A Form of Inherited Cerebellar Ataxia with Saccadic Intrusions, Increased Saccadic Speed, Sensory Neuropathy, and Myoclonus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72602/1/j.1749-6632.2002.tb02850.x.pd

Comparison of Horizontal, Vertical and Diagonal Smooth Pursuit Eye Movements in Normal Human Subjects

AbstractWe compared horizontal and vertical smooth pursuit eye movements in five healthy human subjects. When maintenance of pursuit was tested using predictable waveforms (sinusoidal or triangular target motion), the gain of horizontal pursuit was greater, in all subjects, than that of vertical pursuit; this was also the case for the horizontal and vertical components of diagonal and circular tracking. When initiation of pursuit was tested, four subjects tended to show larger eye accelerations for vertical as opposed to horizontal pursuit; this trend became a consistent finding during diagonal tracking. These findings support the view that different mechanisms govern the onset of smooth pursuit, and its subsequent maintenance when the target moves in a predictable waveform. Since the properties of these two aspects of pursuit differ for horizontal and vertical movements, our findings also point to separate control of horizontal and vertical pursuit. Copyright © 1996 Elsevier Science Ltd

Recognition of 5-Hydroxymethylcytosine by the Uhrf1 SRA Domain

Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with similar affinity. Based on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC and stabilizes the flipped base by hydrogen bond formation with the hydroxyl group

How are gender equality and human rights interventions included in sexual and reproductive health programmes and policies: A systematic review of existing research foci and gaps

The importance of promoting gender equality and human rights in sexual and reproductive health (SRH) programmes and policies has been affirmed in numerous international and regional agreements, most recently the 2030 Agenda for Sustainable Development. Given the critical role of research to determine what works, we aimed to identify research gaps as part of a broader priority setting exercise on integrating gender equality and human rights approaches in SRH programmes and policies. A systematic literature review of reviews was conducted to examine the question: what do we know about how research in the context of SRH programmes and policies has addressed gender equality and human rights and what are the current gaps in research. We searched three databases for reviews that addressed the research question, were published between 1994-2014, and met methodological standards for systematic reviews, qualitative meta-syntheses and other reviews of relevance to the research question. Additional grey literature was identified based on expert input. Articles were appraised by the primary author and examined by an expert panel. An abstraction and thematic analysis process was used to synthesize findings. Of the 3,073 abstracts identified, 56 articles were reviewed in full and 23 were included along with 10 from the grey literature. The majority focused on interventions addressing gender inequalities; very few reviews explicitly included human rights based interventions. Across both topics, weak study designs and use of intermediate outcome measures limited evidence quality. Further, there was limited evidence on interventions that addressed marginalized groups. Better quality studies, longer-term indicators, and measurement of unintended consequences are needed to better understand the impact of these types of interventions on SRH outcomes. Further efforts are needed to cover research on gender equality and human rights issues as they pertain to a broader set of SRH topics and populations.Scopu

Are men well served by family planning programs?

Although the range of contraceptives includes methods for men, namely condoms, vasectomy and withdrawal that men use directly, and the Standard Days Method (SDM) that requires their participation, family planning programming has primarily focused on women. What is known about reaching men as contraceptive users? This paper draws from a review of 47 interventions that reached men and proposes 10 key considerations for strengthening programming for men as contraceptive users. A review of programming shows that men and boys are not particularly well served by programs. Most programs operate from the perspective that women are contraceptive users and that men should support their partners, with insufficient attention to reaching men as contraceptive users in their own right. The notion that family planning is women’s business only is outdated. There is sufficient evidence demonstrating men’s desire for information and services, as well as men’s positive response to existing programming to warrant further programming for men as FP users. The key considerations focus on getting information and services where men and boys need it; addressing gender norms that affect men’s attitudes and use while respecting women’s autonomy; reaching adolescent boys; including men as users in policies and guidelines; scaling up successful programming; filling gaps with implementation research and monitoring & evaluation; and creating more contraceptive options for men

Niemann-Pick disease type C

Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations

Heterochromatin and the molecular mechanisms of 'parent-of-origin' effects in animals.

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatinlike complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed