Isoprenoid Biosynthesis in Plasmodium falciparum

Malaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research

The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass

Although the canonical transforming growth factor β signaling pathway represses skeletal muscle growth and promotes muscle wasting, a role in muscle for the parallel bone morphogenetic protein (BMP) signaling pathway has not been defined. We report, for the first time, that the BMP pathway is a positive regulator of muscle mass. Increasing the expression of BMP7 or the activity of BMP receptors in muscles induced hypertrophy that was dependent on Smad1/5-mediated activation of mTOR signaling. In agreement, we observed that BMP signaling is augmented in models of muscle growth. Importantly, stimulation of BMP signaling is essential for conservation of muscle mass after disruption of the neuromuscular junction. Inhibiting the phosphorylation of Smad1/5 exacerbated denervation-induced muscle atrophy via an HDAC4-myogenin–dependent process, whereas increased BMP–Smad1/5 activity protected muscles from denervation-induced wasting. Our studies highlight a novel role for the BMP signaling pathway in promoting muscle growth and inhibiting muscle wasting, which may have significant implications for the development of therapeutics for neuromuscular disorders

Children Consuming Cassava as a Staple Food are at Risk for Inadequate Zinc, Iron, and Vitamin A Intake

Cassava contains little zinc, iron, and β-carotene, yet it is the primary staple crop of over 250 million Africans. This study used a 24-hour dietary recall to test the hypothesis that among healthy children aged 2–5 years in Nigeria and Kenya, cassava’s contribution to the childrens’ daily diets is inversely related to intakes of zinc, iron, and vitamin A. Dietary and demographic data and anthropometric measurements were collected from 449 Kenyan and 793 Nigerian children. Among Kenyan children 89% derived at least 25% of their dietary energy from cassava, while among the Nigerian children 31% derived at least 25% of energy from cassava. Spearman’s correlation coefficient between the fraction of dietary energy obtained from cassava and vitamin A intake was r = −0.15, P < 0.0001, zinc intake was r = −0.11, P < 0.0001 and iron intake was r = −0.36, P < 0.0001. In Kenya, 59% of children consumed adequate vitamin A, 22% iron, and 31% zinc. In Nigeria, 17% of children had adequate intake of vitamin A, 57% iron, and 41% zinc. Consumption of cassava is a risk factor for inadequate vitamin A, zinc and/or iron intake

Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria

<p>Abstract</p> <p>Background</p> <p>Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava.</p> <p>Methods</p> <p>A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity.</p> <p>Results</p> <p>The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake.</p> <p>Conclusions</p> <p>Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.</p

Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men

Short successive periods of muscle disuse, due to injury or illness, can contribute significantly to the loss of muscle mass with aging ( sarcopenia ). It has been suggested that increasing the protein content of the diet may be an effective dietary strategy to attenuate muscle disuse atrophy. We hypothesized that protein supplementation twice daily would preserve muscle mass during a short period of limb immobilization. Twenty-three healthy older ( 69 ± 1 y ) men were subjected to 5 d of one-legged knee immobilization by means of a full-leg cast with ( PRO group; n = 11 ) or without ( CON group; n = 12 ) administration of a dietary protein supplement ( 20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat ) twice daily. Two d prior to and immediately after the immobilization period, single-slice computed tomography scans of the quadriceps and single-leg 1 repetition maximum strength tests were performed to assess muscle cross-sectional area ( CSA ) and leg muscle strength, respectively. Additionally, muscle biopsies were collected to assess muscle fiber characteristics as well as mRNA and protein expression of selected genes. Immobilization decreased quadriceps’ CSAs by 1.5 ± 0.7% ( P < 0.05 ) and 2.0 ± 0.6% ( P < 0.05 ), and muscle strength by 8.3 ± 3.3% ( P < 0.05 ) and 9.3 ± 1.6% ( P < 0.05 ) in the CON and PRO groups, respectively, without differences between groups. Skeletal muscle myostatin, myogenin, and muscle RING-finger protein-1 ( MuRF1 ) mRNA expression increased following immobilization in both groups ( P < 0.05 ), whereas muscle atrophy F-box/atrogen-1 ( MAFBx ) mRNA expression increased in the PRO group only ( P < 0.05 ). In conclusion, dietary protein supplementation ( ∼20 g twice daily ) does not attenuate muscle loss during short-term muscle disuse in healthy older men. This trial was registered at clinicaltrials.gov as NCT01588808

Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men

Short successive periods of muscle disuse, due to injury or illness, can contribute significantly to the loss of muscle mass with aging (sarcopenia). It has been suggested that increasing the protein content of the diet may be an effective dietary strategy to attenuate muscle disuse atrophy. We hypothesized that protein supplementation twice daily would preserve muscle mass during a short period of limb immobilization. Twenty-three healthy older (69 +/- 1 y) men were subjected to 5 d of one-legged knee immobilization by means of a full-leg cast with (PRO group; n = 11) or without (CON group; n = 12) administration of a dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat) twice daily. Two d prior to and immediately after the immobilization period, single-slice computed tomography scans of the quadriceps and single-leg 1 repetition maximum strength tests were performed to assess muscle cross-sectional area (CSA) and leg muscle strength, respectively. Additionally, muscle biopsies were collected to assess muscle fiber characteristics as well as mRNA and protein expression of selected genes. Immobilization decreased quadriceps' CSAs by 1.5 +/- 0.7% (P <0.05) and 2.0 +/- 0.6% (P <0.05), and muscle strength by 8.3 +/- 3.3% (P <0.05) and 9.3 +/- 1.6% (P <0.05) in the CON and PRO groups, respectively, without differences between groups. Skeletal muscle myostatin, myogenin, and muscle RING-finger protein-1 (MuRF1) mRNA expression increased following immobilization in both groups (P <0.05), whereas muscle atrophy F-box/atrogen-1 (MAFBx) mRNA expression increased in the PRO group only (P <0.05). In conclusion, dietary protein supplementation (similar to 20 g twice daily) does not attenuate muscle loss during short-term muscle disuse in healthy older men. This trial was registered at clinicaltrials.gov as NCT01588808