Daylight hours were utilized to clean the trenches and refurbish weapons' positions in anticipation of another attack during the hours of darkness. On the night of 13-14 June, ant approximately 0255, enemy artillery and mortar fire preceded a CCF screening action against he outpost from the east and west for the purpose of protecting recovery of their dead. This screening force was broken up by friendly defensive fires. Action became sporadic, with light enemy artillery and mortar fire falling on the outpost and MLR. By 0440 the enemy withdrew and all action ceased. The regimental commander took immediate steps to reorganize for renewed attacks, placing Company "G", 15th infantry on the outpost.
Attached to the British 9th (Scottish) Division, the South African 1st Infantry Brigade was deployed to France in mid-April 1916 in anticipation of the upcoming Somme Offensive. Occupying front-line trenches throughout May, and then later in reserve, the Brigade reportedly gained a reputation for imitating Zulu war songs and dances when at the front.
Altogether, our data highlight a coordinated network of REV-ERBα target genes controlling both lipid and amino acid metabolism in skeletal muscle and perhaps in other tissues. We show how normal diurnal rhythms of muscle REV-ERBα might serve to repress these genes in anticipation of the feeding+activity phase, when glucose returns as the predominant fuel source. Furthermore, muscle-specific loss of BMAL1 also leads to loss of REV-ERBα-dependent repression and persistently increased expression of these targets, likely causing increased lipid metabolism and increased protein turnover.
To preserve glucose during periods of fasting, peripheral tissue metabolism shifts to prioritize the use of lipids, ketone bodies, and amino acids as energy substrates . This occurs concomitantly with increased peripheral glucose production derived mostly from amino acids supplied from skeletal muscle protein breakdown. Accordingly, low blood glucose and the resulting low circulating insulin levels are catalysts for increased peripheral lipolysis, muscle protein degradation, and amino acid release. These homeostatic adaptations are readily apparent during starvation, high-fat diet, and endurance exercise. Our data suggest that the same mechanisms are at play and relevant during normal 24-hr fasting/feeding and rest/activity cycles. Indeed, the normal circadian rise in blood glucose concentrations at awakening is exquisitely controlled at multiple levels and by multiple tissues to ensure coordinated maintenance of glycemia and peripheral insulin sensitivity . Our study highlights several examples of how the muscle clock plays an important role in these processes by directly modulating and coordinating local transcriptional programs in anticipation of diurnal oscillations of hormones and metabolites (summarized in Fig 10).
Our data illuminate how BMAL1, REV-ERBα, and their target genes work together to establish a transcriptional logic that defines 24-hr energy state and a coherent fuel selection within the muscle cell, thus maximizing metabolic efficiency. For example, we show how BMAL1-dependent activation of Dgat2 could promote synthesis and storage of neutral lipids, while REV-ERB-dependent repression of lipid metabolism genes could coordinately dial down mobilization and oxidation of lipids. This occurs in conjunction with transcriptional activation of gene programs promoting muscle insulin sensitivity and glucose metabolism in anticipation of the feeding+activity phase . In the absence of BMAL1, muscle cells appear to become untethered from (and thus unable to anticipate) rhythmic systemic nutritional signals and persist in a fasting state, resulting in accumulation and de novo diurnal oscillation of lipids and amino acids. Loss of BMAL1 appears to uncouple glycolysis from oxidation, and divert glycolytic intermediates to alternative sugar, nucleotide, lipid, and amino acid biosynthetic pathways (Figs 5F and 8B, and ). 350c69d7ab