Search

Strategy pundits and practitioners alike have long focused on two main questions. First, what is strategy? In other words, what constitutes a legitimate statement of strategic direction? Second, how do [...]

The article discusses the advantage in the quality and performance of teams learned from observing and creating High Performing Teams (HPTs) over several decades. Topics include underappreciated cultural achievement that all high performing teams exhibit a shared language; and shared information ecosystem that will inevitably develop among team members study to design a new value proposition.

Before the event horizon, theuncertainty stems from the team's inability to predicthow the event horizon will change their ways ofworking. In my work with hundreds of teams at a diverserange of organizations, I have found that HighPerforming Teams are able to commit to a sharedtransformational journey. Event Horizons High-performing teams do not focus only on far-flungpotentials. [Extracted from the article]

ALTHOUGH I'M NOT PRIVY TO other builders' compensation programs, here at Holiday Builders we have restructured ours to provide financial rewards for enhanced performance. The higher up the organizational ladder […]

The head of organizational development at Stoke-on-Tent City Council talks about the importance of acknowledging and building on success. The strategy helped boost both morale and service delivery in the council. The council's appreciative inquiry intervention creates opportunity for change by identifying what is working in a system.

Niemann Pick disease type C1 (NPC1) is an inherited, autosomal recessive, lipid‐storage disorder with major neurological involvement. Purkinje cell death is a prominent feature of the neuropathology of NPC. We have investigated Purkinje cell death in two murine models of NPC1, BALB/c npcnihand C57BLKS/J spm. In both cases, extensive Purkinje cell death was found in the cerebellum. The pattern of Purkinje cell death is complex. First, zebrin II‐negative Purkinje cells disappear, to leave survivors aligned in stripes that closely resemble the pattern revealed by using zebrin II immunocytochemistry. Subsequently, as the disease progresses, additional Purkinje cells die. At the terminal stages of the disease, the surviving Purkinje cells are concentrated in lobules IX and X of the posterior lobe vermis. Purkinje cell degeneration is accompanied by the ectopic expression of tyrosine hydroxylase and the small heat shock protein HSP25, both associated preferentially with the surviving cells. The pattern of cell death thus reflects the fundamental compartmentation of the cerebellum into zones and stripes. J. Comp. Neurol. 456:279–291, 2003. © 2003 Wiley‐Liss, Inc.

The cytoarchitecture of the adult rabbit cerebellum is revealed by using zebrin II/aldolase c immunocytochemistry in both wholemount and sectioned material. Zebrin II is expressed by approximately half of the Purkinje cells of the cerebellar cortex. In most regions these form a symmetrical array of zebrin II‐positive and ‐negative parasagittal bands. Four transverse expression domains are identified in the vermis: (1) an anterior zone, comprising four narrow bands, one at the midline and three laterally to either side, extending throughout the anterior lobe to the primary fissure; (2) a central zone with broad immunoreactive bands separated by narrow zebrin II‐negative bands that disappear caudally to leave no apparent compartmentation; (3) a posterior zone with prominent alternating zebrin II‐positive and ‐negative bands; and (4) a nodular zone in which all Purkinje cells express zebrin II. In the hemispheres a striped topography is found in lobules HVI, HVII, and crus I, and all Purkinje cells are zebrin II+ in the flocculus and paraflocculus. Because of its importance for the classical conditioning of the eyeblink response, we made a detailed analysis of lobule HVI of the hemisphere. The immunocytochemical data show a complex substructure within HVI with three prominent zebrin II‐positive bands (probably homologous with P4a+, P4b+, and P5+ of rodents) separated by two zebrin II‐negative regions (P4− and P4b−). Thus, the organization of the rabbit cerebellum is consistent with the patterns described previously for rat, mouse, and opossum and suggests that there may be a common ground plan for the mammalian cerebellum. J. Comp. Neurol. 444:159–173, 2002. © 2002 Wiley‐Liss, Inc.

The adult mouse cerebellar vermis consists of four transverse zones, each of which is further subdivided into parasagittal stripes. In the adult weaver(wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is abnormal, consistent with the absence of a central zone (∼lobules VI/VII). Because the small, heat shock protein HSP25 is a constitutive marker of parasagittal bands of Purkinje cells in the caudal central zone and the nodular zone (∼lobules IX/X), we used HSP25 immunocytochemistry to show that the patterning abnormalities in wv/wvreflect selective Purkinje cell ectopia rather than the absence of the central zone. A specific HSP25‐immunopositive Purkinje cell ectopia within the central zone was identified. Symmetrical clusters of HSP25‐immunopositive Purkinje cells, which presumably would have formed the parasagittal stripes in the wild type, are present ectopically on either side of the midline in wv/wv. In contrast, in the nodular zone, HSP25‐immunopositive Purkinje cells form a near‐monolayer and are organized into parasagittal stripes. We therefore conclude that specific Purkinje cell clusters in the wv/wvcerebellum fail to disperse and that this ectopia contributes to the topographical abnormalities. J. Comp. Neurol. 439:151–161, 2001. © 2001 Wiley‐Liss, Inc.

Purkinje cells of different molecular phenotypes subdivide the cortex of the cerebellum both rostrocaudally into parasagittal bands and mediolaterally into transverse zones. Superimposed on the Purkinje cell compartmentation, the cerebellar cortex is pleated into a reproducible array of lobes and lobules. During cerebellar development, Purkinje cell bands are formed through the rostrocaudal dispersal of embryonic clusters, triggered primarily by a Reelin‐dependent signaling pathway. In the naturally occurring mouse mutant cerebellar deficient folia(cdf), there is a failure of Purkinje cell dispersion that results in widespread Purkinje cell ectopia in the adult. The ectopia is restricted primarily to that subset of Purkinje cells that does not express zebrin II/aldolase C and that forms ectopic clusters in among the cerebellar nuclei. Most Purkinje cells that express zebrin II are located normally in a monolayer. Thus, the cerebellum of cdfmutants has a failure of Purkinje cell dispersion that is confined primarily to a zebrin II‐negative (zebrin II−) subpopulation. Despite the Purkinje cell ectopia, the parasagittal band organization of the cerebellum is still clear. The shortening of the cortex is distributed evenly over all lobules, with the result that transverse expression boundaries are relocated with respect to the lobules and fissures. The number of Purkinje cells in the cdf/cdfcerebellum is similar to the number in littermate controls. Therefore, it appears that the lesion in cdfresults in the failure of a zebrin II−Purkinje cell subset to disperse either due to a cell intrinsic defect or due to an abnormal interaction between the Purkinje cells and either granule cells or afferent inputs. J. Comp. Neurol. 436:42–51, 2001. © 2001 Wiley‐Liss, Inc.

The dystrophin-associated protein complex (DPC) is required for the maintenance of muscle integrity during the mechanical stresses of contraction and relaxation. In addition to providing a membrane scaffold, members of the DPC such as the α-dystrobrevin protein family are thought to play an important role in intracellular signal transduction. To gain additional insights into the function of the DPC, we performed a yeast two-hybrid screen for dystrobrevin-interacting proteins. Here we describe the identification of a dysbindin, a novel dystrobrevin-binding protein. Dysbindin is an evolutionary conserved 40-kDa coiled-coil-containing protein that binds to α- and β-dystrobrevin in muscle and brain. Dystrophin and α-dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin co-localizes with α-dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum and hippocampus. These findings have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.

Immunohistochemistry and in situ hybridization have been used to survey constitutive heat shock protein (HSP)25 expression in the brain and spinal cord of the developing and adult mouse. The data reveal both transient and sustained patterns of expression and demonstrate robust differences between mice and rats. During development, HSP25 is transiently expressed in neurons of the inferior colliculus, various thalamic subnuclei, and the majority of Purkinje cells in the cerebellum. Sustained expression into adulthood is seen in neurons of the cranial nerve nuclei, spinal cord motoneurons, median preoptic nucleus, and a subset of Purkinje cells. Differences in HSP25 expression between adult rats and mice include the somatic motor nuclei innervating the extraocular muscles, which are HSP25 immunoreactive only in the rat. Similar differences in HSP25 expression are seen during the development of the inferior colliculus, thalamus, and cerebellum, where expression is restricted to mice. J. Comp. Neurol. 434:262–274, 2001. © 2001 Wiley‐Liss, Inc.

NeuroD2 is sufficient to induce cell cycle arrest and neurogenic differentiation in nonneuronal cells. To determine whether this bHLH transcription factor was necessary for normal brain development, we used homologous recombination to replace the neuroD2 coding region with a β-galactosidase reporter gene. The neuroD2 gene expressed the reporter in a subset of neurons in the central nervous system, including in neurons of the neocortex and hippocampus and cerebellum. NeuroD2−/−mice showed normal development until about day P14, when they began exhibiting ataxia and failure to thrive. Brain areas that expressed neuroD2 were smaller than normal and showed higher rates of apoptosis. Cerebella of neuroD2-null mice expressed reduced levels of genes encoding proteins that support cerebellar granule cell survival, including brain-derived neurotrophic factor (BDNF). Decreased levels of BDNF and higher rates of apoptosis in cerebellar granule cells of neuroD2−/−mice indicate that neuroD2 is necessary for the survival of specific populations of central nervous system neurons in addition to its known effects on cell cycle regulation and neuronal differentiation.

The small heat shock protein Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal stripes of Purkinje cells confined to the caudal central zone (∼lobules VI and VII), the nodular zone (∼ventral lobule IX and lobule X), and the paraflocculi/flocculi. During development several distinct phases in Hsp25 expression can be distinguished. Hsp25‐immunopositive Purkinje cells are first seen at birth, when four clusters are visible in the vermis of lobules IV/V, and scattered Hsp25‐immunoreactive Purkinje cells are seen in lobule VIII. By postnatal day 2/3, six narrow parasagittal stripes of Hsp25‐immunopositive Purkinje cells are seen in the vermis of the anterior lobe. In the posterior lobules, most Purkinje cells in the vermis of lobules VIII and IX express Hsp25. This initial limited expression is followed by a phase of widespread expression (postnatal days 6–9) in which Hsp25 immunoreactivity is detected in virtually all Purkinje cells. This global cerebellar expression of Hsp25 then gradually disappears, first in the anterior zone and the hemispheres and subsequently in the posterior zone, to leave the restricted adult expression pattern. Western blotting analysis and immunoprecipitation with anti‐Hsp25 suggest that all immunocytochemistry can be attributed the expression of Hsp25. Furthermore, visual deprivation had no effect on the development of Hsp25 expression in Purkinje cells, suggesting that visuomotor input is not responsible for the establishment of constitutive Hsp25 expression in the cerebellar cortex. J. Comp. Neurol. 429:7–21, 2001. © 2000 Wiley‐Liss, Inc.

Despite the reported absence of the 25‐kDa heat shock protein Hsp25 in the rodent cerebellum, we have determined that Hsp25 is constitutively expressed in a subset of Purkinje cells in the adult cerebellum of the mouse. No other cerebellar neurons are Hsp25 immunoreactive, but there is weak staining associated with blood vessels. In the vermis, Hsp25‐immunoreactive Purkinje cells are confined to two regions: one in lobules VI/VII, the other in lobules IX/X. In each region, only a subset of the Purkinje cells is immunoreactive. These cells are grouped in five parasagittal bands arranged symmetrically about the midline. The boundaries of these expression domains correspond to transverse zones previously inferred from other expression patterns. A third Hsp25‐immunopositive domain is seen in the paraflocculus and flocculus. Again, only a subset of Purkinje cells within the paraflocculus and flocculus express Hsp25, revealing three distinct bands. Previous descriptions of compartmentation antigens have not differentiated between adult populations of Purkinje cells in these regions, suggesting that Hsp25 is a novel compartmentation antigen in the adult cerebellum. J. Comp. Neurol. 416:383–397, 2000. © 2000 Wiley‐Liss, Inc.

The mouse cerebellar cortex is subdivided by an elaborate array of parasagittal and transverse boundaries. The relationship between these two orthogonal patterns of compartmentation is understood poorly. We have combined the use of adult and perinatal molecular markers of compartmentation—zebrin II, calbindin, and an L7/pcp‐2‐lacZtransgene—to resolve some of these issues. Our results indicate that the adult cerebellar vermis is divided along the rostrocaudal axis by three transverse boundaries: through the rostral face of lobule VI, in the caudal half of lobule VII, and across the posterolateral fissure between lobules IX and X. These three boundaries subdivide the vermis into four transverse zones: the anterior zone (lobules I–V), the central zone (lobules VI–VII), the posterior zone (lobules VIII–IX), and the nodular zone (lobule X). The same zones and boundaries also can be identified in the newborn cerebellum. The parasagittal organization is different in each zone: a unique combination of Purkinje cell phenotypes is found in each transverse zone both in the neonate and the adult, and different zones have distinct developmental time tables. Furthermore, the parasagittal bands of Purkinje cells revealed in the adult cerebellar cortex by using antizebrinII immunocytochemistry are discontinuous across the transverse boundaries. These data suggest that the transverse zones of the vermis form first during development and that parasagittal compartmentation develops independently in each transverse zone. J. Comp. Neurol. 412:95–111, 1999. © 1999 Wiley‐Liss, Inc.

A mouse homolog of the DrosophilaDisabled (dab) gene, disabled‐1(mdab1), encodes an adaptor molecule that functions in neural development. Targeted disruption of the mdab1 gene (mdab1–1mice) leads to anomalies in the development of the cerebrum, hippocampus, and cerebellum. Here we describe a number of histologic abnormalities in the cerebellum of the mdab1–1mouse. There is a complete absence of foliation, and most Purkinje cells are clumped in central clusters. However, lamination appears to develop normally in areas where the Purkinje cells and external granular layer are closely apposed. The granular layer forms a thin rind over most of the cerebellar surface, but is subdivided by both transverse and parasagittal boundaries. The Purkinje cells, identified by anti‐zebrin IIin the adult or anti‐calbindinin the new born mdab1–1mutant cerebellum, form a parasagittal banding pattern, similar to but distorted compared with the wild‐type design. The data suggest that the development of the mdab1–1cerebellum parallels the development of reeler. The reelergene encodes an extracellular protein (Reelin) that is secreted by the external granular layer. Because Reelin expression is retained in the mdab1–1mutant mouse, mDab1 p80 may act in a parallel pathway or downstream of Reelin, leading to the transformation of embryonic Purkinje cell clusters into the adult parasagittal bands. J. Comp. Neurol. 402:238–251, 1998. © 1998 Wiley‐Liss, Inc.

This article presents the Phase II results of an on going two-year study of teacher stress. The Phase I results were re ported in the De cember 1981 Bulletin.

The elucidation of the three-dimensional structure of now over 100 proteins provides the basis for describing the nature of interactions stabilizing native protein structure. To understand the forces responsible for maintaining the native structure, it is necessary to analyze the contributions of the specific forces like a hydrogen bond, a salt bridge or a hydrophobic interaction to the overall stability of a protein. Using mutant proteins carrying a single amino acid substitution, specific interactions in a protein can be altered and the effect can be studied. In this paper the results of such studies on stability variants of human haemoglobin and of T4 phage lysozyme are described.

Almost 57 percent of all teachers surveyed by these writers have seriously considered a career change. Other findings of their study are reported here.

Postnatal rats at 7 and 21 days of age were subjected to unilateral hypoxia—ischemia (H/I) by right carotid artery ligation followed by 1.5 to 2 hours of hypoxia (8% oxygen). Brains were frozen at specific intervals of recovery from 0 to 24 hours. Western blots of samples of right and left forebrain were immunodeveloped with a monoclonal antibody specific for ubiquitin, RHUb 1. An elevation of ubiquitin conjugate levels in the right compared with the left forebrain of 7-day-old animals was detectable immediately following H/I and increased by close to 60% of control level within 1 hour of recovery. The conjugate immunoreactivity remained at this level for 6 hours but had declined to control levels by 24 hours of recovery. No such increase was observed in response to hypoxia alone. Similar changes were observed in samples from the 21-day-old rat brain. However, the elevation of ubiquitin conjugate levels was of slower onset and persisted longer than observed for the 7-day-old animals. Immunocytochemical studies of brain fixed by immersion in formaldehyde/acetone/methanol showed that ubiquitin-like immunoreactivity was increased in the right, but not left, cerebral cortex and hippocampus of animals subjected to H/I. The data suggest that elevated ubiquitination may represent a neuroprotective response to H/I.

The mammalian cerebellum consists of parasagittal bands and transverse zones that are laid down early in development. When the adult cerebellum is immunostained for the Purkinje cell‐specific antigen zebrin II (i.e., aldolase C), compartmentation is reflected in alternating zebrin II+(P+) and zebrin II−bands (P−). The zebrin II phenotype is Purkinje cell autonomous; thus, disruptions in the zebrin pattern may reflect early problems in pattern formation. Zebrin II expression has been examined in the weaver(wv) mouse cerebellum. Both zebrin II+and zebrin II−Purkinje cells are present in the homozygous weaver(wv/wv) mouse, but they are not distributed normally. In the posterior vermis, although the zebrin II+bands are wider and multilaminate, the standard compartmentation is present. However, a large zebrin II+cell mass is absent from the central vermis, and analysis of the anterior lobe reveals several missing zebrin II+bands. The cytoarchitectonic defects in wvmice are not simply related to the Purkinje cell abnormalities. Instead, serial reconstruction reveals two transverse boundaries—one rostrally in lobule VI and the other caudally in lobule IX—that delineate cytoarchitectonic transverse zones important in cerebellar development. The abnormal zebrin expression pattern in wv/wvmice may be secondary to the deletion of a transverse zone. This is the first demonstration that Purkinje cell compartmentation can be altered by mutation; therefore, the wvmutation should prove valuable in understanding cerebellar regionalization. J. Comp. Neurol. 394:431–444, 1998. © 1998 Wiley‐Liss, Inc.

It is unclear whether reparative processes in the injured mammalian brain are able to restore the topographic organisation of neuronal connections. To address this question, we have investigated the plasticity of the olivocerebellar system. This pathway has a precise topographic arrangement, in which subsets of inferior olivary neurons project to parasagitally oriented Purkinje cell compartments. Following unilateral transection of the inferior cerebellar peduncle in newborn rats, axons from the contralateral projection cross the cerebellar midline and reinnervate the deafferented hemicerebellum. By this experimental approach, we first analysed the behaviour of calcitonin gene‐related peptide (CGRP)‐immunoreactive climbing fibres. This marker is transiently expressed by a subset of developing inferior olivary axons, which terminate in the cerebellar cortex into several parasagittal strips. We show that transcommissural axons reestablish the original pattern of climbing fibre bands within a few days after lesion. Then, in adult animals injured at birth, we assessed whether the newly formed climbing fibre bands align with zebrin II± Purkinje cell compartments, as in normal conditions. The newly formed projection is organised in parasagitally oriented strips which mirror the distribution of their counterparts on the intact side and are precisely aligned to the heterogeneous Purkinje cell compartments. In addition, the patchy distribution of olivo‐nuclear fibres suggests that specific reinnervation is also achieved in the deep nuclei. Thus, transcommissural olivocerebellar reinnervation is not random, but it is regulated by selective interactions between distinct subsets of olivocerebellar axons and target neurons aimed at reestablishing the correct projection map. J. Comp. Neurol. 379:283–299, 1997. © 1997 Wiley‐Liss, Inc.

MOST proteins are denatured at temperatures above 50–60°C, although some enzymes, especially those from thermophilic organisms, remain active at temperatures up to 80–90 °C. The determination of the three-dimensional structure of the thermostable protease thermolysin showed that heat-stable proteins do not contain unusual structural features absent from less stable proteins1,2. Furthermore, the amino acid sequences of similar proteins from both mesophilic and thermophilic sources have been shown to be homologous, suggesting that the respective structures are similar3,4. Nevertheless, such homologous amino acid sequences also include many differences which obscure those amino acid changes actually responsible for differences in thermostability. We report here the structure of a temperature sensitive (ts) mutant of T4 phage lysozyme. This permits the first direct comparison of two protein structures in which all differences are directly related to a change in thermal stability. It is shown that, except for the replacement of a partially exposed arginine by a histidine, the three-dimensional structure of the ts lysozyme is virtually identical with that of native lysozyme.

The article discusses the highlights of a lecture on The Use of Gels in Aqueous Conservation of Paper by Richard Wolber at the Wellcome Institute, London in June 2013. It notes that Wolber's lecture was organized by the Institute of Conservation (Icon) Book & Paper Group and focused on the use of xanthan gum, gellan gum, and agarose as non-toxic conservation agents. It also acknowledges the help of the Cooperative Training Register (CTR) in organizing the event.

Describes the development of a model of school and university cooperation in the U.S. Aspects involved in the development of cooperative field experience programs between schools and universities; Evaluation of the field experience program that connects the University of Northern Iowa to various public school systems throughout the state; Implications for the development of graduate field work programs and inservice training.

The article reports on efforts which Richard Hawkes, the chief executive of the British learning disabilities charity Scope, is making in 2011 to get communities to become more involved with people with disabilities that need assistance. Hawkes became involved in the efforts in response to the case of a woman named Stefania Woolf, who died in her home and left her disabled daughter Samantha to die from dehydration.

The article discusses a review of federal spending in Great Britain which was conducted by Chancellor George Osborne and may result in budget cuts. In the article the author offers his opinions on the cuts, on the impact they will have on people with learning disabilities and on the British government's inability to understand the difficulties that people with learning disabilities face in life.

The gross anatomical distribution of an antigen is typically mapped using a combination of serial sectioning, immunocytochemistry, and three‐dimensional reconstruction. This is a tedious and time‐consuming procedure, which introduces an array of potential alignment and differential shrinkage errors and requires considerable experience and specialized equipment. In particular, it is unsuited for routine screening applications. To circumvent these problems, this unit presents a routine whole‐mount immunocytochemistry protocol that can be used to map many antigenic distributions in the developing and adult brain. The technique can also be easily adapted to detect anterograde and retrograde transport tracers.