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Profiling stage-dependent changes of protein expression in Caenorhabditis elegans by mass spectrometric proteome analysis leads to the identification of stage-specific marker proteins.

Proteome maps obtained by synchronization of the wild-type Caenorhabditis elegans development reflected stage-dependent molecular differences and revealed dynamic cytoskeletal processes during ontogenesis. Distinct protein spots that may function as molecular markers for the corresponding developmental stages were mass spectrometrically identified. The amount of the Cu(2+)- Zn(2+) superoxide dismutase (CE23550) and an aspartyl proteinase (CE21681) was highest in the first larval stage (L1) and decreased during the ontogenesis from the first larval stage to the adult. Tropomyosin III (CE29059) was prominently present in the first and second larval stage (L1/L2). Abundances of actin 1 or 4 (CE12358 or CE13148) and tropomyosin I (CE28782) were particularly high in multiple spots in the third larval stage (L3). Interestingly, the amount of DIM-1 protein (CE27706), reflected by two spots, was the lowest in this stage. A particular splicing factor (CE31089) was detected only in the fourth larval stage (L4), whereas a spot with high abundance representing the cuticle collagen (CE02272) was only found highly expressed in adult animals (A). In addition, a Ca(2+)-binding protein (CE12368) and one protein spot which has not yet been identified, both reached their maximal spot intensities in the adult stage (A). Moreover, the ASP-1, CCT-5, GPD-1, GPD-2, HSP-6, HSP-16.2, IFB-2, LEC-2, LIN-53, LMN-1, MDH-1, NUD-1, RPA-0, RSP-12, SOD-1, TBB-1, TBB-2, TMY-1, UNC-60, and VIT-2 proteins for which mutants are available and two still unidentified protein spots which were present in all developmental stages, have been reproducibly localized in proteome maps of distinct ontogenesis states.

Animals↗

Prenatal evaluation of kidney function in mice using dynamic contrast-enhanced magnetic resonance imaging.

Glomerular differentiation starts as soon as embryonic stage 12 in mice and suggests that kidneys may be functional at this stage. Dynamic contrast-enhanced magnetic resonance microscopy, a noninvasive imaging technique, was used to assess renal function establishment in utero. Indeed, in adults (n = 3), an intravenous injection of gadolinium-DOTA induced in a first step a massive and rapid drop in kidney signal intensity followed, in a second step, by a drop in bladder signal intensity. The delay in signal changes between kidney and bladder reflected glomerular filtration. Pregnant mice underwent anatomical and dynamic contrast-enhanced magnetic resonance microscopy on postcoital days 12-13 (n = 2), 13-14 (n = 1), 14-15 (n = 3), 15-16 (n = 2), 16-17 (n = 3), 17-18 (n = 3), and 18-19 (n = 1). Kidneys and bladder were unambiguously depicted prior to contrast agent injection on stage 15-16 embryos. Contrast agent injection allowed kidney, detection as early as stage 12-13 but not bladder. Kinetics of signal changes demonstrated that glomerular filtration is established at embryonic stage 15-16 in mice. Thus, anatomical and dynamic contrast-enhanced magnetic resonance microscopy may be a powerful noninvasive method for in vivo prenatal developmental and functional studies.

Animals↗

Change pattern of somatosensory-evoked potentials after occlusion of segmental vessels: possible indicator for spinal cord ischemia.

Paraplegia was reported after occlusion of the segmental vessels during anterior spinal surgery. The aim of this study was to investigate the effect of occlusion of the segmental vessels on the somatosensory-evoked potential (SEP) monitoring and analyze its potential risk for cord ischemia. Thirty-one patients with thoracic scoliosis underwent anterior spinal surgery. T5-T11 segmental vessels on the convexity were occluded with microvascular clamps at the point 2 cm from the intravertebra foramen. The SEPs were recorded 5 min before occlusion and 2, 7, 12 and 17 min after occlusion. The SEPs were analyzed with two indices i.e. P40 latency and P40 amplitude. All SEP waveforms recorded during the test were regular and recognizable. Compared to 5 min before occlusion, the P40 latencies at 2 min and 7 min after occlusion significantly increased 3.39% and 2.76% on an average, the P40 amplitudes at 2 min after occlusion significantly declined 26% (peak to peak) or 22% (peak to baseline) on an average (P<0.05). But the changes of SEPs were temporary. The SEPs began to restore at 12 min after occlusion and returned to the pre-occlusion level at 17 min after occlusion. No neurologic complications occurred in all patients after surgery. These results suggest that SEP is a possible indicator for ischemia of the spinal cord which is a dynamic course and cannot be considered an "all-or-none" phenomenon. Without the factors such as developmental deformities of the spinal cord, vascular variation and potential cord ischemia, occlusion of the segmental vessels would be safe during the anterior spinal surgery.

Adolescent↗

Oscillations and waves of cyclic AMP in Dictyostelium: a prototype for spatio-temporal organization and pulsatile intercellular communication.

The amoebae Dictyostelium discoideum aggregate after starvation in a wavelike manner in response to periodic pulses of cyclic AMP (cAMP) secreted by cells which behave as aggregation centers. In addition to autonomous oscillations, the cAMP signaling system that controls aggregation is also capable of excitable behavior, which consists in the transient amplification of suprathreshold pulses of extracellular cAMP. Since the first theoretical model for slime mold aggregation proposed by Keller and Segel in 1970, many theoretical studies have addressed various aspects of the mechanism and function of cAMP signaling in Dictyostelium. This paper presents a brief overview of these developments as well as some reminiscences of the author's collaboration with Lee Segel in modeling the dynamics of cAMP relay and oscillations. Considered in turn are models for cAMP signaling in Dictyostelium, the developmental path followed by the cAMP signaling system after starvation, the frequency encoding of cAMP signals, and the origin of concentric or spiral waves of cAMP.

Animals↗

A profile of survival.

This article examines the extent to which a general understanding of an individual's reaction to extreme stress situations and patterns of coping can help in the understanding of personal and situational factors which are crucial for successful coping and survival of abused children. During a 14-year follow-up study, abused children who managed to survive the trauma of their childhood and grow up to be well-adjusted individuals were compared with a matched group of children who show, after 14 years, a high degree of psychosocial pathology. The variables which distinguished the two groups were fatalism, self-esteem, cognitive abilities, self-destructiveness, hope and fantasy, behavior patterns and external support. There were no significant differences between the groups as to difficulties in emotional expression in object relations and in their high degree of aggression. Lazarus' model of stress and coping was used to show the dynamics by which children utilize their personal and situational characteristics to survive and avoid future psychological and developmental damage. Implications of the findings for treatment and therapeutic assignments are indicated.

Achievement↗

Asymmetrization of first cleavage by transient disassembly of one spindle pole aster in the leech Helobdella robusta.

Unequal first cleavage is characteristic of a diverse group of protostome animals. In the nematode Caenorhabditis elegans, unequal first cleavage is achieved through the interaction of an apparently symmetric mitotic spindle apparatus with a clearly polarized cell cortex. In the clitellate annelid Tubifex tubifex, by contrast, the spindle is monastral and contains only one gamma-tubulin-reactive centrosome; this monastral spindle is inherently asymmetric throughout mitosis. Here, we have used immunostaining for beta- and gamma-tubulin to follow spindle dynamics during the unequal first cleavage in another clitellate annelid, the leech Helobdella robusta. We find that the mitotic spindle is diastral and symmetric through early metaphase, then becomes asymmetric following the transient down-regulation of one centrosome, as judged by gamma-tubulin immunofluorescence. Low levels of drugs that affect microtubule dynamics can symmetrize the first cleavage without affecting the gamma-tubulin dynamics. Our results provide a striking example of the evolvability of cellular mechanisms underlying an unambiguously homologous developmental process.

Animals↗

A dynamic match-line wedge.

PURPOSE: To implement match-line wedges at the abutting edges of x-ray fields using dynamic collimation. METHODS AND MATERIALS: Experiments were made using a computer-controlled linear accelerator equipped with developmental software that allows for collimator jaw motion while the beam is on. The jaws defining the abutting field edges were programmed to move from 1.5 cm inside to 1.5 cm outside the prescribed field during irradiation. Films were taken in plastic phantoms to assess the resulting edge gradient and to evaluate the sensitivity of this technique to setup errors. RESULTS: The measured edge gradient for a single field was 30% per cm. Parallel-opposed lateral fields produced a gradient of 28% per cm along their midline. A simulated central nervous system irradiation with cranial and spinal fields kept dose variations in the field-match region to less than 10% with setup errors of 3 mm. CONCLUSION: The use of collimator motion during irradiation is an effective and simple means of reducing the dose variation in a field-match region due to setup errors and system tolerances. Treatment time is not increased and labor savings can be achieved when compared to feathering techniques commonly used.

Humans↗

Epilepsy: habilitation and rehabilitation.

Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to a variety of chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. Epilepsy is an evolving disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood, adolescence, and adulthood. The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many aspects of the disease process and its sequelae. This makes neurologists uniquely qualified to manage the rehabilitation team. The impact of the therapeutic milieu on the recovery process may be as important as any specific medical or surgical intervention.

Child↗

Waxing and waning in concert: dynamic comorbidity of conduct disorder with other disruptive and emotional problems over 7 years among clinic-referred boys.

Six waves of structured diagnostic assessments were conducted of 168 clinic-referred 7- to 12-year-olds, over 7 years. Wave-to-wave changes in the number of conduct disorder (CD) behaviors were paralleled by correlated changes in the numbers of symptoms of oppositional defiant disorder (ODD), attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety. In addition, CD in Wave 1 predicted levels of ODD, ADHD, depression, and anxiety in later waves when initial levels of those symptoms were controlled, but only ODD in Wave 1 predicted CD in later waves when initial CD levels were controlled. These findings indicate a striking degree of dynamic comorbidity between CD and other types of psychopathology and provide an initial empirical framework for needed developmental models of comorbidity.

Affective Symptoms↗

HIV spectrum disorders and the family: selected interventions based on stylistic dimensions.

Curvilinear stylistic dimensions of the family, illness stages, individual developmental stages, and the life cycle stage of the family are discussed in relation to HIV spectrum disorders. Centripetal and centrifugal family styles are then used as a framework for presenting intervention strategies that allow the family to continue its developmental process, while working with the centripetal pull that having an AIDS member can exert on family dynamics.

Adaptation, Psychological↗

Variability in comprehension strategy use in children with SLI: a dynamical systems account.

The aim was to investigate the stability of comprehension strategy use in children with specific language impairment (SLI). According to principles of Dynamic Systems Theory, behaviour is both unstable and more easily affected by changes in external variables during developmental transitions. The study examined this prediction directly by comparing the comprehension strategy use of children with SLI in two different conditions. The subjects included 16 school-aged children with SLI (ages 6;8-8;5), and eight chronologically age-matched (CA) controls. One group of children with SLI (n = 8) was in a development transition between animacy and word-order comprehension strategy use, demonstrating the emerging use of word-order sentence comprehension strategies (SLI-T). The second group of children with SLI (n = 8) was not in a developmental transition (SLI-N), demonstrating the use of only animacy comprehension strategies characteristic of younger typically developing children. Children were asked to determine the agent in 54 sentences of the forms (NVN, NNV, VNN) with animacy of the noun as a second factor in each of two different conditions designed to vary external processing demands. Analysis of variance and maximum likelihood estimate analysis revealed that comprehension strategies for both groups of children with SLI differed qualitatively from CA controls. In particular, the findings revealed that comprehension strategy use in children with SLI was highly vulnerable to increases in external processing demands as compared with CA controls, suggesting that comprehension strategies in children with SLI are weakly represented regardless of the strategy they use. Findings from the study also illustrate the impact of intrinsic as well as extrinsic contextual factors on the stability and instability of language processing performance in children with SLI.

Case-Control Studies↗

NFkappaB in neurons? The uncertainty principle in neurobiology.

Nuclear factor kappaB (NFkappaB) is a dynamically modulated transcription factor with an extensive literature pertaining to widespread actions across species, cell types and developmental stages. Analysis of NFkappaB in a complex environment such as neural tissue suffers from a difficulty in simultaneously establishing both activity and location. Much of the available data indicate a profound recalcitrance of NFkappaB activation in neurons, as compared with most other cell types. Few studies to date have sought to distinguish between the various combinatorial dimers of NFkappaB family members. Recent research has illuminated the importance of these problems, as well as opportunities to move past them to the nuances manifest through variable activation pathways, subunit complexity and target sequence preferences.

Animals↗

Calcineurin and cardiac hypertrophy: where have we been? Where are we going?

The heart is a dynamic organ capable of adapting its size and architecture in response to alterations in workload associated with developmental maturation, physiological stimulation and pathological diseases. Such alterations in heart size typically result from the hypertrophic growth of individual myocytes, but not myocyte cellular proliferation. In recent years, a great deal of investigation has gone toward elucidating the molecular signalling machinery that underlies the hypertrophic response and manner in which increased cardiac load promotes alterations in gene expression. To this end, the Ca(2+)-calmodulin-activated phosphatase calcineurin has been proposed as a necessary component of the multi-pathway hypertrophy program in the heart. Despite initial controversy over this hypothesis due to disparate results from pharmacological inhibitory studies in animal models of hypertrophy, compelling data from genetic models with calcineurin inhibition now exist. This review will summarize many of these studies and will attempt to address a number of unanswered issues. In particular, specific downstream mediators of calcineurin signalling will be discussed, as well as the need to identify calcineurin's temporal activation profile, transcriptional targets and cross-communication with other reactive signalling pathways in the heart. Finally, we will present evidence suggesting that calcineurin, as a Ca(2+)-responsive enzyme, may function as an internal load sensor in cardiac myocytes, matching output demands to hypertrophic growth.

Animals↗

Radiological aspects of the vertebral components of osteochondrodysplasias.

Analysis of the individual components of the vertebrae permits the radiologist to identify and understand the fundamental physio-pathologic growth mechanisms affecting shape, size and architecture which operated during development. The achievement of this goal is facilitated by systematically paying attention to changes of the vertebral end-plates, anterior and posterior aspects of the vertebral body, the vertebral rim, neurocentral junction and interpedicular distance. The dynamic changes noted in follow-up studies of the spine in certain dysplasias may reveal the developmental history of the vertebral complex. The dimension of time is an important factor, which the radiologist has a unique opportunity to exploit. Vertebral configuration permits radiological analysis and diagnosis.

Adolescent↗

Developmental crisis in adolescents following severe head injury.

Severe head injury causes significant health and social problems. Among adolescents and young adults such trauma is particularly devastating in that developmental progress is halted and prolonged dependency engendered. It is important for social workers to understand the dynamics of this process in order to help such patients and their families cope with their long-term consequences. Common sequelae of severe head injury are outlined, and various approaches to intervention suggested.

Adult↗

Changes in the proportion and number of Pax(7+ve) and MF20(+ve) myoblasts during chick myogenesis in the head and limb.

Previous studies suggested that all myoblasts are present in the head and limb prior to the commencement of primary myotube formation. As a consequence, these myoblasts must be in various developmental states during myogenesis, i.e. proliferating, differentiating or terminally differentiated. There are few in vivo studies investigating dynamic quantitative changes of subgroups of these myoblasts during myogenesis. In this report, using anti-Pax7 and anti-myosin heavy chain antibodies, we examined the quantitative change of proliferating (Pax7(+ve)) and terminally differentiated (MF20(+ve)) myoblasts during primary and secondary myogenesis in the chick head and limb. Our results show that during primary myogenesis, less than 30% of myoblasts are in the proliferating phase, but as soon as secondary myogenesis begins, over 95% of myoblasts start to proliferate. Moreover, we have found that the proportion of terminally differentiated myoblasts is maintained at a low level (less than 3%) during primary and secondary myogenesis.

Animals↗

Use of monoclonal antibodies developed against chicken coccidia (Eimeria) to study invasion and development of Eimeria reichenowi in Florida sandhill cranes (Grus canadensis).

Eimeria gruis and Eimeria reichenowi are common coccidial parasites of a number of species of cranes. Until recently, little was known about either the site for invasion or the dynamics of early development of the crane coccidia because of the difficulty of identifying sporozoites and early developmental stages of these parasites by conventional staining methods. In the present study, monoclonal antibodies (MAbs) elicited against Eimeria spp. of chickens and turkeys were found to cross-react with sporozoites and developmental stages of E. reichenowi in the tissues of Florida sandhill cranes (Grus canadensis). With these Mabs, E. reichenowi sporozoites were found in specimens taken at 6 hr postinoculation (PI) from just proximal to Meckel's diverticulum in the jejunum to the ileocecal juncture. Fewer were found in the ceca and rectum and none in the duodenal loop. At 24 hr PI, there were markedly fewer sporozoites and their location had shifted to the duodenum. No stages were seen in intestinal cells at 5 days PI (DPI), but trophozoites had developed in the liver and spleen. At 10 DPI, sexual stages were detected in the intestine from the duodenal loop through Meckel's diverticulum but not in other organs. By 14 DPI, numerous developmental stages were detected in the intestine (ceca and jejunum), liver, and lungs but not in the heart, kidney, or brain. The number, location, and maturity of the stages in the ceca differed markedly from those in the jejunum.

Animals↗

Plasmodesmata: gateways for information transfer.

Intercellular communication in plants has evolved to occur via elongated cytoplasmic bridges, called plasmodesmata, that traverse the thick cell walls that surround plant cells. Historically, plasmodesmata have been assigned the mostly passive role of creating cytoplasmic continuity between plant cells enabling free transport of the wealth of small plant metabolites and growth hormones under 1 kDa. When it was discovered that plant viruses pirate plasmodesmata for movement of viral genomes during infection, it was proposed that viruses modified plasmodesmata for transport of very large molecules. Now, there is compelling evidence that plasmodesmata are inherently dynamic, rapidly altering their dimensions to increase their transport capabilities, upon contact with viral as well as developmentally important plant proteins. Further, the study of intercellular transport has prompted analyses of intracellular transport pathways, implicating the cytoskeleton as a major tracking system to plasmodesmata. Thus, plasmodesmata form a three-dimensional network of transportation channels and major checkpoints for information transfer. In the following, current knowledge about structure and function of these connective organelles, and about routing of molecules towards plasmodesmata, will be summarized.

Biological Transport↗