孕激素受体膜元件1在颗粒细胞中的功能及女性生殖中的作用

孕激素受体膜组件1(PGRMC1)是近年来新发现的特殊受体,属于膜相关的孕激素受体(MAPR)蛋白家族。PGRMC1介导孕酮(P4)的抗有丝分裂和抗凋亡作用,并参与了颗粒细胞合成甾体激素的过程。在临床上,PGRMC1的异常表达与卵巢早衰(POF)及多囊卵巢综合征(PCOS)相关。本文就PGRMC1对颗粒细胞功能的影响、与卵泡发育的关系以及在人类生殖中的作用展开综述。     

‘THE LONG GOODBYE’: COGNITIVE ANALYTIC THERAPY WITH CARERS OF PEOPLE WITH DEMENTIA

This paper discusses the use of Cognitive Analytic Therapy (CAT) with carers of people with dementia and raises the wider issue of service delivery and provision of psychological therapy services to carers. Carers experience loss and emotional pain ( McCurry, 2008 ; Miesen, 2006a ; Woods et al., 2003 ) while providing full‐time care to the person with dementia who has complex and changing needs. This frequently results in major depression and anxiety, increasing the possibility of referral to mental health services. Treating carers’ distress is vital not only for their mental health but to enable them to continue in their caring role, without which the current care system would collapse. This need is being addressed in Newham by the tertiary psychology service, Psychotherapy for Older Adults (PTOA), set up in 2006–07 to accept referrals of people over 65 with mental health problems. This paper outlines how the PTOA is well placed to identify and treat carers. We propose that CAT is an effective and flexible therapy in this setting, and illustrate this with a case study. Further research and models for psychotherapeutic service delivery for carers are required.     

Nucleostemin deletion reveals an essential mechanism that maintains the genomic stability of stem and progenitor cells

Stem and progenitor cells maintain a robust DNA replication program during the tissue expansion phase of embryogenesis. The unique mechanism that protects them from the increased risk of replication-induced DNA damage, and hence permits self-renewal, remains unclear. To determine whether the genome integrity of stem/progenitor cells is safeguarded by mechanisms involving molecules beyond the core DNA repair machinery, we created a nucleostemin (a stem and cancer cell-enriched protein) conditional-null allele and showed that neural-specific knockout of nucleostemin predisposes embryos to spontaneous DNA damage that leads to severe brain defects in vivo. In cultured neural stem cells, depletion of nucleostemin triggers replication-dependent DNA damage and perturbs self-renewal, whereas overexpression of nucleostemin shows a protective effect against hydroxyurea-induced DNA damage. Mechanistic studies performed in mouse embryonic fibroblast cells showed that loss of nucleostemin triggers DNA damage and growth arrest independently of the p53 status or rRNA synthesis. Instead, nucleostemin is directly recruited to DNA damage sites and regulates the recruitment of the core repair protein, RAD51, to hydroxyurea-induced foci. This work establishes the primary function of nucleostemin in maintaining the genomic stability of actively dividing stem/progenitor cells by promoting the recruitment of RAD51 to stalled replication-induced DNA damage foci.     

The nutritive adequacy of some Nigerian peasant diets

The nutritive values of six traditional diets of the people of South‐Eastern Nigeria have been evaluated. A bioassay procedure was used; it involved the measurement of Biological Value, True Digestibility of the dietary nitrogen, Net Protein Utilization (operative) and Net Dietary Protein Calories Percent (NDpCals%). The procedures were applied to diets cooked as for human consumption, then dried and fed unmodified to male weaning albino rats. The results showed that in all cases the digestibility of the dietary nitrogen was high but the nutritive value was significantly low. These results are discussed and compared with the FAO recommended practical allowances for NDpCals% for various physiological ages and states.     

The Fifth International Interdisciplinary Conference on Clinical Supervision

Doctoral students in counselor education and supervision programs take a course specific to clinical supervision as part of their doctoral course work. The transition from supervisee to supervisor occurring during this course can be challenging, as it is frequently the first time that students are asked to provide supervision to counselors in training. The purpose of this qualitative research was to gain information about the process of doctoral students' development from supervisees into supervisors. Significant themes emerged from the data related to the transition of becoming supervisors: the importance of creating the supervisory relationship and the need for further supervisory skills.     

Safety assessment of food and feed from biotechnology-derived crops employing RNA-mediated gene regulation to achieve desired traits: A scientific review

Gene expression can be modulated in plants to produce desired traits through agricultural biotechnology. Currently, biotechnology-derived crops are compared to their conventional counterparts, with safety assessments conducted on the genetic modification and the intended and unintended differences. This review proposes that this comparative safety assessment paradigm is appropriate for plants modified to express mediators of RNA-mediated gene regulation, including RNA interference (RNAi), a gene suppression mechanism that naturally occurs in plants and animals. The molecular mediators of RNAi, including long double-stranded RNAs (dsRNA), small interfering RNAs (siRNA), and microRNAs (miRNA), occur naturally in foods; therefore, there is an extensive history of safe consumption. Systemic exposure following consumption of plants containing dsRNAs that mediate RNAi is limited in higher organisms by extensive degradation of ingested nucleic acids and by biological barriers to uptake and efficacy of exogenous nucleic acids. A number of mammalian RNAi studies support the concept that a large margin of safety will exist for any small fraction of RNAs that might be absorbed following consumption of foods from biotechnology-derived plants that employ RNA-mediated gene regulation. Food and feed derived from these crops utilizing RNA-based mechanisms is therefore expected to be as safe as food and feed derived through conventional plant breeding.     

Greenspace programmes for mental health: A survey study to test what works,for whom,and in what circumstances

The health benefits of greenspace are widely acknowledged. Greenspace programmes, defined as health programmes undertaken in outside green areas such as parks, gardens, hills, and forests, are becoming more commonplace. However, there is still limited understanding of the mechanisms by which greenspace programmes are effective. This makes future development and implementation very difficult. We recently developed and published a novel framework for greenspace programmes for mental health showing what works, for whom, and in what circumstances (Masterton et al., 2020). In this current study, the accuracy of the proposed framework was tested for the first time using primary data from greenspace organisations in Scotland. Given the link between mental health and substance use, the applicability of the framework to programmes that support people with problem substance use was also tested. A survey was designed to test the contexts, mechanisms, and outcomes identified within the previously proposed framework. The survey was completed by 64 participants to provide a general overview of the framework's applicability for programmes that support mental health, as well as for programmes that support people with problem substance use. Overall, respondents agreed with all survey statements. This suggests that the framework does effectively represent the underlying context, mechanism, outcome configurations of greenspace programmes for mental health. Furthermore, there were no differences between responses from organisations that support people with problem substance use, and organisations that do not support this client group. This shows that the framework has the potential to be applicable to both greenspace programmes for mental health and greenspace programmes for people with problem substance use. This is a novel finding as, to our knowledge, there is currently no framework looking to explain the contexts, mechanisms, and outcomes necessary for greenspace programmes to be successful for people with problem substance use.     

Caprospinol: moving from a neuroactive steroid to a neurotropic drug

In search of new drugs for Alzheimer's disease, we departed from the classic concepts and investigated the ability of normal and Alzheimer's disease brain to convert cholesterol to steroids, otherwise known as neurosteroids. We identified 22R-hydroxycholesterol to be present in much lower levels in the hippocampus and frontal cortex of Alzheimer's disease than in tissue from age-matched controls. 22R-hydroxycholesterol was shown to protect against β-amyloid (Aβ₄₂)-induced neurotoxicity and block the formation of Aβ oligomers. In search of a 22R-hydroxycholesterol stable analog, we identified the naturally occurring heterospirostenol, (22R,25R)-20α-spirost-5-en-3β-yl hexanoate (caprospinol). The mechanism of action underlying the neuroprotective properties of caprospinol involves, first, the ability of the compound to bind Aβ₄₂ and, second, its interaction with components of the mitochondria respiratory chain. Samaritan Pharmaceuticals is developing caprospinol as a disease-modifying drug for the treatment of Alzheimer's disease. Samaritan Pharmaceuticals filed for an Investigational New Drug application with the FDA in 2006. The pharmacokinetic and pharmacodynamic parts of the application were found satisfactory, and the FDA has requested that additional information is submitted in support of caprospinol's safety prior to initiating the Phase I clinical study.