Structural Geology, Beavertail, Conanicut Island

Guidebook: 55th annual meeting, October 4-6, 1963, Providence, Rhode Island: Trip

Pre-Pennsylvanian Rocks of Aquidneck and Conanicut Islands, Rhode Island

Guidebook for field trips to the Boston area and vicinity : 68th annual meeting, New England Intercollegiate Geological Conference, October 8-10, 1976: Trip B-1

Oncometabolite induced primary cilia loss in pheochromocytoma

Primary cilia are sensory organelles involved in regulation of cellular signaling. Cilia loss is frequently observed in tumors; yet, the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas – endocrine tumors of the adrenal medulla. This is concomitant with transcriptional changes within cilia-mediated signaling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically. Importantly, cilia loss was most dramatic in patients with germline mutations in the pseudohypoxia-linked genes SDHx and VHL. Using a pheochromocytoma cell line derived from rat, we show that hypoxia and oncometabolite-induced pseudohypoxia are key drivers of cilia loss and identify that this is dependent on activation of an Aurora-A/HDAC6 cilia resorption pathway. We also show cilia loss drives dramatic transcriptional changes associated with proliferation and tumorigenesis. Our data provide evidence for primary cilia dysfunction contributing to pathogenesis of pheochromocytoma by a hypoxic/pseudohypoxic mechanism and implicates oncometabolites as ciliary regulators. This is important as pheochromocytomas can cause mortality by mechanisms including catecholamine production and malignant transformation, while hypoxia is a general feature of solid tumors. Moreover, pseudohypoxia-induced cilia resorption can be pharmacologically inhibited, suggesting potential for therapeutic intervention

High-throughput screening of monoclonal antibodies against plant cell wall glycans by hierarchical clustering of their carbohydrate microarray binding profiles

Antibody-producing hybridoma cell lines were created following immunisation with a crude extract of cell wall polymers from the plant Arabidopsis thaliana. In order to rapidly screen the specificities of individual monoclonal antibodies (mAbs), their binding to microarrays containing 50 cell wall glycans immobilized on nitrocellulose was assessed. Hierarchical clustering of microarray binding profiles from newly produced mAbs, together with the profiles for mAbs with previously defined specificities allowed the rapid assignments of mAb binding to antigen classes. mAb specificities were further investigated using subsequent immunochemical and biochemical analyses and two novel mAbs are described in detail. mAb LM13 binds to an arabinanase-sensitive pectic epitope and mAb LM14, binds to an epitope occurring on arabinogalactan-proteins. Both mAbs display novel patterns of recognition of cell walls in plant materials

Genomic comparisons reveal biogeographic and anthropogenic impacts in the koala (Phascolarctos cinereus): a dietary-specialist species distributed across heterogeneous environments

The Australian koala is an iconic marsupial with highly specific dietary requirements distributed across heterogeneous environments, over a large geographic range. The distribution and genetic structure of koala populations has been heavily influenced by human actions, specifically habitat modification, hunting and translocation of koalas. There is currently limited information on population diversity and gene flow at a species-wide scale, or with consideration to the potential impacts of local adaptation. Using species-wide sampling across heterogeneous environments, and high-density genome-wide markers (SNPs and PAVs), we show that most koala populations display levels of diversity comparable to other outbred species, except for those populations impacted by population reductions. Genetic clustering analysis and phylogenetic reconstruction reveals a lack of support for current taxonomic classification of three koala subspecies, with only a single evolutionary significant unit supported. Furthermore, similar to 70% of genetic variance is accounted for at the individual level. The Sydney Basin region is highlighted as a unique reservoir of genetic diversity, having higher diversity levels (i.e., Blue Mountains region; AvHe(corr)-0.20, PL% = 68.6). Broad-scale population differentiation is primarily driven by an isolation by distance genetic structure model (49% of genetic variance), with clinal local adaptation corresponding to habitat bioregions. Signatures of selection were detected between bioregions, with no single region returning evidence of strong selection. The results of this study show that although the koala is widely considered to be a dietary-specialist species, this apparent specialisation has not limited the koala's ability to maintain gene flow and adapt across divergent environments as long as the required food source is available

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evolution of postoperative pituitary adenoma resection cavities assessed by magnetic resonance imaging and implications regarding radiotherapy timing and modality

PURPOSE: This study evaluates the temporal evolution of the spatial relationship between the pituitary adenoma transsphenoidal surgical cavity and the adjacent optic chiasm and discusses implications on timing and choice of radiotherapy modality. METHODS: This retrospective observational review analyzed factors that might influence the postoperative relationship between the surgical cavity and the optic chiasm, including tumor type, craniocaudal tumor and resection cavity dimensions, the preoperative distance between tumor and the optic chiasm, the presence of cavernous sinus invasion, and the choice of intraoperative packing material. Changes observed on magnetic resonance imaging in the preoperative, immediate (within 72 h), and delayed (≥3 months) postoperative periods were compared. RESULTS: Sixty-five patient histories were analyzed. Preoperatively, the pituitary adenoma was apposed to the optic chiasm in 43 patients (66%). Postoperatively, 34 patients (52%) in the immediate postoperative period and 54 patients (83%) in the delayed postoperative period had a distance ≥2 mm between the resection cavity and the optic chiasm. This distance provides a greater margin of safety with adjuvant radiosurgery. Preoperative tumor size showed a strong association with postoperative descent of the optic chiasm. CONCLUSIONS: Preoperative tumor size and degree of mass effect on the optic chiasm predict postoperative changes. In this study, the distance between the resection cavity and the optic chiasm was greater at ≥3 months postoperatively than in the immediate postoperative period, regardless of preoperative mass effect, indicating radiotherapy planning should be deferred to ≥3 months postoperatively when not precluded by aggressive histological characteristics that necessitate more immediate treatment. PRECIS: To investigate the temporal relationship between the postoperative sellar surgical cavity and the adjacent optic apparatus after transsphenoidal resection of pituitary adenomas and the implications for radiotherapy

Homelessness in autistic women: Defining the research agenda

Background: Current evidence suggests that autistic individuals are at high risk for becoming and remaining in a cycle of homelessness. Key risk factors for homelessness disproportionately affect autistic people; however, we have limited understanding of how to best support autistic individuals accessing services. This gap in the evidence base is particularly acute for autistic women. Objective: As a first step to address this gap, we aimed to (1) map gaps in knowledge and practice; (2) identify priority areas for research and (3) develop recommendations for how to implement novel research and practice in this area. Methods: We conducted a collaborative workshop with an interdisciplinary group of 26 stakeholders to address our aims. Stakeholders included autistic women with experience of homelessness, researchers, health professionals, NGO representatives, and service providers. Results and recommendations: Two research priority areas were identified to map the prevalence and demographics of autistic women experiencing homelessness, and to delineate risk and protective factors for homelessness. Priority areas for improving provision of support included staff training to improve communication, awareness of autism and building trust with service providers, and recommendations for practical provision of support by services. Conclusions: Future research is critical to increase our knowledge of the pathways leading to homelessness for autistic women, and barriers to engaging with homelessness and social services. We need to use this knowledge to develop new ways of delivering targeted and inclusive support for autistic women, which could prevent or shorten periods of homelessness