, namely desiccation, indicated that the marked differences between these fungi in their patterns of the post-stress regrowth, cellular leakage and macromolecule decomposition are reproduced during LH of desiccated cells. The concordance of the findings obtained upon these two approaches was also corroborated by an analysis of the post-desiccation LH response of U. maydis mutants (adr1, did4, kel1 and tbp1) that were previously identified as defective in post-peroxide LH restitution of viability. We discuss the findings in terms of their possible relevance to the mechanisms of the ecological and evolutionary adaptation of free-living microorganisms to fluctuating and severely inhospitable environments.