Evaluation of the Impacts of Radio-Marking Devices on Feral Horses and Burros in a Captive Setting

Radio-collars and other radio-marking devices have been invaluable tools for wildlife managers for \u3e40 years. These marking devices have improved our understanding of wildlife spatial ecology and demographic parameters and provided new data facilitating model development for species conservation and management. Although these tools have been used on virtually all North American ungulates, their deployment on feral horses (Equus ferus caballus) or burros (E. asinus) has been limited. To determine if radio-collars and radio-tags could be safely deployed on feral equids, we conducted a 1-year observational study in 2015 to investigate fit and wear of radio-collars on feral horses and burros kept in pastures/pens at the Bureau of Land Management contracted adoption facility in Pauls Valley, Oklahoma, USA. We assessed the impact of radio-collars and transmitter tags on individual behavior, body condition, and evaluated neck surface for effects. We tested 2 radio-collar shapes (teardrop and oval) and a radio-tag (i.e., avian backpack) braided into the mane and tail of horses. Behavior of mares did not differ between radio-collared (n = 12) and control (uncollared; n = 12) individuals. Despite the small sample size, collared burro jennies (n = 4) spent more time standing than controls (n = 4). Stallions wearing radio-collars (n = 9) fed less, moved less, and stood more than controls (n = 8). During the study, we did not detect injuries to the necks of mares or burro jennies, but stallions developed small sores (that healed while still wearing radio-collars and re-haired within 3 months). Two radio-collars occasionally flipped forward over the ears onto the foreheads of stallions. Although our study confirmed that radio-collars could be safely deployed on captive mares and jennies, stallions proved challenging for a variety of reasons. While our conclusions were optimistic, longer studies will be required to ensure radio-collar safety on free-ranging feral horses and burros

Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics

Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets. These findings demonstrate the potential of antisense phosphorodiamidate morpholino oligonucleotides as an FSHD therapeutic option

Non-autistic observers both detect and demonstrate the double empathy problem when evaluating interactions between autistic and non-autistic adults

Consistent with a “double empathy” framework, autistic adults often experience better interaction with autistic compared with non-autistic partners. Here, we examined whether non-autistic observers detect differences in autistic interactions relative to non-autistic and mixed ones. Non-autistic adults (N = 102) rated the interaction quality and traits of 42 autistic and 44 non-autistic male participants interacting in same or mixed-neurotype dyads. Non-autistic interactions and participants were evaluated most positively, with participants rated more favorably when interacting with non-autistic partners and rated as less intelligent and awkward when interacting with autistic partners. Observers perceived mixed interactions as the least successful overall. Whereas non-autistic interactions were rated as smoother and more enjoyable than mixed interactions, they were not rated differently from autistic interactions on any measure of interaction quality. Observers also perceived that non-autistic participants but not autistic participants disclosed more to non-autistic partners. However, they evaluated autistic participants more negatively than their partners in the interaction evaluated them; they disproportionately underestimated trust and intelligence ratings made by autistic participants; and they and reported lower social interest in participants than did the autistic and non-autistic people in the interactions. Collectively, these findings indicate that non-autistic adults both detect and demonstrate the double empathy problem when observing social interactions involving autistic people

Telomere Position Effect (TPE) Regulates DUX4 in Human Facioscapulohumeral Muscular Dystrophy (FSHD)

Telomeres may regulate human disease by at least two independent mechanisms. 1) Replicative senescence occurs once short telomeres generate DNA damage signals that produce a barrier to tumor progression. 2) Telomere Position Effect (TPE) can change gene expression at intermediate telomere lengths in cultured human cells. We here report a human disease, facioscapulohumeral muscular dystrophy (FSHD) where telomere length may well contribute to its pathogenesis. FSHD is age-related and genetically only 25-60 kb from the end of chromosome 4q. We used a floxable telomerase to generate isogenic clones with different telomere lengths from patients and their unaffected siblings. DUX4, the primary candidate for FSHD pathogenesis, is upregulated >10-fold in FSHD myoblasts-myotubes with short versus long telomeres, and its expression is inversely proportional to telomere length. FSHD may represent a human disease in which TPE contributes to its age-related phenotype

A tankönyvellátás változásai a rendszerváltozás után

<p>Percentage of each phylum present in fresh faecal samples collected from domesticated rabbits and rectal samples collected from wild rabbits together with the percentage of sequences which could not be classified within a particular phylum.</p

MicroRNA Regulation of Cell Lineages in Mouse and Human Embryonic Stem Cells

SummaryCell fate decisions of pluripotent embryonic stem (ES) cells are dictated by activation and repression of lineage-specific genes. Numerous signaling and transcriptional networks progressively narrow and specify the potential of ES cells. Whether specific microRNAs help refine and limit gene expression and, thereby, could be used to manipulate ES cell differentiation has largely been unexplored. Here, we show that two serum response factor (SRF)-dependent muscle-specific microRNAs, miR-1 and miR-133, promote mesoderm formation from ES cells but have opposing functions during further differentiation into cardiac muscle progenitors. Furthermore, miR-1 and miR-133 were potent repressors of nonmuscle gene expression and cell fate during mouse and human ES cell differentiation. miR-1's effects were in part mediated by translational repression of the Notch ligand Delta-like 1 (Dll-1). Our findings indicate that muscle-specific miRNAs reinforce the silencing of nonmuscle genes during cell lineage commitment and suggest that miRNAs may have general utility in regulating cell-fate decisions from pluripotent ES cells

What are the barriers to care integration for those at the advanced stages of dementia living in care homes in the UK? Health care professional perspective

yesPeople with advanced dementia are frequently bed-bound, doubly incontinent and able to speak only a few words. Many reside in care homes and may often have complex needs requiring efficient and timely response by knowledgeable and compassionate staff. The aim of this study is to improve our understanding of health care professionals’ attitudes and knowledge of the barriers to integrated care for people with advanced dementia. In-depth, interactive interviews conducted with 14 health care professionals including commissioners, care home managers, nurses and health care assistants in the UK. Barriers to care for people with advanced dementia are influenced by governmental and societal factors which contribute to challenging environments in care homes, poor morale amongst care staff and a fragmentation of health and social care at the end of life. Quality of care for people with dementia as they approach death may be improved by developing collaborative networks to foster improved relationships between health and social care services

Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy

BACKGROUND: Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic repression and increased expression of the deleterious double homeobox 4 (DUX4) gene encoded within the distal D4Z4 repeat. However, many individuals with the genetic requirements for FSHD remain asymptomatic throughout their lives. Here we investigated family cohorts of FSHD1 individuals who were either affected (manifesting) or without any discernible weakness (nonmanifesting/asymptomatic) and their unaffected family members to determine if individual epigenetic status and stability of repression at the contracted 4q35 D4Z4 array in myocytes correlates with FSHD disease. RESULTS: Family cohorts were analyzed for DNA methylation on the distal pathogenic 4q35 D4Z4 repeat on permissive A-type subtelomeres. We found DNA hypomethylation in FSHD1-affected subjects, hypermethylation in healthy controls, and distinctly intermediate levels of methylation in nonmanifesting subjects. We next tested if these differences in DNA methylation had functional relevance by assaying DUX4-fl expression and the stability of epigenetic repression of DUX4-fl in myogenic cells. Treatment with drugs that alter epigenetic status revealed that healthy cells were refractory to treatment, maintaining stable repression of DUX4, while FSHD1-affected cells were highly responsive to treatment and thus epigenetically poised to express DUX4. Myocytes from nonmanifesting subjects had significantly higher levels of DNA methylation and were more resistant to DUX4 activation in response to epigenetic drug treatment than cells from FSHD1-affected first-degree relatives containing the same contraction, indicating that the epigenetic status of the contracted D4Z4 array is reflective of disease. CONCLUSIONS: The epigenetic status of the distal 4qA D4Z4 repeat correlates with FSHD disease; FSHD-affected subjects have hypomethylation, healthy unaffected subjects have hypermethylation, and nonmanifesting subjects have characteristically intermediate methylation. Thus, analysis of DNA methylation at the distal D4Z4 repeat could be used as a diagnostic indicator of developing clinical FSHD. In addition, the stability of epigenetic repression upstream of DUX4 expression is a key regulator of disease and a viable therapeutic target

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames