Observation of Amounts of Movement Practice Provided during Stroke Rehabilitation

Objective To investigate how much movement practice occurred during stroke rehabilitation, and what factors might influence doses of practice provided. Design Observational survey of stroke therapy sessions. Setting Seven inpatient and outpatient rehabilitation sites. Participants We observed a convenience sample of 312 physical and occupational therapy sessions for people with stroke. Interventions Not applicable. Main Outcome Measures We recorded numbers of repetitions in specific movement categories and data on potential modifying factors (patient age, side affected, time since stroke, FIM item scores, years of therapist experience). Descriptive statistics were used to characterize amounts of practice. Correlation and regression analyses were used to determine whether potential factors were related to the amount of practice in the 2 important categories of upper extremity functional movements and gait steps. Results Practice of task-specific, functional upper extremity movements occurred in 51% of the sessions that addressed upper limb rehabilitation, and the average number of repetitions/session was 32 (95% confidence interval [CI]=20–44). Practice of gait occurred in 84% of sessions that addressed lower limb rehabilitation and the average number of gait steps/session was 357 (95% CI=296–418). None of the potential factors listed accounted for significant variance in the amount of practice in either of these 2 categories. Conclusions The amount of practice provided during poststroke rehabilitation is small compared with animal models. It is possible that current doses of task-specific practice during rehabilitation are not adequate to drive the neural reorganization needed to promote function poststroke optimally

Inactivation of the Huntington's Disease Gene (Hdh) Impairs Anterior Streak Formation and Early Patterning of the Mouse Embryo

Background: Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results: In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion: Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease

Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

BACKGROUND: Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdh(ex4/5 )huntingtin deficient embryos. RESULTS: In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. CONCLUSION: Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease

A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene-targeted mice

The retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report, we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1δG) are defective for pRB-dependent repression of E2F target genes. Except for an accelerated entry into S phase in response to serum stimulation, cell cycle regulation in Rb1δG/δG mouse embryonic fibroblasts (MEFs) strongly resembles that of the wild type. In a serum deprivation-induced cell cycle exit, Rb1δG/δG MEFs display a magnitude of E2F target gene derepression similar to that of Rb1-/- cells, even though Rb1δG/δG cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1δG/δG MEFs is responsive to p16 expression and gamma irradiation, indicating that alternate mechanisms can be activated in G1 to arrest proliferation. Some Rb1δG/δG mice die neonatally with a muscle degeneration phenotype, while the others live a normal life span with no evidence of spontaneous tumor formation. Most tissues appear histologically normal while being accompanied by derepression of pRB-regulated E2F targets. This suggests that non- E2F-, pRB-dependent pathways may have a more relevant role in proliferative control than previously identified. © 2014, American Society for Microbiology

Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

Depicting the tree of life in museums: guiding principles from psychological research

The Tree of Life is revolutionizing our understanding of life on Earth, and, accordingly, evolutionary trees are increasingly important parts of exhibits on biodiversity and evolution. The authors argue that in using these trees to effectively communicate evolutionary principles, museums need to take into account research results from cognitive, developmental, and educational psychology while maintaining a focus on visitor engagement and enjoyment. Six guiding principles for depicting evolutionary trees in museum exhibits distilled from this research literature were used to evaluate five current or recent museum trees. One of the trees was then redesigned in light of the research while preserving the exhibit’s original learning goals. By attending both to traditional factors that influence museum exhibit design and to psychological research on how people understand diagrams in general and Tree of Life graphics in particular, museums can play a key role in fostering 21st century scientific literacy

Communicating Phylogeny: Evolutionary Tree Diagrams in Museums

Tree of life diagrams are graphic representations of phylogeny—the evolutionary history and relationships of lineages—and as such these graphics have the potential to convey key evolutionary ideas and principles to a variety of audiences. Museums play a significant role in teaching about evolution to the public, and tree graphics form a common element in many exhibits even though little is known about their impact on visitor understanding. How phylogenies are depicted and used in informal science settings impacts their accessibility and effectiveness in communicating about evolution to visitors. In this paper, we summarize the analysis of 185 tree of life graphics collected from museum exhibits at 52 institutions and highlight some potential implications of how trees are presented that may support or hinder visitors’ understanding about evolution. While further work is needed, existing learning research suggests that common elements among the diversity of museum trees such as the inclusion of anagenesis and absence of time and shared characters might represent potential barriers to visitor understanding