In many countries around the globe, private freehold lands cover large areas. Conservation on these private lands, next to statutory protected areas, promises to play a critical role in efforts for ...reaching internationally agreed environmental protection targets. Lying at the heart of an emerging land system science, in which ecology, economics, geography, psychology, and other social sciences interact, private land conservation is reflecting the intertwined and multiscalar processes of our rapidly transforming world. Situated at this disciplinary meeting point, private land conservation invites a great breadth of approaches and cross-disciplinary work that offer deep insights into social and environmental change, often from surprising angles. Although many questions remain in private land conservation, we can now build on a large body of recent high-quality studies as we push this field forward in both research and practice. The Special Feature “Private Land Conservation - Landowner Motives, Policies, and Outcomes of Conservation Measures in Unprotected Landscapes” brings together contributions that explore the diversity of recent advances in private land conservation science. As an introduction to this Special Feature, first we are reviewing recent dynamics in important social-ecological drivers with bearing on private land conservation science. We go on to introduce the individual contributions to this Special Feature and then examine common themes as they are emerging from these papers, including the need for flexibility in conservation approaches, pursuit of community cobenefits of conservation, increasing consideration of environmental justice questions, and acknowledgment of the importance of social psychology in shaping private land conservation. We conclude with identification of knowledge gaps and recommendations for future research, as we advance from diagnostics to normative work in private land conservation science.
The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, ...colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant problem.
Cannabis agriculture is a multi-billion dollar industry in the United States that is changing rapidly with policy liberalization. Anecdotal observations fuel speculation about associated ...environmental impacts, and there is an urgent need for systematic empirical research. An example from Humboldt County California, a principal cannabis-producing region, involved digitizing 4428 grow sites in 60 watersheds with Google Earth imagery. Grows were clustered, suggesting disproportionate impacts in ecologically important locales. Sixty-eight percent of grows were >500 m from developed roads, suggesting risk of landscape fragmentation. Twenty-two percent were on steep slopes, suggesting risk of erosion, sedimentation, and landslides. Five percent were <100 m from threatened fish habitat, and the estimated 297 954 plants would consume an estimated 700 000 m3 of water, suggesting risk of stream impacts. The extent and magnitude of cannabis agriculture documented in our study demands that it be regulated and researched on par with conventional agriculture.
The permeability transition pore (PTP) is a multi-protein complex at contact sites of the inner with the outer mitochondrial membrane. Research over the past years has led to the concept that the PTP ...occupies a central role in cell death induction. Numerous apoptosis signals convert this protein aggregate into an unspecific pore, thus activating mitochondria for the cellular self-destruction process. Here, we describe the evidence for this and the various approaches being undertaken to elucidate its subunit composition and mode of regulation. In particular, we review data that indicate a role of specific PTP subunits for apoptosis inhibition during tumorigenesis.
Intrinsic and acquired chemoresistance are frequent causes of cancer eradication failure. Thus, long-term cis-diaminedichloroplatine(II) (CDDP) or cisplatin treatment is known to promote tumor cell ...resistance to apoptosis induction via multiple mechanisms involving gene expression modulation of oncogenes, tumor suppressors and blockade of pro-apoptotic mitochondrial membrane permeabilization. Here, we demonstrate that CDDP-resistant non-small lung cancer cells undergo profound remodeling of their endoplasmic reticulum (ER) proteome (>80 proteins identified by proteomics) and exhibit a dramatic overexpression of two protein disulfide isomerases, PDIA4 and PDIA6, without any alteration in ER-cytosol Ca(2+) fluxes. Using pharmacological and genetic inhibition, we show that inactivation of both proteins directly stimulates CDDP-induced cell death by different cellular signaling pathways. PDIA4 inactivation restores a classical mitochondrial apoptosis pathway, while knockdown of PDIA6 favors a non-canonical cell death pathway sharing some necroptosis features. Overexpression of both proteins has also been found in lung adenocarcinoma patients, suggesting a clinical importance of these proteins in chemoresistance.
The DNA commission of the International Society of Forensic Genetics (ISFG) was convened at the 21st congress of the International Society for Forensic Genetics held between 13 and 17 September in ...the Azores, Portugal. The purpose of the group was to agree on guidelines to encourage best practice that can be universally applied to assist with mixture interpretation. In addition the commission was tasked to provide guidance on low copy number (LCN) reporting. Our discussions have highlighted a significant need for continuing education and research into this area. We have attempted to present a consensus from experts but to be practical we do not claim to have conveyed a clear vision in every respect in this difficult subject. For this reason, we propose to allow a period of time for feedback and reflection by the scientific community. Then the DNA commission will meet again to consider further recommendations.
The FOCUS smartphone intervention was developed to provide automated real-time/real-place illness management support to individuals with schizophrenia. The system was specifically designed to be ...usable by people with psychotic disorders who may have cognitive impairment, psychotic symptoms, negative symptoms, and/or low reading levels. FOCUS offers users both prescheduled and on-demand resources to facilitate symptom management, mood regulation, medication adherence, social functioning, and improved sleep. In this study, 33 individuals with schizophrenia or schizoaffective disorder used FOCUS over a 1-month period in their own environments. Participants were able to learn how to use the intervention independently, and all but one participant completed the trial successfully and returned the smartphones intact. Completers used the system on 86.5% of days they had the device, an average of 5.2 times a day. Approximately 62% of use of the FOCUS intervention was initiated by the participants, and 38% of use was in response to automated prompts. Baseline levels of cognitive functioning, negative symptoms, persecutory ideation, and reading level were not related to participants' use of the intervention. Approximately 90% of participants rated the intervention as highly acceptable and usable. Paired samples t tests found significant reductions in psychotic symptoms, depression, and general psychopathology, after 1 month of FOCUS use. This study demonstrated the feasibility, acceptability, and preliminary efficacy of the FOCUS intervention for schizophrenia and introduces a new treatment model which has promise for extending the reach of evidence-based care beyond the confines of a physical clinic using widely available technologies.
The unprecedented accuracy of elevations retrieved from the Ice Cloud and Land Elevation Satellite (ICESat) laser altimeter is investigated and used to characterize the range errors in the ...Environmental Satellite (Envisat) and European Remote Sensing 2 Satellite (ERS-2) radar altimeters over the continental ice sheets. Cross-mission crossover analysis between time-coincident ERS-2-, Envisat-, and ICESat-retrieved elevations and comparisons to an ICESat-derived digital elevation map are used to quantify the radar elevation error budget as a function of surface slope and to investigate the effectiveness of a method to account for the radar altimeter slope-induced error. The precision and accuracy of the elevations retrieved from the ICESat Geoscience Laser Altimeter System and the European Space Agency radar altimeters on ERS-2 and Envisat are calculated over the Greenland and Antarctic ice sheets using a crossover analysis. As a result of this work, the laser precision is found to vary as a function of surface slope from 14 to 59 cm, and the radar precision varies from 59 cm to 3.7 m for ERS-2 and from 28 cm to 2.06 m for Envisat. Envisat elevation retrievals when compared with ICESat results over regions with less than 0.1deg surface slopes show a mean difference of 9plusmn5 cm for Greenland and -40plusmn98 cm over Antarctica. ERS-2 elevation retrievals over these same low surface slope regions differ from ICESat results by -56plusmn72 cm over Greenland and 1.12plusmn1.16 m over Antarctica. At higher surface slopes of 0.7deg to 0.8deg, the Envisat/ICESat differences increase to -2.27plusmn23 m over Greenland and to 0.05plusmn26 m over Antarctica
Introduction Le calcium (Ca2+) est essentiel au couplage excitation-contraction. Il est également un second messager indispensable au couplage excitation métabolisme oxydatif (CEMO). Au cours de ...l’obésité et du diabète de type 2, se développe une cardiomyopathie diabétique (CMD) caractérisé par une dysfonction ventriculaire. Lors d’une CMD, le CEMO subit de nombreuses modifications. L’augmentation de l’oxydation des acides gras est accompagnée d’un effondrement du rapport ATP/O caractéristique d’un découplage au niveau mitochondrial. Ce découplage est dû à une augmentation de l’expression d’UCP, mais pourrait également provenir d’une modification de l’activité de l’AdenineNucleotideTranslocase (ANT). Parallèlement l’homéostasie calcique cellulaire est très perturbée. Cependant la régulation croisée entre le métabolisme mitochondrial et l’homéostasie calcique dans le développement de la pathologie n’est pas clairement définie. Dans cette étude nous nous proposons d’étudier les effets aigus du palmitoyl-carnitine (PC : acide gras saturé à longue chaîne) sur le CEMO dans le cœur sain afin d’en caractériser les voies de régulation. Matériels et méthodes Pour cela nous travaillons sur des cœurs de souris C57BL/6. Résultats L’application de PC, sur des mitochondries isolées, induit une diminution de l’activité de l’ANT ainsi qu’une dépolarisation de la membrane mitochondriale. Cette dépolarisation est également observée lors de l’application de PC sur des cellules fraîchement isolées. Ceci est corrélée à une production massive d’espèce réactive de l’oxygène (ROS) qui est prévenu par l’application d’un inhibiteur spécifique de l’ANT (BA). Parallèlement, le PC augmente la fuite de calcium du réticulum sarcoplasmique en diastole, diminue l’amplitude et ralenti la cinétique des variations transitoires de Ca2+, obtenue sous stimulation de champs. Toutes ces modifications sont prévenues par l’application d’un antioxydant (N-Acetyl-Cystéine), ou du BA. Ces résultats démontrent que le PC, en régulant directement l’activité de ANT, augmente la production mitochondriale de ROS et engendre en conséquences des modifications importantes du CEMO. Conclusion La régulation dynamique de ANT par les acides gras saturés à chaînes longues apparaît comme une cible thérapeutique nouvelle dans le développement de la CMD.
TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ...ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA) using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role). Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5%) of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.
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