Comparing placentas from normal and abnormal pregnancies

This report describes work carried out at a Mathematics-in-Medicine Study Group. It is believed that placenta shape villous network characteristics are strongly linked to the placenta’s efficiency, and hence to pregnancy outcome. We were asked to consider mathematical ways to describe the shape and other characteristics of a placenta, as well as forming mathematical models for placenta development. In this report we propose a number of possible measure of placental shape, form, and efficiency, which can be computed from images already obtained. We also consider various models for the early development of placentas and the growth of the villous tree

Effects of Frequency of Protein Supplementation on Performance by Beef Calves Grazing Dormant Native Range

Stocker calves that graze forages before entering a feedlot account for more than 75% of the beef calves raised in the United States each year. A large proportion of those will be calves born in the spring and weaned in the fall. Modest growth rates are expected when the quality of fall and winter forages is poor. Growing calves in confinement systems during fall and winter typically allows for greater average daily gain (ADG) than graz­ing low-quality forages; however, modest overall costs associated with grazing perennial, dormant forages may be competitive during times when feed prices are relatively high. Providing supplemental protein to beef cows grazing dormant, warm-season, native for­ages (i.e., ≤ 6% crude protein [CP]) has been demonstrated to increase body condition score (BCS), body weight (BW), improve dry matter digestibility (DMD), and for­age dry matter intake (DMI). Furthermore, beef cows grazing low-quality forages and supplemented with protein either daily, every third day, or every sixth day had similar BW and BCS. Reducing the frequency of supplement delivery can reduce labor costs and equipment depreciation without negatively affecting animal performance; however, this practice has variable success when used with growing beef cattle. In previous research, steers supplemented with cottonseed cake 3 times weekly had similar BW gain during win­ter compared to steers supplemented daily. Conversely, in another study, steers graz­ing winter range and supplemented with dried distillers grain daily had greater ADG than steers supplemented 3 times weekly. Therefore, the objective of this study was to evaluate the performance of young, lightweight stocker calves grazing dormant, native tallgrass pastures and supplemented protein either daily or 3 times weekly throughout the winter

The metabolic and molecular mechanisms of hyperammonaemia and hyperethanolaemia induced protein catabolism in skeletal muscle cells

Hyperammonaemia and hyperethanolaemia are thought to be driving factors behind skeletal muscle myopathy in liver disease i.e. cirrhosis. Despite this, the singular and combined impacts of ethanol and ammonia induced protein catabolism are poorly defined. As such, we aimed to dissect out the effects of ammonia and ethanol on muscle catabolism. Murine C2C12 myotubes were treated with ammonium acetate (10 mM) and ethanol (100 mM) either alone or in combination for 4h and/or 24h. Myotube diameter, muscle protein synthesis and anabolic and catabolic signalling pathways were assessed. In separate experiments, cells were co-treated with selected inhibitors of protein breakdown to assess the importance of proteolytic pathways in protein loss with ammonia and ethanol. Ammonia and ethanol in combination resulted in a reduction in myotube width and total protein content, that was greater than the reduction observed with ammonia alone. Both ammonia and ethanol caused reductions in protein synthesis, as assessed by puromycin incorporation. There was also evidence of impairments in regulation of protein translation, and increased protein expression of markers of muscle protein breakdown. Myotube protein loss with ammonia plus ethanol was not affected by autophagy inhibition, but was completely prevented by proteasome inhibition. Thus, combined ammonia and ethanol incubation of C2C12 myotubes exacerbated myotube atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Ubiquitin proteasome-mediated protein breakdown appears to play an important role in myotube protein loss with ethanol and ammonia

Effects of Early or Conventional Weaning on Beef Cow and Calf Performance in Pasture and Drylot Environments

During widespread drought, pasture availability and productivity are reduced. This, coupled with increasing land prices and lease rates, has prompted the evaluation of al­ternative management strategies that decrease grazing pressure on perennial pasture or reduce feed and pasture costs. Weaning early and moving cows from pasture to a drylot environment is used commonly for reducing grazing pressure on perennial pastures. A premature end to lactation reduces cow nutrient requirements and reduces grazing pressure. Removal of the calf further reduces grazing pressure, as calves are significant consumers of forage dry matter (DM) during mid and late lactation. The combina­tion can be used to extend grazing by 0.4 d for each d weaning is executed earlier than normal. Early weaning may result in calves having less value at weaning compared to calves weaned at conventional ages. Retaining ownership of young calves through back­grounding can be useful for increasing their value. Limit-feeding non-lactating cows or cow-calf pairs in confinement can also reduce grazing pressure on pastures, while maintaining cow body condition score (BCS) or body weight (BW). Previous research conducted at the location of this study found that limit-feeding non-lactating cows at 1.9% BW achieved acceptable gains in BW, BCS, and rump fat. Therefore, the objective of our study was to evaluate the performance of beef cows and calves subject to a 56-d early or conventional weaning period in either pasture or drylot environments

Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders

As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often reported. The underlying mechanism has been suggested to involve a decrease in protein synthesis in order to conserve O2. With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-13C-leucine in nine healthy male subjects at sea level and subsequently at high-altitude (4559 m) after 7–9 days of acclimatization. Physical activity levels and food and energy intake were controlled prior to the two experimental conditions with the aim to standardize these confounding factors. Blood samples and expired breath samples were collected hourly during the 4 hour trial and vastus lateralis muscle biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted state. Myofibrillar protein synthesis rate was doubled; 0.041±0.018 at sea-level to 0.080±0.018%⋅hr−1 (p<0.05) when acclimatized to high altitude. The sarcoplasmic protein synthesis rate was in contrast unaffected by altitude exposure; 0.052±0.019 at sea-level to 0.059±0.010%⋅hr−1 (p>0.05). Trends to increments in whole body protein kinetics were seen: Degradation rate elevated from 2.51±0.21 at sea level to 2.73±0.13 µmol⋅kg−1⋅min−1 (p = 0.05) at high altitude and synthesis rate similar; 2.24±0.20 at sea level and 2.43±0.13 µmol⋅kg−1⋅min−1 (p>0.05) at altitude. We conclude that whole body amino acid flux is increased due to an elevated protein turnover rate. Resting skeletal muscle myocontractile protein synthesis rate was concomitantly elevated by high-altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was unaffected by hypoxia. These changed responses may lead to divergent adaptation over the course of prolonged exposure

Suppression of Ribosomal Function Triggers Innate Immune Signaling through Activation of the NLRP3 Inflammasome

Some inflammatory stimuli trigger activation of the NLRP3 inflammasome by inducing efflux of cellular potassium. Loss of cellular potassium is known to potently suppress protein synthesis, leading us to test whether the inhibition of protein synthesis itself serves as an activating signal for the NLRP3 inflammasome. Murine bone marrow-derived macrophages, either primed by LPS or unprimed, were exposed to a panel of inhibitors of ribosomal function: ricin, cycloheximide, puromycin, pactamycin, and anisomycin. Macrophages were also exposed to nigericin, ATP, monosodium urate (MSU), and poly I:C. Synthesis of pro-IL-ß and release of IL-1ß from cells in response to these agents was detected by immunoblotting and ELISA. Release of intracellular potassium was measured by mass spectrometry. Inhibition of translation by each of the tested translation inhibitors led to processing of IL-1ß, which was released from cells. Processing and release of IL-1ß was reduced or absent from cells deficient in NLRP3, ASC, or caspase-1, demonstrating the role of the NLRP3 inflammasome. Despite the inability of these inhibitors to trigger efflux of intracellular potassium, the addition of high extracellular potassium suppressed activation of the NLRP3 inflammasome. MSU and double-stranded RNA, which are known to activate the NLRP3 inflammasome, also substantially inhibited protein translation, supporting a close association between inhibition of translation and inflammasome activation. These data demonstrate that translational inhibition itself constitutes a heretofore-unrecognized mechanism underlying IL-1ß dependent inflammatory signaling and that other physical, chemical, or pathogen-associated agents that impair translation may lead to IL-1ß-dependent inflammation through activation of the NLRP3 inflammasome. For agents that inhibit translation through decreased cellular potassium, the application of high extracellular potassium restores protein translation and suppresses activation of the NLRP inflammasome. For agents that inhibit translation through mechanisms that do not involve loss of potassium, high extracellular potassium suppresses IL-1ß processing through a mechanism that remains undefined

Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis

This study examined fiber type-dependent differences in the regulation of protein synthesis in individual muscle fibers found within the same whole muscle. Specifically, the in vivo SUrface SEnsing of Translation (SUnSET) methodology was used to measure protein synthesis in type 1, 2A, 2X and 2B fibers of the mouse plantaris muscle, in response to food deprivation (FD), and mechanical overload induced by synergist ablation (SA). The results show that 48 h of FD induced a greater decrease in protein synthesis in type 2X and 2B fibers compared to type 1 and 2A fibers. Type 2X and 2B fibers also had the largest FD-induced decrease in total S6 protein and Ser240/244 S6 phosphorylation, respectively. Moreover, only type 2X and 2B fibers displayed a FD-induced decrease in cross-sectional area (CSA). Ten days of SA also induced fiber type-dependent responses, with type 2B fibers having the smallest SA-induced increases in protein synthesis, CSA and Ser240/244 S6 phosphorylation, but the largest increase in total S6 protein. Embryonic myosin heavy chain (MHCEmb) positive fibers were also found in SA muscles and the protein synthesis rates, levels of S6 Ser240/244 phosphorylation, and total S6 protein content, were 3.6-, 6.1- and 2.9-fold greater than that found in fibers from control muscles, respectively. Overall, these results reveal differential responses in the regulation of protein synthesis and fiber size between fiber types found within the same whole muscle. Moreover, these findings demonstrate that changes found at the whole muscle level do not necessarily reflect changes in individual fiber types