Substantial Advances (substantial + advance)

Distribution by Scientific Domains


Selected Abstracts


Flexible control of plant architecture and yield via switchable expression of Arabidopsis gai

PLANT BIOTECHNOLOGY JOURNAL, Issue 5 2003
Tahar Ait-ali
Summary The growth of plants is repressed by DELLA proteins, nuclear regulators whose activities are opposed by the growth-promoting phytohormone gibberellin (GA). Mutations affecting DELLA protein function were previously used by plant breeders to create the high-yielding semidwarf wheat varieties of the green revolution. gai is an Arabidopsis mutant DELLA protein-encoding orthologue of the wheat semidwarfing genes. Here we describe the development of a transgene that confers ethanol-inducible gai expression. Transient induction of gai causes transient growth repression: growth prior to and after treatment is unaffected. Appropriate ethanol treatments result in dwarf plants that produce the same numbers of seeds as untreated controls. This new technology represents a substantial advance in the applicability of genes encoding mutant DELLA proteins to agricultural and horticultural improvement, enhancing the flexibity with which these genes can be used for the sustainable achievement of increased crop plant yields. [source]


Genoarchitectonic profile of developing nuclear groups in the chicken pretectum

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2009
J.L. Ferran
Abstract Earlier results on molecularly coded progenitor domains in the chicken pretectum revealed an anteroposterior subdivision of the pretectum in precommissural (PcP), juxtacommissural (JcP), and commissural (CoP) histogenetic areas, each specified differentially (Ferran et al. [2007] J Comp Neurol 505:379,403). Here we examined the nuclei derived from these areas with regard to characteristic gene expression patterns and gradual histogenesis (eventually, migration patterns). We sought a genoarchitectonic schema of the avian pretectum within the prosomeric model of the vertebrate forebrain (Puelles and Rubenstein [2003] Trends Neurosci 26:469,476; Puelles et al. [2007] San Diego: Academic Press). Transcription-factor gene markers were used to selectively map derivatives of the three pretectal histogenetic domains: Pax7 and Pax6 (CoP); FoxP1 and Six3 (JcP); and FoxP2, Ebf1, and Bhlhb4 (PcP). The combination of this genoarchitectonic information with additional data on Lim1, Tal2, and Nbea mRNA expression and other chemoarchitectonic results allowed unambiguous characterization of some 30 pretectal nuclei. Apart from grouping them as derivatives of the three early anteroposterior domains, we also assigned them to postulated dorsoventral subdomains (Ferran et al. [2007]). Several previously unknown neuronal populations were detected, thus expanding the list of pretectal structures, and we corrected some apparently confused concepts in the earlier literature. The composite gene expression map represents a substantial advance in anatomical and embryological knowledge of the avian pretectum. Many nuclear primordia can be recognized long before the mature differentiated state of the pretectum is achieved. This study provides fundamental notions for ultimate scientific study of the specification and regionalization processes building up this brain area, both in birds and other vertebrates. J. Comp. Neurol. 517:405,451, 2009. © 2009 Wiley-Liss, Inc. [source]


CT analysis after distraction osteogenesis in Pierre Robin Sequence

THE LARYNGOSCOPE, Issue 2 2009
Saswata Roy MD
Abstract Objectives/Hypothesis: Early mandibular lengthening by distraction osteogenesis provides an alternative to traditional methods of airway management in infants with Pierre Robin sequence (PRS). Little evidence in the medical literature quantitatively demonstrates the changes in skeletal, soft tissue, and hypopharyngeal spaces with mandibular distraction. Study Design: Prospective analysis of a cohort of three patients with PRS. Methods: We reviewed a series of infants with PRS and severe upper airway obstruction who underwent mandibular distraction. The infants underwent mandibular lengthening with the same internal, unidirectional distraction osteogenesis device. Standardized serial computed tomography (CT) scans were obtained according to established protocol. Computed tomography data were extracted and analyzed with medical image analysis software for mandibulo-maxillary arch harmony, symmetry, hypopharyngeal airway volume, geniohyoid distance, distraction osteogenesis bone volume, and mandibular length. Results: Mandibulo-maxillary alveolar ridge distances were corrected to 0.5 mm after distraction. Clinical examination showed good arch harmony without open-bite or cross-bite deformities. Mandibular ramus was lengthened by 19.5%; the body, 43.4%. After distraction, total mandibular length was increased by 26.2%; hypopharyngeal airway volume, 192%; posterior distance from pharyngeal wall to tongue base, 198.9%; and geniohyoid distance, 14.1%. Conclusions: Unidirectional internal microdistractors can achieve good mandibulo-maxillary arch harmony. Hypopharyngeal airway volume increases substantially, with an even greater increase in distance between tongue base and posterior pharyngeal wall. As the distal mandibular segment is distracted, the hyoid moves anteriorly, with minor increase in geniohyoid relationship. Internal mandibular microdistraction devices represent a substantial advance in airway obstruction management in infants with micrognathia. Laryngoscope, 2009 [source]


Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanisms

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2008
Mario Bermúdez de León
Abstract Myotonic dystrophy type 1 (DM1) is a dominant neuromuscular disorder caused by the expansion of trinucleotide CTG repeats in the 3,-untranslated region (3,-UTR) of the DMPK gene. Prominent features of classical DM1 are muscle wasting and myotonia, whereas mental retardation is distinctive for congenital DM1. The main nervous system symptoms of DM1 are cognitive impairment, neuroendocrine dysfunction, and personality and behavior abnormalities. It is thought that expansion of CTG repeats causes DM1 pathology through different molecular mechanisms; however, a growing body of evidence indicates that an RNA gain-of-function mechanism plays a major role in the disease development. At the skeletal muscle level, three main molecular events can be distinguished in this model: 1) formation of nuclear foci that are composed at least of mutant DMPK mRNA and recruited RNA-binding proteins, such as splicing regulators and transcription factors; 2) disturbance of alternative splicing of specific genes; and 3) impairment of cell differentiation. Contrasting with the substantial advances in understanding DM1 muscle pathology, the molecular basis of DM1 in the nervous system has just started to be revealed. This review focuses in the DM1 nervous system pathology and provides an overview of the genetic and molecular studies analyzing the effects of the DMPK gene CUG expanded repeats on cell function in neuronal systems. A comparison between the molecular mechanisms of DM1 in the skeletal muscle and those identified in DM1 nervous system models is provided. Finally, future directions in the study of DM1 in the nervous system are discussed. © 2007 Wiley-Liss, Inc. [source]


Major depression: emerging therapeutics

MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2008
Srijan Sen MD
Abstract The first effective antidepressants, monoamine oxidase inhibitors and tricyclic antidepressants, were identified 50 years ago, largely through serendipity. These medications were found to improve mood in a little more than half of depressed patients after a few weeks of chronic use. Almost all antidepressants prescribed today were developed through minor modifications of these original antidepressants and, like monoamine oxidase inhibitors and tricyclic antidepressants, act primarily through monoaminergic mechanisms. Although there have been improvements in side-effect profiles and overdose toxicity, these newer medications have not provided substantial advances in the efficacy and speed of the antidepressant effect for patients. Over the last 2 decades, our understanding of the neurobiology underlying depression has expanded exponentially. Given this expansion, we may be nearing an inflection point in antidepressant drug development, at which useful medicines will be designed through a rational understanding of the biological systems. In this review, we discuss the biological basis and preclinical and clinical evidence for a series of promising classes of antidepressants developed primarily out of a pathophysiologically informed approach. Mt Sinai J Med 75:203,224, 2008. © 2008 Mount Sinai School of Medicine [source]


Pain Processing: Paradoxes and Predictions

PAIN PRACTICE, Issue 1 2001
William J. Martin PhD
Abstract: During the last 25 years, there have been substantial advances in our understanding of the physiology and pathophysiology of pain. The development of animal models that more closely mimic clinical pain in humans has helped elucidate the putative mechanisms by which chronic pain develops and is maintained. However, our increased understanding of the neurobiology of pain has not translated into breakthrough treatments for pain management. As such, chronic pain is still primarily managed by drugs whose primary indication does not include pain (eg, antidepressants, anticonvulsants, antiarrhythmics, local anesthetics). These adjuvant analgesics have come into favor despite the fact that the mechanisms through which these drugs provide pain relief remain either largely unknown or are not selective for a single target. Moreover, the efficacy of adjuvant analgesics in animal models of pain is often validated only after case studies or clinical trials have been reported. This retrospective validation of "novel" analgesics in animal models of pain raises a question of the predictive validity of these models. This article reviews the use of several adjuvant and standard analgesics currently used to treat difficult-to-manage pain. What can these drugs teach us about the development of novel pain medicines? Within this context, the use of animal models of pain to predict analgesic efficacy in clinical pain conditions is considered. [source]


High resolution imaging of the knee on 3-Tesla MRI: A pictorial review

CLINICAL ANATOMY, Issue 5 2008
N. Griffin
Abstract The recent introduction of 3-Tesla MRI offers substantial advances in musculoskeletal applications. High resolution images can now be obtained with shorter data acquisition times. This article provides a pictorial review of 3-Tesla imaging in the knee with descriptions of both normal anatomy and the more common lesions involving the menisci, ligaments, and articular cartilage. A discussion of the issues associated with imaging at higher field strengths is also included. Clin. Anat. 21:374,382, 2008. © 2008 Wiley-Liss, Inc. [source]