The Huqoq Excavation Project : 2014-2017 interim report

Excavations at Huqoq in Israel’s eastern Lower Galilee are bringing to light a Late Roman synagogue, a medieval public building, and the remains of ancient and modern (pre-1948) villages. In this interim report, we describe the major discoveries of the 2014–2017 seasons, including the extraordinary figural mosaics decorating the synagogue floor. Our discoveries provide evidence of a Galilean Jewish community that flourished through the 5th and 6th centuries c.e.—a picture contrasting with recent claims of a decline in Jewish settlement under Byzantine Christian rule. The possibility that the medieval public building might also be a synagogue has important implications for understanding Galilean Jewish settlement in the Middle Ages, about which almost nothing is known. The excavations also shed light on the last phase of the settlement’s long history: the development of the modern village of Yakuk in the 19th through 20th centuries.peer-reviewe

A Cherokee Sword And Shield / Crying For Blood

A Cherokee Sword and Shield: the ᏣᎳᎩ Syllabary in the Face of the Indian Removal ActThis paper examines how Elias Boudinot and Chief John Ross intentionally invoked the Cherokee syllabary and Cherokee communities’ literacy in it to maintain Cherokee personhood and land claims in the 1820s and 1830s. I assert that Boudinot and Ross used the syllabary to prove that Cherokees did not need to be removed from their lands in order to be civilized but could uplift themselves and neighboring Native nations on their homelands. Whether or not Ross or Boudinot truly prioritized Cherokee civilization as important, they intentionally used the existence of the Cherokee syllabary as a rhetorical tool to combat the racist ideas driving the Indian Removal Act. Rooted in Linda Tuhiwai Smith’s insights into the importance of language for carrying on culture and my own positionality as a Cherokee scholar and language learner, this paper also uses the Cherokee syllabary to unsettle the assumptions that Native people are not part of academic audiences and that Native languages have vanished. Crying for Blood: Cherokee Gender, Culture, and Politics during the Anglo-Cherokee War This work responds to Jean O’Brien’s call to not settle for the idea that Indigenous peoples had culture instead of politics and examines how the political decisions made by Cherokees during the Anglo-Cherokee War were based in the cultural practices of kinship and blood law. Often, considerations of this conflict have left culture out of the equation, leaving gaps in our considerations of the complex political negotiations that Cherokees made in the mid-eighteenth century. This essay re-intertwines Cherokee matriarchal culture with the political decisions made during this war, and in doing so, offers a path to better understandings of the importance of Cherokee women in eighteenth-century Cherokee politics

A Multi-Scale Blueprint for Building the Decision Context to Implement Climate Change Adaptation on National Wildlife Refuges in the United States

Climate change and ecological transformation are causing natural resource management to be applied to nonstationary systems. Managers can respond to dynamic ecosystems by resisting, accepting, or directing ecological change. Management response is constrained by a decision context, defined as an interconnected social system of values, rules, and knowledge that affects how problems can be addressed. We provide a multi-scale blueprint for creating a decision context that increases capacity for implementing climate adaptation, including novel approaches in the National Wildlife Refuge System, a continental conservation network administered by the U.S. Fish and Wildlife Service. We use the Tetlin National Wildlife Refuge in Alaska as case study to illustrate blueprint concepts and to provide “proof-of-concept” for application. The blueprint builds on ideas and practices from scenario planning, adaptive management, and adaptive pathway planning, which are approaches that promote action in the face of uncertainty. Management considerations focus on stewarding biodiversity in a changing climate by addressing what futures are possible, what interventions can be used to shape future conditions, and how to coordinate a regional conservation strategy. The blueprint focus on decision context promotes a longer-term social process of engagement that is complementary to, but larger than, any one decision process

A Multi-Scale Blueprint for Building the Decision Context to Implement Climate Change Adaptation on National Wildlife Refuges in the United States

Climate change and ecological transformation are causing natural resource management to be applied to nonstationary systems. Managers can respond to dynamic ecosystems by resisting, accepting, or directing ecological change. Management response is constrained by a decision context, defined as an interconnected social system of values, rules, and knowledge that affects how problems can be addressed. We provide a multi-scale blueprint for creating a decision context that increases capacity for implementing climate adaptation, including novel approaches in the National Wildlife Refuge System, a continental conservation network administered by the U.S. Fish and Wildlife Service. We use the Tetlin National Wildlife Refuge in Alaska as case study to illustrate blueprint concepts and to provide “proof-of-concept” for application. The blueprint builds on ideas and practices from scenario planning, adaptive management, and adaptive pathway planning, which are approaches that promote action in the face of uncertainty. Management considerations focus on stewarding biodiversity in a changing climate by addressing what futures are possible, what interventions can be used to shape future conditions, and how to coordinate a regional conservation strategy. The blueprint focus on decision context promotes a longer-term social process of engagement that is complementary to, but larger than, any one decision process

The Association Between Psychological Distress and Alcohol Use in Modern College Students and the Mediating Properties of Loneliness

Objective: The purpose of this study was to examine the link between psychological distress and drinking behaviors in college students along with the potential mediating role of loneliness. Method: A national sample of 374 undergraduate students in the United States (Mage = 24.2, SDage = 6.6) were administered instruments to measure depression, anxiety, alcohol use, and subjective feelings of loneliness and isolation. Results: Depression and anxiety were statistically significant positive predictors of alcohol use, where more depressive and anxious feelings predicted more drinking behaviors. Additionally, these relationships were mediated through subjective feelings of loneliness and isolation indicating at least part of the variance in drinking behaviors was explained by subject feelings of loneliness. Conclusions: Although longitudinal data with a larger sample is needed, the study suggests that one potential target for intervention to prevent the development of and to treat alcohol use disorders are subjective feelings of loneliness. Reducing the subjective feelings of loneliness experienced by college students may reduce the likelihood of problematic drinking behaviors when those same students experience psychological distress

Genetic and Small-Molecule Modulation of Stat3 in a Mouse Model of Crohn’s Disease

Crohn’s disease (CD), is an inflammatory bowel disease that can affect any part of the gastro-intestinal tract (GI) and is associated with an increased risk of gastro-intestinal cancer. In the current study, we determined the role of genetic and small-molecule modulation of STAT3 in a mouse model of CD. STAT3 has 2 isoforms (α, β) which are expressed in most cells in a 4:1 ratio (α: β). STAT3α has pro-inflammatory and anti-apoptotic functions, while STAT3β has contrasting roles. We used an animal model of CD consisting of intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid and examined the severity of CD in transgenic-mice that express only STAT3α (∆β/∆β), as well as in wild-type (WT) mice administered TTI-101 (formerly C188-9), a small molecule STAT3 inhibitor. We determined that clinical manifestations of CD, such as mortality, rectal-bleeding, colonic bleeding, diarrhea, and colon shortening, were exacerbated in ∆β/∆β transgenic versus cage-control WT mice, while they were markedly decreased by TTI-101 treatment of WT mice. TTI-101 treatment also increased apoptosis of pathogenic CD4+ T cells and reduced colon levels of IL-17-positive cells. Our results indicate that STAT3 contributes to CD and that targeting of STAT3 with TTI-101 may be a useful approach to treating CD

DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations

International audiencePURPOSE: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog (SHH), a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with DISP1 variants. METHODS: This study was based on the identification of at least one pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. RESULTS: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor (SMMCI), and congenital nasal pyriform aperture stenosis (CNPAS). These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (i.e. oligogenic inheritance). CONCLUSION: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of SHH. We also demonstrated that the very rare SMMCI-CNPAS combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant

Using DNA sequencing data to quantify T cell fraction and therapy response

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-α gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31–32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes.</p