Sub-continental-scale carbon stocks of individual trees in African drylands.

The distribution of dryland trees and their density, cover, size, mass and carbon content are not well known at sub-continental to continental scales1-14. This information is important for ecological protection, carbon accounting, climate mitigation and restoration efforts of dryland ecosystems15-18. We assessed more than 9.9 billion trees derived from more than 300,000 satellite images, covering semi-arid sub-Saharan Africa north of the Equator. We attributed wood, foliage and root carbon to every tree in the 0-1,000 mm year-1 rainfall zone by coupling field data19, machine learning20-22, satellite data and high-performance computing. Average carbon stocks of individual trees ranged from 0.54 Mg C ha-1 and 63 kg C tree-1 in the arid zone to 3.7 Mg C ha-1 and 98 kg tree-1 in the sub-humid zone. Overall, we estimated the total carbon for our study area to be 0.84 (±19.8%) Pg C. Comparisons with 14 previous TRENDY numerical simulation studies23 for our area found that the density and carbon stocks of scattered trees have been underestimated by three models and overestimated by 11 models, respectively. This benchmarking can help understand the carbon cycle and address concerns about land degradation24-29. We make available a linked database of wood mass, foliage mass, root mass and carbon stock of each tree for scientists, policymakers, dryland-restoration practitioners and farmers, who can use it to estimate farmland tree carbon stocks from tablets or laptops.

An unexpectedly large count of trees in the West African Sahara and Sahel.

A large proportion of dryland trees and shrubs (hereafter referred to collectively as trees) grow in isolation, without canopy closure. These non-forest trees have a crucial role in biodiversity, and provide ecosystem services such as carbon storage, food resources and shelter for humans and animals1,2. However, most public interest relating to trees is devoted to forests, and trees outside of forests are not well-documented3. Here we map the crown size of each tree more than 3 m2 in size over a land area that spans 1.3 million km2 in the West African Sahara, Sahel and sub-humid zone, using submetre-resolution satellite imagery and deep learning4. We detected over 1.8 billion individual trees (13.4 trees per hectare), with a median crown size of 12 m2, along a rainfall gradient from 0 to 1,000 mm per year. The canopy cover increases from 0.1% (0.7 trees per hectare) in hyper-arid areas, through 1.6% (9.9 trees per hectare) in arid and 5.6% (30.1 trees per hectare) in semi-arid zones, to 13.3% (47 trees per hectare) in sub-humid areas. Although the overall canopy cover is low, the relatively high density of isolated trees challenges prevailing narratives about dryland desertification5-7, and even the desert shows a surprisingly high tree density. Our assessment suggests a way to monitor trees outside of forests globally, and to explore their role in mitigating degradation, climate change and poverty.

Response to concerns about the African fire trends controlled by precipitation over recent decades.

Croplands expanded in Africa over recent decades, even though the increasing trends are spatially heterogeneous.

Nonlinear dynamics of fires in Africa over recent decades controlled by precipitation.

Dynamics of fires in Africa are of critical importance for understanding changes in ecosystem properties and effects on the global carbon cycle. Given increasing fire risk from projected warming on the one hand and a documented human-driven decline in fires on the other, it is still unknown how the complex interplay between climate and human factors affects recent changes of fires in Africa. Moreover, the impact of recent strong El Niño events on fire dynamics is not yet known. By applying an ensemble empirical mode decomposition method to satellite-derived fire burned area, we investigated the spatio-temporal evolution of fires in Africa over 2001-2016 and identified the potential dominant drivers. Our results show an overall decline of fire rates, which is continuous over the time period and mainly caused by cropland expansion in northern sub-Saharan Africa. However, we also find that years of high precipitation have caused an initial increase in fire rates in southern Africa, which reversed to a decline in later years. This decline is caused by a high frequency of dry years leading to very low fuel loads, suggesting that recent drought causes a general reduction of burned areas, in particular in xeric savannas. In some mesic regions (10°-15°S), solar radiation and increased temperature caused increase in fires. These findings show that climate change overrules the impact of human expansion on fire rates at the continental scale in Africa, reducing the fire risk.

Echo Trains in Pulsed Electron Spin Resonance of a Strongly Coupled Spin Ensemble.

We report on a novel dynamical phenomenon in electron spin resonance experiments of phosphorus donors. When strongly coupling the paramagnetic ensemble to a superconducting lumped element resonator, the coherent exchange between these two subsystems leads to a train of periodic, self-stimulated echoes after a conventional Hahn echo pulse sequence. The presence of these multiecho signatures is explained using a simple model based on spins rotating on the Bloch sphere, backed up by numerical calculations using the inhomogeneous Tavis-Cummings Hamiltonian.

Structure-based optimisation of orally active & reversible MetAP-2 inhibitors maintaining a tight 'molecular budget'.

Structure-based led optimisation of orally active reversible Methionine Aminopeptidase-2 (MetAP-2) inhibitors utilising a 'molecular budget' medicinal chemistry strategy is described. The key physicochemical parameters of target molecules (cLogP, molecular size and H-bond donor count) were monitored through straightforward and intuitive use of atom count and distribution. The balance between structure-based design and an awareness of the physicochemical properties of the compounds synthesised enabled the rapid identification of a potent molecule with good oral pharmacokinetic (PK) characteristics by making fewer, higher quality compounds. The resulting candidate quality molecule was validated in a mechanistic cellular assay and a rodent secondary immunisation model.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.

EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations.

In eukaryotes, post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and is involved in repressing gene expression through methylation of histone H3 on lysine 27 (H3K27). EZH2 overexpression is implicated in tumorigenesis and correlates with poor prognosis in several tumour types. Additionally, somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 occur in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. The Y641 residue is the most frequently mutated residue, with up to 22% of germinal centre B-cell DLBCL and follicular lymphoma harbouring mutations at this site. These lymphomas have increased H3K27 tri-methylation (H3K27me3) owing to altered substrate preferences of the mutant enzymes. However, it is unknown whether specific, direct inhibition of EZH2 methyltransferase activity will be effective in treating EZH2 mutant lymphomas. Here we demonstrate that GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.

Mapping gains and losses in woody vegetation across global tropical drylands.

Woody vegetation in global tropical drylands is of significant importance for both the interannual variability of the carbon cycle and local livelihoods. Satellite observations over the past decades provide a unique way to assess the vegetation long-term dynamics across biomes worldwide. Yet, the actual changes in the woody vegetation are always hidden by interannual fluctuations of the leaf density, because the most widely used remote sensing data are primarily related to the photosynthetically active vegetation components. Here, we quantify the temporal trends of the nonphotosynthetic woody components (i.e., stems and branches) in global tropical drylands during 2000-2012 using the vegetation optical depth (VOD), retrieved from passive microwave observations. This is achieved by a novel method focusing on the dry season period to minimize the influence of herbaceous vegetation and using MODerate resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) data to remove the interannual fluctuations of the woody leaf component. We revealed significant trends (P < 0.05) in the woody component (VODwood ) in 35% of the areas characterized by a nonsignificant trend in the leaf component (VODleaf modeled from NDVI), indicating pronounced gradual growth/decline in woody vegetation not captured by traditional assessments. The method is validated using a unique record of ground measurements from the semiarid Sahel and shows a strong agreement between changes in VODwood and changes in ground observed woody cover (r2  = 0.78). Reliability of the obtained woody component trends is also supported by a review of relevant literatures for eight hot spot regions of change. The proposed approach is expected to contribute to an improved assessment of, for example, changes in dryland carbon pools.

Efficient Electrical Spin Readout of NV

Using pulsed photoionization the coherent spin manipulation and echo formation of ensembles of NV^{-} centers in diamond are detected electrically, realizing contrasts of up to 17%. The underlying spin-dependent ionization dynamics are investigated experimentally and compared to Monte Carlo simulations. This allows the identification of the conditions optimizing contrast and sensitivity, which compare favorably with respect to optical detection.

Multiple-Quantum Transitions and Charge-Induced Decoherence of Donor Nuclear Spins in Silicon.

We study single- and multiquantum transitions of the nuclear spins of an ensemble of ionized arsenic donors in silicon and find quadrupolar effects on the coherence times, which we link to fluctuating electrical field gradients present after the application of light and bias voltage pulses. To determine the coherence times of superpositions of all orders in the 4-dimensional Hilbert space, we use a phase-cycling technique and find that, when electrical effects were allowed to decay, these times scale as expected for a fieldlike decoherence mechanism such as the interaction with surrounding ^{29}Si nuclear spins.

Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction.

Although therapeutic interventions of signal-transduction cascades with targeted kinase inhibitors are a well-established strategy, drug-discovery efforts to identify targeted phosphatase inhibitors have proven challenging. Herein we report a series of allosteric, small-molecule inhibitors of wild-type p53-induced phosphatase (Wip1), an oncogenic phosphatase common to multiple cancers. Compound binding to Wip1 is dependent on a 'flap' subdomain located near the Wip1 catalytic site that renders Wip1 structurally divergent from other members of the protein phosphatase 2C (PP2C) family and that thereby confers selectivity for Wip1 over other phosphatases. Treatment of tumor cells with the inhibitor GSK2830371 increases phosphorylation of Wip1 substrates and causes growth inhibition in both hematopoietic tumor cell lines and Wip1-amplified breast tumor cells harboring wild-type TP53. Oral administration of Wip1 inhibitors in mice results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth. To our knowledge, GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase.

Ground- and satellite-based evidence of the biophysical mechanisms behind the greening Sahel.

After a dry period with prolonged droughts in the 1970s and 1980s, recent scientific outcome suggests that the decades of abnormally dry conditions in the Sahel have been reversed by positive anomalies in rainfall. Various remote sensing studies observed a positive trend in vegetation greenness over the last decades which is known as the re-greening of the Sahel. However, little investment has been made in including long-term ground-based data collections to evaluate and better understand the biophysical mechanisms behind these findings. Thus, deductions on a possible increment in biomass remain speculative. Our aim is to bridge these gaps and give specifics on the biophysical background factors of the re-greening Sahel. Therefore, a trend analysis was applied on long time series (1987-2013) of satellite-based vegetation and rainfall data, as well as on ground-observations of leaf biomass of woody species, herb biomass, and woody species abundance in different ecosystems located in the Sahel zone of Senegal. We found that the positive trend observed in satellite vegetation time series (+36%) is caused by an increment of in situ measured biomass (+34%), which is highly controlled by precipitation (+40%). Whereas herb biomass shows large inter-annual fluctuations rather than a clear trend, leaf biomass of woody species has doubled within 27 years (+103%). This increase in woody biomass did not reflect on biodiversity with 11 of 16 woody species declining in abundance over the period. We conclude that the observed greening in the Senegalese Sahel is primarily related to an increasing tree cover that caused satellite-driven vegetation indices to increase with rainfall reversal.

Submillisecond hyperpolarization of nuclear spins in silicon.

In this Letter, we devise a fast and effective nuclear spin hyperpolarization scheme, which is, in principle, magnetic field independent. We use this scheme to experimentally demonstrate polarizations of up to 66% for phosphorus donor nuclear spins in bulk silicon, which are created within less than 100 µs in a magnetic field of 0.35 T at a temperature of 5 K. The polarization scheme is based on a spin-dependent recombination process via weakly coupled spin pairs, for which the recombination time constant strongly depends on the relative orientation of the two spins. We further use this scheme to measure the nuclear spin relaxation time and find a value of ∼100 ms under illumination, in good agreement with the value calculated for nuclear spin flips induced by repeated ionization and deionization processes.

Interaction of Strain and Nuclear Spins in Silicon: Quadrupolar Effects on Ionized Donors.

The nuclear spins of ionized donors in silicon have become an interesting quantum resource due to their very long coherence times. Their perfect isolation, however, comes at a price, since the absence of the donor electron makes the nuclear spin difficult to control. We demonstrate that the quadrupolar interaction allows us to effectively tune the nuclear magnetic resonance of ionized arsenic donors in silicon via strain and determine the two nonzero elements of the S tensor linking strain and electric field gradients in this material to S(11)=1.5×10(22) V/m2 and S(44)=6×10(22) V/m2. We find a stronger benefit of dynamical decoupling on the coherence properties of transitions subject to first-order quadrupole shifts than on those subject to only second-order shifts and discuss applications of quadrupole physics including mechanical driving of magnetic resonance, cooling of mechanical resonators, and strain-mediated spin coupling.

Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27).

Trimethylation of histone H3 on lysine 27 (H3K27me3) is a repressive posttranslational modification mediated by the histone methyltransferase EZH2. EZH2 is a component of the polycomb repressive complex 2 and is overexpressed in many cancers. In B-cell lymphomas, its substrate preference is frequently altered through somatic mutation of the EZH2 Y641 residue. Herein, we identify mutation of EZH2 A677 to a glycine (A677G) among lymphoma cell lines and primary tumor specimens. Similar to Y641 mutant cell lines, an A677G mutant cell line revealed aberrantly elevated H3K27me3 and decreased monomethylated H3K27 (H3K27me1) and dimethylated H3K27 (H3K27me2). A677G EZH2 possessed catalytic activity with a substrate specificity that was distinct from those of both WT EZH2 and Y641 mutants. Whereas WT EZH2 displayed a preference for substrates with less methylation [unmethylated H3K27 (H3K27me0):me1:me2 k(cat)/K(m) ratio = 9:6:1] and Y641 mutants preferred substrates with greater methylation (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1:2:13), the A677G EZH2 demonstrated nearly equal efficiency for all three substrates (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1.1:0.6:1). When transiently expressed in cells, A677G EZH2, but not WT EZH2, increased global H3K27me3 and decreased H3K27me2. Structural modeling of WT and mutant EZH2 suggested that the A677G mutation acquires the ability to methylate H3K27me2 through enlargement of the lysine tunnel while preserving activity with H3K27me0/me1 substrates through retention of the Y641 residue that is crucial for orientation of these smaller substrates. This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EZH2.

Resonant electronic coupling enabled by small molecules in nanocrystal solids.

The future exploitation of the exceptional properties of nanocrystal (NC) thin films deposited from liquid dispersions of nanoparticles relies upon our ability to produce films with improved electrical properties by simple and inexpensive means. Here, we demonstrate that the electronic conduction of solution-processed NC films can be strongly enhanced without the need of postdeposition treatments, via specific molecules adsorbed at the surfaces of adjacent NCs. This effect is demonstrated for Si NC films doped with the strong molecular oxidizing agent tetrafluoro-tetracyanoquinodimethane (F4-TCNQ). Density functional calculations were carried out with molecule-doped superlattice solid models. It is shown that, when populated by electrons, hybrid molecule/NC states edge (and may actually resonate with) the conduction-band states of the NC solid. This provides extra electronic connectivity across the NC network as the molecules effectively flatten the electronic potential barriers for electron transfer across the otherwise vacuum-filled network interstitialcies.

Comparison of optical coherence tomography and histopathology in quantitative assessment of goat talus articular cartilage.

BACKGROUND AND PURPOSE: Optical coherence tomography (OCT) is a light-based imaging technique suitable for depiction of thin tissue layers such as articular cartilage. Quantification of results and direct comparison with a reference standard is needed to confirm the role of OCT in cartilage evaluation. MATERIALS AND METHODS: Goat talus articular cartilage repair was assessed quantitatively with OCT and compared with histopathology using semi-automated analysis software. Osteochondral defects were created centrally in goat tali with subsequent healing over 24 weeks. After sacrifice, the tali were analyzed using OCT and processed into histopathology slides. Cartilage thickness, repair tissue area, and surface roughness were measured. Also, light attenuation coefficient measurements were performed to assess differences in the properties of healthy tissue and repair tissue. RESULTS: Intra-class correlation coefficients for resemblance between the 2 techniques were 0.95 (p < 0.001) for thickness, 0.73 (p = 0.002) for repair tissue area, and 0.63 (p = 0.015) for surface roughness. Light attenuation differed significantly between healthy cartilage (8.2 (SD 3.9) mm(-1)) and repair tissue (2.8 (SD 1.5) mm(-1)) (p < 0.001). INTERPRETATION: Compared to histopathology as the standard reference method, OCT is a reproducible technique in quantitative analysis of goat talus articular cartilage, especially when assessing cartilage thickness and to a lesser extent when measuring repair tissue area and surface roughness. Moreover, differences in local light attenuation suggest measurable variation in tissue structure, enhancing the clinical applicability of quantitative measurements from cartilage OCT images.

Even low levels of tree cover improve dietary quality in West Africa.

Forests are attracting attention as a promising avenue to provide nutritious and "free" food without damaging the environment. Yet, we lack knowledge on the extent to which this holds in areas with sparse tree cover, such as in West Africa. This is largely due to the fact that existing methods are poorly designed to quantify tree cover in drylands. In this study, we estimate how various levels of tree cover across West Africa affect children's (aged 12-59 months) consumption of vitamin A-rich foods. We do so by combining detailed tree cover estimates based on PlanetScope imagery (3 m resolution) with Demographic Health Survey data from >15,000 households. We find that the probability of consuming vitamin A-rich foods increases from 0.45 to 0.53 with an increase in tree cover from the median value of 8.8 to 16.8% (which is the tree cover level at which the predicted probability of consuming vitamin A-rich foods is the highest). Moreover, we observe that the effects of tree cover vary across poverty levels and ecoregions. The poor are more likely than the non-poor to consume vitamin A-rich foods at low levels of tree cover in the lowland forest-savanna ecoregions, whereas the difference between poor and non-poor is less pronounced in the Sahel-Sudan. These results highlight the importance of trees and forests in sustainable food system transformation, even in areas with sparse tree cover.

Facing the challenge of NDVI dataset consistency for improved characterization of vegetation response to climate variability.

Non-linear trend detection in Earth observation time series has become a standard method to characterize changes in terrestrial ecosystems. However, results are largely dependent on the quality and consistency of the input data, and only few studies have addressed the impact of data artifacts on the interpretation of detected abrupt changes. Here we study non-linear dynamics and turning points (TPs) of temperate grasslands in East Eurasia using two independent state-of-the-art satellite NDVI datasets (CGLS v3 and MODIS C6) and explore the impact of water availability on observed vegetation changes during 2001-2019. By applying the Break For Additive Season and Trend (BFAST01) method, we conducted a classification typology based on vegetation dynamics which was spatially consistent between the datasets for 40.86 % (459,669 km2) of the study area. When considering also the timing of the TPs, 27.09 % of the pixels showed consistent results between datasets, suggesting that careful interpretation was needed for most of the areas of detected vegetation dynamics when applying BFAST to a single dataset. Notably, for these areas showing identical typology we found that interrupted decreases in vegetation productivity were dominant in the transition zone between desert and steppes. Here, a strong link with changes in water availability was found for >80 % of the area, indicating that increasing drought stress had regulated vegetation productivity in recent years. This study shows the necessity of a cautious interpretation of the results when conducting advanced characterization of vegetation response to climate variability, but at the same time also the opportunities of going beyond the use of single dataset in advanced time-series approaches to better understanding dryland vegetation dynamics for improved anthropogenic interventions to combat vegetation productivity decrease.