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There is growing interest in geography in the intersections of age, family and the lifecourse with migration. This paper furthers this work by focusing on the themes of intergenerational relationships and transmission within migrant families that have three generations. Using a case study of Greek-Cypriot families living in the UK, specifically the paper explores the experiences of second-generation and third-generation women, as young adults and as mothers, within the context of their relationships with their family members who were born outside of the UK. The gendered networks of power within Greek-Cypriot intergenerational migrant families are examined, with a particular focus on how these impact young women's everyday spatialities and influence their own experiences and practices of motherhood. The paper shows how difference is brought about, played out, contested and accepted between women. Through examining changing ideas of gender and motherhood, we reveal how these differences are negotiated by different generations of women. [ABSTRACT FROM AUTHOR]

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Endocytosis mediates the cellular uptake of numerous molecules from the extracellular space and is a fundamentally important process. In the renal proximal tubule, the scavenger receptor megalin and its co-receptor cubilin mediate endocytosis of low molecular weight proteins from the renal filtrate. However, the extent to which megalin endocytosis relies on different components of the trafficking machinery remains relatively poorly defined in vivo. In this study, we identify a functional requirement for the F-BAR protein pacsin2 in endocytosis in the renal proximal tubule of zebrafish larvae. Pacsin2 is expressed throughout development and in all zebrafish tissues, similar to the mammalian orthologue. Within renal tubular epithelial cells, pacsin2 is enriched at the apical pole where it is localised to endocytic structures. Loss of pacsin2 results in reduced endocytosis within the proximal tubule, which is accompanied by a reduction in the abundance of megalin and endocytic organelles. Our results indicate that pacsin2 is required for efficient endocytosis in the proximal tubule, where it likely cooperates with other trafficking machinery to maintain endocytic uptake and recycling of megalin., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Recycling to the cell surface requires the scission of tubular membrane intermediates emanating from endosomes. Here, we identify the monotopic membrane protein LPS-induced TNF-activating factor (LITAF) and the related protein cell death involved p53 target 1 (CDIP1) as novel membrane curvature proteins that contribute to recycling tubule scission. Recombinant LITAF supports high membrane curvature, shown by its ability to reduce proteoliposome size. The membrane domains of LITAF and CDIP1 partition strongly into ∼50 nm diameter tubules labelled with the recycling markers Pacsin2, ARF6 and SNX1, and the recycling cargoes MHC class I and CD59. Partitioning of LITAF into tubules is impaired by mutations linked to Charcot Marie Tooth disease type 1C. Meanwhile, co-depletion of LITAF and CDIP1 results in the expansion of tubular recycling compartments and stabilised Rab11 tubules, pointing to a function for LITAF and CDIP1 in membrane scission. Consistent with this, co-depletion of LITAF and CDIP1 impairs integrin recycling and cell migration., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Membrane trafficking pathways are essential for the viability and growth of cells, and play a major role in the interaction of cells with their environment. In this At a Glance article and accompanying poster, we outline the major cellular trafficking pathways and discuss how defects in the function of the molecular machinery that mediates this transport lead to various diseases in humans. We also briefly discuss possible therapeutic approaches that may be used in the future treatment of trafficking-based disorders., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

CTP:phosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via the CDP-ethanolamine pathway. Phosphatidylethanolamine is one of the most abundant membrane lipids and is particularly enriched in the brain. We identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy. Using patient fibroblasts we demonstrated that these variants are hypomorphic, result in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR-Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. In conclusion, our data establish PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirm that etherlipid homeostasis is important for the development and function of the brain., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Tenancy sustainment-maintenance of a tenancy to avoid a premature end of tenure-is fundamental to prevention of homelessness. Understanding what enables a successful tenancy is essential in informing interventions designed to support people in leaving homelessness., Objectives: To conduct a systematic review identifying determinants associated with tenancy sustainment following homelessness., Search Methods: A detailed search of 12 electronic databases, as well as gray literature sources, was conducted in 2015 and updated in 2016., Selection Criteria: We included all study designs with a population of homeless or formerly homeless individuals in which tenancy sustainment was the primary outcome. Two reviewers independently carried out abstract and full-text reviews. QualSyst, a validated quality appraisal tool, was used in assessing the methodological quality of articles., Data Collection and Analysis: A data extraction form was developed for the review and was completed by a pair of reviewers to ensure accuracy. The heterogeneity of the studies included indicated that a narrative overview of the results was most appropriate., Main Results: Forty-three articles reporting 38 studies were included. Determinants were categorized at 4 levels: individual, interpersonal, community, and structural. Participation in specific programs (e.g., Housing First), receipt of social support, and older age were identified as positive determinants of tenancy sustainment., Conclusions: This systematic review is the first, to our knowledge, to focus solely on tenancy sustainment as a primary outcome. Although a range of determinants associated with tenancy sustainment were identified, it was difficult to draw strong conclusions owing to the heterogeneity of the studies. Despite being a fundamental concept in homelessness research, tenancy sustainment is poorly defined and conceptualized. A deeper understanding of tenancy sustainment will inform the development and evaluation of interventions that support people in leaving homelessness and maintaining tenancies. Public Health Implications. Housing stability is central to preventing homelessness and addressing the numerous public health concerns that can co-occur with homelessness. Our review highlights that a standardized approach to measuring housing stability and more high-quality intervention studies are essential.

One explanation given for the high microbial diversity found in soils is that they contain a large inactive biomass that is able to persist in soils for long periods of time. This persistent microbial fraction may help to buffer the functionality of the soil community during times of low nutrients by providing a reservoir of specialized functions that can be reactivated when conditions improve. A study was designed to test the hypothesis: in soils lacking fresh root or detrital inputs, microbial community composition may persist relatively unchanged. Upon addition of new inputs, this community will be stimulated to grow and break down litter similarly to control soils. Soils from two of the Detrital Input and Removal Treatments (DIRT) at the H. J. Andrews Experimental Forest, the no-input and control treatment plots, were used in a microcosm experiment where Douglas-fir needles were added to soils. After 3 and 151 days of incubation, soil microbial DNA and RNA was extracted and characterized using quantitative PCR (qPCR) and 454 pyrosequencing. The abundance of 16S and 28S gene copies and RNA copies did not vary with soil type or amendment; however, treatment differences were observed in the abundance of archaeal ammonia-oxidizing amoA gene abundance. Analysis of ∼110,000 bacterial sequences showed a significant change in the active (RNA-based) community between day 3 and day 151, but microbial composition was similar between soil types. These results show that even after 12 years of plant litter exclusion, the legacy of community composition was well buffered against a dramatic disturbance.

Amyloid fibrils are self-assembled protein aggregates implicated in a number of human diseases. Fragmentation-dominated models for the self-assembly of amyloid fibrils have had important successes in explaining the kinetics of amyloid fibril formation but predict fibril length distributions that do not match experiments. Here we resolve this inconsistency using a combination of experimental kinetic measurements and computer simulations. We provide evidence for a structural transition that occurs at a critical fibril mass concentration, or CFC, above which fragmentation of fibrils is suppressed. Our simulations predict the formation of distinct fibril length distributions above and below the CFC, which we confirm by electron microscopy. These results point to a new picture of amyloid fibril growth in which structural transitions that occur during self-assembly have strong effects on the final population of aggregate species with small, and potentially cytotoxic, oligomers dominating for long periods of time at protein concentrations below the CFC.

Background: Leiomyomas are the most common of uterine neoplasms and a major cause of visits to gynecologists. While most often straightforward in their presentation and management, they can undergo various kinds of asymptomatic degeneration that drastically alters their appearance and muddies the process of diagnosis., Case: A 51-year-old woman was referred with a large adnexal mass that appeared on ultrasound to be a simple ovarian cyst. Because of its 10-cm diameter in a postmenopausal patient who could not guarantee close follow-up, surgery was performed. Normal ovaries were encountered, along with a large uterine cyst, identified as a degenerative leiomyoma., Conclusion: Our case appears to be the largest simple cystic degenerative uterine leiomyoma reported and illustrates the possible diagnostic confusions. Subtle clues may differentiate uterine from adnexal cystic structures sonographically, but this case illustrates that while extremely valuable, sonographic evaluation in gynecology is not infallible.

Investigations by reversed-phase HPLC into the stability of ethacrynic acid in buffered aqueous solutions containing either sodium or ammonium ions showed that the extent of degradation was influenced both by the species and concentration of the cation. A reported incompatibility between ethacrynic acid and the ammonium ion, attributed to the influence of the ammonium ion on an equilibrium existing between ethacrynic acid and one of its known degradation products, was shown to be due to the generation of an additional degradation product in ammonium-containing solutions only. This product was isolated and identified. Different pathways of degradation were shown to be operative in sodium- and ammonium-containing solutions. The addition of formaldehyde or a formaldehyde scavenger (hydroxyammonium chloride) was found to influence the rate of loss of ethacrynic acid, but the decomposition products provided no evidence for the existence of the reported equilibrium.

Neonatal seizures have been observed as early as the first hour of life. It has been postulated that for certain central nervous system disorders, seizure activity may occur in utero. This report describes two cases of spontaneous fetal seizure activity diagnosed by real-time ultrasound.

An accurate, reproducible, and specific reversed-phase high-performance liquid chromatographic (HPLC) system was developed for the determination of ethacrynic acid and its degradation products. The method was used in stability studies of the drug in the solid state, in solution, and in dosage forms. Three degradation products were isolated by preparative chromatography and identified by several techniques, principally NMR and MS. TLC Rt and HPLC response factors are quoted. A degradation scheme consistent with the observed stability profiles is proposed.

One hundred thirty-five patients undergoing vaginal hysterectomy were randomly assigned to one of three regimens of prophylactic antibiotics. There was no statistically significant difference among the three groups in the incidence of postoperative pelvic cellulitis, fever index, or duration of hospitalization. A single preoperative dose of cefazolin was as effective as three perioperative doses of cefazolin or a single dose of cefonicid in preventing postoperative infectious morbidity.