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1.
Glob Chang Biol ; 27(18): 4403-4419, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34166562

ABSTRACT

Extreme droughts are expected to increase in frequency and severity in many regions of the world, threatening multiple ecosystem services provided by forests. Effective strategies to adapt forests to such droughts require comprehensive information on the effects and importance of the factors influencing forest resistance and resilience. We used a unique combination of inventory and dendrochronological data from a long-term (>30 years) silvicultural experiment in mixed silver fir and Norway spruce mountain forests along a temperature and precipitation gradient in southwestern Germany. We aimed at examining the mechanisms and forest stand characteristics underpinning the resistance and resilience to past mild and severe droughts. We found that (i) fir benefited from mild droughts and showed higher resistance (i.e., lower growth loss during drought) and resilience (i.e., faster return to pre-drought growth levels) than spruce to all droughts; (ii) species identity determined mild drought responses while species interactions and management-related factors strongly influenced the responses to severe droughts; (iii) intraspecific and interspecific interactions had contrasting effects on the two species, with spruce being less resistant to severe droughts when exposed to interaction with fir and beech; (iv) higher values of residual stand basal area following thinning were associated with lower resistance and resilience to severe droughts; and (v) larger trees were resilient to mild drought events but highly vulnerable to severe droughts. Our study provides an analytical approach for examining the effects of different factors on individual tree- and stand-level drought response. The forests investigated here were to a certain extent resilient to mild droughts, and even benefited from such conditions, but were strongly affected by severe droughts. Lastly, negative effects of severe droughts can be reduced through modifying species composition, tree size distribution and stand density in mixed silver fir-Norway spruce forests.


Subject(s)
Droughts , Ecosystem , Climate Change , Europe , Forests , Norway
2.
Mov Disord ; 36(11): 2653-2662, 2021 11.
Article in English | MEDLINE | ID: mdl-34288097

ABSTRACT

BACKGROUND: In patients with medically refractory essential tremor, unilateral magnetic resonance-guided focused ultrasound thalamotomy can improve contralateral tremor. However, this procedure does not address ipsilateral symptoms. OBJECTIVE: The objective of the current study was to determine whether bilateral thalamotomies can be performed with an acceptable safety profile where benefits outweigh adverse effects. METHODS: We conducted a prospective, single-arm, single-blinded phase 2 trial of second-side magnetic resonance-guided focused ultrasound thalamotomy in patients with essential tremor. Patients were followed for 3 months. The primary outcome was the change in quality of life relative to baseline, as well as the answer to the question "Given what you know now, would you treat the second side again?". Secondary outcomes included tremor, gait, speech, and adverse effects. RESULTS: Ten patients were analyzed. The study met both primary outcomes, with the intervention resulting in clinically significant improvement in quality of life at 3 months (mean Quality of Life in Essential Tremor score difference, 19.7; 95%CI, 8.0-31.4; P = 0.004) and all patients reporting that they would elect to receive the second-side treatment again. Tremor significantly improved in all patients. Seven experienced mild adverse effects, including 2 with transient gait impairment and a fall, 1 with dysarthria and dysphagia, and 1 with mild dysphagia persisting at 3 months. CONCLUSIONS: Staged bilateral magnetic resonance-guided focused ultrasound thalamotomy can be performed with a reasonable safety profile similar to that seen with unilateral thalamotomy and improves the tremor and quality of life of patients with essential tremor. Longer-term follow-up and continued accrual in the phase 3 trial will be required to validate these findings. © 2021 International Parkinson and Movement Disorder Society.


Subject(s)
Essential Tremor , Essential Tremor/surgery , Humans , Magnetic Resonance Imaging/methods , Prospective Studies , Quality of Life , Thalamus/surgery , Treatment Outcome
3.
Can J Neurol Sci ; 48(1): 31-37, 2021 01.
Article in English | MEDLINE | ID: mdl-32631474

ABSTRACT

Cortical spreading depolarization (CSD) is recognized as a cause of transient neurological symptoms (TNS) in various clinical entities. Although scientific literature has been flourishing in the field of CSD, it remains an underrecognized pathophysiology in clinical practice. The literature evoking CSD in relation to subdural hematoma (SDH) is particularly scarce. Patients with SDH frequently suffer from TNS, most being attributed to seizures despite an atypical semiology, evolution, and therapeutic response. Recent literature has suggested that a significant proportion of those patients' TNS represent the clinical manifestations of underlying CSD. Recently, the term Non-Epileptical Stereoytpical Intermittent Symptoms (NESIS) has been proposed to describe a subgroup of patients presenting with TNS in the context of SDH. Indirect evidence and recent research suggest that the pathophysiology of NESIS could represent the clinical manifestation of CSD. This review should provide a concise yet thorough review of the current state of literature behind the pathophysiology of CSD with a particular focus on recent research and knowledge regarding the presence of CSD in the context of subdural hematoma. Although many questions remain in the evolution of knowledge in this field would likely have significant diagnostic, therapeutic, and prognostic implications.


Subject(s)
Cortical Spreading Depression , Hematoma, Subdural, Chronic , Electroencephalography , Hematoma, Subdural, Chronic/complications , Hematoma, Subdural, Chronic/diagnostic imaging , Humans , Prognosis , Seizures
4.
Glob Chang Biol ; 26(8): 4521-4537, 2020 08.
Article in English | MEDLINE | ID: mdl-32388882

ABSTRACT

Global climate change is expected to further raise the frequency and severity of extreme events, such as droughts. The effects of extreme droughts on trees are difficult to disentangle given the inherent complexity of drought events (frequency, severity, duration, and timing during the growing season). Besides, drought effects might be modulated by trees' phenotypic variability, which is, in turn, affected by long-term local selective pressures and management legacies. Here we investigated the magnitude and the temporal changes of tree-level resilience (i.e., resistance, recovery, and resilience) to extreme droughts. Moreover, we assessed the tree-, site-, and drought-related factors and their interactions driving the tree-level resilience to extreme droughts. We used a tree-ring network of the widely distributed Scots pine (Pinus sylvestris) along a 2,800 km latitudinal gradient from southern Spain to northern Germany. We found that the resilience to extreme drought decreased in mid-elevation and low productivity sites from 1980-1999 to 2000-2011 likely due to more frequent and severe droughts in the later period. Our study showed that the impact of drought on tree-level resilience was not dependent on its latitudinal location, but rather on the type of sites trees were growing at and on their growth performances (i.e., magnitude and variability of growth) during the predrought period. We found significant interactive effects between drought duration and tree growth prior to drought, suggesting that Scots pine trees with higher magnitude and variability of growth in the long term are more vulnerable to long and severe droughts. Moreover, our results indicate that Scots pine trees that experienced more frequent droughts over the long-term were less resistant to extreme droughts. We, therefore, conclude that the physiological resilience to extreme droughts might be constrained by their growth prior to drought, and that more frequent and longer drought periods may overstrain their potential for acclimation.


Subject(s)
Droughts , Pinus sylvestris , Europe , Germany , Spain , Trees
5.
Glob Chang Biol ; 25(11): 3781-3792, 2019 11.
Article in English | MEDLINE | ID: mdl-31436853

ABSTRACT

Extreme climate events (ECEs) such as severe droughts, heat waves, and late spring frosts are rare but exert a paramount role in shaping tree species distributions. The frequency of such ECEs is expected to increase with climate warming, threatening the sustainability of temperate forests. Here, we analyzed 2,844 tree-ring width series of five dominant European tree species from 104 Swiss sites ranging from 400 to 2,200 m a.s.l. for the period 1930-2016. We found that (a) the broadleaved oak and beech are sensitive to late frosts that strongly reduce current year growth; however, tree growth is highly resilient and fully recovers within 2 years; (b) radial growth of the conifers larch and spruce is strongly and enduringly reduced by spring droughts-these species are the least resistant and resilient to droughts; (c) oak, silver fir, and to a lower extent beech, show higher resistance and resilience to spring droughts and seem therefore better adapted to the future climate. Our results allow a robust comparison of the tree growth responses to drought and spring frost across large climatic gradients and provide striking evidence that the growth of some of the most abundant and economically important European tree species will be increasingly limited by climate warming. These results could serve for supporting species selection to maintain the sustainability of forest ecosystem services under the expected increase in ECEs.


Subject(s)
Droughts , Fagus , Climate Change , Ecosystem , Forests , Trees
6.
Plant Cell Environ ; 40(9): 1972-1983, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28634999

ABSTRACT

Adjustment mechanisms of trees to changes in soil-water availability over long periods are poorly understood, but crucial to improve estimates of forest development in a changing climate. We compared mature trees of Scots pine (Pinus sylvestris) and European larch (Larix decidua) growing along water-permeable channels (irrigated) and under natural conditions (control) at three sites in inner-Alpine dry valleys. At two sites, the irrigation had been stopped in the 1980s. We combined measurements of basal area increment (BAI), tree height and gas-exchange physiology (Δ13 C) for the period 1970-2009. At one site, the Δ13 C of irrigated pine trees was higher than that of the control in all years, while at the other sites, it differed in pine and larch only in years with dry climatic conditions. During the first decade after the sudden change in water availability, the BAI and Δ13 C of originally irrigated pine and larch trees decreased instantly, but subsequently reached higher levels than those of the control by 2009 (15 years afterwards). We found a high plasticity in the gas-exchange physiology of pine and larch and site-specific responses to changes in water availability. Our study highlights the ability of trees to adjust to new conditions, thus showing high resilience.


Subject(s)
Adaptation, Physiological , Gases/metabolism , Larix/physiology , Pinus sylvestris/physiology , Water/physiology , Agricultural Irrigation , Carbon Isotopes , Europe , Geography , Larix/growth & development , Oxygen Isotopes , Pinus sylvestris/growth & development , Soil/chemistry , Xylem/physiology
7.
Arterioscler Thromb Vasc Biol ; 35(12): 2677-85, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26449749

ABSTRACT

OBJECTIVE: In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient-derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. APPROACH AND RESULTS: We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC-derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells-expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. CONCLUSIONS: Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering.


Subject(s)
Cell Differentiation , Diabetes Mellitus, Type 1/pathology , Endothelial Progenitor Cells/pathology , Induced Pluripotent Stem Cells/pathology , Neovascularization, Pathologic , Animals , Animals, Genetically Modified , Antigens, CD/metabolism , Cadherins/metabolism , Case-Control Studies , Cell Hypoxia , Cell Line , Cell Separation , Cell Shape , Diabetes Mellitus, Type 1/blood , Endothelial Progenitor Cells/drug effects , Endothelial Progenitor Cells/metabolism , Endothelial Progenitor Cells/transplantation , Green Fluorescent Proteins/biosynthesis , Green Fluorescent Proteins/genetics , Heterografts , Humans , Hyaluronic Acid/chemistry , Hydrogels , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/transplantation , Lipoproteins, LDL/metabolism , Nitric Oxide Synthase Type III/metabolism , Phenotype , Tumor Necrosis Factor-alpha/pharmacology , Zebrafish/genetics , Zebrafish/metabolism , von Willebrand Factor/metabolism
10.
New Phytol ; 203(1): 94-109, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24635031

ABSTRACT

Higher atmospheric CO2 concentrations (c(a)) can under certain conditions increase tree growth by enhancing photosynthesis, resulting in an increase of intrinsic water-use efficiency (i WUE) in trees. However, the magnitude of these effects and their interactions with changing climatic conditions are still poorly understood under xeric and mesic conditions. We combined radial growth analysis with intra- and interannual δ(13)C and δ(18)O measurements to investigate growth and physiological responses of Larix decidua, Picea abies, Pinus sylvestris, Pinus nigra and Pseudotsuga menziesii in relation to rising c(a) and changing climate at a xeric site in the dry inner Alps and at a mesic site in the Swiss lowlands. (i)WUE increased significantly over the last 50 yr by 8-29% and varied depending on species, site water availability, and seasons. Regardless of species and increased (i)WUE, radial growth has significantly declined under xeric conditions, whereas growth has not increased as expected under mesic conditions. Overall, drought-induced stomatal closure has reduced transpiration at the cost of reduced carbon uptake and growth. Our results indicate that, even under mesic conditions, the temperature-induced drought stress has overridden the potential CO2 'fertilization' on tree growth, hence challenging today's predictions of improved forest productivity of temperate forests.


Subject(s)
Larix/growth & development , Pinus sylvestris/growth & development , Pseudotsuga/growth & development , Trees/growth & development , Water/physiology , Carbon Isotopes/analysis , Climate Change , Droughts , Forests , Italy , Oxygen Isotopes/analysis , Plant Transpiration , Seasons , Switzerland
11.
Tree Physiol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874315

ABSTRACT

Disentangling the factors influencing the climate sensitivity of trees is crucial to understanding the susceptibility of forests to climate change. Reducing tree-to-tree competition and mixing tree species are two strategies often promoted to reduce the drought sensitivity of trees, but it is unclear how effective these measures are in different ecosystems. Here, we studied the growth and physiological responses to climate and severe droughts of silver fir and Douglas-fir growing in pure and mixed conditions at three sites in Switzerland. We used tree-ring width (TRW) data and carbon (δ13C), oxygen (δ18O) and hydrogen (δ2H) stable isotope ratios from tree-ring cellulose to gain novel information on water relations and the physiology of trees in response to drought and how tree species mixture and competition modulate these responses. We found significant differences in isotope ratios between trees growing in pure and mixed conditions for the two species, although these differences varied between sites, e.g. trees growing in mixed conditions had higher δ13C values and TRW than trees growing in pure conditions for two of the sites. For both species, differences between trees in pure and mixed conditions regarding their sensitivity to temperature, precipitation, climatic water balance and vapor pressure deficit (VPD) were minor. Further, trees growing in pure and mixed conditions showed similar responses of TRW and isotope ratios to the past severe droughts of 2003, 2015 and 2018. Competition had only a significantly negative effect on δ13C of silver fir, which may suggest a decrease in photosynthesis due to higher competition for light and nutrients. Our study highlights that tree species mixture may have only moderate effects on the radial growth and physiological responses of silver fir and Douglas-fir to climatic conditions and that site condition effects may dominate over mixture effects.

12.
Sci Total Environ ; 912: 169068, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38049004

ABSTRACT

The record-breaking drought in 2018 caused premature leaf discoloration and shedding (early browning) in many beech (Fagus sylvatica L.) dominated forests in Central Europe. However, a high degree of variability in drought response among individual beech trees was observed. While some trees were severely impacted by the prolonged water deficits and high temperatures, others remained vital with no or only minor signs of crown vitality loss. Why some beech trees were more susceptible to drought-induced crown damage than others and whether growth recovery is possible are poorly understood. Here, we aimed to identify growth characteristics associated with the variability in drought response between individual beech trees based on a sample of 470 trees in northern Switzerland. By combining tree growth measurements and crown condition assessments, we also investigated the possible link between crown dieback and growth recovery after drought. Beech trees with early browning exhibited an overall lower growth vigor before the 2018 drought than co-occurring vital beech trees. This lower vigor is mainly indicated by lower overall growth rates, stronger growth declines in the past decades, and higher growth-climate sensitivity. Particularly, warm previous year summer conditions negatively affected current growth of the early-browning trees. These findings suggest that the affected trees had less access to critical resources and were physiologically limited in their growth predisposing them to early browning. Following the 2018 drought, observed growth recovery potential corresponded to the amount of crown dieback and the local climatic water balance. Overall, our findings emphasize that beech-dominated forests in Central Europe are under increasing pressure from severe droughts, ultimately reducing the competitive ability of this species, especially on lowland sites with shallow soils and low water holding capacity.


Subject(s)
Fagus , Fagus/physiology , Droughts , Forests , Seasons , Trees , Water
13.
Sci Total Environ ; 913: 169692, 2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38160816

ABSTRACT

To enhance our understanding of forest carbon sequestration, climate change mitigation and drought impact on forest ecosystems, the availability of high-resolution annual forest growth maps based on tree-ring width (TRW) would provide a significant advancement to the field. Site-specific characteristics, which can be approximated by high-resolution Earth observation by satellites (EOS), emerge as crucial drivers of forest growth, influencing how climate translates into tree growth. EOS provides information on surface reflectance related to forest characteristics and thus can potentially improve the accuracy of forest growth models based on TRW. Through the modelling of TRW using EOS, climate and topography data, we showed that species-specific models can explain up to 52 % of model variance (Quercus petraea), while combining different species results in relatively poor model performance (R2 = 13 %). The integration of EOS into models based solely on climate and elevation data improved the explained variance by 6 % on average. Leveraging these insights, we successfully generated a map of annual TRW for the year 2021. We employed the area of applicability (AOA) approach to delineate the range in which our models are deemed valid. The calculated AOA for the established forest-type models was 73 % of the study region, indicating robust spatial applicability. Notably, unreliable predictions predominantly occurred in the climate margins of our dataset. In conclusion, our large-scale assessment underscores the efficacy of combining climate, EOS and topographic data to develop robust models for mapping annual TRW. This research not only fills a critical void in the current understanding of forest growth dynamics but also highlights the potential of integrated data sources for comprehensive ecosystem assessments.


Subject(s)
Ecosystem , Remote Sensing Technology , Forests , Trees , Climate Change , Europe, Eastern , Europe
14.
Glob Chang Biol ; 19(10): 3184-99, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23712589

ABSTRACT

The ability of tree species to cope with anticipated decrease in water availability is still poorly understood. We evaluated the potential of Norway spruce, Scots pine, European larch, black pine, and Douglas-fir to withstand drought in a drier future climate by analyzing their past growth and physiological responses at a xeric and a mesic site in Central Europe using dendroecological methods. Earlywood, latewood, and total ring width, as well as the δ(13) C and δ(18) O in early- and latewood were measured and statistically related to a multiscalar soil water deficit index from 1961 to 2009. At the xeric site, δ(13) C values of all species were strongly linked to water deficits that lasted longer than 11 months, indicating a long-term cumulative effect on the carbon pool. Trees at the xeric site were particularly sensitive to soil water recharge in the preceding autumn and early spring. The native species European larch and Norway spruce, growing close to their dry distribution limit at the xeric site, were found to be the most vulnerable species to soil water deficits. At the mesic site, summer water availability was critical for all species, whereas water availability prior to the growing season was less important. Trees at the mesic were more vulnerable to water deficits of shorter duration than the xeric site. We conclude that if summers become drier, trees growing on mesic sites will undergo significant growth reductions, whereas at their dry distribution limit in the Alps, tree growth of the highly sensitive spruce and larch may collapse, likely inducing dieback and compromising the provision of ecosystem services. However, the magnitude of these changes will be mediated strongly by soil water recharge in winter and thus water availability at the beginning of the growing season.


Subject(s)
Droughts , Pinaceae/growth & development , Carbon Isotopes , Italy , Oxygen Isotopes , Soil/chemistry , Switzerland , Temperature , Water/analysis
15.
Sci Total Environ ; 794: 148514, 2021 Nov 10.
Article in English | MEDLINE | ID: mdl-34218146

ABSTRACT

An increase in frequency, intensity and duration of drought events affects forested ecosystems. Trees react to these changes by adjusting stomatal conductance to maximize the trade-off between carbon gains and water losses. A better understanding of the consequences of these drought-induced physiological adjustments for tree growth could help inferring future productivity potentials of boreal forests. Here, we used samples from a forest inventory network in Canada where a decline in growth rates of black spruce (Picea mariana (Mill.) B.S.P.) and jack pine (Pinus banksiana Lamb.) occurred in 1988-1992, an exceptionally dry period, to verify if this growth decline resulted from physiological adjustments of trees to drought. We measured carbon and oxygen isotope ratios in growth rings of 95 spruces and 49 pines spanning 1985-1993. We used 13C discrimination (Δ13C) and 18O enrichment (Δ18O) as proxies for intrinsic water use efficiency and stomatal conductance, respectively. We studied how inter-annual variability in isotopic signals was linked to climate moisture index, vapor pressure deficit and annual snowfall amount. We found significantly lower Δ13C values over 1988-1990, and significantly higher Δ18O values in 1988-1989 and 1991 compared to the 1985-1993 averages. We also observed that a low climatic water balance and a high vapor pressure deficit were linked with low Δ13C and high Δ18O in the two study species, in parallel with low growth rates. The latter effect persisted into the year following drought for black spruce, but not for jack pine. These findings highlight that small differences in physiological parameters between species could translate into large differences in post-drought recovery. The stronger and longer lasting impact on black spruce compared to jack pine suggests a less efficient carbon use and a lower acclimation potential to future warmer and drier climate conditions.


Subject(s)
Picea , Pinus , Canada , Droughts , Ecosystem , Trees
16.
Sci Total Environ ; 784: 147222, 2021 Aug 25.
Article in English | MEDLINE | ID: mdl-34088042

ABSTRACT

Recent studies have identified strong relationships between delayed recovery of tree growth after drought and tree mortality caused by subsequent droughts. These observations raise concerns about forest ecosystem services and post-drought growth recovery given the projected increase in drought frequency and extremes. For quantifying the impact of extreme droughts on tree radial growth, we used a network of tree-ring width data of 1689 trees from 100 sites representing most of the distribution of two drought tolerant, deciduous oak species (Quercus petraea and Quercus robur). We first examined which climatic factors and seasons control growth of the two species and if there is any latitudinal, longitudinal or elevational trend. We then quantified the relative departure from pre-drought growth during droughts, and how fast trees were able to recover the pre-drought growth level. Our results showed that growth was more related to precipitation and climatic water balance (precipitation minus potential evapotranspiration) than to temperature. However, we did not detect any clear latitudinal, longitudinal or elevational trends except a decreasing influence of summer water balance on growth of Q. petraea with latitude. Neither species was able to maintain the pre-drought growth level during droughts. However, both species showed rapid recovery or even growth compensation after summer droughts but displayed slow recovery in response to spring droughts where none of the two species was able to fully recover the pre-drought growth-level over the three post-drought years. Collectively, our results indicate that oaks which are considered resilient to extreme droughts have also shown vulnerability when droughts occurred in spring especially at sites where long-term growth is not significantly correlated with climatic factors. This improved understanding of the role of drought seasonality and climate sensitivity of sites is key to better predict trajectories of post-drought growth recovery in response to the drier climate projected for Europe.


Subject(s)
Quercus , Climate Change , Droughts , Ecosystem , Europe , Forests , Trees
17.
BMC Dev Biol ; 10: 15, 2010 Feb 12.
Article in English | MEDLINE | ID: mdl-20152028

ABSTRACT

BACKGROUND: Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration. RESULTS: The expression of BMP-2 and SOX-9 in developing and regenerating axolotl limbs corresponded to the first digits forming in the anterior portion of the autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused hypomorphic limbs (during development and regeneration) but did not affect the expression of BMP-2 and SOX-9. Overexpression of BMP-2 in regenerating limbs caused a loss of digits. Overexpression of Noggin (BMP inhibitor) in regenerating limbs also resulted in a loss of digits. Histological analysis indicated that the loss due to BMP-2 overexpression was the result of increased cell condensation and apoptosis while the loss caused by Noggin was due to a decrease in cell division. CONCLUSION: The expression of BMP-2 and its target SOX-9 was independent of sonic hedgehog signaling in developing and regenerating limbs. Their expression correlated with chondrogenesis and the appearance of skeletal elements has described in other tetrapods. Overexpression of BMP-2 did not cause the formation of extra digits, which is consistent with the hypothesis that it is not the secondary signal of sonic hedgehog. However, it did cause the formation of hypomorphic limbs as a result of increased cellular condensation and apoptosis. Taken together, these results suggest that BMP-2 does not have a direct role in patterning regenerating limbs but may be important to trigger condensation prior to ossification and to mediate apoptosis.


Subject(s)
Ambystoma mexicanum/physiology , Apoptosis , Bone Morphogenetic Protein 2/metabolism , Extremities/physiology , Hedgehog Proteins/metabolism , Animals , Bone Morphogenetic Protein 2/genetics , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cloning, Molecular , Hedgehog Proteins/genetics , Mice , Regeneration , SOX9 Transcription Factor/metabolism
18.
J Exp Zool B Mol Dev Evol ; 314(8): 684-97, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-20718005

ABSTRACT

Urodele amphibians, such as the axolotl (Ambystoma mexicanum), have the unique faculty among vertebrates to regenerate lost appendages (limbs and tail) and other body parts (apex of the heart, forebrain and jaw) after amputation. Interestingly, axolotls never seem to form scar tissue at the site of amputation once regeneration is completed. Before now, very few studies were directly focused on the description of the events happening during wound healing after a skin injury in salamanders. In this paper, we directly investigated skin wound healing after excisional wounding which removed the epidermis, dermis and basement membrane in the axolotl. Axolotls were wounded with a 1.5-mm skin biopsy punch. Results show rapid re-epithelialization of the wound within 8 hrs after wounding. Histological analysis of wound healing confirmed the absence of tissue fibrosis throughout the process and shows that skin integrity is re-established by 90 days after wounding. Results also reveal the absence of neutrophils in the wound area, suggestive of a lack of or low inflammatory response. The expression of proteins central to wound healing seemed different than in mammals as α-smooth muscle actin was absent and transforming growth factor ß-1 was only transiently expressed during wound healing in the axolotl. Finally, subcutaneous injections of bleomycin were performed to verify whether the induction of scar tissue was possible in axolotls. Surprisingly, results show that axolotls are not resistant to bleomycin-induced tissue fibrosis, but the resulting scar tissue does not seem to contain significant amounts of collagen.


Subject(s)
Ambystoma mexicanum/metabolism , Wound Healing/physiology , Animals , Antibiotics, Antineoplastic , Bleomycin , Cicatrix/pathology , Fibrosis/chemically induced , Gene Expression Regulation , Neutrophils/cytology , Skin/cytology , Skin/injuries , Time Factors , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
19.
Neurosurgery ; 87(1): 96-103, 2020 07 01.
Article in English | MEDLINE | ID: mdl-31555809

ABSTRACT

BACKGROUND: Transient neurological symptoms (TNS) are frequent in patients with subdural hematomas (SDH) and many will receive a diagnosis of epilepsy despite a negative workup. OBJECTIVE: To explore if patients with TNS and a negative epilepsy workup (cases) evolved differently than those with a positive EEG (controls), which would suggest the existence of alternative etiologies for TNS. METHODS: We performed a single-center, retrospective, case-control study of patients with TNS post-SDH. The demographics and clinical and semiological features of cases and controls were compared. The outcome and response to antiepileptic drugs were also assessed and a scoring system developed to predict negative EEG. RESULTS: Fifty-nine patients with SDH-associated TNS were included (39 cases and 20 controls). Demographic characteristics were comparable in both groups. Dysphasia and prolonged episodes were associated with a negative EEG. Clonic movements, impaired awareness, positive symptomatology, complete response to antiepileptic drugs, and mortality were associated with a positive EEG. Using semiological variables, we created a scoring system with a 96.6% sensitivity and 100% specificity in predicting case group patients. The differences observed between both groups support the existence of an alternative etiology to seizures in our case group. We propose the term NESIS (NonEpileptic, Stereotypical, and Intermittent Symptoms) to refer to this subgroup and hypothesize that TNS in these patients might result from cortical spreading depolarization. CONCLUSION: We describe NESIS as a syndrome experienced by SDH patients with specific prognostic and therapeutic implications. Independent validation of this new entity is now required.


Subject(s)
Hematoma, Subdural/diagnosis , Hematoma, Subdural/physiopathology , Seizures/diagnosis , Seizures/physiopathology , Stereotypic Movement Disorder/diagnosis , Stereotypic Movement Disorder/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Electroencephalography/methods , Female , Hematoma, Subdural/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Seizures/epidemiology , Stereotypic Movement Disorder/epidemiology , Young Adult
20.
Nat Commun ; 10(1): 742, 2019 02 14.
Article in English | MEDLINE | ID: mdl-30765694

ABSTRACT

Historical and future trends in net primary productivity (NPP) and its sensitivity to global change are largely unknown because of the lack of long-term, high-resolution data. Here we test whether annually resolved tree-ring stable carbon (δ13C) and oxygen (δ18O) isotopes can be used as proxies for reconstructing past NPP. Stable isotope chronologies from four sites within three distinct hydroclimatic environments in the eastern United States (US) were compared in time and space against satellite-derived NPP products, including the long-term Global Inventory Modeling and Mapping Studies (GIMMS3g) NPP (1982-2011), the newest high-resolution Landsat NPP (1986-2015), and the Moderate Resolution Imaging Spectroradiometer (MODIS, 2001-2015) NPP. We show that tree-ring isotopes, in particular δ18O, correlate strongly with satellite NPP estimates at both local and large geographical scales in the eastern US. These findings represent an important breakthrough for estimating interannual variability and long-term changes in terrestrial productivity at the biome scale.


Subject(s)
Carbon Isotopes/metabolism , Ecosystem , Oxygen Isotopes/metabolism , Seasons , Trees/metabolism , Algorithms , Conservation of Natural Resources/methods , Geography , Models, Biological , Satellite Imagery/methods , Trees/growth & development , United States
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