40 research outputs found
Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy
No full textBACKGROUND: Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1alpha, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. METHOD: Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by challenging the mice by denervation or ablation of synergistic muscles. RESULTS: Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy respo of muscles was based on the suppressed phosphorylation of PKB/Akt via feedback inhibition by mTORC1 and subsequent increased expression of the E3 ubiquitin ligases MuRF1 and atrogin-1/MAFbx. In contrast, expression of both E3 ligases was not increased in soleus muscle suggesting the presence of compensatory mechanisms in this muscle. CONCLUSIONS: Our study shows that the mTORC1- and the PKB/Akt-FoxO pathways are tightly interconnected and differentially regulated depending on the muscle type. These results indicate that long-term activation of the mTORC1 signaling axis is not a therapeutic option to promote muscle growth because of its strong feedback induction of the E3 ubiquitin ligases involved in protein degradation
Signatures of adaptation to plant parasitism in nematode genomes
No full textEach author is, or was, at the time of the work, a paid employee of their affiliated organization. The James Hutton Institute receives funding from the Scottish Government. TK is funded by JSPS KAKENHI Grant Numbers 20353659 and 23248024 Date of Acceptance: 27/11/2013Plant-parasitic nematodes cause considerable damage to global agriculture. The ability to parasitize plants is a derived character that appears to have independently emerged several times in the phylum Nematoda. Morphological convergence to feeding style has been observed, but whether this is emergent from molecular convergence is less obvious. To address this, we assess whether genomic signatures can be associated with plant parasitism by nematodes. In this review, we report genomic features and characteristics that appear to be common in plant-parasitic nematodes while absent or rare in animal parasites, predators or free-living species. Candidate horizontal acquisitions of parasitism genes have systematically been found in all plant-parasitic species investigated at the sequence level. Presence of peptides that mimic plant hormones also appears to be a trait of plant-parasitic species. Annotations of the few genomes of plant-parasitic nematodes available to date have revealed a set of apparently species-specific genes on every occasion. Effector genes, important for parasitism are frequently found among those species-specific genes, indicating poor overlap. Overall, nematodes appear to have developed convergent genomic solutions to adapt to plant parasitism.Peer reviewe
Recommended from our members
Homeodomain Transcription Factor Pitx2 is Required for Muscle Maintenance and Energy Homeostasis
No full textSkeletal muscle, the largest organ in the body in mass, is composed by 600 specialized muscles in humans with unique biochemical, physiological and metabolic identities. Skeletal muscles control body movement, locomotion, and nutrient balance. Muscle formation requires precisely orchestrated environmental signals and regulatory gene networks in time and space. Gene perturbations result in myopathies and systemic metabolic diseases. Pitx2, a homeobox gene, is expressed in muscle anlagen, specifies craniofacial and abdominal muscles and regulates skeletal muscle higher order assembly. Null Pitx2 mutant mice die at embryonic day 10-14 due to multiple organ arrest. To investigate the cellular and molecular functions of Pitx2 in skeletal muscles, we generated a mouse model in which, Pitx2 was selectively disrupted in fetal/neonatal myofibers under the influence of the muscle creatine kinase (Mck) driver (Pitx2MCK). Muscle function and energy production were defective in Pitx2MCK mice. Oxidative fibers were distorted, the Foxo3-dependent mitophagy pathway was activated and the contractile apparatus was compromised followed by glucose and lipid exhaustion. The catabolic state of the skeletal muscle resulted in systemic metabolic dysfunction, insulin sensitivity, cirrhotic liver, bone loss, increased white adipocytes and morbid obesity, all characteristics of the Metabolic Syndrome. Our findings establish Pitx2 as a novel player of muscle integrity and energy homeostasis
Reaction time and intelligence:Comparing associations based on two response modes
No full textPeople who score highly on intelligence tests also tend to have faster and less variable reaction times. Effect size estimates for the reaction time-intelligence association are larger in samples that are more representative of the population. However, such samples have often been tested on a reaction time device that requires reading a number and processing its association with a specific response location (Cox, Huppert, & Whichelow, 1993). Here, we use this device and another reaction time device (Dykiert et al., 2010) that is similar, except that the responses require less processing; subjects simply press a button that is adjacent to the stimulus light. We focus on the possibility that lights as stimuli require less higher-order cognitive engagement than numbers, and then test whether parameters from these two tasks are highly correlated and similarly associated with age and higher cognitive abilities. Both tasks measured simple and choice reaction times and their intra-individual variation across trials. The parameters of the two tasks were very highly correlated and parameters from both tasks were similarly associated with age, social factors, and differences in higher cognitive abilities. The respective choice reaction time parameters from either task accounted for much of the age- and higher cognitive ability-associations of the other task's parameters. These findings are important in establishing that the effect sizes of higher cognitive ability associations with processing speed measures may be found when the processing demands are minimal.(C) 2013 Elsevier Inc. All rights reserved.</p
Pengaruh Program Pengembangan Infrastruktur Sosial Ekonomi Wilayah (PISEW) terhadap Pengembangan Wilayah di Kecamatan Naman Teran Kabupaten Karo
No full textKabupaten Karo in 2013 have PNPM Pisew fund of Rp 5.2 billion . This fund is used for Kawasan Strategis Kabupaten (KSK) of Rp 2 billion, and regular Rp.400 million for the eight districts in Kabupaten Karo. One of the goals of the PISEW program is to accelerate the economic development of a society based on local resources. The scope of activities includes small scale rural infrastructure development with the built infrastructure categories : a) Transport (roads, bridges, bridge ); b) Increased Agricultural production (ertiary); c) Marketing of agricultural (rural markets); d) Water Supply and Sanitation (Water Infrastructure, MCK ); e) Health (posyandu development, and rehabilitation of health centers puskesdes); and f) Education (rehabilitation of primary schools and secondary schools first, Provision meubeler).
The purpose of this study was to determine the effect of socio-economic infrastructure development program on regional development in the kecamatan Naman Teran, and perceptions about the work of social and economic infrastructure development in the kecamatan Naman Teran.
The population in this study was all the people residing in the district Naman Teran , amounting to 12 916 inhabitants. The number of samples obtained at 99.24 is rounded up to 100 people. The author uses the method of random sampling.
Based on the research results of the partial test can be seen that the public perception variables are variables that have the most significant effect is positive and the resulting t value of 3.892 with 0.000 sig. And based on the results obtained by the coefficient of determination of 0.418. This indicates that 41.8 % variable socio-economic infrastructure development program (X1) and perceptions (X2) explains their effects on the development of variable region (Y) in kecamatan Naman Teran, while another 58.2 % is a variable that is not examined .Kabupaten Karo untuk tahun 2013 memproleh dana PNPM Pisew sebesar Rp 5,2 miliar. Dana ini dipergunakan untuk Kawasan Strategis Kabupaten (KSK) sebesar Rp 2 miliar, dan reguler Rp.400 juta untuk delapan kecamatan yang ada di Kabupaten Karo. Salah satu tujuan dari program PISEW adalah mempercepat pembangunan ekonomi masyarakat yang berbasis sumberdaya lokal. Adapun lingkup kegiatan meliputi pembangunan infrastruktur skala kecil perdesaan dengan kategori infrastruktur yang dibangun: a) Transportasi (jalan, jembatan, titian); b) Peningkatan produksi Pertanian (irigasi tersier); c) Pemasaran hasil pertanian (pasar desa); d) Air Bersih dan sanitasi (Prasarana Air Bersih, MCK); e) Kesehatan (pembangunan posyandu, puskesdes dan rehabilitasi puskesmas); dan f) Pendidikan (rehabilitasi sekolah dasar dan sekolah menegah pertama, Penyediaan Meubeler).
Tujuan penelitian ini adalah untuk mengetahui pengaruh program pengembangan infrastruktur sosial ekonomi terhadap pengembangan wilayah di kecamatan Naman Teran, dan persepsi masyarakat mengenai hasil kerja pengembangan infrastruktur sosial ekonomi di kecamatan Naman Teran.
Populasi dalam penelitian ini adalah seluruh masyarakat yang berada di kecamatan Naman Teran yang berjumlah 12.916 jiwa. Jumlah sampel yang didapat sebesar 99,24 dibulatkan menjadi 100 orang. Penulis menggunakan metode sampel random sampling.
Berdasarkan hasil penelitian uji parsial dapat diketahui bahwa variabel persepsi masyarakat merupakan variabel yang memiliki pengaruh positif serta paling signifikan yaitu nilai thitung yang dihasilkan sebesar 3,892 dengan nilai sig 0,000. Dan berdasarkan hasil penelitian diperoleh nilai koefisien determinasi sebesar 0,418. Hal ini menunjukkan bahwa 41.8% variabel program pengembangan infrastruktur sosial ekonomi (X1) dan persepsi masyarakat (X2) menjelaskan pengaruhnya terhadap variabel pengembangan wilayah (Y) di kecamatan Naman Teran, sedangkan 58,2% merupakan variabel lain yang tidak diteliti.119 HalamanTesis Magiste
A conditional mouse model for the characterization of mTORC1 function in muscle and brain
No full textThe Ser/Thr kinase mammalian target of rapamycin (mTOR) regulates cell growth in
response to extracellular stimulation with growth factors and to intracellular factors
that sense the nutritional and the energy state of the cell. mTOR forms two distinct
multiprotein complexes, the rapamycin-sensitive mTOR complex 1 (mTORC1) and
mTORC2. Most characterized functions of mTOR are mediated by mTORC1.
However, direct investigation of the in vivo function in most tissues including brain
and muscle has been occluded by the early embryonic lethality of deficient mice for
all mTORC1 members. Here, I describe the generation and characterization of mice
that are deficient for raptor, an essential component of mTORC1, in skeletal muscle
fibers and the developing brain.
Analysis of the raptor-deficient brain reveals a general growth defect that evenly
affects the whole organ. A decrease in cell size and cell number underlies the
observed microcephaly. This is in accordance to earlier studies which assign to
mTORC1 a role as controller of cell size and cell cycle. Beside this, mTORC1
controls several more specific aspects of brain development. Glial differentiation is
disturbed and this is paralleled by a decrease of Stat3 activity, a member of the
Jak/Stat pathway that was previously involved in gliogenesis. Loss of the glial
network in the dentate gyrus likely causes malformations of the developing granule
cell layer. Furthermore, I describe an unexpected role of mTORC1 in the formation of
hippocampal and cortical layers.
Muscle-specific knockout (ko) mice develop a progressive muscle dystrophy and
show changes in muscle metabolism. Based on alterations in the activation state and
expression levels, we provide evidence that this phenotype is accounted for by
PGC1alpha as well as Akt/PKB.
In summary, this work provides evidence, that raptor is important for postnatal
survival both, in muscle and the brain. Beside the generalized changes in cell growth,
both ko models provide first evidence in vivo that mTORC1 regulates specific
aspects of metabolism and that it differentially affects both glial and neuronal
differentiation by affecting cell-specific pathways
Measurement of charm fragmentation fractions in photoproduction at HERA
No full textThe production of D^0, D^*+, D^+, D_s+ and Lambda_c^+ charm hadrons and their antiparticles in ep scattering at HERA has been studied with the ZEUS detector, using a total integrated luminosity of 372 pb^-1. The fractions of charm quarks hadronising into a particular charm hadron were derived. In addition, the ratio of neutral to charged D-meson production rates, the fraction of charged D mesons produced in a vector state, and the stangeness-suppression factor have been determined. The measurements have been performed in the photoproduction regime. The charm hadrons were reconstructed in the range of transverse momentum p_T >3.8 GeV and pseudorapidity |eta|<1.6. The charm fragmentation fractions are compared to previous results from HERA and from e+e-experiments. The data support the hypothesis that fragmentation is independent of the production process
