HDACs and the senescent phenotype of WI-38 cells

BACKGROUND: Normal cells possess a limited proliferative life span after which they enter a state of irreversible growth arrest. This process, known as replicative senescence, is accompanied by changes in gene expression that give rise to a variety of senescence-associated phenotypes. It has been suggested that these gene expression changes result in part from alterations in the histone acetylation machinery. Here we examine the influence of HDAC inhibitors on the expression of senescent markers in pre- and post-senescent WI-38 cells. RESULTS: Pre- and post-senescent WI-38 cells were treated with the HDAC inhibitors butyrate or trichostatin A (TSA). Following HDAC inhibitor treatment, pre-senescent cells increased p21(WAF1 )and β-galactosidase expression, assumed a flattened senescence-associated morphology, and maintained a lower level of proteasome activity. These alterations also occurred during normal replicative senescence of WI-38 cells, but were not accentuated further by HDAC inhibitors. We also found that HDAC1 levels decline during normal replicative senescence. CONCLUSION: Our findings indicate that HDACs impact numerous phenotypic changes associated with cellular senescence. Reduced HDAC1 expression levels in senescent cells may be an important event in mediating the transition to a senescent phenotype

The increase in hydric volume is associated to contractile impairment in the calf after the world's most extreme mountain ultra-marathon.

BACKGROUND: Studies have recently focused on the effect of running a mountain ultra-marathon (MUM) and their results show muscular inflammation, damage and force loss. However, the link between peripheral oedema and muscle force loss is not really established. We tested the hypothesis that, after a MUM, lower leg muscles' swelling could be associated with muscle force loss. The knee extensor (KE) and the plantar flexor (PF) muscles' contractile function was measured by supramaximal electrical stimulations, potentiated low- and high-frequency doublets (PS10 and PS100) of the KE and the PF were measured by transcutaneous electrical nerve stimulation and bioimpedance was used to assess body composition in the runners (n = 11) before (Pre) and after (Post) the MUM and compared with the controls (n = 8). RESULTS: The maximal voluntary contraction of the KE and the PF significantly decreased by 20 % Post-MUM in the runners. Hydration of the non-fat mass (NF-Hyd) and extracellular water volume (Ve) were increased by 12 % Post-MUM (p < 0.001) in the runners. Calf circumference (+2 %, p < 0.05) was also increased. Significant relationships were found for percentage increases in Ve and NF-Hyd with percentage decrease in PS10 of the PF (r = -0.68 and r = -0.70, p < 0.05) and with percentage increase of calf circumference (r = 0.72 and r = 0.73, p < 0.05) in the runners. CONCLUSIONS: The present study suggests that increases in circumference and in hydric volume are associated to contractile impairment in the calf in ultra-marathon runners

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon.

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (-13±17% and -10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (-24±13% and -26±19%, P<0.01) with alteration of the central activation ratio (-24±24% and -28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: -18±18% and PF: -20±15%, P<0.01) and peak twitch (KE: -33±12%, P<0.001 and PF: -19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·(1)), lactate dehydrogenase (1145±511 UI·L(-1)), C-Reactive Protein (13.1±7.5 mg·L(-1)) and myoglobin (449.3±338.2 µg·L(-1)) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half

Movement-Related Cortical Potential Amplitude Reduction after Cycling Exercise Relates to the Extent of Neuromuscular Fatigue.

Exercise-induced fatigue affects the motor control and the ability to generate a given force or power. Surface electroencephalography allows researchers to investigate movement-related cortical potentials (MRCP), which reflect preparatory brain activity 1.5 s before movement onset. Although the MRCP amplitude appears to increase after repetitive single-joint contractions, the effects of large-muscle group dynamic exercise on such pre-motor potential remain to be described. Sixteen volunteers exercised 30 min at 60% of the maximal aerobic power on a cycle ergometer, followed by a 10-km all-out time trial. Before and after each of these tasks, knee extensor neuromuscular function was investigated using maximal voluntary contractions (MVC) combined with electrical stimulations of the femoral nerve. MRCP was recorded during 60 knee extensions after each neuromuscular sequence. The exercise resulted in a significant decrease in the knee extensor MVC force after the 30-min exercise (-10 ± 8%) and the time trial (-21 ± 9%). The voluntary activation level (VAL; -6 ± 8 and -12 ± 10%), peak twitch (Pt; -21 ± 16 and -32 ± 17%), and paired stimuli (P100 Hz; -7 ± 11 and -12 ± 13%) were also significantly reduced after the 30-min exercise and the time trial. The first exercise was followed by a decrease in the MRCP, mainly above the mean activity measured at electrodes FC1-FC2, whereas the reduction observed after the time trial was related to the FC1-FC2 and C2 electrodes. After both exercises, the reduction in the late MRCP component above FC1-FC2 was significantly correlated with the reduction in P100 Hz (r = 0.61), and the reduction in the same component above C2 was significantly correlated with the reduction in VAL (r = 0.64). In conclusion, large-muscle group exercise induced a reduction in pre-motor potential, which was related to muscle alterations and resulted in the inability to produce a maximal voluntary contraction

Use of artificial intelligence in analytical systems for the clinical laboratory

The incorporation of information-processing technology into analytical systems in the form of standard computing software has recently been advanced by the introduction of artificial intelligence (AI), both as expert systems and as neural networks

A clone-free, single molecule map of the domestic cow (Bos taurus) genome.

BackgroundThe cattle (Bos taurus) genome was originally selected for sequencing due to its economic importance and unique biology as a model organism for understanding other ruminants, or mammals. Currently, there are two cattle genome sequence assemblies (UMD3.1 and Btau4.6) from groups using dissimilar assembly algorithms, which were complemented by genetic and physical map resources. However, past comparisons between these assemblies revealed substantial differences. Consequently, such discordances have engendered ambiguities when using reference sequence data, impacting genomic studies in cattle and motivating construction of a new optical map resource--BtOM1.0--to guide comparisons and improvements to the current sequence builds. Accordingly, our comprehensive comparisons of BtOM1.0 against the UMD3.1 and Btau4.6 sequence builds tabulate large-to-immediate scale discordances requiring mediation.ResultsThe optical map, BtOM1.0, spanning the B. taurus genome (Hereford breed, L1 Dominette 01449) was assembled from an optical map dataset consisting of 2,973,315 (439 X; raw dataset size before assembly) single molecule optical maps (Rmaps; 1 Rmap = 1 restriction mapped DNA molecule) generated by the Optical Mapping System. The BamHI map spans 2,575.30 Mb and comprises 78 optical contigs assembled by a combination of iterative (using the reference sequence: UMD3.1) and de novo assembly techniques. BtOM1.0 is a high-resolution physical map featuring an average restriction fragment size of 8.91 Kb. Comparisons of BtOM1.0 vs. UMD3.1, or Btau4.6, revealed that Btau4.6 presented far more discordances (7,463) vs. UMD3.1 (4,754). Overall, we found that Btau4.6 presented almost double the number of discordances than UMD3.1 across most of the 6 categories of sequence vs. map discrepancies, which are: COMPLEX (misassembly), DELs (extraneous sequences), INSs (missing sequences), ITs (Inverted/Translocated sequences), ECs (extra restriction cuts) and MCs (missing restriction cuts).ConclusionAlignments of UMD3.1 and Btau4.6 to BtOM1.0 reveal discordances commensurate with previous reports, and affirm the NCBI's current designation of UMD3.1 sequence assembly as the "reference assembly" and the Btau4.6 as the "alternate assembly." The cattle genome optical map, BtOM1.0, when used as a comprehensive and largely independent guide, will greatly assist improvements to existing sequence builds, and later serve as an accurate physical scaffold for studies concerning the comparative genomics of cattle breeds

Alterations of neuromuscular function after the world's most challenging mountain ultra-marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time = 122.43 hours \ub117.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean \ub1 SD maximal voluntary contraction force declined significantly at Mid- ( 1213\ub117% and 1210\ub116%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- ( 1224\ub113% and 1226\ub119%, P<0.01) with alteration of the central activation ratio ( 1224\ub124% and 1228\ub134% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: 1218\ub118% and PF: 1220\ub115%, P<0.01) and peak twitch (KE: 1233\ub112%, P<0.001 and PF: 1219\ub114%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719\ub13045 Ul\ub71), lactate dehydrogenase (1145\ub1511 UI\ub7L 121), C-Reactive Protein (13.1\ub17.5 mg\ub7L 121) and myoglobin (449.3\ub1338.2 \ub5g\ub7L 121) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half

Prospects for integrated soil fertility management using organic and inorganic inputs: evidence from smallholder African agricultural systems

This paper reviews current organic nutrient management practices and their integration with mineral fertilizers in Sub-Saharan Africa with a view to understanding the potential impacts on a range of input markets. A number of different organic nutrient management practices have been found to be technically and financially beneficial, but they differ considerably as to their effectiveness and resource requirements. A review of African smallholder experiences with integrated soil fertility management practices finds growing use, both indigenously and through participation in agricultural projects. Patterns of use vary considerably across heterogeneous agroecological conditions, communities and households, but are stimulated by profitable commercially oriented agricultural opportunities. The potential for integrated soil fertility management to expand markets for organic inputs, labor, credit, and fertilizer is explored. We found that there are few direct analyses of these links and indirect evidence at this point in time is inconclusiv