Increased drought severity tracks warming in the United States' largest river basin.

Across the Upper Missouri River Basin, the recent drought of 2000 to 2010, known as the "turn-of-the-century drought," was likely more severe than any in the instrumental record including the Dust Bowl drought. However, until now, adequate proxy records needed to better understand this event with regard to long-term variability have been lacking. Here we examine 1,200 y of streamflow from a network of 17 new tree-ring-based reconstructions for gages across the upper Missouri basin and an independent reconstruction of warm-season regional temperature in order to place the recent drought in a long-term climate context. We find that temperature has increasingly influenced the severity of drought events by decreasing runoff efficiency in the basin since the late 20th century (1980s) onward. The occurrence of extreme heat, higher evapotranspiration, and associated low-flow conditions across the basin has increased substantially over the 20th and 21st centuries, and recent warming aligns with increasing drought severities that rival or exceed any estimated over the last 12 centuries. Future warming is anticipated to cause increasingly severe droughts by enhancing water deficits that could prove challenging for water management.

Local groundwater decline exacerbates response of dryland riparian woodlands to climatic drought.

Dryland riparian woodlands are considered to be locally buffered from droughts by shallow and stable groundwater levels. However, climate change is causing more frequent and severe drought events, accompanied by warmer temperatures, collectively threatening the persistence of these groundwater dependent ecosystems through a combination of increasing evaporative demand and decreasing groundwater supply. We conducted a dendro-isotopic analysis of radial growth and seasonal (semi-annual) carbon isotope discrimination (Δ13 C) to investigate the response of riparian cottonwood stands to the unprecedented California-wide drought from 2012 to 2019, along the largest remaining free-flowing river in Southern California. Our goals were to identify principal drivers and indicators of drought stress for dryland riparian woodlands, determine their thresholds of tolerance to hydroclimatic stressors, and ultimately assess their vulnerability to climate change. Riparian trees were highly responsive to drought conditions along the river, exhibiting suppressed growth and strong stomatal closure (inferred from reduced Δ13 C) during peak drought years. However, patterns of radial growth and Δ13 C were quite variable among sites that differed in climatic conditions and rate of groundwater decline. We show that the rate of groundwater decline, as opposed to climate factors, was the primary driver of site differences in drought stress, and trees showed greater sensitivity to temperature at sites subjected to faster groundwater decline. Across sites, higher correlation between radial growth and Δ13 C for individual trees, and higher inter-correlation of Δ13 C among trees were indicative of greater drought stress. Trees showed a threshold of tolerance to groundwater decline at 0.5 m year-1 beyond which drought stress became increasingly evident and severe. For sites that exceeded this threshold, peak physiological stress occurred when total groundwater recession exceeded ~3 m. These findings indicate that drought-induced groundwater decline associated with more extreme droughts is a primary threat to dryland riparian woodlands and increases their susceptibility to projected warmer temperatures.

Response of riparian vegetation to short- and long-term hydrologic variation.

Increasing demand for river water now conflicts with an increasing desire to maintain riparian ecosystems. Efficiently managing river flows for riparian vegetation requires an understanding of the time scale of flow effects, but this information is limited by the absence of long-term studies of vegetation change in response to flow variation. To investigate the influence of short- and long-term flow variability and dam operation on riparian vegetation, we determined the occurrence of 107 plant species in 133 permanent plots of known inundating discharge along the Gunnison River in Colorado on five different occasions between 1990 and 2013. Individual species moved up and down the gradient of inundating discharge coincident with increases and decreases in mean annual flow, and the correlations between flow and species occurrence were strongest when flows were weighted by time before vegetation sampling with a median half-life of 1.5 years. Some tall, rhizomatous, perennial species, however, responded to flows on a longer time scale. Logistic regression of species occurrence showed a significant relation with inundation duration for 70 out of 107 species. Plot species richness and total vegetative cover decreased in association with desiccation at low inundation durations and with fluvial disturbance at high inundation durations. Within-plot similarity in species occurrence between years decreased strongly with increasing inundation duration. Moderate inundation durations were dominated by tall, rhizomatous, perennial herbs, including invasive Phalaris arundinacea (reed canary grass). Over the 23-year study period, species richness declined, and the proportion of rhizomatous perennials increased, consistent with the hypothesis that decreases in flow peaks and increases in low flows caused by flow regulation have decreased establishment opportunities for disturbance-dependent species. In summary, annual-scale changes in vegetation were strongly influenced by flow variation, and decadal-scale changes were influenced by decreases in fluvial disturbance from upstream flow regulation beginning decades prior to the onset of this study.

Population genomic analysis suggests strong influence of river network on spatial distribution of genetic variation in invasive saltcedar across the southwestern United States.

Understanding the complex influences of landscape and anthropogenic elements that shape the population genetic structure of invasive species provides insight into patterns of colonization and spread. The application of landscape genomics techniques to these questions may offer detailed, previously undocumented insights into factors influencing species invasions. We investigated the spatial pattern of genetic variation and the influences of landscape factors on population similarity in an invasive riparian shrub, saltcedar (Tamarix L.) by analysing 1,997 genomewide SNP markers for 259 individuals from 25 populations collected throughout the southwestern United States. Our results revealed a broad-scale spatial genetic differentiation of saltcedar populations between the Colorado and Rio Grande river basins and identified potential barriers to population similarity along both river systems. River pathways most strongly contributed to population similarity. In contrast, low temperature and dams likely served as barriers to population similarity. We hypothesize that large-scale geographic patterns in genetic diversity resulted from a combination of early introductions from distinct populations, the subsequent influence of natural selection, dispersal barriers and founder effects during range expansion.

Sildenafil, nifedipine and acetazolamide do not allow for blood flow through intrapulmonary arteriovenous anastomoses during exercise while breathing 100% oxygen.

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) is known to increase in healthy humans during exercise while breathing room air, but is prevented or significantly reduced during exercise while breathing 100% O2, potentially due to vasoconstriction of IPAVAs. Thus, pharmacological interventions that target known pathways regulating the cardiopulmonary circulation may be able to prevent the hyperoxia-induced reduction in IPAVA blood flow (Q̇ IPAVA ) during exercise. In nine healthy human subjects, we investigated the effects of sildenafil (100 mg p.o.), nifedipine (20 mg p.o.) and acetazolamide (250 mg p.o. three times a day for 3 days) on Q̇ IPAVA at rest and during cycle ergometer exercise at 50, 100, 150, 200 and 250 W, while breathing room air (normoxia) and 100% O2 (hyperoxia). Transthoracic saline contrast echocardiography and a 0-5 bubble scoring system were used to detect and assess Q̇ IPAVA qualitatively; ultrasound was used to assess the blood flow velocity oftricuspid regurgitation and the left ventricular outflow tract blood flow to calculate pulmonary artery systolic pressure (PASP) and cardiac output, respectively. Without drugs, bubble scores increased significantly to ≥2 at 150 W in normoxia and to ≤2 at 200 W in hyperoxia. Only nifedipine consistently increased cardiac output at rest and during low-intensity exercise in normoxia and hyperoxia. However, there was no detectable effect of any drug on Q̇ IPAVA ; specifically, bubble scores were the same during exercise in either normoxia or hyperoxia. Accordingly, the reduction in Q̇ IPAVA during exercise while breathing 100% O2 is likely not to be due to the independent pharmacological mechanisms of action associated with sildenafil, nifedipine or acetazolamide.

CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity.

CRM1 plays an important role in the nuclear export of cargo proteins bearing nuclear exporting signal sequences. Leptomycin B (LMB), a well-known CRM1 inhibitor, possesses strong antitumor properties. However, its toxicity prevents it from being clinically useful. In this study, we demonstrate that a novel compound, CBS9106, inhibits CRM1-dependent nuclear export, causing arrest of the cell cycle and inducing apoptosis in a time- and dose-dependent manner for a broad spectrum of cancer cells, including multiple myeloma cells. CBS9106 reduces CRM1 protein levels significantly without affecting CRM1 mRNA expression. This effect could be reversed by adding bortezomib or LMB. Moreover, CBS9106-biotin allows capture of CRM1 protein by streptavidin beads in a competitive manner with LMB and vice versa. Mass spectrometric analysis shows that CBS9106 reacts with a synthetic CRM1 peptide that contains Cys528 but not with a Cys528 mutant peptide. Oral administration of CBS9106 significantly suppresses tumor growth and prolongs survival in mice bearing tumor xenograft without a significant loss in body weight. A reduced level of CRM1 protein is also observed in tumor xenografts isolated from mice treated with CBS9106. Taken together, these results indicate that CBS9106 is a novel reversible CRM1 inhibitor and a promising clinical candidate.

Imaging of common hip pathologies in runners.

Running is an increasingly popular sport and form of exercise. Because of the importance of the hip in the biomechanics involved with running, forming the primary connection between the axial and appendicular skeleton of the lower extremities, accurate diagnosis and reporting of hip pathology are vital for appropriate management. This review provides an overview of the most common hip pathologies and injuries encountered in runners. Radiologic studies, primarily conventional radiography and magnetic resonance imaging (MRI) provide useful diagnostic information and should be used in combination with clinical findings to help guide therapeutic management.

Genetic and environmental influences on leaf phenology and cold hardiness of native and introduced riparian trees.

To explore the roles of plasticity and genetic variation in the response to spatial and temporal climate variation, we established a common garden consisting of paired collections of native and introduced riparian trees sampled along a latitudinal gradient. The garden in Fort Collins, Colorado (latitude 40.6°N), included 681 native plains cottonwood (Populus deltoides subsp. monilifera) and introduced saltcedar (Tamarix ramosissima, T. chinensis and hybrids) collected from 15 sites at 29.2-47.6°N in the central United States. In the common garden both species showed latitudinal variation in fall, but not spring, leaf phenology, suggesting that the latitudinal gradient in fall phenology observed in the field results at least in part from inherited variation in the critical photoperiod, while the latitudinal gradient in spring phenology observed in the field is largely a plastic response to the temperature gradient. Populations from higher latitudes exhibited earlier bud set and leaf senescence. Cold hardiness varied latitudinally in both fall and spring for both species. For cottonwood, cold hardiness began earlier and ended later in northern than in southern populations. For saltcedar northern populations were hardier throughout the cold season than southern populations. Although cottonwood was hardier than saltcedar in midwinter, the reverse was true in late fall and early spring. The latitudinal variation in fall phenology and cold hardiness of saltcedar appears to have developed as a result of multiple introductions of genetically distinct populations, hybridization and natural selection in the 150 years since introduction.

A case of epididymoorchitis without testicular infarction presenting with reversal of diastolic testicular flow on Doppler ultrasonography.

An acute scrotum is a common clinical scenario prompting urologic involvement. Scrotal ultrasonography with Doppler is the main imaging modality utilized for the evaluation of an acute scrotum and can help distinguish testicular torsion from epididymoorchitis, two common causes of testicular pain. Testicular infarction is a rare but potential complication of epididymoorchitis. We report a case of epididymoorchitis presenting with reversal of testicular diastolic flow concerning for impending testicular infarction but with a non-ischemic testis on scrotal exploration and repeat scrotal ultrasonography post-operatively.

Short- and long-term responses of riparian cottonwoods (Populus spp.) to flow diversion: Analysis of tree-ring radial growth and stable carbon isotopes.

Long duration tree-ring records with annual precision allow for the reconstruction of past growing conditions. Investigations limited to the most common tree-ring proxy of ring width can be difficult to interpret, however, because radial growth is affected by multiple environmental processes. Furthermore, studies of living trees may miss important effects of drought on tree survival and forest changes. Stable carbon isotopes can help distinguish drought from other environmental factors that influence tree-ring width and forest stand condition. We quantified tree-ring radial expansion and stable carbon isotope ratios (δ13C) in riparian cottonwoods (Populus angustifolia and P. angustifolia x P.trichocarpa) along Snake Creek in Nevada, USA. We investigated how hydrological drought affected tree growth and death at annual to half-century scales in a partially dewatered reach (DW) compared to reference reaches immediately upstream and downstream. A gradual decline in tree-ring basal area increment (BAI) began at DW concurrent to streamflow diversion in 1961. BAI at DW diverged from one reference reach immediately but not from the other until nearly 50 years later. In contrast, tree-ring δ13C had a rapid and sustained increase following diversion at DW only, providing the stronger and clearer drought signal. BAI and δ13C were not significantly correlated prior to diversion; after diversion they both reflected drought and were correlated for DW trees only. Cluster analyses distinguished all trees in DW from those in reference reaches based on δ13C, but BAI patterns left trees intermixed across reaches. Branch and tree mortality were also highest and canopy vigor was lowest in DW. Results indicate that water scarcity strongly limited cottonwood photosynthesis following flow diversion, thus reducing carbon assimilation, basal growth and survival. The dieback was not sudden, but occurred over decades as carbon deficits mounted and depleted streamflow left trees increasingly vulnerable to local meteorological drought.

Erosional consequence of saltcedar control.

Removal of nonnative riparian trees is accelerating to conserve water and improve habitat for native species. Widespread control of dominant species, however, can lead to unintended erosion. Helicopter herbicide application in 2003 along a 12-km reach of the Rio Puerco, New Mexico, eliminated the target invasive species saltcedar (Tamarix spp.), which dominated the floodplain, as well as the native species sandbar willow (Salix exigua Nuttall), which occurred as a fringe along the channel. Herbicide application initiated a natural experiment testing the importance of riparian vegetation for bank stability along this data-rich river. A flood three years later eroded about 680,000 m(3) of sediment, increasing mean channel width of the sprayed reach by 84%. Erosion upstream and downstream from the sprayed reach during this flood was inconsequential. Sand eroded from channel banks was transported an average of 5 km downstream and deposited on the floodplain and channel bed. Although vegetation was killed across the floodplain in the sprayed reach, erosion was almost entirely confined to the channel banks. The absence of dense, flexible woody stems on the banks reduced drag on the flow, leading to high shear stress at the toe of the banks, fluvial erosion, bank undercutting, and mass failure. The potential for increased erosion must be included in consideration of phreatophyte control projects.

Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint.

Cell cycle G(2) checkpoint abrogation is an attractive strategy for sensitizing cancer cells to DNA-damaging anticancer agent without increasing adverse effects on normal cells. However, there is no single proven molecular target for this therapeutic approach. High-throughput screening for molecules inhibiting CHK1, a kinase that is essential for the G(2) checkpoint, has not yet yielded therapeutic G(2) checkpoint inhibitors, and the tumor suppressor phenotypes of ATM and CHK2 suggest they may not be ideal targets. Here, we optimized two G(2) checkpoint-abrogating peptides, TAT-S216 and TAT-S216A, based on their ability to reduce G(2) phase accumulation of DNA-damaged cells without affecting M phase accumulation of cells treated with a microtubule-disrupting compound. This approach yielded a peptide CBP501, which has a unique, focused activity against molecules that phosphorylate Ser(216) of CDC25C, including MAPKAP-K2, C-Tak1, and CHK1. CBP501 is >100-fold more potent than TAT-S216A and retains its selectivity for cancer cells. CBP501 is unusually stable, enters cells rapidly, and increases the cytotoxicity of DNA-damaging anticancer drugs against cancer cells without increasing adverse effects. These findings highlight the potency of CBP501 as a G(2)-abrogating drug candidate. This report also shows the usefulness of the cell cycle phenotype-based protocol for identifying G(2) checkpoint-abrogating compounds as well as the potential of peptide-based compounds as focused multitarget inhibitors.

Well-ordered self-assembled monolayer surfaces can be used to enhance the growth of protein crystals.

A series of hydrophobic self-assembled monolayers (SAMs) was generated by the adsorption of undecanethiol, dodecanethiol, and octadecanethiol onto transparent gold-coated glass microscope slides. Protein crystallization trials using droplets deposited on the surfaces of the optically transparent SAMs were compared to those for which the droplets were deposited on the surfaces of conventional silanized glass microscope slides. For the five distinct proteins examined in the crystallization trials (i.e., lysozyme, alpha-lactalbumin, hemoglobin, thaumatin, and catalase), the SAMs generally afforded, (1) a faster rate of crystallization, (2) a larger crystal size; and (3) a broader range of crystallization conditions than that afforded by silanized glass. The greatest enhancements were observed with the highly ordered SAMs derived from octadecanethiol, which are evaluated here for the first time.

Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent.

Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

CBS9106-induced CRM1 degradation is mediated by cullin ring ligase activity and the neddylation pathway.

Chromosome region maintenance 1 (CRM1) mediates the nuclear export of proteins and mRNAs, and is overexpressed in various cancers. Recent studies have also reported that CRM1 protein expression is a negative prognostic factor in patients with cancer. Therefore, CRM1 is considered a potential target for anticancer therapy. Our previous study demonstrated that CBS9106, a synthetic small-molecular inhibitor of CRM1, decreases CRM1 protein through proteasomal degradation without affecting CRM1 mRNA levels. However, the mechanism by which CRM1 is degraded is not well understood. Here, we demonstrate a novel signaling pathway that plays an important role in CBS9106-induced CRM1 degradation. We found that MLN4924, a selective inhibitor of NEDD8-activating enzyme (NAE), effectively inhibits cullin neddylation and attenuates CBS9106-induced CRM1 degradation in a time- and dose-dependent manner. MLN4924 also attenuated CBS9106-induced nuclear accumulation of Ran-binding protein 1 (RanBP1), cell growth inhibition, and apoptosis. Furthermore, RNAi-mediated knockdown of neddylation pathway proteins (NEDD8 and UBA3) or cullin ring ligase (CRL) component protein (Rbx1) attenuated CRM1 protein degradation and G1 phase cell-cycle arrest by CBS9106. Knockdown of CSN5 or CAND1 also partially inhibited CBS9106-induced CRM1 degradation. These findings demonstrate that CBS9106-induced CRM1 degradation is conferred by CRL activity involving the neddylation pathway, and that this response to CBS9106 leads to cell growth inhibition and apoptosis.

Latitudinal variation in cold hardiness in introduced Tamarix and native Populus.

To investigate the evolution of clinal variation in an invasive plant, we compared cold hardiness in the introduced saltcedar (Tamarix ramosissima, Tamarix chinensis, and hybrids) and the native plains cottonwood (Populus deltoides subsp. monilifera). In a shadehouse in Colorado (41°N), we grew plants collected along a latitudinal gradient in the central United States (29-48°N). On 17 occasions between September 2005 and June 2006, we determined killing temperatures using freeze-induced electrolyte leakage and direct observation. In midwinter, cottonwood survived cooling to -70°C, while saltcedar was killed at -33 to -47°C. Frost sensitivity, therefore, may limit northward expansion of saltcedar in North America. Both species demonstrated inherited latitudinal variation in cold hardiness. For example, from September through January killing temperatures for saltcedar from 29.18°N were 5-21°C higher than those for saltcedar from 47.60°N, and on September 26 and October 11, killing temperatures for cottonwood from 33.06°N were >43°C higher than those for cottonwood from 47.60°N. Analysis of nine microsatellite loci showed that southern saltcedars are more closely related to T. chinensis while northern plants are more closely related to T. ramosissima. Hybridization may have introduced the genetic variability necessary for rapid evolution of the cline in saltcedar cold hardiness.