Replacing prelinguistic behaviors with functional communication

This study evaluated the effectiveness of a teacher-implemented intervention package designed to replace prelinguistic behaviors with functional communication. Four young children with autism participated in a multiple-probe design across three communicative functions. Initially, three existing communication functions were selected for each child. Next, the existing prelinguistic behaviors that the children used to achieve these functions were identified. Replacement forms that were considered more recognizable and symbolic were defined to achieve these same functions. After a baseline phase, teachers received inservice training, consultation, and feedback on how to encourage, acknowledge, and respond to the replacement forms. During intervention, the replacement forms increased and prelinguistic behaviors decreased in most cases. The results suggested that the teacher-implemented intervention was effective in replacing prelinguistic behaviors with alternative forms of functional communication.

Rehabilitation outcomes for brain injured patients in Australia: functional status, length of stay and discharge destination

This study describes the rehabilitation length of stay (LOS), discharge destination and discharge functional status of 149 patients admitted with traumatic brain injury (TBI) to an Australian hospital over a 5-year period. Hospital charts of patients admitted between 1993-1998 were reviewed. Average LOS over the 5-year time period was 61.8 days and only decreased nominally over this time. Longer LOS was predicted by lower admission motor FIM scores and presence of comorbidities. Mean admission and discharge motor FIM scores were 58 and 79, which represented a gain of 21 points. Higher discharge motor FIM scores were predicted by higher admission motor FIM scores and younger age. FIM gain was predicted by cognitive status and age. Most patients, 88%, were discharged back to the community, with 30% changing their living setting or situation. Changing living status was predicted by living alone and having poorer functional status on admission.

Functional roles of abdominal and back muscles during isometric axial rotation of the trunk

Electromyographic (EMG) studies have shown that a large number of trunk muscles are recruited during axial rotation. The functional roles of these trunk muscles in axial rotation are multiple and have not been well investigated. In addition, there is no information on the coupling torque at different exertion levels during axial rotation. The aim of the study was to investigate the functional roles of rectus abdominis. external oblique. internal oblique, latissimus dorsi, iliocostalis lumborum and multifidus during isometric right and left axial rotation at 100%, 70%, 50% and 30% maximum voluntary contractions (MVC) in a standing position. The coupling torques in sagittal and coronal planes were measured during axial rotation to examine the coupling nature of torque at different levels of exertions. Results showed that the coupled sagittal torque switches from nil to flexion at maximum exertion of axial rotation. Generally, higher EMG activities were shown at higher exertion levels for all the trunk muscles. Significant differences in activity between the right and left axial rotation exertions were demonstrated in external oblique, internal oblique, latissimus dorsi and iliocostalis lumborum while no difference was shown in rectus abdominis and multifidus. These results demonstrated the different functional roles of trunk muscles during axial rotation. This is important considering that the abdominal and back muscles not only produce torque but also maintain the spinal posture and stability during axial rotation exertions. The changing coupling torque direction in the sagittal plane when submaximal to maximal exertions were compared may indicate the complex nature of the kinetic coupling of trunk muscles. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

Protein targeting to the plasma membrane of adult skeletal muscle fiber: An organized mosaic of functional domains

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta -dystroglycan, dystrophin, and caveolin-3, These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta -dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta -dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expressed domain-specific markers, We found that each marker protein was targeted to distinct microdomains, The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division. (C) 2001 Academic Press.

Functional heterogeneity within rhodamine123(lo) Hoechst33342(lo/sp) primitive hemopoietic stem cells revealed by pyronin Y

Objective. The aim of this study was to determine the function of primitive hematopoietic stem cells (PHSC) at phases G(0) and G(1) of the cell cycle. Materials and Methods. A combination of supravital dyes rhodamine123 (Rh), Hoechst33342 (Ho), and pyronin (PY) was used to isolate the G(0) and G(1) subsets of PHSC. A competitive repopulation assay was used to evaluate their in vivo function. Results. We confirmed that the Rh(lo)Lin(-)Kit(+)Sca-1(+) PHSC were relatively quiescent when compared with the more mature Rh(hi)Lin(-)Kit(+)Sca-1 HSC and Rh(hi)Lin(-)Kit(+)Sca-1(-) progenitors. In addition, cells with Rh(lo)Lin(-)Kit(+)Sca-1(+), Rh(lo)Ho(lo)Lin(-)Sca-1(+), or Rh(lo)Ho(sp)Lin(-)Sca-1(+) phenotypes identified the same cell population. We further subfractionated the Rh(lo)Ho(lo/sp)Lin(-)Sca-1(+) PHSC using PY into PYlo and PYhi subsets. Limiting dilution analysis revealed that the frequency of long-term in vivo competitive repopulating units (CRU) of the (PYRhHolo/sp)-Rh-lo-Ho-lo PHSC was 1 in 10 cells, whereas there was at least a three-fold lower frequency in those isolated at the G(1) phase (PYhi) We found a dose-dependent PY-mediated cytotoxicity that at moderate concentration affected most of the murine hematopoietic compartment but spared the early HSC compartment. Conclusion. Our data confirm that the HSC compartment is hierarchically ordered on the basis of quiescence and further extend this concept to PY-mediated cytotoxicity. PY supravital dye can be used to reveal functional heterogeneity within the (RhHolosp)-Ho-lo PHSC population but is of limited use in dissecting the relatively more mature hematopoietic stem/progenitor cell population. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.

Functional annotation of a full-length mouse cDNA collection

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Relationship between endosomes and lysosomes

Delivery of endocytosed macromolecules to lysosomes occurs by means of direct fusion of late endosomes with lysosomes. This has been formally demonstrated in a cell-free content mixing assay using late endosomes and lysosomes from rat liver. There is evidence from electron microscopy Studies that the same process occurs in intact cells. The fusion process results in the formation of hybrid organelles from which lysosomes are reformed. The discovery of the hybrid organelle has opened up three areas of investigation: (i) the mechanism of direct fusion of late endosomes and lysosomes, (ii) the mechanism of re-formation of lysosomes from the hybrid organelle, and (iii) the function of the hybrid organelle. Fusion has analogies with homotypic vacuole fusion in yeast. It requires syntaxin 7 as part of the functional trans-SNARE [SNAP receptor, where SNAP is soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein] complex and the release of lumenal calcium to achieve membrane fusion. Reformation of lysosomes from the hybrid organelle occurs by a maturation process involving condensation of lumenal content and probably removal of some membrane proteins by vesicular traffic. Lysosomes may thus be regarded as a type of secretory granule, storing acid hydrolases in between fusion events with late endosomes. The hybrid organelle is predicted to function as a 'cell stomach', acting as a major site of hydrolysis of endocytosed macromolecules.

Laminin 10/11: an alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration

We have investigated the expression and function of the isoforms of laminin bearing the alpha(5) chain, i.e. laminin-10/11 in neonatal and adult human skin. By immunostaining human skin derived from a variety of anatomic sites, we found that the laminin-alpha(5) chain is expressed abundantly in the basement membrane underlying the interfollicular epidermis and the blood vessels in the dermis. Interestingly, while the expression level of the well-studied laminin-5 isoform did not change significantly with age, laminin-10/11 (a5 chain) appeared to decrease in the basement membrane underlying the epidermis, in adult skin. In contrast, the levels of laminin-10/11 in the basement membrane underlying blood vessels remained unchanged in neonatal vs. adult skin. Importantly, in vitro cell adhesion assays demonstrated that laminin-10/11 is a potent adhesive substrate for both neonatal and adult keratinocytes and that this adhesion is mediated by the alpha(3)beta(1), and alpha(6)beta(4) integrins. Adhesion assays performed with fractionated basal keratinocytes showed that stem cells, transit amplifying cells and early differentiating cells all adhere to purified laminin-10/11 via these receptors. Further, laminin-10/11 provided a proliferative signal for neonatal foreskin keratinocytes, adult breast skin keratinocytes, and even a human papillomavirus type-18 transformed tumorigenic keratinocyte cell line in vitro. Finally, laminin-10/11 was shown to stimulate keratinocyte migration in an in vitro wound healing assay. These results provide strong evidence for a functional role for laminin-10/11 in epidermal proliferation during homeostasis, wound healing and neoplasia.

The number of long-lasting functional memory CD8(+) T cells generated depends on the nature of the initial nonspecific stimulation

The mechanism of generation of memory cytotoxic T cells (CTL) following immunization remains controversial. Using tumor protection and IFN-gamma ELISPOT assays in mice to detect functional CTL, we show that the initial effector CTL burst size after immunization is not directly related to the amount of functional memory CTL formed, suggesting that memory CTL are unlikely to arise stochastically from effector CTL. Induction of MHC class II-restricted T helper cells at the time of immunization by inclusion of a T helper peptide or protein in the immunogen, is necessary to generate memory CTL, although no T helper cell induction is required to generate effector CTL to a strong MHC class I-binding peptide. Host protective T cell memory correlates with the number of CTL epitope responsive IFN-gamma-secreting memory T cells as measured in an ELISPOT assay at the time of tumor challenge. We conclude that a different antigen presenting environment is required to induce long-lasting functional memory CTL, and non-cognate stimulation of the immune system is essential to allow generation of a long-lasting host protective memory CTL response.

Functional assessment tools for paediatric clients with Juvenile Chronic Arthritis: An update and review for occupational therapists

Juvenile chronic arthritis (JCA) is one cause of chronic illness and disability in childhood. Traditional clinical assessment of clients with JCA include objective measures of joint deformity, joint swelling, range of motion, duration of morning stiffness, pain, walking speed, running speed and muscle strength. In many instances, these traditional measures have little or no significance or relevance to paediatric clients and their parents whereas functional skills used in everyday living are more likely to be meaningful. Measures of physical, social, and psychological functioning ensure a comprehensive health assessment. Responsible occupational therapy assessment and management of paediatric clients diagnosed with JCA requires the use of reliable, valid and sensitive measures of function. Several instruments are now available which measure a child's or adolescent's functional abilities. In this paper, JCA and the impact of JCA on functional development are reviewed. As well, seven functional assessment tools designed for use with paediatric clients with JCA which occupational therapists can use in their clinical practice will be appraised. The various characteristics of these tools are discussed in order to assist practitioners and researchers in selecting the functional instrument which best meets their needs.

Carbene and nitrene rearrangements: A theoretical study of cyclic allenes and carbenes, carbodiimides, and azirines

B3LYP/6-31G(d) calculations of structures, energies, and infrared spectra of several rearrangement products of (hetero)aromatic nitrenes and carbenes are reported. 3-Isoquinolylnitrene 36 ring closes to the azirine 37 prior to ring expansion to the potentially stable but unobserved seven-membered-ring carbodiimide 38 and diazacycloheptatrienylidene C-s-39S. A new, stable cycloheptatrienylidene, C-s-19S, is located on the naphthylcarbene energy surface. 4-Quinolylnitrene undergoes reaction via the azirine 50 in solution, but ring expansion to the stable seven-membered-ring ketenimine 47 under Ar matrix photolysis conditions. There is excellent agreement between calculated infrared spectra of 1,5-diazacyclohepta-1,2,4,6-tetraene 54 (obtained by photolysis of 4-pyridyl azide), 1-azacyclohepta-1,2,4,6-tetraene 5, 1-azacyclohepta-1,3,5,6-tetraene 55, and 1-azacyclohepta-1,3,4,6-tetraene 56 and the available experimental data.

2-pyrazinylnitrene and 4-pyrimidylnitrene. Ring expansion to 1,3,5-triazacyclohepta-1,2,4,6-tetraene and ring opening to (2-isocyanovinyl)carbodiimide

Tetrazolo[1,5-a]pyrazine/2-azidopyrazine 9T/9A undergo photolysis in Ar matrix at cryogenic temperatures to yield 1,3,5-triazacyclohepta-1,2,4,6-tetraene 21 as the first observable intermediate, and 1-cyanoimidazole 11 and (2-isocyanovinyl)carbodiimide 22 as the final products. The latter tautomerizes to 2-(isocyanovinyl)cyanamide 23 on warming to 40 K. The same intermediate 21 and the same final products are obtained on matrix photolysis of the isomeric tetrazolo[1,5-c]pyrimidine/4-azidopyrimidine 24T/24A. These photolysis results as well as those of the previously reported thermal ring contraction of N-15-labeled 2-pyrazinyl- and 4-pyrimidylnitrenes to 1-cyanoimidazoles can all be rationalized in terms of selective ring opening of 21 or nitrine 10 to a nitrile ylide zwitterion 28 prior to formation of the final products, 11 and 22. The results are supported by high-level ab initio and DFT calculations (CASPT2-CASSCF(6,6), G3(MP2), and B3LYP/6-31+G*) of the energies and IR spectra of the intermediates and products.

Expert review of an approach to functional capacity evaluation

Functional capacity evaluation (FCE) is a widely used tool in work rehabilitation, despite the limited examination of the soundness of its measurement properties. This paper outlines the development of a new approach to FCE, the GAPP FCE, and reports on the findings of an expert review of aspects of its content validity and technical adequacy and how it meets established test criteria. Five expert occupational therapists reviewed the materials of the GAPP FCE then completed a questionnaire related to the content validity, technical adequacy and safety, reliability, validity, practicality and utility of the GAPP FCE. The experts gave support to most aspects of these criteria. The main issue identified by the review was related to interpretation and extrapolation of the FCE results for return to work. This and other issues are discussed in relation to recent developments in FCE and plans for future development of the GAPP FCE.

From molecular complexes to zwitterions and final products. Reactions between C3O2 and amines

The formation of molecular complexes (prereactive intermediates) between C3O2 and amines (ammonia, dimethylamine, trimethylamine, and 4-(dimethylamino)pyridine) as well as the subsequent transformation of the complexes into C3O2-amine zwitterions in cryogenic matrixes (ca. 40 K) has been observed. In the case of dimethylamine, the formation of tetramethylmalonamide has also been documented. Calculations using density functional theory (B3LYP/6-31G(2d, p)) are used to assign all above species and are in excellent agreement with the IR spectra.

Spatial structure and habitat variation in a grasshopper hybrid zone

A hybrid zone between the grasshoppers Chorthippus brunneus and C. jacobsi (Orthoptera: Acrididae) in northern Spain has been analyzed for variation in morphology and ecology. These species are readily distinguished by the number of stridulatory pegs on the hind femur. Both sexes are fully winged and inhabit disturbed habitats throughout the study area. We develop a maximum-likelihood approach to fitting a two-dimensional cline to geographical variation in quantitative traits and for estimating associations of population mean with local habitat. This method reveals a cline in peg number approximately 30 km south of the Picos de Europa Mountains that shows substantial deviations in population mean compared with the expectations of simple tension zone models. The inclusion of variation in local vegetation in the model explains a significant proportion of the residual variation in peg number, indicating that habitat-genotype associations contribute to the observed spatial pattern. However, this association is weak, and a number of populations continue to show strong deviations in mean even after habitat is included in the final model. These outliers may be the result of long-distance colonization of sites distant from the cline center or may be due to a patchy pattern of initial contact during postglacial expansion. As well as contrasting with the smooth hybrid zones described for Chorthippus parallelus, this situation also contrasts with the mosaic hybrid zones observed in Gryllus crickets and in parts of the hybrid zone between Bombina toad species, where habitat-genotype associations account for substantial amounts of among-site variation.