Hazards to golden-mantled ground squirrels and associated secondary hazard potential from strychnine baiting for forest pocket gophers

Radio telemetry and capture-recapture techniques were used to evaluate the hazards to golden-mantled ground squirrels (Spermophilus lateralis) from hand baiting with 0.5% strychnine-treated oats for western pocket gophers (Thomomys mazama) on conifer plantations in eastern Oregon. Toxicology data were collected on field-killed and caged ground squirrels and on caged mink (Mustela vison), great horned owls (Bubo virginianus), and red-tailed hawks (Buteo jamaicensis). Ground squirrel populations were reduced 50 to 75% following underground baiting for pocket gophers. Maximum amount of strychnine alkaloid found in cheek pouches and carcass of a field-killed golden-mantled ground squirrel was 2.88 mg. Mean amount of strychnine in carcasses was 0.35 mg; almost all occurred in the gut. The estimated LD50 for mink was 0.6 mg/kg. The lowest lethal dose for great horned owls and red-tailed hawks was 7.7 mg/kg and 10.2 mg/kg, respectively. The LD50 for owls and hawks was not determined. Long-term effects on golden-mantled ground squirrel populations and secondary hazard potential to owls and hawks were judged to be minimal. Wild mustelids as large as mink could be adversely affected by consuming the gut content of strychnine-killed golden-mantled ground squirrels

MESTRANOL AS A REPELLENT TO PROTECT DOUGLAS-FIR SEED FROM DEER MICE

Mestranol** [3-Methoxy-19-nor-l7α-pregna-l,3,5 (10)-trien-20-yn-l7-ol (C21H26O2)] was tested at 2 percent (active) as a repellent for protecting Douglas-fir (Pseudotsuga menziesii) seed from deer mice (Peromyscus maniculatus). In 5-day laboratory bioassays, deer mice consumed 61 to 66 percent fewer mestranol-treated seeds than control seeds; these results were about equal to those with a standard 0.5 percent (active) endrin seed treatment. Deer mice showed a progressive aversion to the mestranol seed treatment from 24 percent to 76 percent in 5 days. Thereafter, with minimal reinforcement, avoidance was maintained at 90 to 99 percent for 6 months. In six field trials in Washington, Oregon, and California, areas seeded with 2 percent mestranol-treated Douglas-fir seed yielded 1.6 to 5.9 times more germinants than areas seeded with control seed. In three of these areas, endrin seed treatments were included; they yielded 1.2 to 3.4 times more germinants than the mestranol treatment and 1.9 to 17.3 times more germinants than the control seed. Although the endrin treatments yielded higher numbers of germinants, the mestranol treatments in these tests generally resulted in acceptable numbers of germinants for first-year stocking. Mestranol\u27s nontoxic, nonpersistent properties plus the aversion shown by deer mice to mestranol in our tests makes it a leading candidate as a Douglas-fir seed protectant in western United States

Climate adaptation by crop migration.

Many studies have estimated the adverse effects of climate change on crop yields, however, this literature almost universally assumes a constant geographic distribution of crops in the future. Movement of growing areas to limit exposure to adverse climate conditions has been discussed as a theoretical adaptive response but has not previously been quantified or demonstrated at a global scale. Here, we assess how changes in rainfed crop area have already mediated growing season temperature trends for rainfed maize, wheat, rice, and soybean using spatially-explicit climate and crop area data from 1973 to 2012. Our results suggest that the most damaging impacts of warming on rainfed maize, wheat, and rice have been substantially moderated by the migration of these crops over time and the expansion of irrigation. However, continued migration may incur substantial environmental costs and will depend on socio-economic and political factors in addition to land suitability and climate

Peptide Technologies in the Development of Chemical Tools for Chromatin‐Associated Machinery

Discerning a mechanistic understanding of the cause‐and‐effect relationships between chromatin post‐translational modifications (PTMs) and DNA accessibility for replication, transcription, and repair is an elusive goal being pursued using molecular and cellular biology, biochemistry, and more recently chemical inhibition. Chemical intervention of the chromatin‐associated complexes that regulate PTM maintenance and chromatin structure faces numerous challenges due to the broad surface‐groove interactions between many of these proteins and histones; yet, the increasing interest in understanding chromatin‐modifying complexes suggests tractable lead compounds will be critical for elucidating the mechanisms of chromatin dysregulation in disease states and validating the druggability of these domains. Peptides and peptidomimetics afford several advantages to efficient inhibitor development including a rational starting point, modular assembly, and retention of secondary structure. Numerous peptide technologies have been employed in the chromatin field to characterize substrate interactions, evaluate ligand selectivity, and optimize potent peptidomimetic inhibitors. We describe the progress and advantages of these efforts, and provide a perspective on their implications for future chemical probe and drug discovery efforts. Drug Dev Res 78 : 300–312, 2017. © 2017 Wiley Periodicals, Inc

Mind-Body Skills Groups for Adolescents with Depression in Primary Care: A Pilot Study

Objective: To determine acceptability and preliminary effectiveness of Mind-Body Skills Groups (MBSGs) as a treatment for depressed adolescents in primary care. Methods: A single arm clinical trial was conducted. A 10-week MBSG program was implemented in primary care. Participants completed self-report measures at baseline, post-intervention, and 3-months following the MBSGs. Measures included the Children’s Depression Inventory-2, Suicidal Ideation Questionnaire, Mindful Attention Awareness Scale, Self-Efficacy for Depressed Adolescents, rumination subscale of the Children’s Response Style Questionnaire, and a short acceptability questionnaire. Results: Participants included 43 adolescents. The total depression scores significantly improved following the MBSG intervention and continued to improve significantly from post-treatment to follow-up. Mindfulness, self-efficacy, rumination, and suicidal ideation all had significant improvement following the intervention. Acceptability of the program was strong, and attendance was excellent. Discussion: Preliminary evidence suggests that MBSGs are an acceptable treatment for primary care settings and lead to improved depression symptoms in adolescents.Sandra Eskenazi Mental Health Center and the Herbert Simon Family Foundation (070241-00002B

Glutamate receptor activation triggers OPA1 release and induces apoptotic cell death in ischemic rat retina

PurposeGlutamate receptor activation-induced excitotoxicity has been hypothesized to cause retinal ganglion cell (RGC) death in glaucoma and to link mitochondrial dysfunction in both acute and chronic neurodegenerative disorders. However, the relationships among elevated intraocular pressure (IOP), glutamate receptor-mediated excitotoxicity, and mitochondrial dysfunction in glaucoma remains unknown. The goal of this study was to determine whether the N- methyl D-aspartate (NMDA) glutamate receptor antagonist MK801 can block optic atrophy 1 (OPA1) release and subsequent apoptotic cell death, as well as whether acute IOP elevation triggers OPA1 release and alters OPA1 gene and protein expression in the rat retina after ischemia.MethodsSprague Dawley rats received injections of MK801 (10 mg/kg) or vehicle and then transient retinal ischemia was induced by acute IOP elevation. Following subcellular fractionation, changes in cytoplasmic and mitochondrial OPA1 were assessed by western blot analysis. Also, the expression of OPA1 mRNA was measured by Taqman qPCR, the distribution of OPA1 protein was assessed by immunohistochemistry, and apoptotic cell death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.ResultsThe ~65 and 90 kDa isoforms of OPA1 were increased in the cytosol in the rat retina at 6 h and at 12 h, but only the 90 kDa isoform of OPA1 was decreased at 12 h after ischemia induced by acute IOP elevation. This suggests that ischemic insult induced OPA1 release from the mitochondria in retinas. Pretreatment with MK801 blocked this effect and significantly increased OPA1 immunoreactivity in the inner retinal layers, as well as OPA1 gene expression and total protein expression in retinas at 12 h after ischemia. Further, pretreatment with MK801 prevented apoptotic cell death in retinas at 12 h after ischemia. Following acute IOP elevation, Bcl-2 mRNA expression in retinas was decreased at 3 h and 6 h but increased at 12 h and 24 h. In contrast, Bax mRNA expression in these retinas was increased in the first 12 h and then plateaued. Moreover, pretreatment with MK801 increased Bcl-2 mRNA expression, but did not alter the course of Bax mRNA expression.ConclusionsThese results indicate that OPA1 release from mitochondria triggered by acute IOP elevation is inhibited by blockade of glutamate receptor activation. Because this effect was accompanied by increases of Bcl-2 expression, no changes of Bax expression, and blockade of apoptosis, these findings indicate that glutamate receptor activation following acute IOP elevation may lead to a distinct mitochondria-mediated cell death pathway in ischemic retina. These results support further studies to determine whether ischemia-induced OPA1 release may be an important component of the biochemical cascade leading to pressure-related ischemic damage in glaucomatous retina

Molecular Acoustic Angiography: A New Technique for High-resolution Superharmonic Ultrasound Molecular Imaging

Ultrasound molecular imaging utilizes targeted microbubbles to bind to vascular targets such as integrins, selectins, and other extracellular binding domains. After binding, these microbubbles are typically imaged using low pressures and multi-pulse imaging sequences. In this article, we present an alternative approach for molecular imaging using ultrasound which relies on superharmonic signals produced by microbubble contrast agents. Bound bubbles were insonified near resonance using a low frequency (4 MHz) and superharmonic echoes were received at high frequencies (25–30 MHz). While this approach was observed to produce declining image intensity during repeated imaging in both in vitro and in vivo experiments due to bubble destruction, the feasibility of superharmonic molecular imaging was demonstrated for transmit pressures which are sufficiently high to induce shell disruption in bound microbubbles. This approach was validated using microbubbles targeted to the αvβ3 integrin in a rat fibrosarcoma model (n=5), and combined with superharmonic images of free microbubbles to produce high contrast, high resolution 3D volumes of both microvascular anatomy and molecular targeting. Image intensity over repeated scans and the effect of microbubble diameter were also assessed in vivo, indicating that larger microbubbles yield increased persistence in image intensity. Using ultrasound-based acoustic angiography images rather than conventional B-mode ultrasound to provide the underlying anatomical information facilitates anatomical localization of molecular markers. Quantitative analysis of relationships between microvasculature and targeting information indicated that most targeting occurred within 50 µm of a resolvable vessel (>100 µm diameter). The combined information provided by these scans may present new opportunities for analyzing relationships between microvascular anatomy and vascular targets, subject only to limitations of the current mechanically-scanned system and microbubble persistence to repeated imaging at moderate mechanical indices

Increased optic atrophy type 1 expression protects retinal ganglion cells in a mouse model of glaucoma

PurposeThe goal of this study is to determine whether increased optic atrophy type 1 (OPA1) expression protects against retinal ganglion cell (RGC) death in glaucomatous DBA/2J mice.MethodsIntraocular pressure in DBA/2J mice was measured, and pre-glaucomatous DBA/2J mice eyes were transfected with recombinant adeno-associated virus serotype 2 (AAV2) constructs including AAV2-wild type (WT) mOPA1 for two months. Increased OPA1 expression was confirmed by western blotting and RGC survival was assessed by retrograde labeling with FluoroGold. In addition, apoptotic cell death and mitochondrial structure were determined in AAV2-WT mOPA1-transfected differentiated RGC-5 cells exposed to elevated hydrostatic pressure (30 mmHg) for three days.ResultsWT AAV2-mOPA1 transfection significantly increased 90 kDa and 80 kDa OPA1 isoforms in the retina of glaucomatous DBA/2J mice. OPA1 immunoreactivity was increased in the inner nuclear layer, inner plexiform layer, and ganglion cell layer in nine month-old glaucomatous DBA/2J mice transfected with AAV2-WT mOPA1. Overexpression of OPA1 significantly increased RGC survival at two months after AAV2-WT mOPA1 transfection, and decreased activation of both astroglia and microglia in the retina of glaucomatous DBA/2J mice. Also, overexpression of OPA1 in differentiated RGC-5 cells resulted in less apoptotic cell death and blocked mitochondrial fission following elevated hydrostatic pressure.ConclusionsOPA1 can directly modulate RGC survival, and increasing OPA1 expression may protect against RGC death in glaucomatous optic neuropathy