LH3, a "homologue" of the mastadenoviral E1B 55-kDa protein is a structural protein of atadenoviruses

Ovine adenovirus serotype 7 (OAdV), the prototype atadenovirus, has gene homologues for most mastadenovirus structural proteins but lacks proteins V and IX. Instead, OAdV has structural proteins of 32 and 42 kDa although the gene encoding the latter had not previously been identified. The presently reported studies of OAdV virions have now identified a minor structural polypeptide of approximately 40 kDa as the product of the L1 52/55-kDa gene and, more surprisingly, shown that the 42-kDa protein is encoded by LH3. This gene product was previously thought to be a homologue of mastadenovirus E1B 55 kDa, which is a multi-functional, non-structural protein that cooperates with E1A in cell transformation. The lack of transforming activity previously demonstrated for OAdV combined with a structural role for the LH3 product indicates that the protein has a different function in atadenoviruses. We discuss the abundance and likely core location of LH3 in the virion and the possible derivation of the E1B 55-kDa gene from the LH3 gene.     

Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population

Context  Premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are frequent in the general population, with estimated prevalences of 1 per 259 females and 1 per 813 males. Several articles have recently described the presence of late-onset neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified syndrome are cerebellar ataxia and intention tremor. Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction. Objective  To study the penetrance of the fragile X–associated tremor/ataxia syndrome (FXTAS) among premutation carriers. Design, Setting, and Participants  Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion. Main Outcome Measures  Penetrance of intention tremor and ataxia among adult carriers (aged =" BORDER="0">50 years) of premutation expansions of the FMR1 gene. Results  Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and =" BORDER="0">80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P = .003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P<.05). Female carrier scores were also higher than those of female controls (P<.05) on 2 of the 3 neurological rating scales, but no participant was identified with probable or definite FXTAS. Conclusions  The study demonstrates that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing FXTAS. Since male premutation carriers are relatively common in the general population, older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of family history.      

Design of interactive and dynamic anatomical visualizations: the implication of cognitive load theory

In improving the teaching and learning of anatomical sciences, empirical research is needed to develop a set of guiding principles that facilitate the design and development of effective dynamic visualizations. Based on cognitive load theory (CLT), effective learning from dynamic visualizations requires the alignment of instructional conditions with the cognitive architecture of learners and their levels of expertise. By improving the effectiveness and efficiency of dynamic visualizations, students will be able to be more successful in retaining visual information that mediates their understanding of complex and difficult aspects of anatomy. This theoretical paper presents instructional strategies generated by CLT and provides examples of some instructional implications of CLT on the design of dynamic visualizations for teaching and learning of anatomy.     

Dynamic reorganization of the astrocyte actin cytoskeleton elicited by cAMP and PACAP: a role for phosphatidylInositol 3-kinase inhibition

Cyclic AMP (cAMP)-raising agents induce astrocytes grown in vitro to adopt a stellate morphology resembling their in vivo appearance, through the depolymerization of actomyosin stress fibres. The signalling pathways responsible for cAMP-induced astrocyte stellation have thus far remained largely elusive. We showed in this study that the neurotrophic peptide PACAP (pituitary adenylate cyclase-activating polypeptide) mimicked the effect of forskolin, a direct activator of adenylate cyclase, on the actin cytoskeleton of primary rat astrocytes. The depolymerization of stress fibres induced by PACAP or forskolin was prevented by the expression of a constitutively active mutant of RhoA, but not by a protein kinase A (PKA) blocker, indicating that cAMP-raising agents act upstream of RhoA, in a PKA-independent manner. In addition, PACAP and forskolin inhibited basal Akt phosphorylation, and basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3-kinase (PI 3-K) activities. Incubation with a PI 3-K blocker resulted in the depolymerization of stress fibres. This effect was blocked by the expression of a constitutively active mutant of RhoA, indicating that PI 3-K inhibition acted upstream of RhoA. Together, these data demonstrate for the first time that depolymerization of stress fibres, and the resulting astrocyte stellation, induced by stimulation of cAMP production involves the inhibition of the PI 3-K-RhoA pathway.     

Assessing level of consciousness and cognitive changes from vegetative state to full recovery

Although investigations addressing cognitive recovery from the vegetative state have been reported, to date there have been no detailed studies of these patients combining both neuropsychology and functional imaging to monitor and record the recovery of consciousness. This paper describes the recovery of a specific vegetative state (VS) case. The patient (OG) remained in the vegetative state for approximately two months, increasing her level of awareness to a minimally conscious state, where she continued for approximately 70 days. In the course of the ensuing 18 months, she was able to reach an acceptable level of cognitive functioning, with partial levels of independence. Throughout this two year period, she received continuous cognitive evaluation, for which several different tools were applied including coma and low functioning scales, full cognitive batteries, and structural and functional magnetic resonance imaging (MRI). We present here preliminary data on fMRI using a word presentation paradigm before and after recovery; we also discuss the difficulty of how to determine level of consciousness using the tools currently available, and the subsequent improvement in different cognitive domains. We confirm that accurate diagnosis and proper cognitive assessment are critical for the rehabilitation of patients with disorders of consciousness.     

Autism spectrum traits in children with mood and anxiety disorders

The autism spectrum disorders (ASDs) can present with symptoms commonly found in mood and anxiety disorders. The Social Communication Questionnaire (SCQ), Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale (SRS) were used to screen children in a mood disorders research clinic setting for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent male, 63%) completed at least one scale, and 50 children completed all three. The prevalence of those screening positive for a possible ASD on one instrument was 62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio, 4.59 [95% confidence interval (CI) = 1.40-15.11]) of those scoring in the "ASD-likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37; odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to develop valid and reliable instruments to screen for ASDs in children presenting outside of ASD clinics.