Cainozoic igneous rocks in the Bingara to Inverell area, northeastern New South Wales

Three Cainozoic intraplate volcanic suites in the Bingara to Inverell area, northeastern New South Wales, have been discriminated on the basis of differing geophysical responses and contrasting K–Ar ages. Major isotopic and chemical characteristics can also be used to distinguish the three suites. These newly defined suites are the Middle Eocene–Early Oligocene Maybole Volcanic Suite; the Late Oligocene–Early Miocene Delungra Volcanic Suite; and the Middle Miocene Langari Hill Volcanic Suite. Four basaltic volcanic units within the Delungra Volcanic Suite have also been distinguished: Mount Russell Volcanics; Derra Derra Volcanics; Inverell Volcanics; and Bingara Volcanics. The Maybole Volcanic Suite is dominated by mafic volcanic rocks of alkaline affinity. These rocks include hawaiite, transitional basalt, basanite and rare phonolite (not included in this study). Volcanogenic and non-volcanogenic sedimentary units are minor but significant components, hosting world-class concentrations of sapphires in the Inverell–Glen Innes region. The Maybole Volcanic Suite occupies the eastern portion of the study area, forming ridges that outline the radial drainage pattern of the deeply eroded Eocene–Oligocene Maybole shield volcano. The Delungra Volcanic Suite is geochemically diverse and consists of alkaline members (Inverell and Bingara Volcanics) and tholeiitic members (Mount Russell and Derra Derra Volcanics). These are dominated by mafic lava flows with minor interflow sedimentary horizons. The Delungra Volcanic Suite forms broad elevated plains and prominent plugs in the central and western portions of the study area. Diamond occurrences in the Bingara district are spatially associated with the Bingara and Derra Derra Volcanics. The Langari Hill Volcanic Suite consists of a mafic tholeiitic lava flow that is spatially restricted to a prominent east–west ridge east of Inverell overlying the Maybole Volcanic Suite. The Langari Hill Volcanic Suite is significantly younger than the Maybole and Delungra Volcanic suites and represents the youngest recognised volcanic episode in the Bingara–Inverell area

MITOCHONDRIAL HEALTHDURING THE DEVELOPMENT OF CANCER CACHEXIA IN FEMALE MICE

Lauren C. Westervelt1, Seongkyun Lim1, Megan E. Rosa-Caldwell1, Wesley S. Haynie1, Kirsten R. Dunlap1, Lisa T. Jansen1, Michael P. Wiggs2, Tyrone A. Washington1, Nicholas P. Greene, FACSM1 1University of Arkansas, Fayetteville, AR; 2University of Texas at Tyler, Tyler, TX Cancer-cachexia is a debilitating syndrome characterized by weight loss, anemia, and wasting of adipose tissue and skeletal muscle. Muscle mass in both males and females is a strong predictor of quality of life and morbidity during cancer treatment. Mitochondrial dysfunction during cachexia has been well described in males, specifically our laboratory has found mitochondrial deteriorations to precede muscle loss in male models of cancer-cachexia. However, if these aberrations are conserved between sexes has yet to be investigated. PURPOSE: The purpose of this study was to investigate muscle mitochondrial health during cancer-cachexia development in female mice. METHODS:40 femaleC57BL/6Jmice were implanted with ~1X106Lewis Lung Carcinoma (LLC) cells into the right hind flank. Tumors were allowed to develop up to 4 weeks. After3-4 weeks of tumor development, a clear dichotomy was noted in tumor burden. As such, tumor injected females were divided into high tumor (HT, tumor size\u3e 2000mg) and low tumor groups (LT, tumor sizeRESULTS: Tibialis anterior muscle masses were ~4mg (~10%) lower in HT compared to LT and CON. Similarly, plantaris muscle masses were ~1.5mg (~11%) lower in HT compared to LT and CON. Finally, gastrocnemius masses were ~4 mg (~5%) lower in HT compared to LT and CON animals. LT and CON animals showed no differences in muscle weights. Analysis of pMitoTimer demonstrated no differences between groups. CONCLUSION:LT had negligible muscle wasting when compared to HT, these differences in muscle loss did not appear to correspond to alterations in mitochondrial health. This directly contrasts prior literature in male models of cachexia suggesting divergent mechanisms between males and females in the development of cachexia. As such, further examination of why females had a dichotomy in tumor development and subsequent wasting mechanisms are necessary in order to further understand mechanisms contributing to development of cachexia. ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award Number: R15 AR069913/AR/NIAMS

OXIDATIVE METABOLISM DURING THE TIME-COURSE OF DISUSE ATROPHY IN MALE AND FEMALE MICE

Madeline G. Amos1, Megan E. Rosa-Caldwell1, Wesley S. Haynie1, Kirsten R. Dunlap1, Seongkyun Lim1, Lisa T. Jansen1, Jacob L. Brown1, David E. Lee1, TyroneA.Washington1, Michael P. Wiggs2, Nicholas P. Greene, FACSM11University of Arkansas, Fayetteville, AR; 2University of Texas at Tyler, Tyler, TX Muscle loss is an important predictor of morbidity and mortality across a variety of diseases. Males and females appear to differ on clinical outcomes in relation to disuse-induced muscle loss, however reasons for these different responses have not been investigated. PURPOSE: To investigate measures of muscle oxidative metabolism during the time-course of disuse-induced atrophy in male and female mice. METHODS: Disuse atrophy was induced using hindlimb unloading in50male and 50 female mice for 0 (CON), 1, 2, 3,or 7 days(n=~10/group). Muscle sections of the tibialis anterior were stained for succinate dehydrogenase (SDH,a measure of oxidative metabolism) and cross sectional area(CSA).CSAby SDH staining was used to investigate the effect of disuse on different muscle fiber phenotypes. mRNA content of Pparawas measured in the gastrocnemius, soleus, and extensor digitorum longus(EDL)muscles. Data were analyzed within each sex by one way ANOVA and trend analysis with p\u3c0.05 indicating statistical significance. RESULTS: CSA of SDH positive fibers progressively decreased in both male and female mice. CON animals (male and female) had SDH positive fiber CSA of ~400 μm2and 7 day unloaded animals had CSAs of ~300 μm2.Both male and female mice had an SDH negative CSA of ~650 μm2, with no significant differences in fiber CSA noted across groups. In the gastrocnemius muscle, Ppara content was ~50-60% lower at 1 day of unloading in males and females and remained depressed in all experimental groups. In soleus muscles of females, Ppara was ~60% lower at days 1, 2, and 3 compared to CON, but then recovered back to CON levels. Whereas in males, Pparawas ~60% lower with 1 day of unloading and remained depressed in 1, 2, 3, and 7 day groups. In females ,there were no differences in Ppara content in EDL across all groups. In males, there was ~50-75% lower Ppara in EDL content that reached statistical significance at 2 days unloading and remained depressed throughout intervention groups. CONCLUSION: Disuse results in muscle loss in both male and females and appears to result in similar alterations to oxidative metabolism across multiple tissues. Future studies should investigate if improving oxidative metabolism is protective against disuse atrophy in males and females. ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award number: R15 AR069913/AR/NIAM

SEX DIFFERENCES IN ANABOLIC REGULATORS DURING DEVELOPMENT OF ATROPHIC PATHOLOGY IN HINDLIMB UNLOADING-INDUCED DISUSE

1Lisa T. Jansen, 1Megan E. Rosa-Caldwell, 1Wesley S. Haynie, 1Seongkyun Lim, 1Kirsten R. Dunlap, 1Jacob L. Brown, 1David E. Lee, 1Richard A. Perry 2Michael P. Wiggs, 1Tyrone A. Washington, 1Nicholas P. Greene, FACSM 1University of Arkansas, Fayetteville, Arkansas; 2University of Texas at Tyler, Tyler, Texas Muscle atrophy is a comorbidity in many disease conditions, contributing to accelerated disease progression/terminal outcomes. Muscle wasting results from uncoordinated protein synthesis and protein degradation, as either decreased protein synthesis or increased protein degradation yield reductions in muscle mass and functionality. Atrophic conditions differentially affect discrete muscle types. For many diseases, onset and progression of muscle atrophy presents differently between sexes; yet, most research has focused on muscle wasting pathologies in males alone; thus, data on gender differences in anabolic regulatory gene responses following atrophic stimuli are sparse. While Deptor is a regulator of mTOR/protein synthetic activity, Pgc-14 and IGF-1 have been identified as key mediators in myocyte growth. PURPOSE: To assess gene content outcomes of anabolic regulators Pgc-14, IGF-1, and Deptor, in female and male mice during initiation and progression of disuse atrophy across multiple fiber types. METHODS: 100 female and male C57BL/6J mice were hindlimb unloaded for 0h, 24h, 48, 72 and 168h, to induce muscle atrophy. At assigned endpoints, soleus and gastrocnemius muscles were excised and processed for mRNA analysis of Pgc-14, IGF-1, and Deptor using RT-PCR. Data were analyzed by one-way ANOVA within each sex, . Pre-planned contrast comparisons determined sex differences at each time point. RESULTS: Soleus and gastrocnemius masses presented lower at 24h in female (-11.8%, -9%; p\u3c0.05) and 48h in male (-16%, -13%; p\u3c0.05) compared to control. In soleus, mRNA content of Pgc-14 declined over time in females, while spiking \u3e9, \u3e6-fold in males at 72h and 168h (p\u3c0.05). In contrast, IGF-1 showed higher content in females at 72h and 168h (+77%, +27%; p\u3c0.05) than males. In gastrocnemius, Pgc-14 content spiked \u3e3-fold in females at 24h (p\u3c0.05). Female IGF-1 content was significantly elevated compared to male at 72h (p\u3c0.05). Deptor content in gastrocnemius was \u3e3-fold from baseline at 24h in females and \u3e2-fold from baseline at 48h in males (p\u3c0.05). CONCLUSION: Anabolic regulator responses to atrophic stimuli differ across sex, muscle tissue and time course of muscle atrophy. These early findings could suggest Deptor as a novel therapeutic target to ameliorate muscle wasting conditions. ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award number: R15 AR069913/AR/NIAMS

A TIME COURSE STUDY OF MITOCHONDRIAL QUALITY IN HINDLIMB UNLOADED MICE: A SEX COMPARISON

Kirsten R. Dunlap1, Megan E. Rosa-Caldwell1, Jacob L. Brown1, David E. Lee1, Wesley S. Haynie1, Richard A. Perry1, Lisa T. Jansen1, Seongkyun Lim1, Katarina A. Bejarano1, Michael P. Wiggs2, Tyrone A. Washington1, & Nicholas P. Greene1 1University of Arkansas, Fayetteville, Arkansas; 2University of Texas at Tyler, Tyler, TX Muscle atrophy is a significant pathology and major contributor to mortality across a variety of diseases. However, little is known regarding the etiology of the initiating events and progression of atrophy, demonstrating a critical need to understand cellular events promoting atrophy during pathological conditions. More so, the role of biological sex on cellular underpinnings of atrophy also remains unclear. Evidence from our laboratory suggests that a deterioration in mitochondrial quality in male mice is a precursor to cancer-induced muscle atrophy, however it is unknown if this is a conserved mechanism across other atrophic conditions, such as disuse. As such, studying mitochondrial quality alterations during the development of disuse atrophy, may provide basis for development of therapeutic interventions. PURPOSE: To evaluate mitochondrial quality during the progression of disuse atrophy between male and female mice. METHODS: Male and female C57BL/6J were transfected with pMitoTimer, a fluorescent reporter of mitochondrial quality, in the right flexor digitorum brevis at 6wks of age. After 2wks of recovery, animals were hindlimb unloaded for 0(CON), 24, 48, 72 or 168 hours to induce disuse atrophy. At designated time points, mice were humanely euthanized and tissues were collected for analysis of mitochondrial quality by pMitoTimer. Data within sex were analyzed via one-way ANOVA with Tukey post-hoc, α set at 0.05. Pairwise contrasts were used to analyze data between sex at each time point, α set at 0.01. RESULTS: Gastrocnemius weight was significantly lower at 48 hours in males (12%) and at 24 hours in females (7%) compared to same sex control (p\u3c0.05). Significantly greater pMitoTimer red/green ratios were observed at 24 hours in males (62%) and at 168 hours in females (37%) compared to same sex control (p\u3c0.05) indicative of mitochondrial network degeneration at these time points. CONCLUSION: Mitochondrial network degeneration preceded disuse-induced atrophy in male mice. However, in female mice degeneration of the mitochondrial network is not apparent until well after onset of muscle wasting. Our data suggest divergent deterioration of the mitochondrial network between biological sexes during disuse atrophy. ACKNOWLEDGEMENTS: This study was funded by the National Institutes of Health, Award number: R15 AR069913/AR/NIAMS