Mitochondrial Permeability Uncouples Elevated Autophagy and Lifespan Extension.

Autophagy is required in diverse paradigms of lifespan extension, leading to the prevailing notion that autophagy is beneficial for longevity. However, why autophagy is harmful in certain contexts remains unexplained. Here, we show that mitochondrial permeability defines the impact of autophagy on aging. Elevated autophagy unexpectedly shortens lifespan in C. elegans lacking serum/glucocorticoid regulated kinase-1 (sgk-1) because of increased mitochondrial permeability. In sgk-1 mutants, reducing levels of autophagy or mitochondrial permeability transition pore (mPTP) opening restores normal lifespan. Remarkably, low mitochondrial permeability is required across all paradigms examined of autophagy-dependent lifespan extension. Genetically induced mPTP opening blocks autophagy-dependent lifespan extension resulting from caloric restriction or loss of germline stem cells. Mitochondrial permeability similarly transforms autophagy into a destructive force in mammals, as liver-specific Sgk knockout mice demonstrate marked enhancement of hepatocyte autophagy, mPTP opening, and death with ischemia/reperfusion injury. Targeting mitochondrial permeability may maximize benefits of autophagy in aging.

An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.

Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.

Organic carbon concentrations in 3.5-billion-year-old lacustrine mudstones of Mars.

The Sample Analysis at Mars instrument stepped combustion experiment on a Yellowknife Bay mudstone at Gale crater, Mars revealed the presence of organic carbon of Martian and meteoritic origins. The combustion experiment was designed to access refractory organic carbon in Mars surface sediments by heating samples in the presence of oxygen to combust carbon to CO2. Four steps were performed, two at low temperatures (less than ∼550 °C) and two at high temperatures (up to ∼870 °C). More than 950 µg C/g was released at low temperatures (with an isotopic composition of δ13C = +1.5 ± 3.8‰) representing a minimum of 431 µg C/g indigenous organic and inorganic Martian carbon components. Above 550 °C, 273 ± 30 µg C/g was evolved as CO2 and CO (with estimated δ13C = -32.9‰ to -10.1‰ for organic carbon). The source of high temperature organic carbon cannot be definitively confirmed by isotopic composition, which is consistent with macromolecular organic carbon of igneous origin, meteoritic infall, or diagenetically altered biomass, or a combination of these. If from allochthonous deposition, organic carbon could have supported both prebiotic organic chemistry and heterotrophic metabolism at Gale crater, Mars, at ∼3.5 Ga.

Depleted carbon isotope compositions observed at Gale crater, Mars.

Obtaining carbon isotopic information for organic carbon from Martian sediments has long been a goal of planetary science, as it has the potential to elucidate the origin of such carbon and aspects of Martian carbon cycling. Carbon isotopic values (δ13CVPDB) of the methane released during pyrolysis of 24 powder samples at Gale crater, Mars, show a high degree of variation (-137 ± 8‰ to +22 ± 10‰) when measured by the tunable laser spectrometer portion of the Sample Analysis at Mars instrument suite during evolved gas analysis. Included in these data are 10 measured δ13C values less than -70‰ found for six different sampling locations, all potentially associated with a possible paleosurface. There are multiple plausible explanations for the anomalously depleted 13C observed in evolved methane, but no single explanation can be accepted without further research. Three possible explanations are the photolysis of biological methane released from the subsurface, photoreduction of atmospheric CO2, and deposition of cosmic dust during passage through a galactic molecular cloud. All three of these scenarios are unconventional, unlike processes common on Earth.

SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction.

Hereditary spastic paraplegia type 15 (HSP15) is a neurodegenerative condition caused by the inability to produce SPG15 protein, which leads to lysosomal swelling. However, the link between lysosomal aberrations and neuronal death is poorly explored. To uncover the functional consequences of lysosomal aberrations in disease pathogenesis, we analyze human dermal fibroblasts from HSP15 patients as well as primary cortical neurons derived from an SPG15 knockout (KO) mouse model. We find that SPG15 protein loss induces defective anterograde transport, impaired neurite outgrowth, axonal swelling and reduced autophagic flux in association with the onset of lysosomal abnormalities. Additionally, we observe lipid accumulation within the lysosomal compartment, suggesting that distortions in cellular lipid homeostasis are intertwined with lysosomal alterations. We further demonstrate that SPG15 KO neurons exhibit synaptic dysfunction, accompanied by augmented vulnerability to glutamate-induced excitotoxicity. Overall, our study establishes an intimate link between lysosomal aberrations, lipid metabolism and electrophysiological impairments, suggesting that lysosomal defects are at the core of multiple neurodegenerative disease processes in HSP15.

Association between Residential Greenness and Allostatic Load: A Cohort Study.

The association between residential greenness and allostatic load (AL), a marker of composite physiological burden and predictor of chronic disease, remains understudied. This study comprised 212,600 UK Biobank participants recruited over 2007 and 2010 at the baseline. Residential greenness was modeled as the normalized difference vegetation index (NDVI) from high spatial resolution (0.50 m) color infrared imagery and measured within a 0.5 km radial catchment. AL was measured as a composite index from 13 biomarkers comprising three physiological systems (metabolic, cardiovascular, and inflammatory systems) and two organ systems (liver and kidney). Multilevel mixed-effects generalized linear models with a random intercept for UK Biobank assessment centers were employed to examine the association between residential greenness and AL. Each interquartile range (IQR = 0.24) increment in NDVI greenness was associated with lower AL (beta (ß) = -0.28, 95% confidence interval (CI) = -0.55, -0.01). Consistently, relative to the lowest NDVI greenness quintile, participants in the highest quintile had lower AL (ß = -0.64, 95% CI = -1.02, -0.26). The proportion of the association between greenness and AL mediated by the physical activity was 3.2%. In conclusion, residential greenness was protectively associated with AL, a composite marker of wear and tear and general health.

An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD.

Dysfunction and degeneration of synapses is a common feature of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene is the main genetic cause of ALS/FTD (C9ALS/FTD). The repeat expansion leads to reduced expression of the C9orf72 protein. How C9orf72 haploinsufficiency contributes to disease has not been resolved. Here we identify the synapsin family of synaptic vesicle proteins, the most abundant group of synaptic phosphoproteins, as novel interactors of C9orf72 at synapses and show that C9orf72 plays a cell-autonomous role in the regulation of excitatory synapses. We mapped the interaction of C9orf72 and synapsin to the N-terminal longin domain of C9orf72 and the conserved C domain of synapsin, and show interaction of the endogenous proteins in synapses. Functionally, C9orf72 deficiency reduced the number of excitatory synapses and decreased synapsin levels at remaining synapses in vitro in hippocampal neuron cultures and in vivo in the hippocampal mossy fibre system of C9orf72 knockout mice. Consistent with synaptic dysfunction, electrophysiological recordings identified impaired excitatory neurotransmission and network function in hippocampal neuron cultures with reduced C9orf72 expression, which correlated with a severe depletion of synaptic vesicles from excitatory synapses in the hippocampus of C9orf72 knockout mice. Finally, neuropathological analysis of post-mortem sections of C9ALS/FTD patient hippocampus with C9orf72 haploinsufficiency revealed a marked reduction in synapsin, indicating that disruption of the interaction between C9orf72 and synapsin may contribute to ALS/FTD pathobiology. Thus, our data show that C9orf72 plays a cell-autonomous role in the regulation of neurotransmission at excitatory synapses by interaction with synapsin and modulation of synaptic vesicle pools, and identify a novel role for C9orf72 haploinsufficiency in synaptic dysfunction in C9ALS/FTD.

Resistance training for Black men with depressive symptoms: a pilot randomized controlled trial to assess acceptability, feasibility, and preliminary efficacy.

BACKGROUND: Depression is under-recognized in Black men, who are less likely to seek or have access to psychiatric treatment. Resistance training (RT; i.e., weight lifting) can improve depressive symptoms and may be more acceptable to Black men, but its effects have not been examined for Black men with depressive symptoms. METHODS: Fifty Black men with depressive symptoms were randomized to either (a) 12 weeks of RT (coupled with Behavioral Activation techniques to promote adherence) or (b) an attention-control group (Health, Wellness, and Education; HWE). Both groups met twice/week for 12 weeks, and follow-up assessments were done at end-of-treatment (EOT) and 6 months after enrollment. Changes in physical activity and muscular strength were collected as a manipulation check. The primary outcome was interviewer assessed symptoms of depression using the Quick Inventory of Depression Symptomology (QIDS). Secondary outcomes included self-reported depressive symptoms, anxiety, and stress. The association between change in QIDS from baseline to EOT and concurrent changes in physical activity and muscular strength in the RT group were explored as an initial assessment of mechanism. Longitudinal mixed effects regression models with subject-specific intercepts were used to examine intervention effects. RESULTS: A sample with high rates of medical comorbidities (e.g., 44% HIV positive), substance use (e.g., 34% smoking), and negative social determinates of health (e.g., 50% unemployed) was enrolled. Recruitment, engagement, and retention data indicate that the intervention and design were feasible. The RT group showed greater gains in self-reported exercise (b = 270.94, SE = 105.69, p = .01) and muscular strength (b = 11.71, SE = 4.23, p = .01 for upper body and b = 4.24, SE = 2.02, p = .04 for lower body) than the HWE group. The RT group had greater reductions in QIDS scores at both EOT (b = -3.00, SE = 1.34, p = .01) and 6 months (b = -2.63, SE = 1.81, p = .04). The RT group showed a greater reduction in anxiety at EOT (b = -2.67, SE = 1.06, p = .02). Findings regarding self-reported depressive symptoms and stress were non-significant, but in the expected direction with effect sizes in the small to medium range. In the RT group, improvement on the QIDS between baseline and EOT was associated with concurrent improvements in physical activity (b = 21.03, SE = 11.16, p = .02) and muscular strength (b = 1.27, SE = .44, p = .03 for upper body and b = .75, SE = .14, p = .03 for lower body). CONCLUSIONS: Results suggest that RT is feasible and may be efficacious for reducing depressive symptoms among underserved urban Black men. TRIAL REGISTRATION: ClinicalTrial.gov #: NCT03107039 (Registered 11/04/2017).

Herriott cell spot imaging increases the performance of tunable laser spectrometers.

With the availability of high-power (milliwatts) single-mode tunable laser sources that operate at room temperature across the infrared (IR) region, tunable laser spectrometers have seen an explosion of growth in applications that include commercial, Earth and planetary science, and medical and industrial sensing. While the laser sources themselves have shown steady improvement, the detection architecture of using a single-element detector at one end of a multipass cell has remained unchanged over the last few decades. We present here an innovative new approach using a detector array coupled to an IR-transmissive mirror to image all or part of the multipass spot pattern of the far mirror and record spectra for each pixel. This novel approach offers improved sensitivity, increased dynamic range, laser power normalization, contaminant subtraction, resilience to misalignment, and reduces the instrument power requirement by avoiding the need for "fringe-wash" heaters. With many tens of pixels representing each spot during the laser spectral scan, intensity and optical fringe amplitude and phase information are recorded. This allows selection and manipulation (e.g., co-addition, subtraction) of the pixel output spectra to minimize optical interference fringes thereby increasing sensitivity. We demonstrate a factor of ∼20 sensitivity improvement over traditional single-element detection. Dynamic range increase of a factor of ∼100 is also demonstrated through spot selection representing different pathlengths. Additionally, subtracting the spectrum of the first spot from that of the higher pass normalizes the laser power and removes the contribution of contaminant gas and fringes in the fore-optics region. These initial results show that this imaging method is particularly advantageous for multi-channel laser spectrometers, and, once the image field is analyzed, pixel selection can be used to minimize data rate and volume collection requirements. This technique could be beneficial to enhanced-cavity detection schemes.

The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy.

A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). C9orf72 encodes two C9orf72 protein isoforms of unclear function. Reduced levels of C9orf72 expression have been reported in C9ALS/FTD patients, and although C9orf72 haploinsufficiency has been proposed to contribute to C9ALS/FTD, its significance is not yet clear. Here, we report that C9orf72 interacts with Rab1a and the Unc-51-like kinase 1 (ULK1) autophagy initiation complex. As a Rab1a effector, C9orf72 controls initiation of autophagy by regulating the Rab1a-dependent trafficking of the ULK1 autophagy initiation complex to the phagophore. Accordingly, reduction of C9orf72 expression in cell lines and primary neurons attenuated autophagy and caused accumulation of p62-positive puncta reminiscent of the p62 pathology observed in C9ALS/FTD patients. Finally, basal levels of autophagy were markedly reduced in C9ALS/FTD patient-derived iNeurons. Thus, our data identify C9orf72 as a novel Rab1a effector in the regulation of autophagy and indicate that C9orf72 haploinsufficiency and associated reductions in autophagy might be the underlying cause of C9ALS/FTD-associated p62 pathology.

Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis.

As clinical evidence supports a negative impact of dysfunctional energy metabolism on the disease progression in amyotrophic lateral sclerosis, it is vital to understand how the energy metabolic pathways are altered and whether they can be restored to slow disease progression. Possible approaches include increasing or rerouting catabolism of alternative fuel sources to supplement the glycolytic and mitochondrial pathways such as glycogen, ketone bodies and nucleosides. To analyse the basis of the catabolic defect in amyotrophic lateral sclerosis we used a novel phenotypic metabolic array. We profiled fibroblasts and induced neuronal progenitor-derived human induced astrocytes from C9orf72 amyotrophic lateral sclerosis patients compared to normal controls, measuring the rates of production of reduced nicotinamide adenine dinucleotides from 91 potential energy substrates. This approach shows for the first time that C9orf72 human induced astrocytes and fibroblasts have an adenosine to inosine deamination defect caused by reduction of adenosine deaminase, which is also observed in induced astrocytes from sporadic patients. Patient-derived induced astrocyte lines were more susceptible to adenosine-induced toxicity, which could be mimicked by inhibiting adenosine deaminase in control lines. Furthermore, adenosine deaminase inhibition in control induced astrocytes led to increased motor neuron toxicity in co-cultures, similar to the levels observed with patient derived induced astrocytes. Bypassing metabolically the adenosine deaminase defect by inosine supplementation was beneficial bioenergetically in vitro, increasing glycolytic energy output and leading to an increase in motor neuron survival in co-cultures with induced astrocytes. Inosine supplementation, in combination with modulation of the level of adenosine deaminase may represent a beneficial therapeutic approach to evaluate in patients with amyotrophic lateral sclerosis.

Reduced Glucose Tolerance and Skeletal Muscle GLUT4 and IRS1 Content in Cyclists Habituated to a Long-Term Low-Carbohydrate, High-Fat Diet.

Very little is known about how long-term (>6 months) adaptation to a low-carbohydrate, high-fat (LCHF) diet affects insulin signaling in healthy, well-trained individuals. This study compared glucose tolerance; skeletal muscle glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) content; and muscle enzyme activities representative of the main energy pathways (3-hydroxyacetyl-CoA dehydrogenase, creatine kinase, citrate synthase, lactate dehydrogenase, phosphofructokinase, phosphorylase) in trained cyclists who followed either a long-term LCHF or a mixed-macronutrient (Mixed) diet. On separate days, a 2-hr oral glucose tolerance test was conducted, and muscle samples were obtained from the vastus lateralis of fasted participants. The LCHF group had reduced glucose tolerance compared with the Mixed group, as plasma glucose concentrations were significantly higher throughout the oral glucose tolerance test and serum insulin concentrations peaked later (LCHF, 60 min; Mixed, 30 min). Whole-body insulin sensitivity was not statistically significantly different between groups (Matsuda index: LCHF, 8.7 ± 3.4 vs. Mixed, 12.9 ± 4.6; p = .08). GLUT4 (LCHF: 1.13 ± 0.24; Mixed: 1.44 ± 0.16; p = .026) and IRS1 (LCHF: 0.25 ± 0.13; Mixed: 0.46 ± 0.09; p = .016) protein content was lower in LCHF muscle, but enzyme activities were not different. We conclude that well-trained cyclists habituated to an LCHF diet had reduced glucose tolerance compared with matched controls on a mixed diet. Lower skeletal muscle GLUT4 and IRS1 contents may partially explain this finding. This could possibly reflect an adaptation to reduced habitual glucose availability rather than the development of a pathological insulin resistance.

Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels.

Defective axonal transport is an early neuropathological feature of amyotrophic lateral sclerosis (ALS). We have previously shown that ALS-associated mutations in Cu/Zn superoxide dismutase 1 (SOD1) impair axonal transport of mitochondria in motor neurons isolated from SOD1 G93A transgenic mice and in ALS mutant SOD1 transfected cortical neurons, but the underlying mechanisms remained unresolved. The outer mitochondrial membrane protein mitochondrial Rho GTPase 1 (Miro1) is a master regulator of mitochondrial axonal transport in response to cytosolic calcium (Ca2+) levels ([Ca2+]c) and mitochondrial damage. Ca2+ binding to Miro1 halts mitochondrial transport by modifying its interaction with kinesin-1 whereas mitochondrial damage induces Phosphatase and Tensin Homolog (PTEN)-induced Putative Kinase 1 (PINK1) and Parkin-dependent degradation of Miro1 and consequently stops transport. To identify the mechanism underlying impaired axonal transport of mitochondria in mutant SOD1-related ALS we investigated [Ca2+]c and Miro1 levels in ALS mutant SOD1 expressing neurons. We found that expression of ALS mutant SOD1 reduced the level of endogenous Miro1 but did not affect [Ca2+]c. ALS mutant SOD1 induced reductions in Miro1 levels were Parkin dependent. Moreover, both overexpression of Miro1 and ablation of PINK1 rescued the mitochondrial axonal transport deficit in ALS mutant SOD1-expressing cortical and motor neurons. Together these results provide evidence that ALS mutant SOD1 inhibits axonal transport of mitochondria by inducing PINK1/Parkin-dependent Miro1 degradation.

Exploring a new structured professional judgment measure (impulsivity measure related to violence) after an average follow-up of 10 years: A study of Finnish offenders.

BACKGROUND: Identification of the risk factors underlying impulsivity related to violent acts is an essential component of risk assessment and management to reduce violent offending. AIMS: Our aim was to develop a clinically useful measure for assessing impulsivity related to violence. Our research questions were which items in the newly developed measure are associated with later violent recidivism and what is the measure's predictive validity? METHODS: A new scale, the impulsivity measure related to violence (IMP-V), was studied by completing the scale, blind to outcome, from information in the forensic psychiatric examination reports of 63 of a 1-year referral cohort of 181 Finnish offenders. Data on reoffending for up to 15 years after release were collected from official criminal records. RESULTS: The predictive accuracy of the IMP-V continuous ratings was 78% and for the categorical summary risk ratings 77%. Univariate analyses of categorical summary risk ratings of the risk factors revealed that, with two exceptions, each additional score on the IMP-V was associated with a significant increase in violence recidivism. CONCLUSIONS: These preliminary results indicate that the IMP-V is a promising decision-enhancing guide for assessing the risk of violence in impulsive people and that the measure is worth developing for use with impulsivity-prone offenders and forensic psychiatric patients. The IMP-V organises information on the nature of impulsivity in violence-prone persons and thus also creates opportunities for more effective risk management.

Gluconeogenesis during endurance exercise in cyclists habituated to a long-term low carbohydrate high-fat diet.

KEY POINTS: Blood glucose is an important fuel for endurance exercise. It can be derived from ingested carbohydrate, stored liver glycogen and newly synthesized glucose (gluconeogenesis). We hypothesized that athletes habitually following a low carbohydrate high fat (LCHF) diet would have higher rates of gluconeogenesis during exercise compared to those who follow a mixed macronutrient diet. We used stable isotope tracers to study glucose production kinetics during a 2 h ride in cyclists habituated to either a LCHF or mixed macronutrient diet. The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but similar rates of gluconeogenesis compared to those on the mixed diet. The LCHF cyclists did not compensate for reduced dietary carbohydrate availability by increasing glucose synthesis during exercise but rather adapted by altering whole body substrate utilization. ABSTRACT: Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycaemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however, these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied seven well-trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or a mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2 h laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6-(2) H2 ]-glucose and the ingestion of (2) H2 O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9 mg kg(-1)  min(-1) , Mixed, 7.8 ± 1.1 mg kg(-1)  min(-1) , P < 0.01; Exercise GLY: LCHF, 3.2 ± 0.7 mg kg(-1)  min(-1) , Mixed, 5.3 ± 0.9 mg kg(-1)  min(-1) , P < 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4 mg kg(-1)  min(-1) , Mixed, 2.5 ± 0.3 mg kg(-1)  min(-1) , P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable, whereas glucose oxidation and GLY are influenced by dietary factors.

A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2.

The target of rapamycin complex 2 (TORC2) pathway is evolutionarily conserved and regulates cellular energetics, growth and metabolism. Loss of function of the essential TORC2 subunit Rictor (RICT-1) in Caenorhabditis elegans results in slow developmental rate, reduced brood size, small body size, increased fat mass and truncated lifespan. We performed a rict-1 suppressor RNAi screen of genes encoding proteins that possess the phosphorylation sequence of the AGC family kinase SGK, a key downstream effector of TORC2. Only RNAi to dpy-21 suppressed rict-1 slow developmental rate. DPY-21 functions canonically in the ten-protein dosage compensation complex (DCC) to downregulate the expression of X-linked genes only in hermaphroditic worms. However, we find that dpy-21 functions outside of its canonical role, as RNAi to dpy-21 suppresses TORC2 mutant developmental delay in rict-1 males and hermaphrodites. RNAi to dpy-21 normalized brood size and fat storage phenotypes in rict-1 mutants, but failed to restore normal body size and normal lifespan. Further dissection of the DCC via RNAi revealed that other complex members phenocopy the dpy-21 suppression of rict-1, as did RNAi to the DCC effectors set-1 and set-4, which methylate histone 4 on lysine 20 (H4K20). TORC2/rict-1 animals show dysregulation of H4K20 mono- and tri-methyl silencing epigenetic marks, evidence of altered DCC, SET-1 and SET-4 activity. DPY-21 protein physically interacts with the protein kinase SGK-1, suggesting that TORC2 directly regulates the DCC. Together, the data suggest non-canonical, negative regulation of growth and reproduction by DPY-21 via DCC, SET-1 and SET-4 downstream of TORC2 in C. elegans.

Sharing rotting wood in the shade: ectomycorrhizal communities of co-occurring birch and hemlock seedlings.

Coarse woody debris (CWD) is an important nursery environment for many tree species. Understanding the communities of ectomycorrhizal fungi (ECMF)and the effect of ECMF species on tree seedling condition in CWD will elucidate the potential for ECMF-mediated effects on seedling dynamics. In hemlock-dominated stands, we characterized ECMF communities associated with eastern hemlock (Tsuga canadensis (L.) Carr) and yellow birch (Betula alleghaniensis Britt) seedling pairs growing on CWD. Seedling foliage and CWD were analyzed chemically, and seedling growth, canopy cover, and canopy species determined. Thirteen fungal taxa, 12 associated with birch, and 6 with hemlock, were identified based on morphology and ITS sequencing. Five species were shared by co-occurring birch and hemlock, representing 75% of ectomycorrhizal root tips. Rarified ECMF taxon richness per seedling was higher on birch than hemlock. Nonmetric multidimensional scaling revealed significant correlations between ordination axes, the mutually exclusive ECMF Tomentella and Lactarius spp., foliar N and K, CWD pH, and exchangeable Ca and Mg. Seedlings colonized by Lactarius and T. sublilacina differed significantly in foliar K and N, and CWD differed in exchangeable Ca and Mg. CWD pH and nutrient concentrations were low but foliar macro-nutrient concentrations were not. We hypothesize that the dominant ECMF are adapted to low root carbohydrate availability typical in shaded environments but differ in their relative supply of different nutrients.

Synthesis of air-stable, volatile uranium(IV) and (VI) compounds and their gas-phase conversion to uranium oxide films.

Four air-stable, volatile uranium heteroarylalkenolates have been synthesized and characterized by three synthetic approaches and their gas phase deposition to uranium oxide films has been examined.