Renewal of Collaborative Research: Economically Viable Forest Harvesting Practices That Increase Carbon Sequestration

Forests provide wildlife habitat, water and air purification, climate moderation, and timber and nontimber products. Concern about climate change has put forests in the limelight as sinks of atmospheric carbon. The C stored in the global vegetation, mostly in forests, is nearly equivalent to the amount present in atmospheric CO{sub 2}. Both voluntary and government-mandated carbon trading markets are being developed and debated, some of which include C sequestration resulting from forest management as a possible tradeable commodity. However, uncertainties regarding sources of variation in sequestration rates, validation, and leakage remain significant challenges for devising strategies to include forest management in C markets. Hence, the need for scientifically-based information on C sequestration by forest management has never been greater. The consequences of forest management on the US carbon budget are large, because about two-thirds of the {approx}300 million hectare US forest resource is classified as 'commercial forest.' In most C accounting budgets, forest harvesting is usually considered to cause a net release of C from the terrestrial biosphere to the atmosphere. However, forest management practices could be designed to meet the multiple goals of providing wood and paper products, creating economic returns from natural resources, while sequestering C from the atmosphere. The shelterwood harvest strategy, which removes about 30% of the basal area of the overstory trees in each of three successive harvests spread out over thirty years as part of a stand rotation of 60-100 years, may improve net C sequestration compared to clear-cutting because: (1) the average C stored on the land surface over a rotation increases, (2) harvesting only overstory trees means that a larger fraction of the harvested logs can be used for long-lived sawtimber products, compared to more pulp resulting from clearcutting, (3) the shelterwood cut encourages growth of subcanopy trees by opening up the forest canopy to increasing light penetration. Decomposition of onsite harvest slash and of wastes created during timber processing releases CO{sub 2} to the atmosphere, thus offsetting some of the C sequestered in vegetation. Decomposition of soil C and dead roots may also be temporarily stimulated by increased light penetration and warming of the forest floor. Quantification of these processes and their net effect is needed. We began studying C sequestration in a planned shelterwood harvest at the Howland Forest in central Maine in 2000. The harvest took place in 2002 by the International Paper Corporation, who assisted us to track the fates of harvest products (Scott et al., 2004, Environmental Management 33: S9-S22). Here we present the results of intensive on-site studies of the decay of harvest slash, soil respiration, growth of the remaining trees, and net ecosystem exchange (NEE) of CO{sub 2} during the first six years following the harvest. These results are combined with calculations of C in persisting off-site harvest products to estimate the net C consequences to date of this commercial shelterwood harvest operation. Tower-based eddy covariance is an ideal method for this study, as it integrates all C fluxes in and out of the forest over a large 'footprint' area and can reveal how the net C flux, as well as gross primary productivity and respiration, change following harvest. Because the size of this experiment precludes large-scale replication, we are use a paired-airshed approach, similar to classic large-scale paired watershed experiments. Measurements of biomass and C fluxes in control and treatment stands were compared during a pre-treatment calibration period, and then divergence from pre-treatment relationships between the two sites measured after the harvest treatment. Forests store carbon (C) as they accumulate biomass. Many forests are also commercial sources of timber and wood fiber. In most C accounting budgets, forest harvesting is usually considered to cause a net release of C from the terrestrial biosphere to the atmosphere. However, it might also be possible for commercial use of forests to contribute to terrestrial sequestration of C. The objective of the our research project is to determine whether shelterwood cutting regimes now being adopted in the commercial forests of Maine and other areas of the country can achieve these multiple goals

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations

partially_open16Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML). Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.partially_openembargoed_20230131Pollyea, Daniel A; DiNardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop MPollyea, Daniel A; Dinardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop

Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease

BACKGROUND: One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear. METHODS: Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD. RESULTS: Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I–II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051). CONCLUSION: The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung

Ephrin-A5 Suppresses Neurotrophin Evoked Neuronal Motility, ERK Activation and Gene Expression

During brain development, growth cones respond to attractive and repulsive axon guidance cues. How growth cones integrate guidance instructions is poorly understood. Here, we demonstrate a link between BDNF (brain derived neurotrophic factor), promoting axonal branching and ephrin-A5, mediating axonal repulsion via Eph receptor tyrosine kinase activation. BDNF enhanced growth cone filopodial dynamics and neurite branching of primary neurons. We show that ephrin-A5 antagonized this BDNF-evoked neuronal motility. BDNF increased ERK phosphorylation (P-ERK) and nuclear ERK entry. Ephrin-A5 suppressed BDNF-induced ERK activity and might sequester P-ERK in the cytoplasm. Neurotrophins are well established stimulators of a neuronal immediate early gene (IEG) response. This is confirmed in this study by e.g. c-fos, Egr1 and Arc upregulation upon BDNF application. This BDNF-evoked IEG response required the transcription factor SRF (serum response factor). Notably, ephrin-A5 suppressed a BDNF-evoked neuronal IEG response, suggesting a role of Eph receptors in modulating gene expression. In opposite to IEGs, long-term ephrin-A5 application induced cytoskeletal gene expression of tropomyosin and actinin. To uncover specific Eph receptors mediating ephrin-As impact on neurotrophin signaling, EphA7 deficient mice were analyzed. In EphA7 deficient neurons alterations in growth cone morphology were observed. However, ephrin-A5 still counteracted neurotrophin signaling suggesting that EphA7 is not required for ephrin and BDNF crosstalk. In sum, our data suggest an interaction of ephrin-As and neurotrophin signaling pathways converging at ERK signaling and nuclear gene activity. As ephrins are involved in development and function of many organs, such modulation of receptor tyrosine kinase signaling and gene expression by Ephs might not be limited to the nervous system

Human and mouse neuroinflammation markers in Niemann‐Pick disease, type C1

Niemann‐Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post‐mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C‐X‐C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL‐3, IL‐10 and IL‐13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147148/1/jimd0083.pd

Reconstruction and identification of τ lepton decays to hadrons and ντ at CMS

This paper describes the algorithms used by the CMS experiment to reconstruct and identify tau -> hadrons + nu(tau) decays during Run 1 of the LHC. The performance of the algorithms is studied in proton-proton collisions recorded at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The algorithms achieve an identification efficiency of 50-60%, with misidentification rates for quark and gluon jets, electrons, and muons between per mille and per cent levels

Reconstruction and identification of tau lepton decays to hadrons and tau neutrino at CMS

This paper describes the algorithms used by the CMS experiment to reconstruct and identify tau to hadrons + tau neutrino decays during Run 1 of the LHC. The performance of the algorithms is studied in proton-proton collisions recorded at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The algorithms achieve an identification efficiency of 50-60%, with misidentification rates for quark and gluon jets, electrons, and muons between per mille and per cent levels.Comment: Replaced with published version. Added journal referenc

Experimental traumatic brain injury

Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury

Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity

We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity