Light stimulus frequency dependence of activity in the rat visual system as studied with high-resolution BOLD fMRI

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL.     

Impact of Pulsed Direct Current on Embryos,Larvae, and Young Juveniles of Atlantic Cod and its Implications for Electrotrawling of Brown Shrimp

The application of electrical pulses in fishing gear is considered a promising option to increase the sustainability of demersal trawl fisheries. In the electrotrawl fishery for brown shrimp Crangon crangon, an electrical field selectively induces a startle response in the shrimp. Other benthic organisms remain mainly on the seafloor and escape underneath a hovering trawl. Previous experiments have indicated that this pulse has no short-term major harmful effects on adult fish and invertebrates. However, the impact on young marine life stages is still unknown. Because brown shrimp are caught in shallow coastal zones and estuaries, which serve as important nurseries or spawning areas for a wide range of marine species, electrotrawling on these grounds could harm embryos, larvae, and juveniles. We carried out experiments with different developmental stages of Atlantic Cod Gadus morhua, which are considered vulnerable to electrical pulses. Three embryonic stages, four larval stages, and one juvenile stage of Atlantic Cod were exposed to a homogeneous electrical field of 150 V_peak/m for 5 s, mimicking a worst-case scenario. We detected no significant differences in embryo mortality rate between control and exposed groups. However, for the embryonic stage exposed at 18 d postfertilization, the initial hatching rate was lower. Larvae that were exposed at 2 and 26 d posthatch exhibited higher mortality rates than the corresponding nonexposed control groups. In the other larval and juvenile stages, no short-term impact of exposure on survival was observed. Morphometric analysis of larvae and juveniles revealed no differences in measurements or deformations of the yolk, notochord, eye, or head. Although exposure to a worst-case electrical field did not impact survival or development for six of the eight young life stages of Atlantic Cod, the observed delayed hatching rate and decreased survival for larvae might indicate an impact of electric pulses and warrant further research.

Received July 20, 2016; accepted April 14, 2017     

Coingestion of carbohydrate and protein hydrolysate stimulates muscle protein synthesis during exercise in young men, with no further increase during subsequent overnight recovery

We investigated the effect of carbohydrate and protein hydrolysate ingestion on whole-body and muscle protein synthesis during a combined endurance and resistance exercise session and subsequent overnight recovery. Twenty healthy men were studied in the evening after consuming a standardized diet throughout the day. Subjects participated in a 2-h exercise session during which beverages containing both carbohydrate (0.15 g x kg(-1) x h(-1)) and a protein hydrolysate (0.15 g x kg(-1) x h(-1)) (C+P, n = 10) or water only (W, n = 10) were ingested. Participants consumed 2 additional beverages during early recovery and remained overnight at the hospital. Continuous i.v. infusions with L-[ring-(13)C(6)]-phenylalanine and L-[ring-(2)H(2)]-tyrosine were applied and blood and muscle samples were collected to assess whole-body and muscle protein synthesis rates. During exercise, whole-body and muscle protein synthesis rates increased by 29 and 48% with protein and carbohydrate coingestion (P < 0.05). Fractional synthetic rates during exercise were 0.083 +/- 0.011%/h in the C+P group and 0.056 +/- 0.003%/h in the W group, (P < 0.05). During subsequent overnight recovery, whole-body protein synthesis was 19% greater in the C+P group than in the W group (P < 0.05). However, mean muscle protein synthesis rates during 9 h of overnight recovery did not differ between groups and were 0.056 +/- 0.004%/h in the C+P group and 0.057 +/- 0.004%/h in the W group (P = 0.89). We conclude that, even in a fed state, protein and carbohydrate supplementation stimulates muscle protein synthesis during exercise. Ingestion of protein with carbohydrate during and immediately after exercise improves whole-body protein synthesis but does not further augment muscle protein synthesis rates during 9 h of subsequent overnight recovery.     

Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses

Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta-analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta–meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet-related and occupational factors are very relevant.     

Brain responses to ambient temperature fluctuations in fish: reduction of blood volume and initiation of a whole-body stress response

Spatial and temporal ambient temperature variations directly influence cellular biochemistry and thus the physiology of ectotherms. However, many aquatic ectothermic species maintain coordinated sensorimotor function during large acute body-temperature changes, which points to a compensatory mechanism within the neural system. Here we used high-resolution functional magnetic resonance imaging to study brain responses to a drop of 10 degrees C of ambient water temperature in common carp. We observed a strong drainage of blood out of the brain as of 90 s after the onset of the temperature drop, which would be expected to reduce entry of cold blood arriving from the gills so that the change in brain temperature would be slower. Although oxygen content in the brain thus decreased, we still found specific activation in the preoptic area (involved in temperature detection and stress responses), the pituitary pars distalis (stress response), and inactivation of the anterior part of the midbrain tegmentum and the pituitary pars intermedia. We propose that the blood drainage from the brain slows down the cooling of the brain during an acute temperature drop. This could help to maintain proper brain functioning including sensorimotor activity, initiation of the stress response, and the subsequent behavioral responses.     

Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men

BACKGROUND: The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover. OBJECTIVE: We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living. DESIGN: Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period. RESULTS: Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P < 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P < 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P < 0.01) subjects, with no significant differences between groups. CONCLUSIONS: Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.     

Greater whole-body myofibrillar protein breakdown in cachectic patients with chronic obstructive pulmonary disease

BACKGROUND: Experimental studies indicate that greater skeletal muscle protein breakdown is a trigger for the cachexia that often is prevalent in chronic obstructive pulmonary disease (COPD). OBJECTIVE: We compared myofibrillar protein breakdown (MPB) with whole-body (WB) protein breakdown (PB) in 9 cachectic COPD patients [x +/- SEM forced expiratory volume in 1 s (FEV(1)): 48 +/- 4% of predicted], 7 noncachectic COPD patients (FEV(1): 53 +/- 5% of predicted), and 7 age-matched healthy control subjects, who were matched by body mass index with the noncachectic patients. DESIGN: After the subjects fasted overnight (10 h) and discontinued the maintenance medication, a primed constant and continuous infusion protocol was used to infuse L-[ring-(2)H(5)]-phenylalanine and L-[ring-(2)H(2)]-tyrosine to measure WB protein turnover and L-[(2)H(3)]-3-methylhistidine to measure WB MPB. Three arterialized venous blood samples were taken between 80 and 90 min of infusion to measure amino acid concentrations and tracer enrichments. RESULTS: Body composition, WB protein turnover, and WB MPB did not differ significantly between the noncachectic COPD and control subjects. Cachectic COPD patients had lower fat mass and fat-free mass values (both: P < 0.01) than did the noncachectic COPD patients. WB MPB was significantly (P < 0.05) higher in the cachectic COPD group (18 +/- 3 nmol . kg(-1) . min(-1)) than in the combined control and noncachectic COPD groups (10 +/- 1 nmol . kg(-1) . min(-1)), but WB protein turnover did not differ significantly between the groups. Correlations with fat-free mass were significant (P < 0.05) for plasma glutamate and branched-chain amino acids, and that for WB MPB trended toward significance (P = 0.07). CONCLUSION: Cachexia in clinically stable patients with moderate COPD is characterized by increased WB MPB, which indicates that myofibrillar protein wasting is an important target for nutritional and pharmacologic modulation.