Beyond a warming fingerprint: individualistic biogeographic responses to heterogeneous climate change in California.

Understanding recent biogeographic responses to climate change is fundamental for improving our predictions of likely future responses and guiding conservation planning at both local and global scales. Studies of observed biogeographic responses to 20th century climate change have principally examined effects related to ubiquitous increases in temperature - collectively termed a warming fingerprint. Although the importance of changes in other aspects of climate - particularly precipitation and water availability - is widely acknowledged from a theoretical standpoint and supported by paleontological evidence, we lack a practical understanding of how these changes interact with temperature to drive biogeographic responses. Further complicating matters, differences in life history and ecological attributes may lead species to respond differently to the same changes in climate. Here, we examine whether recent biogeographic patterns across California are consistent with a warming fingerprint. We describe how various components of climate have changed regionally in California during the 20th century and review empirical evidence of biogeographic responses to these changes, particularly elevational range shifts. Many responses to climate change do not appear to be consistent with a warming fingerprint, with downslope shifts in elevation being as common as upslope shifts across a number of taxa and many demographic and community responses being inconsistent with upslope shifts. We identify a number of potential direct and indirect mechanisms for these responses, including the influence of aspects of climate change other than temperature (e.g., the shifting seasonal balance of energy and water availability), differences in each taxon's sensitivity to climate change, trophic interactions, and land-use change. Finally, we highlight the need to move beyond a warming fingerprint in studies of biogeographic responses by considering a more multifaceted view of climate, emphasizing local-scale effects, and including a priori knowledge of relevant natural history for the taxa and regions under study

Cutaneous stimulation of the digits and lips evokes responses with different adaptation patterns in primary somatosensory cortex

Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5 s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation

Isotopic characterization of nitrogen oxides (NOx), nitrous acid (HONO), and nitrate (pNO3−) from laboratory biomass burning during FIREX

New techniques have recently been developed and applied to capture reactive nitrogen species, including nitrogen oxides (NOx=NO+NO2), nitrous acid (HONO), nitric acid (HNO3), and particulate nitrate (pNO−3), for accurate measurement of their isotopic composition. Here, we report – for the first time – the isotopic composition of HONO from biomass burning (BB) emissions collected during the Fire Influence on Regional to Global Environments Experiment (FIREX, later evolved into FIREX-AQ) at the Missoula Fire Science Laboratory in the fall of 2016. We used our newly developed annular denuder system (ADS), which was verified to completely capture HONO associated with BB in comparison with four other high-time-resolution concentration measurement techniques, including mist chamber–ion chromatography (MC–IC), open-path Fourier transform infrared spectroscopy (OP-FTIR), cavity-enhanced spectroscopy (CES), and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF). In 20 “stack” fires (direct emission within ∼5 s of production by the fire) that burned various biomass materials from the western US, δ15N–NOx ranges from −4.3 ‰ to +7.0 ‰, falling near the middle of the range reported in previous work. The first measurements of δ15N–HONO and δ18O–HONO in biomass burning smoke reveal a range of −5.3 ‰ to +5.8 ‰ and +5.2 ‰ to +15.2 ‰, respectively. Both HONO and NOx are sourced from N in the biomass fuel, and δ15N–HONO and δ15N–NOx are strongly correlated (R2=0.89, p\u3c0.001), suggesting HONO is directly formed via subsequent chain reactions of NOx emitted from biomass combustion. Only 5 of 20 pNO−3 samples had a sufficient amount for isotopic analysis and showed δ15N and δ18O of pNO−3 ranging from −10.6 ‰ to −7.4 ‰ and +11.5 ‰ to +14.8 ‰, respectively. Our δ15N of NOx, HONO, and pNO−3 ranges can serve as important biomass burning source signatures, useful for constraining emissions of these species in environmental applications. The δ18O of HONO and NO−3 obtained here verify that our method is capable of determining the oxygen isotopic composition in BB plumes. The δ18O values for both of these species reflect laboratory conditions (i.e., a lack of photochemistry) and would be expected to track with the influence of different oxidation pathways in real environments. The methods used in this study will be further applied in future field studies to quantitatively track reactive nitrogen cycling in fresh and aged western US wildfire plumes

Digital Quantification of Gene Expression in Sequential Breast Cancer Biopsies Reveals Activation of an Immune Response

Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted

Sulfation of L-Selectin Ligands by an HEV-Restricted Sulfotransferase Regulates Lymphocyte Homing to Lymph Nodes

AbstractLymphocytes home to lymph nodes, using L-selectin to bind specific ligands on high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an essential posttranslational modification for ligand activity. Here, we show that genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted to HEV, results in the loss of the binding of recombinant L-selectin to the luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost from the luminal aspects of HEV. These results establish a critical role for HEC-GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic target

Thoracic and Lumbar Vertebral Bone Mineral Density Changes in a Natural Occurring Dog Model of Diffuse Idiopathic Skeletal Hyperostosis

Ankylosing spinal disorders can be associated with alterations in vertebral bone mineral density (BMD). There is however controversy about vertebral BMD in patients wuse idiopathic skeletal hyperostosis (DISH). DISH in Boxer dogs has been considered a natural occurring disease model for DISH in people. The purpose of this study was to compare vertebral BMD between Boxers with and without DISH. Fifty-nine Boxers with (n=30) or without (n=29) DISH that underwent computed tomography were included. Vertebral BMD was calculated for each thoracic and lumbar vertebra by using an earlier reported and validated protocol. For each vertebral body, a region of interest was drawn on the axial computed tomographic images at three separate locations: immediately inferior to the superior end plate, in the middle of the vertebral body, and superior to the inferior end plate. Values from the three axial slices were averaged to give a mean Hounsfield Unit value for each vertebral body. Univariate statistical analysis was performed to identify factors to be included in a multivariate model. The multivariate model including all dogs demonstrated that vertebral DISH status (Coefficient 24.63; 95% CI 16.07 to 33.19; p <0.001), lumbar vertebrae (Coefficient -17.25; 95% CI -23.42 to -11.09; p < 0.01), and to a lesser extent higher age (Coefficient -0.56; 95% CI -1.07 to -0.05; p = 0.03) were significant predictors for vertebral BMD. When the multivariate model was repeated using only dogs with DISH, vertebral DISH status (Coefficient 20.67; 95% CI, 10.98 to 30.37; p < 0.001) and lumbar anatomical region (Coefficient -38.24; 95% CI, -47.75 to -28.73; p < 0.001) were again predictors for vertebral BMD but age was not. The results of this study indicate that DISH can be associated with decreased vertebral BMD. Further studies are necessary to evaluate the clinical importance and pathophysiology of this finding