unseen iceberg: plant roots in arctic tundra Iversen, Colleen M; Sloan, Victoria L; Sullivan, Patrick F ...
The New phytologist,
January 2015, Volume:
205, Issue:
1
Journal Article
Peer reviewed
Open access
CONTENTS: 34 I. 35 II. 35 III. 41 IV. 43 V. 49 VI. 50 VII. 51 VIII. 52 53 References 53 SUMMARY: Plant roots play a critical role in ecosystem function in arctic tundra, but root dynamics in these ...ecosystems are poorly understood. To address this knowledge gap, we synthesized available literature on tundra roots, including their distribution, dynamics and contribution to ecosystem carbon and nutrient fluxes, and highlighted key aspects of their representation in terrestrial biosphere models. Across all tundra ecosystems, belowground plant biomass exceeded aboveground biomass, with the exception of polar desert tundra. Roots were shallowly distributed in the thin layer of soil that thaws annually, and were often found in surface organic soil horizons. Root traits – including distribution, chemistry, anatomy and resource partitioning – play an important role in controlling plant species competition, and therefore ecosystem carbon and nutrient fluxes, under changing climatic conditions, but have only been quantified for a small fraction of tundra plants. Further, the annual production and mortality of fine roots are key components of ecosystem processes in tundra, but extant data are sparse. Tundra root traits and dynamics should be the focus of future research efforts. Better representation of the dynamics and characteristics of tundra roots will improve the utility of models for the evaluation of the responses of tundra ecosystems to changing environmental conditions.
Structural variants (SVs) rearrange large segments of DNA
and can have profound consequences in evolution and human disease
. As national biobanks, disease-association studies, and clinical genetic ...testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD)
have become integral in the interpretation of single-nucleotide variants (SNVs)
. However, there are no reference maps of SVs from high-coverage genome sequencing comparable to those for SNVs. Here we present a reference of sequence-resolved SVs constructed from 14,891 genomes across diverse global populations (54% non-European) in gnomAD. We discovered a rich and complex landscape of 433,371 SVs, from which we estimate that SVs are responsible for 25-29% of all rare protein-truncating events per genome. We found strong correlations between natural selection against damaging SNVs and rare SVs that disrupt or duplicate protein-coding sequence, which suggests that genes that are highly intolerant to loss-of-function are also sensitive to increased dosage
. We also uncovered modest selection against noncoding SVs in cis-regulatory elements, although selection against protein-truncating SVs was stronger than all noncoding effects. Finally, we identified very large (over one megabase), rare SVs in 3.9% of samples, and estimate that 0.13% of individuals may carry an SV that meets the existing criteria for clinically important incidental findings
. This SV resource is freely distributed via the gnomAD browser
and will have broad utility in population genetics, disease-association studies, and diagnostic screening.
Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic ...syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein) and the facial skin (facial skin arteries) by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M) and 5-hydroxytryptamine (5HT; 10-9-10-5M) and the vasodilator acetylcholine (10-9-10-5M) was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01). In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006) and veins (P = 0.009) from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof.
The density and phenotype of tumour-associated macrophages have been linked with prognosis in a range of solid tumours. While there is strong preclinical evidence that tumour-associated macrophages ...promote aspects of tumour progression, it can be challenging to infer clinical activity from surface markers and ex vivo behaviour. We investigated the association of macrophage infiltration with prognosis and functional changes in the tumour microenvironment in primary human melanoma.
Fifty-seven formalin-fixed, paraffin-embedded primary melanomas were analysed by immunohistochemical analysis of CD68, CD163, inducible nitric oxide synthase (iNOS) and arginase expression. RNA sequencing was performed on serial sections of 20 of the stained tumours to determine the influence of macrophage infiltration on gene expression.
CD68
cells are a functionally active subset of macrophages that are associated with increased iNOS and arginase staining and altered gene expression. In comparison, while there is a greater accumulation of CD163
macrophages in larger tumours, these cells are comparatively inactive, with no association with the level of iNOS or arginase staining, and no effect on gene expression within the tumour. The infiltration of either subset of macrophages did not correlate to overall survival.
Thus, melanomas contain distinct macrophage populations with diverse phenotypes, but with no observable prognostic role.
Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces ...tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P<0.01) final volume (0.158 ± 0.037 cm3) than in control mice (0.051 ± 0.007 cm3). However, PDAC tumour growth was unaffected. Immunofluorescent analysis of SCC tumours did not show differences in vessel density (CD31/alpha-smooth muscle actin) or cell proliferation (Ki67) after 11β-HSD1 inhibition, and immunohistochemistry of SCC tumours did not show changes in inflammatory cell (CD3- or F4/80-positive) infiltration. In culture, the growth/viability (assessed by live cell imaging) of SCC cells was not affected by UE2316 or corticosterone. Second Harmonic Generation microscopy showed that UE2316 reduced Type I collagen (P<0.001), whilst RNA-sequencing revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated SCC tumours. 11β-HSD1 inhibition increases SCC tumour growth, likely via suppression of inflammatory/immune cell signalling and extracellular matrix deposition, but does not promote tumour angiogenesis or growth of all solid tumours.
In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific ...clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies.
Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the ...systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers.
Eight adult male rhesus macaques underwent ventilation with sedation for 48-96 hours in a critical care setting. Three of these NHPs underwent "sham" procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy.
Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72-96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed.
A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.
Beyond its anti-fibrinolytic mechanism, tranexamic acid has been suggested to have anti-inflammatory properties which may contribute to the survival benefit it provides to trauma patients. The ...objective of this study was to assess possible immunomodulatory effects of tranexamic acid as well as potential amelioration of end-organ injury in a rodent hemorrhagic shock model. Controlled hemorrhagic shock was induced in adult Sprague Dawley rats to a mean arterial pressure of 30 mmHg. Groups of 10 rats were administered intravenous tranexamic acid (300mg/kg) or vehicle control (normal saline) intravenously 15 minutes after the induction of shock. After 60 minutes of hemorrhagic shock, resuscitation was started. Animals were euthanized at six, 24, or 72 hours from the start of shock. Serum laboratory values to include inflammatory biomarkers were measured, and end organ histology was evaluated. Tranexamic acid treatment was associated with a significant decrease in serum IL-1β at six and 24 hours and IL-10 at 24 hours from start of shock compared to vehicle control. Histologic analysis demonstrated mild decreases in both perivascular pulmonary edema and follicular mesenteric lymph node hyperplasia in the tranexamic acid treatment group but also increased myocardial lymphocytic infiltration with necrosis and degeneration. Tranexamic acid was also associated with a small but significant increase in peripheral neutrophil count as well as a significant decrease in neutrophil aggregation in pulmonary tissue at six hours post-injury. These data thus demonstrate a mixed effect of tranexamic acid. While there was an improvement in pulmonary edema and a suppressive effect on several key inflammatory mediators, there was also increased myocardial degeneration and necrosis, which is possibly related to the pro-thrombotic effect of tranexamic acid.
Introduction
Non-iatrogenic aerodigestive injuries are infrequent but potentially fatal. We hypothesize that advances in management and adoption of innovative therapies resulted in improved survival.
...Methods
Trauma registry review at a university Level 1 center from 2000 to 2020 that identified adults with aerodigestive injuries requiring operative or endoluminal intervention. Demographics, injuries, operations, and outcomes were abstracted. Univariate analysis was performed, P < .05 was statistically significant.
Results
95 patients had 105 injuries: 68 tracheal and 37 esophageal (including 10 combined). Mean age 30.9 (± 14), 87.4% male, 82.1% penetrating, and 28.4% with vascular injuries. Median ISS, chest AIS, admission BP, Shock Index, and lactate were 26 (16-34), 4 (3-4), 132 (113-149) mmHg, .8 (.7-1.1), and 3.1 (2.4-5.6) mmol/L, respectively. There were 46 cervical and 22 thoracic airway injuries; 5 patients in extremis required preoperative ECMO. 66 airway injuries were surgically repaired and 2 definitively managed with endobronchial stents. There were 24 cervical, 11 thoracic, 2 abdominal esophageal injuries—all repaired surgically. Combined tracheoesophageal injuries were individually managed and buttressed. 4 airway complications were successfully managed, and 11 esophageal complications managed conservatively, stented, or resected. Mortality was 9.6%, half from intraoperative hemorrhage. Specific mortality: tracheobronchial 8.8%, esophageal 10.8%, and combined 20%. Mortality was significantly associated with higher ISS (P = .01), vascular injury (P = .007), blunt mechanism (P = .01), bronchial injury (P = .01), and years 2000-2010 (P = .03), but not combined tracheobronchial injury.
Conclusion
Mortality is associated with several variables, including vascular trauma and years 2000-2010. The use of ECMO and endoluminal stents in highly selected patients and institutional experience may account for 97.8% survival over the past decade.
Somatic mutations during stem cell division are responsible for several cancers. In principle, a similar process could occur during the intense cell proliferation accompanying human brain ...development, leading to the accumulation of regionally distributed foci of mutations. Using dual platform >5000-fold depth sequencing of 102 genes in 173 adult human brain samples, we detect and validate somatic mutations in 27 of 54 brains. Using a mathematical model of neurodevelopment and approximate Bayesian inference, we predict that macroscopic islands of pathologically mutated neurons are likely to be common in the general population. The detected mutation spectrum also includes DNMT3A and TET2 which are likely to have originated from blood cell lineages. Together, these findings establish developmental mutagenesis as a potential mechanism for neurodegenerative disorders, and provide a novel mechanism for the regional onset and focal pathology in sporadic cases.
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