The Effects of Physical Activity on Hepatic Lipid Metabolism During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) develops as a result of physical inactivity and overnutrition. Changing dietary behaviors and increasing physical activity are common strategies used for weight-loss; however, it remains unclear what additional benefits are provided by incorporating physical activity in a weight-loss program for the treatment of NAFLD. The purpose of this study was to determine how physical activity reduces hepatic steatosis and changes the expression of hepatic lipogenic genes during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight-loss for 8-weeks. After 8-weeks of weight-loss, reductions in body and liver mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Reductions in body mass and HOMA-IR in the Diet and Diet+PA groups were matched by reductions in hepatic triglyceride levels. In the Diet+PA group, liver triglyceride and cholesterol levels were significantly (P\u3c0.05) lower than all other groups. The greater reduction in hepatic triglyceride levels from physical activity was due to significant (P\u3c0.05) reductions in the expression of lipogenic FASN and SCD-1 mRNA. Interestingly, physical activity did not alter fatty acid uptake or fatty acid oxidation as observed with CD36 and CPT-1a mRNA levels, respectively. Based on these findings, the addition of physical activity to a diet-induced weight-loss intervention provides a more effective approach for the treatment of NAFLD than dieting alone. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ Liver mass (g) 1.2 ± 0.1 2.9 ± 0.2* 1.2 ± 0.1† 1.2 ± 0.1† Triglyceride (mg/dL) 99.4 ± 8.7 96.7 ± 5.5 88.3 ± 6.1 88.4 ± 4.8 Cholesterol (mg/dL) 153.5 ± 10.1 246.0 ± 8.7* 148.2 ± 15.5† 127.6 ± 4.7*,† HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† Liver Tg (mg/mg tissue) 1.18 ± 0.14 2.53 ± 0.05* 0.96 ± 0.15† 0.58 ± 0.07*,†,‡ Liver Chol (μg/mg tissue) 437.0 ± 43.0 585.2 ± 54.4* 527.0 ± 56.5 324.0 ± 27.3*,†,‡ FASN mRNA 1.00 ± 0.20 1.90 ± 0.34* 2.10 ± 0.54* 0.46 ± 0.11*,†,‡ CD36/FAT mRNA 1.00 ± 0.22 0.19 ± 0.20* 0.97 ± 0.10† 0.80 ± 0.04† SCD-1 mRNA 1.00 ± 0.28 1.94 ± 0.83* 0.76 ± 0.13† 0.44 ± 0.05*,†,‡ CPT-1a mRNA 1.00 ± 0.18 0.74 ± 0.04* 0.62 ± 0.08* 0.73 ± 0.05* Note. Data are presented as mean ± SEM.*Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

The Effects of Physical Activity on Markers of Hepatic Inflammation During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) represents a continuum that begins with accumulation of lipid in hepatic cells progressing to hepatic steatosis with inflammation (steatohepatitis), fibrosis, and cirrhosis. Weight-loss using dietary modification and physical activity are common strategies used for the treatment of NAFLD; however, it remains to be determined the effects of physical activity on hepatic inflammation during weight-loss. The purpose of this study was to determine the therapeutic role of physical activity on plasma and hepatic inflammatory markers during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight loss for 8-weeks. After 8-weeks, reductions in body mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Despite significant (P\u3c0.05) reductions in body mass and HOMA-IR, plasma TNF-α remained elevated in the Diet and Diet+PA groups. Moreover, Diet+PA plasma TNF-α was significantly (P\u3c0.05) greater than the HFD obese controls. Elevated plasma TNF-α in the Diet+PA was matched by a greater hepatic expression of IL-1β and IL-6 mRNA when compared to all groups. Interestingly, the expression of TGF-β1 mRNA was significantly (P\u3c0.05) reduced in the Diet+PA when compared to all groups. The elevated plasma TNF-α and expression of IL-1β and IL-6 mRNA are likely due to physical activity. It remains unclear as to the pro-inflammatory effects of physical activity during weight-loss; however, this may be part of a protective adaption to regular exercise. Furthermore, the reduced hepatic TGF-β1 mRNA levels suggest a protective strategy against fibrogenesis in the spectrum of liver disease. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† IL-6 (pg/mL) 6.4 ± 0.7 6.2 ± 1.0 5.9 ± 0.9 6.4 ± 0.9 TNF-α (pg/mL) 30.8 ± 6.7 60.6 ± 5.3* 74.0 ± 8.1* 82.5 ± 7.7*,† IL-1β mRNA 1.00 ± 0.51 0.97 ± 0.34 1.20 ± 0.59 2.83 ± 0.62*,†,‡ IL-6 mRNA 1.00 ± 0.45 1.53 ± 0.50 1.16 ± 0.72 2.36 ± 0.55*,†,‡ TNF-α mRNA 1.00 ± 0.09 0.89 ± 0.08 0.94 ± 0.14 0.83 ± 0.06 TGF-β1 mRNA 1.00 ± 0.06 1.02 ± 0.06 1.02 ± 0.10 0.84 ± 0.05† Note. Data are presented as mean ± SEM. *Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

Development of New Measurements and Tools to Mitigate Fescue Toxicosis in Beef Cattle

The objective of this study was to identify new ways to determine the severity of fescue toxicosis and identify genetic differences in fescue impacted traits as a basis in understanding how cattle could be selected for tolerance to fescue toxicosis. We identified across breed and within breed differences in heat stress related traits and growth rate in pregnant cows exposed to toxic fescue. In addition, new biomarkers were identified to differentiate susceptible and tolerant cattle in the form of specific fecal and vaginal microbes. Finally, we identified differentially expressed (DE) genes in high versus low tolerant cattle on toxic fescue. These findings may allow more accurate diagnosis of fescue toxicosis and provide a glimpse into the genes and microorganisms that may impact tolerance or susceptibility to toxic fescue

Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease

Introduction: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. Methods: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Results: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50–90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Discussion: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease

Unfitness to Plead. Volume 1: Report.

This has been produced along with Volume 2: Draft Legislation as a combined document Presented to Parliament pursuant to section 3(2) of the Law Commissions Act 1965 Ordered by the House of Commons to be printed on 12 January 201

Beef cattle that respond differently to fescue toxicosis have distinct gastrointestinal tract microbiota

Tall fescue (Lolium arundinaceum) is a widely used forage grass which shares a symbiosis with the endophytic fungus Epichloë coenophiala. The endophyte produces an alkaloid toxin that provides herbivory, heat and drought resistance to the grass, but can cause fescue toxicosis in grazing livestock. Fescue toxicosis can lead to reduced weight gain and milk yields resulting in significant losses to the livestock industry. In this trial, 149 Angus cows across two farms were continuously exposed to toxic, endophyte-infected, fescue for a total of 13 weeks. Of those 149 cows, 40 were classified into either high (HT) or low (LT) tolerance groups according to their growth performance (weight gain). 20 HT and 20 LT cattle balanced by farm were selected for 16S rRNA gene and ITS1 region Illumina MiSeq amplicon sequencing to compare the fecal microbiota of the two tolerance groups. This study reveals significantly (P\u3c0.05) different bacterial and fungal microbiota between HT and LT cattle, and indicates that fungal phylotypes may be important for an animal’s response to fescue toxicosis: We found that fungal phylotypes affiliating to the Neocallimastigaceae, which are known to be important fiber-degrading fungi, were consistently more abundant in the HT cattle. Whereas fungal phylotypes related to the genus Thelebolus were more abundant in the LT cattle. This study also found more pronounced shifts in the microbiota in animals receiving higher amounts of the toxin. We identified fungal phylotypes which were consistently more abundant either in HT or LT cattle and may thus be associated with the respective animal’s response to fescue toxicosis. Our results thus suggest that some fungal phylotypes might be involved in mitigating fescue toxicosis. The results of our study provide a basis for investigating the functional role of the gastrointestinal microbiota in fescue toxicosis in more detail in the future

KSU Trombone Choir

Kennesaw State University School of Music presents Trombone Choir.https://digitalcommons.kennesaw.edu/musicprograms/1340/thumbnail.jp

Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease.

Familial Alzheimer's disease (FAD) is caused by autosomal dominant mutations in the PSEN1, PSEN2 or APP genes, giving rise to considerable clinical and pathological heterogeneity in FAD. Here we investigate variability in clinical data and the type and distribution of Aβ pathologies throughout the cortical layers of different FAD mutation cases. Brain tissue from 20 FAD cases [PSEN1 pre-codon 200 (n = 10), PSEN1 post-codon 200 (n = 6), APP (n = 4)] were investigated. Frontal cortex sections were stained immunohistochemically for Aβ, and Nissl to define the cortical layers. The frequency of different amyloid-beta plaque types was graded for each cortical layer and the severity of cerebral amyloid angiopathy (CAA) was determined in cortical and leptomeningeal blood vessels. Comparisons were made between FAD mutations and APOE4 status, with associations between pathology, clinical and genetic data investigated. In this cohort, possession of an APOE4 allele was associated with increased disease duration but not with age at onset, after adjusting for mutation sub-group and sex. We found Aβ pathology to be heterogeneous between cases although Aβ load was highest in cortical layer 3 for all mutation groups and a higher Aβ load was associated with APOE4. The PSEN1 post-codon 200 group had a higher Aβ load in lower cortical layers, with a small number of this group having increased cotton wool plaque pathology in lower layers. Cotton wool plaque frequency was positively associated with the severity of CAA in the whole cohort and in the PSEN1 post-codon 200 group. Carriers of the same PSEN1 mutation can have differing patterns of Aβ deposition, potentially because of differences in risk factors. Our results highlight possible influences of APOE4 genotype, and PSEN1 mutation type on Aβ deposition, which may have effects on the clinical heterogeneity of FAD

Detection and localisation of hesitant steps in people with Alzheimer's disease navigating routes of varying complexity.

People with Alzheimer's disease (AD) have characteristic problems navigating everyday environments. While patients may exhibit abnormal gait parameters, adaptive gait irregularities when navigating environments are little explored or understood. The aim of this study was to assess adaptive locomotor responses of AD subjects in a complex environment requiring spatial navigation. A controlled environment of three corridors was set up: straight (I), U-shaped (U) and dog-leg (S). Participants were asked to walk along corridors as part of a counterbalanced repeated-measures design. Three groups were studied: 11 people with posterior cortical atrophy (PCA), 10 with typical Alzheimer's disease (tAD) and 13 controls. Spatio-temporal gait parameters and position within the corridors were monitored with shoe-mounted inertial measurement units (IMUs). Hesitant steps were identified from statistical analysis of the distribution of step time data. Walking paths were generated from position data calculated by double integration of IMU acceleration. People with PCA and tAD had similar gait characteristics, having shorter steps and longer step times than controls. Hesitant steps tended to be clustered within certain regions of the walking paths. IMUs enabled identification of key gait characteristics in this clinical population (step time, length and step hesitancy) and environmental conditions (route complexity) modifying their expression