Crystal structure of the PsbQ protein of photosystem II from higher plants

The smallest extrinsic polypeptide of the water-oxidizing complex (PsbQ) was extracted and purified from spinach (Spinacia oleracea) photosystem II (PSII) membranes. It was then crystallized in the presence of Zn²⁺ and its structure was determined by X-ray diffraction at 1.95-Å resolution using the multi-wavelength anomalous diffraction method, with the zinc as the anomalous scatterer. The crystal structure shows that the core of the protein is a four-helix bundle, whereas the amino-terminal portion, which possibly interacts with the photosystem core, is not visible in the crystal. The distribution of positive and negative charges on the protein surface might explain the ability of PsbQ to increase the binding of Cl⁻ and Ca²⁺ and make them available to PSII.     

The economics and greenhouse gas balance of land conversion to Jatropha: the case of Tanzania

Due to higher oil prices, abundance of labor and suitable land and its stable political climate, Tanzania attracted many investments in Jatropha. Although several studies on Jatropha's economic potential are available, its true economics are still uncertain. This paper aims to add to the growing body of knowledge on the socio‐economic performance of the Jatropha system by (i) studying the economic potential (net present value – NPV) of the current most prevailing Jatropha system for Tanzanian farmers and its regional differences, by (ii) making a greenhouse gas (GHG) balance and its economic value of the Jatropha activities on regional level, and by (iii) calculating break‐even thresholds for yield and seed price. Therefore, regional yield modeling, regional life‐cycle assessment, and NPV calculations based on Monte Carlo simulations, each with its set of assumptions, are combined. This study shows positive economic potential of Jatropha cultivation in most of the Tanzanian regions. However, the results also show that 13 of 20 Tanzanian regions will not attain a net positive GHG balance within 10 years. This indicates that the environmental impacts might be more restrictive for Jatropha's sustainability potential in Tanzania than the socio‐economic potential. These results are based on the combination of three models, which consists of strong interdisciplinary modeling work. However, this modeling also contains simplifications (e.g., no opportunity cost for ‘marginal’ land) and uncertainties (e.g., using globally modeled potential yield estimations), which have to be considered in the interpretation of the results.     

Smurf2 regulates hematopoietic stem cell self‐renewal and aging

The age‐dependent decline in the self‐renewal capacity of stem cells plays a critical role in aging, but the precise mechanisms underlying this decline are not well understood. By limiting proliferative capacity, senescence is thought to play an important role in age‐dependent decline of stem cell self‐renewal, although direct evidence supporting this hypothesis is largely lacking. We have previously identified the E3 ubiquitin ligase Smurf2 as a critical regulator of senescence. In this study, we found that mice deficient in Smurf2 had an expanded hematopoietic stem cell (HSC) compartment in bone marrow under normal homeostatic conditions, and this expansion was associated with enhanced proliferation and reduced quiescence of HSCs. Surprisingly, increased cycling and reduced quiescence of HSCs in Smurf2‐deficient mice did not lead to premature exhaustion of stem cells. Instead, HSCs in aged Smurf2‐deficient mice had a significantly better repopulating capacity than aged wild‐type HSCs, suggesting that decline in HSC function with age is Smurf2 dependent. Furthermore, Smurf2‐deficient HSCs exhibited elevated long‐term self‐renewal capacity and diminished exhaustion in serial transplantation. As we found that the expression of Smurf2 was increased with age and in response to regenerative stress during serial transplantation, our findings suggest that Smurf2 plays an important role in regulating HSC self‐renewal and aging.     

Genomic profiling of solid tumors harboring BRD4-NUT and response to immune checkpoint inhibitors

BackgroundThe translocation t(15:19) produces the oncogenic BRD4-NUT fusion which is pathognomonic for NUT carcinoma (NC), which is a rare, but extremely aggressive solid tumor. Comprehensive genomic profiling (CGP) by hybrid-capture based next generation sequencing of 186+ genes of a cohort of advanced cancer cases with a variety of initial diagnoses harboring BRD4-NUT may shed further insight into the biology of these tumors and possible options for targeted treatment.Case presentationThirty-one solid tumor cases harboring a BRD4-NUT translocation are described, with only 16% initially diagnosed as NC and the remainder carrying other diagnoses, most commonly NSCLC—NOS (22%) and lung squamous cell carcinoma (NSCLC-SCC) (16%). The cohort was all microsatellite stable and harbored a low Tumor Mutational Burden (TMB, mean 1.7 mut/mb, range 0–4). In two index cases, patients treated with immune checkpoint inhibitors (ICPI) had unexpected partial or better responses of varying duration. Notably, four cases – including the two index cases - were negative for PD-L1 expression. Neo-antigen prediction for BRD4-NUT and then affinity modeling of the peptide-MHC (pMHC) complex for an assessable index case predicted very high affinity binding, both on a ranked (99.9%) and absolute (33 nM) basis.ConclusionsCGP identifies BRD4-NUT fusions in advanced solid tumors which carry a broad range of initial diagnoses and which should be re-diagnosed as NC per guidelines. A hypothesized mechanism underlying responses to ICPI in the low TMB, PD-L1 negative index cases is the predicted high affinity of the BRD4-NUT fusion peptide to MHC complexes. Further study of pMHC affinity and response to immune checkpoint inhibitors in patients with NC harboring BRD4-NUT is needed to validate this therapeutic hypothesis.     

Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study

Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00548405","term_id":"NCT00548405"}}NCT00548405     

The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI

The mechanism by which sweet proteins elicit a response on the T1R2-T1R3 sweet taste receptor is still mostly unknown but has been so far related to the presence of "sweet fingers" on the protein surface able to interact with the same mechanism as that of low molecular mass sweeteners. In the search for the identification of sweet fingers, we have solved the solution structure of G16A MNEI, a structural mutant that shows a reduction of one order of magnitude in sweetness with respect to its parent protein, MNEI, a single-chain monellin. Comparison of the structures of wild-type monellin and its G16A mutant shows that the mutation does not affect the structure of potential glucophores but produces a distortion of the surface owing to the partial relative displacement of elements of secondary structure. These results show conclusively that sweet proteins do not possess a sweet finger and strongly support the hypothesis that the mechanism of interaction of sweet-tasting proteins with the recently identified T1R2-T1R3 GPC receptor is different from that of low molecular mass sweeteners.     

Coexistence trend contingent to Mediterranean oaks with different leaf habits

In a previous work we developed a mathematical model to explain the co‐occurrence of evergreen and deciduous oak groups in the Mediterranean region, regarded as one of the distinctive features of Mediterranean biodiversity. The mathematical analysis showed that a stabilizing mechanism resulting from niche difference (i.e. different water use and water stress tolerance) between groups allows their coexistence at intermediate values of suitable soil water content. A simple formal derivation of the model expresses this hypothesis in a testable form linked uniquely to the actual evapotranspiration of forests community. In the present work we ascertain whether this simplified conclusion possesses some degree of explanatory power by comparing available data on oaks distributions and remotely sensed evapotranspiration (MODIS product) in a large‐scale survey embracing the western Mediterranean area. Our findings confirmed the basic assumptions of model addressed on large scale, but also revealed asymmetric responses to water use and water stress tolerance between evergreen and deciduous oaks that should be taken into account to increase the understating of species interactions and, ultimately, improve the modeling capacity to explain co‐occurrence.     

Engaging Transformation: Using Seasonal Rounds to Anticipate Climate Change

Human Ecology - Seasonal rounds are deliberative articulations of a community’s sociocultural relations with their ecological system. The process of visualizing seasonal rounds informs...