This edited collection disrupts dominant narratives about space, states, and borders, bringing comparative ethnographic and geographic scholarship in conversation with one another to illuminate the ...varied ways in which space becomes socialized via political, economic, and cognitive appropriation. Societies must, first and foremost, do more than wrangle over ownership and land rights - they must dwell in space. Yet, historically the interactions between the state's territorial imperative with previous forms of landscape management have unfolded in a variety of ways, including top-down imposition, resistance, and negotiation between local and external actors. These interactions have resulted in hybrid forms of territoriality, and are often fraught with fundamentally different perceptions of landscape. This book foregrounds these experiences and draws attention to situations in which different social constructions of space and territory coincide, collide, or overlap. Each ethnographic case in this volume presents forms of territoriality that are contingent upon contested histories, politics, landscape, the presence or absence of local heterogeneity and the involvement of multiple external actors with differing motivations - ultimately all resulting in the potential for conflict or collaboration and divergent implications for conceptions of community, autochthony and identity.
Colorectal cancer represents an important oncological challenge both for its incidence, which makes it an important health problem, and for its biological complexity, which has made clinical results ...very difficult in terms of outcome for this category of patients. To date these diseases should not be treated as a single entity but it is necessary to distinguish colorectal cancers based on characteristics that nowadays are essential to have greater therapeutic benefits. These include the sideness of the disease, the state of microsatellites, the presence of prognostic and predictive mutations of response to treatments currently available in clinical practice, which are associated with new therapeutic targets. The greatest challenge in the future will be to circumvent the resistance mechanisms that make this disease very difficult to treat with good long-term results by studying effective combination treatments with a good toxicity profile. Once such combinations or targeted treatments are consolidated, it will be desirable to shift the best therapies to the first line treatment to make them immediately accessible to the patient. It will also be essential to refine the selection of patients who can benefit from these treatments.
This article focuses on the debates among resilience, sustainability, adaptation, and transformation concepts. The conceptualization and application of sustainability and resilience thinking in the ...human-environmental interactions, social-ecological systems, and global environmental change literature remain dominant, which provide a common interdisciplinary and policy language where research in socio-environmental systems can converge. Yet, the lack of clarity and multiplicity among and between these concepts and paradigms allows them to continue to be widely adopted in different sectors of society. Drawing on five case studies from different geographical locations, these diverse applications of resilience, sustainability, adaptation, and transformation are explored from disciplinary and interdisciplinary perspectives. The diversity in the operationalization and use of the concepts and paradigms can result in applications that undermine goals of sustainability or resilience when a particular resource is prioritized over others or is applied in a way that results in inequitable outcomes. Findings from the cases reinforce the importance of being explicit about the spatial, temporal, and institutional boundaries drawn because proposed solutions will vary in their effectiveness if attention to scale, stressors, worldviews, and actors are not addressed holistically. We suggest the ongoing adoption of sustainability, resilience, adaptation, and transformation requires clear and explicit definitions, that draw from decolonized methodologies, goals, in-depth analysis of potential unintended consequences, and situated understanding of how these concepts and the associated paradigms are embedded in particular contexts.
Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome ...Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi;
= 0.002), GS-626510 (C-MYC/BETi;
< 0.000001 and
= 0.0005), and copanlisib (PIK3CAi;
= 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.
The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome ...sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.
Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were ...matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRDchromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer.
This article discusses the roles, challenges and opportunities of non-Indigenous academics working at the interface of Indigenous and non-Indigenous knowledges. Sustainability scientists have both ...questioned and advocated for cross-cultural research, and in this article we reflect on what working across different ways of knowing entails for non-Indigenous researchers at the professional, personal and epistemological level. Grounded on our experiences of on-going engagement with Indigenous communities, this article explores multiple pathways of taking Indigenous knowledges seriously while working in “Western” academic settings. In doing so, it highlights issues around the role and responsibility of non-Indigenous researchers in decolonising the (re)production of knowledges and the multiple contexts in which this can take place in sustainability science. It then deals with some of the challenges and ethical dilemmas we have encountered along the way, mainly with regards to issues of representation, translation in a broader sense, participation, and authority. Finally, this article discusses some of the epistemological consequences of engaging in such work, and how despite being fraught with tensions and contradictions, it can help to foster spaces of plural co-existence.
Although Indigenous Peoples make significant contributions to global environmental governance and were prominent actors at the 2015 Paris Climate Summit, COP21, they remain largely invisible in ...conventional, mainstream, and academic accounts of COP21. In this article, we adopt feminist collaborative event ethnography to draw attention to often marginalized and unrecognized actors and help make visible processes that are often invisible in the study of power and influence at sites of global environmental governance. Specifically, we integrate current approaches to power from international relations and political ecology scholarship to investigate how Indigenous Peoples, critical actors for solving global environmental challenges, access, navigate, and cultivate power at COP21 to shape global environmental governance. Through conceptual and methodological innovations that illuminate how Indigenous Peoples overcome structural and spatial barriers to engagement, this article demonstrates how attention to the politics of representation through pluralistic approaches to power can help expand the repertoire of possibilities for advancing global environmental governance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Intact Forest Landscapes (IFLs) are global conservation units that aim to combat fragmentation, alteration, degradation, and loss of global forests. ILFs are typically recognized for their ...biodiversity, carbon storage, protection of hydroecological systems and other ecosystem services. However, IFLs are distinctive among other conservation efforts because they do not immediately prioritize conservation approaches that have goals of alleviating human poverty or improving well-being. The prevailing view is that IFL conservation should engage with ecocentric models of conservation. In this article, we leverage political ecology's analytical attention to power, institutions, identities, and scales to make suggestions on ways in which to integrate biocentric conservation considerations into IFL practices. From a scoping literature review, we found the following areas are especially critical for the future of IFL conservation: (1) prioritizing Indigenous Peoples and Local Communities (IPLC) as actors and beneficiaries of conservation; (2) identifying the value of knowledge integration and co-production for conservation; (3) addressing heterogenous communities and equity impacts, and (4) the need for procedural mechanisms in conservation initiatives that support nesting Indigenous Peoples and Local Communities management and governance in polycentric systems. Furthermore, the development of diagnostic questions of scaling community-based conservation and adaptive strategies beyond their original scope in terms of community definitions, landscape and political context may be beneficial for addressing multi-stakeholder needs, identifying more equitable approaches, sharing strategies and obtaining successful outcomes in IFL conservation. Keywords: Indigenous peoples and local communities, large intact landscapes, forests, conservation
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