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Many neurodevelopmental disorders (NDDs) are the result of mutations on the X chromosome. One severe NDD resulting from mutations on the X chromosome is CDKL5 deficiency disorder (CDD). CDD is an epigenetic, X-linked NDD characterized by intellectual disability (ID), pervasive seizures and severe sleep disruption, including recurring hospitalizations. CDD occurs at a 4:1 ratio, with a female bias. CDD is driven by the loss of cyclin-dependent kinase-like 5 (CDKL5), a serine/threonine kinase that is essential for typical brain development, synapse formation and signal transmission. Previous studies focused on male subjects from animal models, likely to avoid the complexity of X mosaicism. For the first time, we report translationally relevant behavioral phenotypes in young adult (8-20 weeks) females and males with robust signal size, including impairments in learning and memory, substantial hyperactivity and increased susceptibility to seizures/reduced seizure thresholds, in both sexes, and in two models of CDD preclinical mice, one with a general loss-of-function mutation and one that is a patient-derived mutation.

Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies to treat genetic disorders, although effective in vivo delivery systems for these proteins remain a major translational hurdle. We describe the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein (ZF-MSC) in transgenic mouse models and young rhesus monkeys. Secreted ZF protein from mouse ZF-MSC was detectable within the hippocampus 1 week following intracranial or cisterna magna (CM) injection. Secreted ZF activated the imprinted paternal Ube3a in a transgenic reporter mouse and ameliorated motor deficits in a Ube3a deletion Angelman Syndrome (AS) mouse. Intrathecally administered autologous rhesus MSCs were well-tolerated for 3 weeks following administration and secreted ZF protein was detectable within the cerebrospinal fluid (CSF), midbrain, and spinal cord. This approach is less invasive when compared to direct intracranial injection which requires a surgical procedure.

A significant number of X-linked genes escape from X chromosome inactivation and are associated with a distinct epigenetic signature. One epigenetic modification that strongly correlates with X-escape is reduced DNA methylation in promoter regions. Here, we created an artificial escape by editing DNA methylation on the promoter of CDKL5, a gene causative for an infantile epilepsy, from the silenced X-chromosomal allele in human neuronal-like cells. We identify that a fusion of the catalytic domain of TET1 to dCas9 targeted to the CDKL5 promoter using three guide RNAs causes significant reactivation of the inactive allele in combination with removal of methyl groups from CpG dinucleotides. Strikingly, we demonstrate that co-expression of TET1 and a VP64 transactivator have a synergistic effect on the reactivation of the inactive allele to levels >60% of the active allele. We further used a multi-omics assessment to determine potential off-targets on the transcriptome and methylome. We find that synergistic delivery of dCas9 effectors is highly selective for the target site. Our findings further elucidate a causal role for reduced DNA methylation associated with escape from X chromosome inactivation. Understanding the epigenetics associated with escape from X chromosome inactivation has potential for those suffering from X-linked disorders.

Kinship is core to Aboriginal culture, values and wellbeing. However, the strength of culture and relationships is often not fully recognised or respected by Westernised systems. This article highlights cultural strengths through use of a detailed case study narrative illustrating the importance of community self-determination when an Aboriginal child needs to be relocated to other carers/family members. Situated within an Aboriginal participatory action research methodology, we utilised a case study method where a participant and co-author (*Amelia) collaborated with two academics to tell her story as an illustration of the strengths of community and kinship that can support vulnerable children. Through this partnership we learn the importance of Aboriginal community involvement in Amelia’s progression from early childhood experience of family violence to thriving young adulthood. We confirm the importance of including Aboriginal knowledges and practices in raising at-risk Aboriginal children and we contribute to social work practice knowledges by learning from Indigenous experience. We conclude that social work needs to build on the strengths of Aboriginal communities’ abilities by valuing kinship support systems.IMPLICATIONS When faced with adversity such as family violence, Aboriginal culture can be a protective factor.Social workers need to understand the importance of culture in the healing process for Aboriginal children.Keeping Aboriginal children connected to culture is paramount for long-term recovery and the ability to create healthy relationships.When faced with adversity such as family violence, Aboriginal culture can be a protective factor.Social workers need to understand the importance of culture in the healing process for Aboriginal children.Keeping Aboriginal children connected to culture is paramount for long-term recovery and the ability to create healthy relationships. [ABSTRACT FROM AUTHOR]

This article explores the complexity of women's experiences of coercive control during childbearing, birthing and postpartum and investigates the importance of health practitioners' responses to women's experiences. Research questions were: 'What cues, from women's lived experiences, indicate that coercive control is being exerted by their partners?' and 'how can health practitioners recognise coercive control during pregnancy, birthing and post-partum?'. The qualitative study drew on relational empowerment to access rich data. Sixteen women in Australia participated in the research. Following the temporal sequence of pregnancy, birthing and postpartum, health workers responses are examined. Themes identified included: reproductive coercion followed by coercive control of ante-natal care, control during birthing, intersections with cultural expectations, partner's self-obsession, grandstanding after a birth, and women's feelings of isolation. Women's experience of coercive control, their sense of isolation or, alternatively, support ultimately affected their ability to remove themselves and their children from the abusive situation. Health practitioners' responses either helped women to identify their partner's behaviors as abusive or exacerbated women's feelings of isolation. The research suggests that health practitioners' acknowledgement of coercive control, and the involvement of social workers conversant with feminist informed dynamics of domestic violence, can impact positively on women's agency., Author(s): Fiona Buchanan [sup.1] , Cathy Humphreys [sup.2] Author Affiliations: (1) grid.1026.5, 0000 0000 8994 5086, Justice and Society, University of South Australia, , GPO Box 2471, 5001, Adelaide, South [...]

Social workers must be prepared to work with all members of society given their commitment to social justice. This article reports the findings of a study examining the preparedness of Vietnamese social work practitioners to practise with sexual minorities. The study employed a mixed-methods approach, comprising a paper-based survey (N = 292) and semi-structured interviews (N = 12). The findings indicate that most practitioners felt ill-equipped to work with clients who identified as lesbian or gay. The discussion highlights the lack of formal and in-service training in this practice area. Implications for social work education are discussed. [ABSTRACT FROM AUTHOR]

Until now, research into the effects of domestic violence on the formation of relationships between women and their babies has been from an attachment theory perspective. The research reported in this article takes a different approach. Innovative qualitative research methods are used to uncover knowledge about the formation of such relationships from the lived experiences of sixteen women who have mothered babies while enduring domestic violence. Analysis of the findings in this study identifies domestic violence constitutes an environment of sustained hostility where women respond with maternal protectiveness to maximise their babies' physical and psychological safety whether or not they had attained a secure relationship. However, women recognize domestic violence constricts space to form close mother/ baby relationships. Supported by these findings, this research suggests policy and practice concerned with relationships between women and babies subjected to domestic violence address protectiveness and space to attach. The article concludes with suggestions for further research. Keywords Domestic violence * Women * Babies . Relationships * Safety * Attachment * Protection, The Effects of Domestic Violence on the Formation of Relationships between Women and their Babies: 'I was too Busy Protecting my Baby to Attach' Currently, child development services and the [...]

Abstract Previously, we have shown that alleles of the BM1500 microsatellite, located 3.6 kb downstream of the leptin gene in cattle, were associated with carcass fat measures in a population of 154 unrelated beef bulls. Subsequently, a cytosine (C) to thymine (T) transition that encoded an amino acid change of an arginine to a cysteine was identified in exon 2 of the leptin gene. A PCR-RFLP was designed and allele frequencies in four beef breeds were correlated with levels of carcass fat. The T allele was associated with fatter carcasses and the C allele with leaner carcasses. The frequencies of the SNP alleles among breeds indicated that British breeds have a higher frequency of the T allele whereas the continental breeds have a higher occurrence of the C allele. A ribonuclease protection assay was developed to quantify leptin mRNA in a separate group of animals selected by genotype. Animals homozygous for thymine expressed higher levels of leptin mRNA. This may suggest that the T allele, which adds an extra cysteine to the protein, imparts a partial loss of biological function and hence could be the causative mutation.

Background: If women's use of agency to protect their children from domestic abuse is considered at all, it is usually in terms of women staying or leaving abusive partners. Elsewhere women's mothering, when they are enduring domestic abuse, is viewed from a perspective that focuses on finding deficits by observation and categorising the relationship between them and their children. Objective: The study, which informs this article, looked to the lived experiences of women who had mothered while enduring domestic abuse to better understand their thoughts, feelings and actions during that time. Participants and methods: The qualitative study considers the lived experience of 16 women, residing in South Australia, who raised young children while enduring domestic abuse. Semi-structured interviews followed by focus groups, which utilised creative methodologies were employed to collect data. Results: The study casts light on myriad ways that women exercise agency to protect their children. When lived experiences inform our understanding, it becomes clear that many women enduring domestic abuse exercise their agency to protect their children. Conclusion: We posit that, if agency is not a focus of enquiry it is overlooked by social workers focusing on deficits when considering mothering in domestic abuse. Too often, women are perceived solely as passive victims, unable or unwilling to protect vulnerable children. Yet important strategies to enable empowerment of both women and children are uncovered if social workers acknowledge and work with women and children to focus on the ways women exercise agency to protect. [ABSTRACT FROM AUTHOR]

Abstract Background Carcass quantity (lean meat yield) and quality (degree of marbling) in beef cattle determines much of their economic value. Consequently, it is important to study genes that are part of the appetite pathway and that may ultimately affect carcass composition. Pro-opiomelanocortin is a prohormone that codes for many different peptides, several of which are involved in the appetite pathway. A single nucleotide polymorphism (SNP) c.288C>T in pro-opiomelanocortin (POMC) has previously been associated with hot carcass weight (HCW) and shipping weight (Ship wt) in beef cattle. Results While developing a commercial real time PCR test for POMC c.288C>T a 12 bp deletion (POMC c.293_304delTTGGGGGCGCGG) was identified. The deletion results in the removal of four amino acids (a valine, two glycines, and an alanine). Both the POMC c.288C>T and the deletion were genotyped in 386 crossbred steers and evaluated for associations with carcass traits. The animals with one copy of the deletion had a significantly smaller carcass rib-eye area (7.91 cm2; P = 0.02) in comparison to homozygous normal animals. Significant associations were observed between POMC c.288C>T with start-of-finishing weight (SOF WT; P = 0.04), hot carcass weight (HCW; P = 0.02), average fat and grade fat (both P = 0.05), carcass rib-eye area (REA; P = 0.03) and marbling (P = 0.02). Conclusions These results suggest that it could be beneficial for beef producers to know both the deletion and POMC c.288C>T genotypes when making marketing and culling decisions.

Summary: This article reports on a project that explored the complexities of engaging and working with men when domestic violence is noticed in a couple counselling context. There are concerns and controversy surrounding domestic violence and couple counselling; however, it has also been noted that many couples want to remain together and voluntarily approach services for couple counselling. The project reported on in this paper adopted a qualitative methodological design influenced by participatory action research ideas and memory work methods to analyse engagement of men used by nine social work family relationship counsellors. Findings: Counsellors used narrative therapy ideas to maintain a stance of curiosity when working with couples when domestic violence was noticed. Curiosity was described as a way of opening up conversations to explore power differences and gender relations and as a method to balance safety with engagement. Specific engagement strategies identified included identifying ethics as a conversation point to explore the effects of power, violence and fear perpetrated by the male partners; exploring dynamics of power and control in relationships and exploring other possibilities in relationships. Applications: Alongside debates about the effectiveness and success in domestic violence men's perpetration intervention programmes, there is a need to look at engagement of men more broadly. Family relationship counselling can be viewed as an opportunity to engage with men where domestic violence is noticed. Engagement of men is an important piece of practice that can potentially set up effective and successful behaviour change when responding to domestic violence. [ABSTRACT FROM AUTHOR]

Qualitative research into sensitive and emotionally laden topics can pose a number of challenges for researchers. This paper presents reflections from two social work researchers who have led multiple feminist-based qualitative research studies about research participation enabling positive experiences for women who have survived domestic violence. It is argued, women can identify new insights, find alternative ways of looking at their experiences, and access opportunities to debrief in a unique way in the research interview setting that differs from counselling experiences. The authors use the metaphor of ‘opening doors’ to show how women construct their research participation experience in similar ways and how researchers can draw on social work skills to enhance positive experiences for women. [ABSTRACT FROM AUTHOR]