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1.
Article in English | MEDLINE | ID: mdl-38349031

ABSTRACT

WHAT IS KNOWN ON THE SUBJECT?: We know that there are similar rates of borderline personality disorder (BPD) diagnosed in both men and women; however, some research suggests that BPD is diagnosed later and less frequently in men. Some research suggests that males diagnosed with BPD present differently to women, but not much is known about how this influences the care men receive in inpatient mental health hospitals. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper is the first to specifically ask inpatient staff about men diagnosed with BPD, and to hear about their perceptions and experiences. It identified that some staff do not feel as knowledgeable in identifying and treating BPD in men compared to women. Some staff talked about how emotional difficulties like BPD are often not the first thought when men present with distress compared to women. Staff also talked about needing a safe, open and transparent working culture to be able to ask questions and to be questioned on their own assumptions, biases or lack of training. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This paper suggests that inpatient staff may hold some assumptions about men and their emotions, such as assuming that they are less likely to struggle with emotional difficulties like BPD. Staff anxieties about risk management may influence how they perceive and care for men in inpatient wards. The findings suggest that male-specific training in identifying and treating BPD should be provided for staff on inpatient wards, to improve knowledge and confidence. ABSTRACT: INTRODUCTION: Research highlights discrepancies in recognition of borderline personality disorder (BPD) in men, despite similar rates of prevalence across genders. AIM: To investigate inpatient mental health professionals' experiences of delivering treatment for males with a diagnosis of BPD. METHOD: Six mental health professionals working within adult acute inpatient wards completed a semi-structured interview. All participants were members of the nursing team. Thematic analysis was used to analyse the data. RESULTS: Five themes were identified: Gender Differences, Stereotyping, Facilitators to Care Delivery, Barriers to Care Delivery and Ways to Improve Care. Participants talked of a lack of awareness and understanding of BPD in males impacting both diagnosis and treatment in an acute inpatient setting. DISCUSSION: There may be factors ranging from gender stereotypes, limited knowledge and understanding of gender differences in presentations, and personal/organisational cultures influencing the formulation and treatment of males with a diagnosis of BPD in inpatient settings. IMPLICATIONS FOR PRACTICE: The findings suggest that gender stereotypes such as masculine norms may influence how male patients' emotional difficulties are understood and managed, and that additional training in male-specific issues to improve knowledge and care provision. This research will support inpatient staff, service leads and clinical educators to identify ways to adapt care provision for men.

2.
Nat Commun ; 14(1): 5294, 2023 08 31.
Article in English | MEDLINE | ID: mdl-37652930

ABSTRACT

Saccharomyces cerevisiae is a workhorse of industrial biotechnology owing to the organism's prominence in alcohol fermentation and the suite of sophisticated genetic tools available to manipulate its metabolism. However, S. cerevisiae is not suited to overproduce many bulk bioproducts, as toxicity constrains production at high titers. Here, we employ a high-throughput assay to screen 108 publicly accessible yeast strains for tolerance to 20 g L-1 adipic acid (AA), a nylon precursor. We identify 15 tolerant yeasts and select Pichia occidentalis for production of cis,cis-muconic acid (CCM), the precursor to AA. By developing a genome editing toolkit for P. occidentalis, we demonstrate fed-batch production of CCM with a maximum titer (38.8 g L-1), yield (0.134 g g-1 glucose) and productivity (0.511 g L-1 h-1) that surpasses all metrics achieved using S. cerevisiae. This work brings us closer to the industrial bioproduction of AA and underscores the importance of host selection in bioprocessing.


Subject(s)
Pichia , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Pichia/genetics , Sorbic Acid
3.
ACS Synth Biol ; 10(11): 2896-2903, 2021 11 19.
Article in English | MEDLINE | ID: mdl-34748704

ABSTRACT

While nepetalactone, the active ingredient in catnip, is a potent insect repellent, its low in planta accumulation limits its commercial viability as an alternative repellent. Here we describe for the first time de novo nepetalactone synthesis in Saccharomyces cerevisiae, enabling sustainable and scalable production. Nepetalactone production required introducing eight exogenous genes including the cytochrome P450 geraniol-8-hydroxylase, the bottleneck of the heterologous pathway. Combinatorial assessment of geraniol-8-hydroxylase and cytochrome P450 reductase variants, and copy-number variations were used to overcome this bottleneck. We found that several reductases improved hydroxylation activity and increasing geraniol-8-hydroxylase gene copy number improved 8-hydroxygeraniol titers. The accumulation of an unwanted metabolite implied inefficient channeling of carbon through the pathway. With the native yeast old yellow enzymes previously shown to use monoterpene intermediates as substrates, both homologues were deleted. These deletions increased 8-hydroxygeraniol yield, resulting in 3.10 mg/L/OD600 of nepetalactone from simple sugar in microtiter plates. This optimized pathway will benefit the development of high yielding strains for the scale up production of nepetalactone.


Subject(s)
Cyclopentane Monoterpenes/metabolism , Insect Repellents/metabolism , Pyrones/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , DNA Copy Number Variations/genetics , Monoterpenes/metabolism , NADPH-Ferrihemoprotein Reductase/genetics , NADPH-Ferrihemoprotein Reductase/metabolism , Signal Transduction/genetics , Terpenes/metabolism
4.
Front Microbiol ; 8: 1265, 2017.
Article in English | MEDLINE | ID: mdl-28769880

ABSTRACT

Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics.

5.
Blood ; 102(9): 3120-8, 2003 Nov 01.
Article in English | MEDLINE | ID: mdl-12855562

ABSTRACT

Our laboratory recently identified a quiescent class of pluripotent hematopoietic stem cells (PHSCs) that are lineage negative (Linneg), lack c-Kit, and are able to give rise to c-Kit-positive (c-Kitpos) PHSCs in vivo. This population fails to proliferate in vitro but has delayed reconstituting activity in vivo. In this study, we purified these cells to enrich for the PHSCs and we identified in vitro conditions capable of supporting their maturation. The c-Kit-negative (c-Kitneg) cells exhibited differential expression of Sca-1, CD34, CD43, CD45, and Thy 1.2. We purified the cells based on Sca-1, as it is expressed on active PHSCs. We detected pre-colony-forming unit spleen (pre-CFU-s) activity in both the Sca-1neg and Sca-1pos populations, indicating the presence of primitive PHSCs in both populations. However, our in vitro studies suggest that the Sca-1pos population is enriched for PHSCs. The in vitro systems that support the growth of these dormant cells include a modified long-term marrow culture and various stromal cell lines. In modified long-term bone marrow cultures, c-Kitneg cells gave rise to c-Kitpos PHSCs, with long-term reconstitution activity in vivo. Thus we have established an in vitro system to examine PHSC maturation that will allow us to study the mediators of the c-Kitneg to c-Kitpos transition.


Subject(s)
Cell Culture Techniques/methods , Hematopoietic Stem Cells/cytology , Pluripotent Stem Cells/cytology , Proto-Oncogene Proteins c-kit/genetics , Animals , Antigens, Ly/analysis , Bone Marrow Cells/cytology , Cell Division , Cell Separation , Coculture Techniques , Gene Expression Regulation , Hematopoietic Stem Cells/metabolism , Membrane Proteins/analysis , Mice , Mice, Inbred C57BL , Pluripotent Stem Cells/metabolism , Stromal Cells/cytology
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