Geochronology of the Tectonic, Stratigraphic, and Magmatic Evolution of Neoproterozoic to Early Paleozoic, North American Cordillera and Cryogenian Glaciation

Neoproterozoic sedimentary successions contain evidence for some of the most extreme climate fluctuations, breakup of the paleo-supercontinent Rodina, multiple low-latitude global glaciations, and the resultant evolution and radiation of complex life. The stratigraphic record of these events are found on all major continents and have been associated with, in part, global ‘Snowball Earth’ events. However, the understanding and integration of these, and related phenomenon, are limited by disparate and imprecise age constraints that prohibit clear correlation between locations. This research focused on high-precision geochronology within an integrated framework of sedimentology, stratigraphy, and geochemistry to resolve the timing and duration of Neoproterozoic Rodinian rifting and ‘Snowball Earth’ glaciation recorded in rock units across Idaho. A tandem approach to U-Pb zircon geochronology and geochemistry, combining laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) and high-precision U-Pb chemical abrasion-isotope dilution thermal ionization mass spectrometry (CA-IDTIMS), was used to establish a high-fidelity record of pre-, syn-, and post-Rodinian rift sediments, glacigenic sediments, and rift-related magmatism across Idaho. Results from this research have: 1) documented prolonged pre-to-post Rodinian rifting and basin subsidence; 2) provided the first geochronologic evidence of Cambrian – Ordovician strata in central Idaho; 3) placed firm age constraints on long-duration Sturtian glaciation; 4) provided evidence of Marinoan glaciation; 5) documented duration and pulse of regional rift-related magmatism; 6) showed the need for in situ and isotope dilution analytical techniques to establish clear age constraints in this time and place

Testing Religiosity’s Impacts on Willingness to Communicate With Sexual Minority Members

The area of religiosity’s impact on an individual’s attitudes has been researched in a variety of cross-cultural ways, sometimes relating to attitudes about homosexuality. However, the behavioral manifestations of these attitudes have not been studied a great deal, particularly regarding communication behaviors. In this study, 61 university students were surveyed about their intercultural communication patterns, levels of religious commitment, and attitudes toward gay men and lesbian women. The purpose of this study was to extend research in this field. Correlation analyses demonstrated that highly religious individuals tended to be more apprehensive to communicate interculturally, especially with members of a sexual minority, and also reported greater prejudice against sexual minority members. Communication literature would benefit from further research on how communication behaviors across the sexuality barrier actually occur

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited. We describe a minipig model that exhibits clinical hallmarks of NF1, including café au lait macules, neurofibromas, and optic pathway glioma. Spontaneous loss of heterozygosity is observed in this model, a phenomenon also described in NF1 patients. Oral administration of a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge, this model provides an unprecedented opportunity to study the complex biology and natural history of NF1 and could prove indispensable for development of imaging methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted therapies

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations i

A Robust Age Model for the Cryogenian Pocatello Formation of Southeastern Idaho (Northwestern USA) from Tandem in situ and Isotope Dilution U-Pb Dating of Volcanic Tuffs and Epiclastic Detrital Zircons

Tandem in situ and isotope dilution U-Pb analysis of zircons from pyroclastic volcanic rocks and both glacial and non-glacial sedimentary strata of the Pocatello Formation (Idaho, northwestern USA) provides new age constraints on Cryogenian glaciation in the North American Cordillera. Two dacitic tuffs sampled within glacigenic strata of the lower diamictite interval of the Scout Mountain Member yield high-precision chemical abrasion isotope dilution U-Pb zircon eruption and depositional ages of 696.43 ± 0.21 and 695.17 ± 0.20 Ma. When supplemented by a new high-precision detrital zircon maximum depositional age of ≤ 670 Ma for shoreface and offshore sandstones unconformably overlying the lower diamictite, these data are consistent with correlation of the lower diamictite to the early Cryogenian (ca. 717–660 Ma) Sturtian glaciation. These 670–675 Ma zircons persist in beds above the upper diamictite and cap dolostone units, up to and including a purported “reworked fallout tuff,” which we instead conclude provides only a maximum depositional age of ≤ 673 Ma from epiclastic volcanic detritus. Rare detrital zircons as young as 658 Ma provide a maximum depositional age for the upper diamictite and overlying cap dolostone units. This new geochronological framework supports litho- and chemostratigraphic correlations of the lower and upper diamictite intervals of the Scout Mountain Member of the Pocatello Formation with the Sturtian (716–660 Ma) and Marinoan (≤ 650–635 Ma) low-latitude glaciations, respectively. The Pocatello Formation thus contains a more complete record of Cryogenian glaciations than previously postulated

Laminin-332 alters connexin profile, dye coupling and intercellular Ca(2+ )waves in ciliated tracheal epithelial cells

BACKGROUND: Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin α3β3γ2 (LM-332) proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC). METHODS: Functional coupling of RTEC was monitored by microinjection of the negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of physiologically significant molecules was evaluated by the mechanism and extent of propagated intercellular Ca(2+ )waves. Expression of connexin (Cx) mRNA and proteins were assayed by reverse transcriptase – polymerase chain reaction and immunocytochemistry, respectively. RESULTS: When compared to RTEC grown on collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in dye transfer. Although mechanical stimulation of RTEC grown on either LM-332/collagen or collagen alone resulted in intercellular Ca(2+ )waves, the mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen propagated Ca(2+)waves via extracellular purinergic signaling whereas RTEC grown on collagen used gap junctions. Comparison of RTEC grown on collagen or LM-332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins. CONCLUSION: Alterations in airway basement membrane proteins such as LM-332 can induce connexin reorganizations and result in altered cellular communication mechanisms that could contribute to airway tissue function

Vascular Expression of Hemoglobin Alpha in Antarctic Icefish Supports Iron Limitation as Novel Evolutionary Driver

Frigid temperatures of the Southern Ocean are known to be an evolutionary driver in Antarctic fish. For example, many fish have reduced red blood cell (RBC) concentration to minimize vascular resistance. Via the oxygen-carrying protein hemoglobin, RBCs contain the vast majority of the body’s iron, which is known to be a limiting nutrient in marine ecosystems. Since lower RBC levels also lead to reduced iron requirements, we hypothesize that low iron availability was an additional evolutionary driver of Antarctic fish speciation. Antarctic Icefish of the family Channichthyidae are known to have an extreme alteration of iron metabolism due to loss of RBCs and two iron-binding proteins, hemoglobin and myoglobin. Loss of hemoglobin is considered a maladaptive trait allowed by relaxation of predator selection since extreme adaptations are required to compensate for the loss of oxygen-carrying capacity. However, iron dependency minimization may have driven hemoglobin loss instead of a random evolutionary event. Given the variety of functions that hemoglobin serves in the endothelium, we suspected the protein corresponding to the 3’ truncated Hbα fragment (Hbα-3’f) that was not genetically excluded by icefish may still be expressed as a protein. Using whole mount confocal microscopy, we show that Hbα-3’f is expressed in the vascular endothelium of icefish retina, suggesting this Hbα fragment may still serve an important role in the endothelium. These observations support a novel hypothesis that iron minimization could have influenced icefish speciation with the loss of the iron-binding portion of Hbα in Hbα-3’f, as well as hemoglobin β and myoglobin

Collectrin (Tmem27) deficiency in proximal tubules causes hypertension in mice and a TMEM27 variant associates with blood pressure in males in a Latino cohort

Collectrin (Tmem27), an angiotensin-converting enzyme 2 homologue, is a chaperone of amino acid transporters in the kidney and endothelium. Global collectrin knockout (KO) mice have hypertension, endothelial dysfunction, exaggerated salt sensitivity, and diminished renal blood flow. This phenotype is associated with altered nitric oxide and superoxide balance and increased proximal tubule (PT) Na+/H+ exchanger isoform 3 (NHE3) expression. Collectrin is located on the X chromosome where genome-wide association population studies have largely been excluded. In the present study, we generated PT-specific collectrin KO (PT KO) mice to determine the precise contribution of PT collectrin in blood pressure homeostasis. We also examined the association of human TMEM27 single-nucleotide polymorphisms with blood pressure traits in 11,926 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Hispanic/Latino participants. PT KO mice exhibited hypertension, and this was associated with increased baseline NHE3 expression and diminished lithium excretion. However, PT KO mice did not display exaggerated salt sensitivity or a reduction in renal blood flow compared with control mice. Furthermore, PT KO mice exhibited enhanced endothelium-mediated dilation, suggesting a compensatory response to systemic hypertension induced by deficiency of collectrin in the PT. In HCHS/SOL participants, we observed sex-specific single-nucleotide polymorphism associations with diastolic blood pressure. In conclusion, loss of collectrin in the PT is sufficient to induce hypertension, at least in part, through activation of NHE3. Importantly, our model supports the notion that altered renal blood flow may be a determining factor for salt sensitivity. Further studies are needed to investigate the role of the TMEM27 locus on blood pressure and salt sensitivity in humans. NEW & NOTEWORTHY The findings of our study are significant in several ways: 1) loss of an amino acid chaperone in the proximal tubule is sufficient to cause hypertension, 2) the results in global and proximal tubule-specific collectrin knockout mice support the notion that vascular dysfunction is required for salt sensitivity or that impaired renal tubule function causes hypertension but is not sufficient to cause salt sensitivity, and 3) our study is the first to implicate a role of collectrin in human hypertension

Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation

BACKGROUND: Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive. METHODS: Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining. RESULTS: Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome. CONCLUSION: These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage