Pliocene Sinistral Slip across the Adobe Hills, Eastern California-Western Nevada: Kinematics of Fault Slip Transfer across the Mina Deflection

The Adobe Hills region (California and Nevada, USA) is a faulted volcanic field located within the western Mina deflection, a right-stepping zone of faults that connects the northern Eastern California shear zone (ECSZ) to the south with the Walker Lane belt (WLB) to the north. New detailed geologic mapping, structural studies, and 40Ar/39Ar geochronology in the Adobe Hills allow us to calculate fault slip rates and test predictions for the kinematics of fault slip transfer into the Mina deflection. The Adobe Hills are dominated by Pliocene tuffaceous sandstone, basaltic lavas that yield 40Ar/39Ar ages between 3.13 ± 0.02 and 3.43 ± 0.01 Ma, and basaltic cinder cones. These Pliocene units unconformably overlie Middle Miocene latite ignimbrite that yields an 40Ar/39Ar age of 11.17 ± 0.04 Ma, and Quaternary tuffaceous sands, alluvium, and lacustrine deposits cap the sequence. Northwest-striking normal faults, west-northwest–striking dextral faults, and northeast-striking sinistral faults cut all units; the northeast-striking sinistral faults are the youngest and most well developed fault set. We calculate ∼0.1 mm/yr of approximately east-west horizontal extension and northwest dextral shear since the Pliocene. The prominent northeast-striking sinistral faults offset basalt ridgelines, normal fault–hanging-wall intersections, a channelized basalt flow, a basalt flow edge, and a basalt flow contact a net minimum of 921 ± 184 to 1318 ± 264 m across the Adobe Hills. These measured sinistral offsets yield a minimum Pliocene sinistral fault slip rate of 0.2–0.5 mm/yr; our preferred minimum slip rate is 0.4–0.5 mm/yr. The geometry and orientation of the prominent sinistral faults are consistent with simple shear/couple clockwise block rotation within a broad dextral shear zone. Vertical axis block rotation data are needed to test this interpretation. We propose that a set of faults subparallel to Sierra Nevada–North America motion and associated releasing steps, located west of the White Mountains fault zone and east of the Long Valley Caldera, transfer a portion of dextral Owens Valley fault slip northwestward onto the sinistral faults in the Adobe Hills. Dextral slip distributed across faults between the White Mountains fault zone and the Sierra Nevada and east of the Fish Lake Valley fault zone may account for the apparent discrepancy between summed long-term geologic slip rates and present-day geodetic rates across the northern ECSZ. Fault slip in the Adobe Hills is part of a regional pattern of initiation and renewal of dextral, sinistral, and normal fault slip during the Pliocene that extends from lat ∼40°N to ∼36°N within the ECSZ-WLB and along the western margin of the Basin and Range Province. This regional deformation episode may be related to changes in gravitational potential energy

Melanistic Tundra Voles, Microtus oeconomus, from Central Yukon

Colour aberrations are not commonly observed in voles (e.g., Microtus and Myodes); thus, individual observations are of interest. We report two observations of melanism in Tundra Voles, Microtus oeconomus, collected from central Yukon. These are the second and third records of melanistic Tundra Voles, and the first reports from non-insular populations

In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer

The immune system spontaneously responds to tumor-associated antigens in peripheral blood of colorectal cancer (CRC) patients. Regulatory T cells (Treg) are suspected of influencing the interaction between the tumor and immune system and thus the course of malignant diseases. However, the function of Tregs in the development of T cell responses and on the clinical course of CRC is not clear. We analyzed Treg infiltration (FOXP3 staining) in situ in 40 CRC patients and investigated whether there is a correlation to disease stage, systemic T cell response, and survival. Treg infiltration was significantly higher in CRC than in healthy colon. Stromal Treg infiltration was significantly higher than epithelial infiltration in CRC. Furthermore, Treg infiltration in the tumor was significantly higher in limited disease than in metastatic CRC. The average Treg infiltration rate in the tumor was non-significantly higher in patients without systemic TAA-specific T cell response. Survival did not differ between patients with high Treg infiltration and those with low Treg infiltration. In conclusion, a direct link between Treg infiltration in the tumor and the development of a systemic T cell response in CRC cannot be proven. However, local Treg infiltration was significantly higher in limited disease, in which a systemic TAA-directed T cell responses is less frequently observed

Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR)

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM1(58–66 )and CMVpp65(495–503 )peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization

First Records of the Southern Red-backed Vole, Myodes gapperi, in the Yukon

Twenty Southern Red-backed Voles, Myodes gapperi, were collected in July 2004 in the LaBiche River valley of southeastern Yukon. Specimens were identified using morphological characteristics and analysis of cytochrome b gene sequences. These are the first records of this species in the Yukon. No Northern Red-backed Voles, M. rutilus, were collected and it is not known whether the two species are sympatric or parapatric in the Yukon. Further survey work is needed in southeastern Yukon to better delineate the extent of the northwestern range of this species and the extent, if any, of introgression with M. rutilus

First Records of the Northern Long-eared Bat, Myotis septentrionalis, in the Yukon Territory

Three adult male Northern Long-eared Bats, Myotis septentrionalis, were captured in mist nets in July 2004 in the LaBiche River Valley, southeastern Yukon. These are the first records of M. septentrionalis in the Yukon. Further survey work is needed to delineate the extent of the range and population structure of this and other species of bats in northwestern North America

Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients

Several immunotherapeutic approaches rely on antigen-specific T-cells. Restrictions in the T-cell receptor (TCR) repertoire were reported as indicator of anti-tumor cytotoxic T-lymphocyte (CTL) response in various tumor entities. It is unclear yet whether a TCR restriction in peripheral blood mirrors the tumor compartment. We compared the expression of TCR Vβ-families for the quantification of TCR repertoire alterations in blood and tissue samples from patients with colorectal carcinoma. Blood samples from patients with colorectal carcinoma and healthy volunteers and tissue samples of normal colonic mucosa and colorectal carcinoma were analyzed. Relative Vβ-family quantification was performed based on quantitative reverse transcribed PCR. Standard deviation and average mean of the single families were determined. Two variables describing the degree of Vβ-repertoire restriction were defined. Forty-eight blood samples and 37 tissue samples were analyzed. TCR repertoire restriction was higher in blood of tumor patients than in blood of healthy controls (p < 0.05). No difference in the degree of TCR repertoire restriction was found between carcinoma and unaffected colon tissue. We found no corresponding elevated TCR families among the different compartments blood, normal colon, and carcinoma tissue of the same patient. In conclusion, we observed a repertoire restriction in peripheral blood as well as in tumor tissue of cancer patients. However, in tumor tissue, repertoire alterations were comparable to normal mucosa, suggesting compartment-specific TCR distribution rather than alterations due to tumor-T-cell interaction questioning the presence of highly restricted clonal T-cell expansions in colorectal cancer as they have been described in other, assumingly more immunogenic tumor entities

T cell responses against tumor associated antigens and prognosis in colorectal cancer patients

INTRODUCTION: Spontaneous T cell responses against specific tumor-associated antigens (TAA) are frequently detected in peripheral blood of tumor patients of various histiotypes. However, little is known about whether these circulating, spontaneously occurring, TAA-reactive T cells influence the clinical course of disease. METHODS: Fifty-four HLA-A2 positive colorectal cancer patients had been analyzed for the presence of T cell responses against epitopes derived from the TAA Ep-CAM, her-2/neu, and CEA either by ELISPOT assay or by intracellular cytokine staining. Then, Kaplan-Meier survival analysis was performed comparing T-cell-responders and T-cell-non-responders. For comparison, a group of T-cell-non-responders was compiled stringently matched to T-cell-responders based on clinical criteria and also analyzed for survival. RESULTS: Sixteen out of 54 patients had a detectable T cell response against at least one of the three tested TAA. Two out of 21 patients (9.5%) with limited stage of disease (UICC I and II) and 14 out of 33 patients (42.4%) with advanced disease (UICC III and IV) were T cell response positive. Comparing all T-cell-responders (n = 16) and all T-cell-non-responders (n = 38), no survival difference was found. In an attempt to reduce the influence of confounding clinical factors, we then compared 16 responders and 16 non-responders in a matched group survival analysis; and again no survival difference was found (p = 0.7). CONCLUSION: In summary, we found no evidence that spontaneous peripheral T cell responses against HLA-A2-binding epitopes of CEA, her-2/neu and Ep-CAM are a strong prognostic factor for survival

Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

BACKGROUND: Interferon (IFN)-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS) stimulation in vitro. RESULTS: Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. CONCLUSION: Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in autoimmunity and tumor rejection by including and/or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy