An Updated Review on Head and Neck Cancer Treatment with Radiation Therapy.

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

A Low-Cost, Open-Source, Compliant Hand for Enabling Sensorimotor Control for People with Transradial Amputations.

In this paper, we describe the design and implementation of a low-cost, open-source prosthetic hand that enables both motor control and sensory feedback for people with transradial amputations. We integrate electromyographic pattern recognition for motor control along with contact reflexes and sensory substitution to provide feedback to the user. Compliant joints allow for robustness to impacts. The entire hand can be built for around $550. This low cost makes research and development of sensorimotor prosthetic hands more accessible to researchers worldwide, while also being affordable for people with amputations in developing nations. We evaluate the sensorimotor capabilites of our hand with a subject with a transradial amputation. We show that using contact reflexes and sensory substitution, when compared to standard myoelectric prostheses that lack these features, improves grasping of delicate objects like an eggshell and a cup of water both with and without visual feedback. Our hand is easily integrated into standard sockets, facilitating long-term testing of sensorimotor capabilities.

The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice.

The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate that the activation of mTOR signaling is a viable target for therapies that are aimed at preventing muscle atrophy during periods of mechanical unloading.

The Arabidopsis AtRaptor genes are essential for post-embryonic plant growth.

BACKGROUND: Flowering plant development is wholly reliant on growth from meristems, which contain totipotent cells that give rise to all post-embryonic organs in the plant. Plants are uniquely able to alter their development throughout their lifespan through the generation of new organs in response to external signals. To identify genes that regulate meristem-based growth, we considered homologues of Raptor proteins, which regulate cell growth in response to nutrients in yeast and metazoans as part of a signaling complex with the target of rapamycin (TOR) kinase. RESULTS: We identified AtRaptor1A and AtRaptor1B, two loci predicted to encode Raptor proteins in Arabidopsis. Disruption of AtRaptor1B yields plants with a wide range of developmental defects: roots are thick and grow slowly, leaf initiation and bolting are delayed and the shoot inflorescence shows reduced apical dominance. AtRaptor1A AtRaptor1B double mutants show normal embryonic development but are unable to maintain post-embryonic meristem-driven growth. AtRaptor transcripts accumulate in dividing and expanding cells and tissues. CONCLUSION: The data implicate the TOR signaling pathway, a major regulator of cell growth in yeast and metazoans, in the maintenance of growth from the shoot apical meristem in plants. These results provide insights into the ways in which TOR/Raptor signaling has been adapted to regulate plant growth and development, and indicate that in plants, as in other eukaryotes, there is some Raptor-independent TOR activity.

The Arabidopsis Mei2 homologue AML1 binds AtRaptor1B, the plant homologue of a major regulator of eukaryotic cell growth.

BACKGROUND: TOR, the target of the antibiotic rapamycin in both yeast and mammalian cells, is a potent cell growth regulator in all eukaryotes. It acts through the phosphorylation of downstream effectors that are recruited to it by the binding partner Raptor. In Arabidopsis, Raptor activity is essential for postembryonic growth. Though comparative studies suggest potential downstream effectors, no Raptor binding partners have been described in plants. RESULTS: AtRaptor1B, a plant Raptor homologue, binds the AML1 (Arabidopsis Mei2-like 1) protein in a yeast two-hybrid assay. This interaction is mediated by the N-terminal 219 residues of AML1, and marks AML1 as a candidate AtTOR kinase substrate in plants. The AML1 N-terminus additionally carries transcriptional activation domain activity. Plants homozygous for insertion alleles at the AML1 locus, as well as plants homozygous for insertion alleles at all five loci in the AML gene family, bolt earlier than wild-type plants. CONCLUSION: AML1 interacts with AtRaptor1B, homologue of a protein that recruits substrates for phosphorylation by the major cell-growth regulator TOR. Identification of AML1 as a putative downstream effector of TOR gives valuable insights into the plant-specific mode of action of this critical growth regulator.

Diversification of genes encoding mei2 -like RNA binding proteins in plants.

A predominantly plant-based family of genes encoding RNA binding proteins is defined by the presence of a highly conserved RNA binding motif first described in the mei2 gene of the fission yeast Schizosaccharomyces pombe. In silico analyses reveal nine mei2 -like genes in Arabidopsis thaliana and six in Oryza sativa. These predicted genes group into four distinct clades, based on overall sequence similarity and subfamily-specific sequence elements. In situ analysis show that Arabidopsis genes from one of these clades, TEL1 and TEL2, are specifically expressed in central zone of the shoot apical meristem and the quiescent center of the root apical meristem, suggesting that they may somehow function to maintain indeterminacy in these tissues. By contrast, members of two sister clades, AML1 through AML5, are expressed more broadly, a trend that was confirmed by Q-PCR analysis. mei2 -like transcripts with similar sequences showed similar expression patterns, suggesting functional redundancy within the four clades. Phenotypic analyses of lines that contain T-DNA insertions to individual mei2 -like genes reveal no obvious phenotypes, further suggesting redundant activities for these gene products.