The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional studies (...) in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis. (shrink)

Phagocytosis is an uptake of large particles governed by the actin-based cytoskeleton. Binding of particles to specific cell surface receptors is the first step of phagocytosis. In higher Eucaryota, the receptors able to mediate phagocytosis are expressed almost exclusively in macrophages, neutrophils, and monocytes, conferring immunodefence properties to these cells. Receptor clustering is thought to occur upon particle binding, that in turn generates a phagocytic signal. Several pathways of phagocytic signal transduction have been identified, including the activation of tyrosine kinases (...) and (or) serine/threonine kinase C in pivotal roles. Kinase activation leads to phosphorylation of the receptors and other proteins, recruited at the sites of phagocytosis. Monomeric GTPases of the Rho and ARF families are likely to be engaged downstream of activated receptors. The GTPases, in cooperation with phosphatidylinositol 4-phosphate 5-kinase and phosphatidylinositol 3-kinase lipid modifying enzymes, can modulate locally the assembly of the submembranous actin filament system leading to particle internalization. BioEssays 21:422–431, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

A partir de los desafíos pedagógicos que se diseñaron en los pilares educativos de este siglo a raíz del Informe Delors, planteamos el reto que debe asumir el educador en relación a los contextos de aprendizaje de valores a partir de propuestas dinámicas desde un entorno pragmático, teniendo en cuenta el aprendizaje de competencias que comprende el actual diseño educativo. Enmarcamos esta propuesta pedagógica como desafío al que se enfrentan los educadores al hacer frente a la formación social de la (...) ciudadanía en relación al manejo de los conflictos como propuesta axiológica para el desarrollo de competencias axiológicas en la ciudadanía. Por ello proponemos algunos recursos pedagógicos desde la dimensión moral, desde la educación en valores, sobre los que construir una conjunción armónica de las identidades y de las diferencias en nuestras sociedades plurales y de inicios de este siglo.From the pedagogical challenges that were designed in the educational pillars of this century following the Delors Report, we posed the challenge to be assumed by the teacher in relation to the contexts of learning values from dynamic proposals from a pragmatic environment, taking into consideration the learning of skills that includes the current educational design. We frame this as a pedagogical challenge that educators face in dealing with the social formation of citizens in relation to conflict management as a proposal for developing axiological skills in citizenship. We, therefor propose some educational resources from the moral dimension, from education on values, on which to build a harmonious conjunction of identities and differences in our diverse societies and the beginning of this century. (shrink)

Researching for the sources of the Ars geomantiae – the oldest divinatory handbook of Western geomancy, translated from Arabic into Latin by Hugo of Santalla in 12th-century northern Spain – led to a double outcome: on the one hand, it showed the nature of Hugo’s cultural competence, imbued with the texts and scientific knowledge of his time; on the other hand, it revealed a series of historico-philosophical and philological data relating to the appearance of his version. In particular, the analysis (...) of the three explicit sources of the Sayings attributed to Socrates, of the Centiloquium of pseudo-Ptolemy and of the Isagoge ad Techne Galieni of Iohannitius has allowed not only to give a direct insight into the fundamental contribution of Arabic culture in the 12th-century translation of scientific studies, but also to carry out a more certain clarification on the dating of the Ars geomantiae and its placement within the translating activity of the master of Santalla. Finally, the question of the hermeticity of the text, raised by the reference to Enoch, one of the three Hermes of Abu- Ma’šar’s legend, has specified to what extent the Ars geomantiae belongs to the Hermetic tradition. (shrink)

What role could have intrinsic motivation toward reading in an extraordinary situation like the recent confinement? This research examines the relationship between intrinsic reading motivation and reading habits in an adult population considering types of reading, gender, and distress generated by the coronavirus disease 2019 pandemic. Participants were 3,849 adults from Spain who were surveyed about their reading practices: before, during the first weeks, and after several weeks of confinement. Linear mixed effects models were used to analyze data. Results showed (...) a three-way interaction between reading frequency, IRM, and type of reading. Also, distress seems to pose a differential impact depending on the type of reading. The higher the IRM, the lesser the time devoted to study/work reading and the more to social and news reading. In this sense, IRM can function as a protective factor of reading behavior but only for leisure reading. Results support previous findings of the importance of consciously promoting this type of motivation in all individuals beyond educational contexts, since it seems to be positively related to well-being. Other results and implications are discussed. (shrink)

Rho GTPases are critically important and are centrally positioned regulators of the actomyosin cytoskeleton. By influencing the organization and architecture of the cytoskeleton, Rho proteins play prominent roles in many cellular processes including adhesion, migration, intra‐cellular transportation, and proliferation. The most important method of Rho GTPase regulation is via the GTPase cycle; however, post‐translational modifications (PTMs) also play critical roles in Rho protein regulation. Relative to other PTMs such as lipidation or phosphorylation that have been extensively characterized, protein (...) oxidation is a regulatory PTM that has been poorly studied. Protein oxidation primarily occurs from the reaction of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), with amino acid side chain thiols on cysteine (Cys) and methionine (Met) residues. The versatile redox modifications of cysteine residues exemplify their integral role in cell signalling processes. Here we review prominent members of the Rho GTPase family and discuss how lipidation, phosphorylation, and oxidation on conserved cysteine residues affects their regulation and function. (shrink)

The Rho GTPases—Rho, Rac and Cdc42—act as molecular switches, cycling between an active GTP‐bound state and an inactive GDP‐bound state, to regulate the actin cytoskeleton. It has recently become apparent that the Rho GTPases can be activated in subcellular zones that appear semi‐stable, yet are dynamically maintained. These Rho GTPase activity zones are associated with a variety of fundamental biological processes including symmetric and asymmetric cytokinesis and cellular wound repair. Here we review the basic features of Rho GTPase (...) activity zones, suggest that these zones represent a fundamental signaling mechanism, and discuss the implications of zone properties from the perspective of both their function and how they are likely to be controlled. BioEssays 28: 983–993, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Dynamin is a GTPase that regulates late events in clathrin‐coated vesicle formation. Our current working model suggests that dynamin is targeted to coated pits in its unoccupied or GDP‐bound form, where it is initially distributed uniformly throughout the clathrin lattice. GTP/GDP exchange triggers its release from these sites and its assembly into short helices that encircle the necks of invaginated coated pits like a collar. GTP hydrolysis, which is required for vesicle detachment, presumably induces a concerted conformation change, tightening (...) the collar. Unlike most of its GTPase cousins that serve as molecular switches, dynamin has a low affinity for GTP, a very high intrinsic rate of GTP hydrolysis and functions as a homo‐oligomer. A concerted conformational change resulting from coordinated GTP hydrolysis by the dynamin oligomer might be sufficient to generate force. In this case, dynamin would be the first GTPase identified that acts as a structural protein with mechano‐chemical function. (shrink)

The origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras‐family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during eukaryote evolution had secretory, (...) and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented. BioEssays 25:1129–1138, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Rho proteins belong to the small GTPases superfamily. They function as molecular switches that, in response to diverse stimuli, control key signaling and structural aspects of the cell. Although early studies proposed a role for Rho GTPases in cellular transformation, this effect was underestimated due to the fact that no genetic mutations affecting Rho‐encoding genes were found in tumors. Recently, it has become evident that Rho GTPases participate in the carcinogenic process by either overexpression of some of the members of (...) the family with oncogenic activity, downmodulation of other members with suggested tumor suppressor activity, or by alteration of upstream modulators or downstream effectors. Thus, alteration of the levels of expression of different members of the family of Rho GTPases has been detected in many types of human tumors leading to a great interest in the cellular effects elicited by these oncoproteins. This essay reviews the current evidence of dysregulation of Rho signaling by overexpression in human tumors. BioEssays 27:602–613, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Ran is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras‐like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in both its (...) nuclear localization, and its lack of sites required for post‐translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions. (shrink)

Rho, a member of the Ras superfamily of small GTPases, has multiple biological roles: it regulates signal trasduction pathways linking extracellular growth factors to the assembly of actin stress fibres and focal adhesion complexes; it is required for G1 progression and activates the SRF transcription factor when quiescent fibroblasts are stimulated to grow; and it plays a role later in the cell cycle during cytokinesis. Two groups have recently succeeded in identifying downstream effectors of Rho that may mediate some of (...) these biological effects. One protein identified by both groups is protein kinase N (PKN), a serine/threonine kinase whose catalytic domain is closely related to that of protein kinase C(1,2). (shrink)

Spontaneous polarization without spatial cues, or symmetry breaking, is a fundamental problem of spatial organization in biological systems. This question has been extensively studied using yeast models, which revealed the central role of the small GTPase switch Cdc42. Active Cdc42‐GTP forms a coherent patch at the cell cortex, thought to result from amplification of a small initial stochastic inhomogeneity through positive feedback mechanisms, which induces cell polarization. Here, I review and discuss the mechanisms of Cdc42 activity self‐amplification and dynamic (...) turnover. A robust Cdc42 patch is formed through the combined effects of Cdc42 activity promoting its own activation and active Cdc42‐GTP displaying reduced membrane detachment and lateral diffusion compared to inactive Cdc42‐GDP. I argue the role of the actin cytoskeleton in symmetry breaking is not primarily to transport Cdc42 to the active site. Finally, negative feedback and competition mechanisms serve to control the number of polarization sites. (shrink)

Tumor progression involves the transition from normal to malignant cells, through a series of cumulative alterations. During this process, invasive and migratory properties are acquired, enabling cells to metastasize (reach and grow in tissues far from their origin). Numerous cellular changes take place during epithelial malignancy, and disruption of E‐cadherin based cell‐cell adhesion is a major event. The small Rho GTPases (Rho, Rac and Cdc42) have been implicated in multiple steps during cellular transformation, including alterations on the adhesion status of (...) the tumor cells. This review focuses on recent in vivo evidence that implicates RhoGTPases in epithelial tumor progression. In addition, we discuss different hypotheses to explain disruption of cadherin‐mediated cell–cell adhesion, directly or indirectly, through activation of Rho GTPases. Understanding the molecular mechanism of how cadherin adhesion and RhoGTPases interplay in normal cells and how this balance is altered during cellular transformation will provide clues as to how to interfere with tumor progression. © 2003 Wiley Periodicals, Inc. BioEssays 25:452–463, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Small GTPases in the Rho family act as major nodes with functions beyond cytoskeletal rearrangements shaping the Caenorhabditis elegans embryo during development. These small GTPases are key signal transducers that integrate diverse developmental signals to produce a coordinated response in the cell. In C. elegans, the best studied members of these highly conserved Rho family small GTPases, RHO‐1/RhoA, CED‐10/Rac, and CDC‐42, are crucial in several cellular processes dealing with cytoskeletal reorganization. In this review, we update the functions described for the (...) Rho family small GTPases in spindle orientation and cell division, engulfment, and cellular movements during C. elegans embryogenesis, focusing on the Rho subfamily Rac.Please also see the video abstract here. (shrink)

A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this process (...) remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole‐like structures of pathogens, thereby paving the way for the development of broadly effective anti‐microbial strategies for public health. (shrink)

RAS GTPases play essential roles in normal development and are direct drivers of human cancers. Three decades of study have failed to wholly characterize pathways stimulated by activated RAS, driven by engagement with ‘effector’ proteins that have RAS binding domains (RBDs). Bone fide effectors must bind directly to RAS GTPases in a nucleotide‐dependent manner, and this interaction must impart a clear change in effector activity. Despite this, for most proteins currently deemed effectors there is little mechanistic understanding of how binding (...) to the GTPase alters protein function. There has also been limited effort to comprehensively resolve the specificity of effector binding to the full array of RAS superfamily GTPase proteins. This review will summarize what is known about RAS‐driven activation for an array of potential effector proteins, focusing on structural and mechanistic effects and highlighting how little is still known regarding this key paradigm of cellular signal transduction. (shrink)

Two works: the first is a commentary on Book Lambda of Aristotle's Metaphysics; the second is a section of Avicenna's commentary on the so-called "Theology of Aristotle.

The highly homologous Rac1 and Rac2 GTPases are co‐expressed in cells of haematopoietic origin and are likely to show some functional redundancy. While disruption of the Rac2 gene in mice has provided insight into some of its functions, Rac1 null mice are embryonic lethal and only recently has conditional gene disruption been possible. Consequently, two articles1,2 have recently elucidated some overlapping and unique key roles of Rac1 and Rac2 in haematopoietic processes including specialized roles in innate and humoral immunity. BioEssays (...) 26:221–224, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Metastasis is one of the clinical parameters that has a strong negative influence on the prognosis of cancer patients. In recent years, significant advances have furthered our understanding of this process at the molecular and biological levels. This paper will discuss recent discoveries relating to the earliest, intra‐tumoral stages of metastasis in cancer cells, specifically focusing on: (i) the development of metastatic traits during primary tumorigenesis; (ii) intrinsic and extrinsic cancer cell programs associated with malignant traits; (iii) the intra‐tumoral migration (...) patterns of cancer cells and the dynamic roles played by the Rho/Rac GTPases and epithelial‐mesenchymal transitions in this process; and (iv) the genetic strategies used by metastatic cancer cells to promote intra‐tumoral cell migration and their subsequent escape to peripheral tissues. Finally, the therapeutic and diagnostic relevance of this information will be discussed, as well as potential future developments. (shrink)

The vav proto‐oncogene encodes a 95 kDa protein which is expressed exclusively in hematopoietic cells. Analysis of the deduced amino acid sequence has revealed the presence of a src‐homology 2 (SH2) domain, 2 SH3 domains, a cysteine‐rich region with similarity to protein kinase C, and a region highly similar to proteins with guanine nucleotide exchange activity on ras‐like GTPases. Recent work has shown that vav is tyrosine phosphorylated in response to stimulation of surface membrane receptors in a variety of hematopoietic (...) cell lines. Vav may play a role in hematopoietic cell signaling by coupling tyrosine kinase pathways to ras‐like GTPases through the regulation of guanine nucleotide exchange. (shrink)

إنَّ الخطاب الصوفي يتموقع في عرفان العقل العربي كأبرز الخطابات الروحية والفنية المؤثرة في الساحة الثقافية العربية، وهذا لما يمتلكه من شروط ومعايير خوَّلته أن يقتحم بمنجزه أسوار المشهد المعرفي الإنساني، من هذا المنطلق ستحاول هذه الدراسة الاقتراب من بعض قضاياه الضاربة في عمق هذا الخطاب، بوصفه يرسم العلاقة الحوارية بين اللغة الرمزية في بعدها المفهومي والمعرفي، المرتكزة على إمكانات الدلالة وإنتاج المعنى، وبين مفهوم المخيال الصوفي كبعد أنطولوجي/جمالي، يؤسِّس للعدسات التصوَّرية الملأى بالفضاءات الكاشفة والجامعة لمسارات إبداع المخيال الصوفي؛ المتجلية (...) أنوارُهُ وجودًا وشهودًا، والذي يشكّل في مجموعه بنية فاعلة في منظومة النسق العرفاني، ومحل إعراب هذا المخيال في إنتاج معنى منفتح يؤطر مفهوم العرفان الصوفي ويضبط إمكاناته المختلفة المنصهرة في بوتقةِ رؤيةٍ شاملة لمسارات الإبداع الروحي والنفسي للإنسان. إن بعض القضايا المطروحة في هذا الكتاب قد أسالت حبرا، وأثارت نقاشا لا يزال صداه إلى اليوم كـ " إشكالية الإنسان الكامل في الفكر الصوفي " و" جدل الحقيقة والشريعة في الفكر الصوفي " و" الرمزية الحرفية في الفكر الصوفي" خاصة عند محي الدين بن عربي، ومنها بعض القضايا التي حاولت تقديم رؤية فيها، انطلاقا من المعطى العرفاني الصوفي، كـ " الأبعاد العرفانية لخطاب الموت في الفكر الصوفي " و" عقلاء مجانين الصوفية بين خطاب الجنون وجنون الخطاب ". (shrink)

Rnd3/RhoE has two distinct functions, regulating the actin cytoskeleton and cell proliferation. This might explain why its expression is often altered in cancer and by multiple stimuli during development and disease. Rnd3 together with its relatives Rnd1 and Rnd2 are atypical members of the Rho GTPase family in that they do not hydrolyse GTP. Rnd3 and Rnd1 both antagonise RhoA/ROCK‐mediated actomyosin contractility, thereby regulating cell migration, smooth muscle contractility and neurite extension. In addition, Rnd3 has been shown to have (...) a separate role in inhibiting cell cycle progression by reducing translation of cell cycle regulators, including cyclin D1 and Myc. We propose that Rnd3 could act as a tumour suppressor to limit proliferation, but when mutations bypass this activity of Rnd3, it can promote cancer invasion through its effects in the actin cytoskeleton. (shrink)

Detecting and interpreting extracellular spatial signals is essential for cellular orientation within complex environments, such as during directed cell migration or growth in multicellular development. Although the molecular understanding of how cells read spatial signals like chemical gradients is still lacking, recent work has revealed that stochastic processes at different temporal and spatial scales are at the core of this gradient sensing process in a wide range of eukaryotes. Fast biochemical reactions like those underlying GTPase activity dynamics form a (...) functional module together with slower cell morphological changes driven by membrane remodelling. This biochemical‐morphological module explores the environment by stochastic local concentration sampling to determine the source of the gradient signal, enabling efficient signal detection and interpretation before polarised growth or migration towards the gradient source is initiated. Here we review recent data describing local sampling and propose a model of local fast and slow feedback counteracted by gradient‐dependent substrate limitation to be at the core of gradient sensing by local sampling. (shrink)

Toxoplasma gondii is a highly successful parasite capable of infecting virtually all warm-blooded animals by actively invading nucleated host cells and forming a modified compartment where it replicates within the cytosol. The parasite-containing vacuole provides a safe haven, even in professional phagocytes such as macrophages, which normally destroy foreign microbes. In an effort to eliminate the parasite, the host up-regulates a family of immunity-related p47 GTPases (IRGs), which are recruited to the parasite-containing vacuole, resulting in membrane rupture and digestion of (...) the parasite. To avoid this fate, highly virulent strains of Toxoplasma coat the external surface of their vacuole with a secretory serine/threonine kinase, known as ROP18. At this host-pathogen interface, ROP18 phosphorylates and inactivates IRGs, thereby protecting the parasite from killing. These findings reveal a novel molecular mechanism by which the parasite disarms host innate immunity. (shrink)

Both RalA and RalB interact with the ubiquitous calcium sensor, calmodulin (CaM). New structural and biophysical characterisation of these interactions strongly suggests that, in the native membrane‐associated state, only RalA can be extracted from the membrane by CaM and this non‐canonical interaction could underpin the divergent signalling roles of these closely related GTPases. The isoform specificity for RalA exhibited by CaM is hypothesised to contribute to the disparate signalling roles of RalA and RalB in mitochondrial dynamics. This would lead to (...) CaM shuttling RalA to the mitochondrial membrane but leaving RalB localisation unperturbed, and in doing so triggering mitochondrial fission pathways rather than mitophagy. (shrink)

Recently, Gao et al. and Chappie et al. elucidated the crystal structures of the polytetrameric stalk domain of the dynamin‐like virus resistance protein, MxA, and of the G‐domain dimer of the large, membrane‐deforming GTPase, dynamin, respectively. Combined, they provide a hypothetical oligomeric structure for the complete dynamin protein. Here, it is discussed how the oligomers are expected to form and how they participate in dynamin mediated vesicle fission during the process of endocytosis. The proposed oligomeric structure is compared with (...) the novel mechanochemical model of dynamin function recently proposed by Bashkirov et al. and Pucadyil and Schmid. In conclusion, the new model of the dynamin oligomer has the potential to explain how short self‐limiting fissogenic dynamin assemblies are formed and how concerted GTP hydrolysis is achieved. The oligomerisation of two other dynamin superfamily proteins, the guanylate binding proteins (GBPs) and the immunity‐related GTPases (IRGs), is addressed briefly. (shrink)

Transient receptor potential vanilloid 4 (TRPV4), a member of the TRP superfamily, is a broadly expressed, cell surface‐localized cation channel that is activated by a variety of environmental stimuli. Importantly, TRPV4 has been increasingly implicated in the regulation of cellular morphology. Here we propose that TRPV4 and the cytoskeletal remodeling small GTPase RhoA together constitute an environmentally sensitive signaling complex that contributes to pathological cell cytoskeletal alterations during neurological injury and disease. Supporting this hypothesis is our recent work demonstrating (...) direct physical and bidirectional functional interactions of TRPV4 with RhoA, which can lead to activation of RhoA and reorganization of the actin cytoskeleton. Furthermore, a confluence of evidence implicates TRPV4 and/or RhoA in pathological responses triggered by a range of acute neurological insults ranging from stroke to traumatic injury. While initiated by a variety of insults, TRPV4–RhoA signaling may represent a common pathway that disrupts axonal regeneration and blood–brain barrier integrity. These insights also suggest that TRPV4 inhibition may represent a safe, feasible, and precise therapeutic strategy for limiting pathological TRPV4–RhoA activation in a range of neurological diseases. (shrink)

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy‐related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple (...) regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. (shrink)

ABSTRACT This paper discusses keys to the moral procurement, treatment and disposition of remains used for scientific research, specifically those donated to the University of Tennessee’s Anthropological Research Facility (ARF). The ARF is an outdoor laboratory dedicated to better understanding the fate of human remains in forensic contexts, and focuses its research on decomposition, time since death estimates, body location and recovery techniques, and skeletal analysis. Historically, many donations were unclaimed bodies received from medical examiners (although it will be shown (...) that this trend is changing), and it has been argued that the use of unclaimed bodies for medical or scientific purposes is a violation of autonomy since no consent was given by the individual. It is argued here, however, that the domain of autonomous choice extends to one’s own corpse only insofar as expressed wishes are made known prior to one’s death, and that in the absence of expressed intent toward final disposition, it is acceptable for institutions to receive donations from medical examiners or family members. This paper also discusses other philosophical issues related to donation, consent and autonomy, and the forensic benefits of research conducted at the Anthropological Research Facility. (shrink)

Seed development in this paper has been classified into the three landmark stages of cell division, organ initiation and maturation, based on morphological changes, and the available literature. The entire process proceeds at the behest of an interplay of various specific and general transcription factors (TFs). Monocots and dicots utilize overlapping, as well as distinct, TF networks during the process of seed development. The known TFs in rice and Arabidopsis have been chronologically categorized into the three stages. The main regulators (...) of seed development contain B3 or HAP3 domains. These interact with bZIP and AP2 TFs. Other TFs that play an indispensable role during the process contain homeobox‐, NAC‐, MYB‐, or ARF‐domains. This paper is a comprehensive analysis of the TFs essential for seed development and their interactions. An understanding of this interplay will not only help unravel an integrated developmental process, but will also pave the way for biotechnological applications. (shrink)

Kitāb al-Mabādiʼ wa-al-ghāyāt fi-̄mā tataḍammanah ḥurūf al-muʻjam min al-ʻajāʼib al-āyāt -- Kitāb Mīm wa-al-wāw wa-al-nūn -- Kitāb al-Alif, wa-huwa kitāb al-aḥadīyah -- Kitāb al-bāʼ, wa-huwa Kitāb al-ḥaqāʼiq al-ilahīyah -- Risālat al-ḥarf wa-al-maʻná, wa-huwa tafhīm maʻānī al-ḥurūf -- Kitāb al-yāʼ, wa-huwa Kitāb al-hūw -- Risālat al-kalām fi ̄ḥurūf al-muʻjam wa-maʻānīhā -- Risālat al-ʻiqd al-manẓūm fī khawāṣṣ al-ḥurūf.

The proteins encoded by the ras proto‐oncogenes play critical roles in normal cellular growth, differentiation and development in addition to their potential for malignant transformation. Several proteins that are involved in the control of the activity of p21ras have now been characterised. p120GAP stimulates the GTPase activity of p21ras and hence acts as a negative regulator of ras proteins. It may be controlled by tyrosine phosphorylation or association with tyrosine phosphorylated proteins. The neurofibromatosis type 1 (NF 1) gene also (...) encodes a potential GTPase activating protein which is likely to be subject to a different control mechanism. Guanosine nucleotide exchange factors for p21ras have now been identified: these may be positive regulators of ras protein function. It appears that p21ras is subject to rapid regulation by several distinct mechanisms which are likely to vary in different cell types; the ras proteins are thereby able to act as very sensitive cellular monitors of the extracellular environment. (shrink)

This article examines Thai policy towards Malaysia and Myanmar in the post-Cold War period and argues that bilateral relations between Thailand and these countries have deteriorated considerably. The immediate reason for the change is the collapse of structural arrangements associated with the Cold War, in particular the Indochina Security Complex and domestic political developments in Thailand and Myanmar. Whereas a number of issues like illegal migration, fishing and insurgency have contributed to the deteriorated relations, the situation has been reasonably well (...) managed. Factors contributing to the stability of the situation include regular bilateral dialogue and exchanges as well as common membership in a number of multilateral fora like ASEAN, ARF, AFTA and APEC. (shrink)

The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF‐G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states of (...) translocation are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF‐G and GTP hydrolysis. EF‐G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. (shrink)

Auxin is a key regulator of plant developmental processes. Its effects on transcription are mediated by the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. ARFs tightly control specific auxin responses necessary for proper plant growth and development. Recent research has revealed that regulated ARF protein accumulation and ARF nucleo‐cytoplasmic partitioning can determine auxin transcriptional outputs. In this review, we explore these recent findings and consider the potential for regulated ARF accumulation in driving auxin responses in plants.

Cellular mechanisms whereby quiescent stem cells sense tissue injury and transition to an activated state are largely unknown. Quiescent skeletal muscle stem cells (MuSCs, also called satellite cells) have elaborate, heterogeneous projections that rapidly retract in response to muscle injury. They may therefore act as direct sensors of their niche environment. Retraction is driven by a Rac‐to‐Rho GTPase activity switch that promotes downstream MuSC activation events. These and other observations lead to several hypotheses: (1) projections are morphologically dynamic at (...) quiescence, providing a surveillance function for muscle damage; (2) quiescent projection dynamics are regulated by the relative balance of Rac and Rho activities promoted by niche‐derived cues; (3) projections, particularly their associated filopodia, sense tissue damage via changes to the biomechanical properties of the niche and/or detection of signaling cues released by damaged myofibers; and (4) the dynamic nature of projections results in a population of MuSCs with heterogeneous functional properties. These concepts may extend to other types of quiescent stem cells, as well as prove useful in translational research settings. (shrink)

Intercellular signaling by growth factors, hormones and neurotransmitters produces second messenger molecules such as cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG). Protein Kinase A and Protein Kinase C are the principal effector proteins of these prototypical second messengers in certain cell types. Recently, novel receptors for cAMP and DAG have been identified. These proteins, designated EPAC (Exchange Protein directly Activated by cAMP) or cAMP‐GEF (cAMP regulated Guanine nucleotide Exchange Factor) and CalDAG‐GEF (Calcium and Diacylglycerol regulated Guanine nucleotide Exchange Factor) or (...) RasGRP (Ras Guanine nucleotide Releasing Protein) are able to mediate some of the physiologic effects of the second messengers in a protein‐kinase‐independent fashion. These proteins are exchange factors for Ras family GTPases that operate in pathways that run parallel to the classic kinase‐dependent pathways. The rapidly emerging recognition of the functions of these “non‐kinase” effectors in diverse processes such as insulin secretion, thymocyte development, asthma and malignant transformation creates new opportunities for discovery and identifies potential new therapeutic targets. BioEssays 26:730–738, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is integrated (...) into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

There are many morphologically distinct membrane structures with different functions at the surface of epithelial cells. Among these, adherens junctions (AJ) and tight junctions (TJ) are responsible for the mechanical linkage of epithelial cells and epithelial barrier function, respectively. In the process of new cell–cell adhesion formation between two epithelial cells, such as after wounding, AJ form first and then TJ form on the apical side of AJ. This process is very complicated because AJ formation triggers drastic changes in the (...) organization of actin cytoskeleton, the activity of Rho family of small GTPases, and the lipid composition of the plasma membrane, all of which are required for subsequent TJ formation. In this review, the authors focus on the relationship between AJ and TJ as a representative example of specialization of plasma membrane regions and introduce recent findings on how AJ formation promotes the subsequent formation of TJ. (shrink)