Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.

Non-communicable diseases are projected to become the most common causes of death in Africa by 2030. The impact on health of epidemiological and nutritional transitions in sub-Saharan Africa remains unclear. To assess the trends of dietary fatty acids over time in Uganda, we examined fatty acids in serum collected from individuals in rural south-west Uganda, at three time points over two decades. Independent cross-sectional samples of 915 adults and children were selected from the general population cohort in 1990 (n 281), 2000 (n 283) and 2008 (n 351). Serum phospholipid fatty acids were measured by GC. Multivariate regression analyses were performed to compare the geometric means of fatty acids by time period. Serum fatty acid profiling showed high proportions of SFA, cis-MUFA and industrial trans-fatty acids (iTFA), likely to be biomarkers of high consumption of palm oil and hydrogenated fats. In contrast, proportions of n-6 and n-3 PUFA from vegetable oils and fish were low. From 1990 to 2008, serum phospholipids showed increases in absolute amounts of SFA (17·3 % increase in adults and 26·4 % in children), MUFA (16·7 % increase in adults and 16·8 % in children) and n-6:n-3 PUFA (40·1 % increase in adults and 39·8 % in children). The amount of elaidic acid, iTFA from hydrogenated fats, increased in children (60·1 % increase). In this rural Ugandan population, we show evidence of unfavourable trends over time of dietary fatty acids.

Background: Recent research has supported the efficacy of schema therapy as a treatment for personality disorders. A group format has been developed (group schema therapy; GST), which has been suggested to improve both the clinical and cost-effectiveness of the treatment. Aims: Efficacy studies of GST need to assess treatment fidelity. The aims of the present study were to improve, describe and evaluate a fidelity measure for GST, the Group Schema Therapy Rating Scale – Revised (GSTRS-R). Method: Following a pilot study on an initial version of the scale (GSTRS), items were revised and guidelines were modified in order to improve the reliability of the scale. Students highly experienced with the scale rated recorded GST therapy sessions using the GSTRS-R in addition to a group cohesion measure, the Harvard Community Health Plan Group Cohesiveness Scale – II (GCS-II). The scores were used to assess internal consistency and inter-rater reliability. Discriminant validity was assessed by comparing the scores on the GSTRS-R with the GCS-II. Results: The GSTRS-R displayed substantial internal consistency and inter-rater reliability, and adequate discriminate validity, evidenced by a weak positive correlation with the GCS-II. Conclusions: Overall, the GSTRS-R is a reliable tool that may be useful for evaluating therapist fidelity to GST model, and assisting GST training and supervision. Initial validity was supported by a weak association with GCS-II, indicating that although associated with cohesiveness, the instrument also assesses factors specific to GST. Limitations are discussed.

The Immobilisation Science Laboratory, University of Sheffield, is working with Magnox South Ltd to develop a range of glass formulations that are suitable for vitrification of the Wet Intermediate Level Waste (WILW) envelope arising from decommissioning of the Hinkley Point ‘A’ (HPA) power station. Four waste mixtures or permutations are under consideration for volume reduction and immobilisation by vitrification. The inorganic fractions of several of the wastes are suitable for vitrification as they largely consist of SiO2, MgO, Fe2O3, Na2O, Al2O3 and CaO. However, difficulties may arise from the high organic and sulphurous contents of certain waste streams, particularly spent ion exchange (IEX) resins. IEX resin wastes may be the key factor in limiting waste loading, and possible thermal pretreatments of IEX resin to decrease C and S contents prior to vitrification have been investigated. Our results suggest that lowtemperature (90 °C) pretreatment is more favourable than hightemperature (250, 450, 1000 °C) pretreatment. A thorough desktop study has provided initial candidate glass compositions which have been downselected on the basis of glass forming ability, melting temperature, viscosity, liquidus temperature, chemical durability and potential sulphate capacity. Early results for two of the candidate glass formulations indicate that formation of an amorphous product with at least 35 wt % (dry waste) loading is achievable for HPA IEX resin wastes.

Damage to, or deterioration of, the keratinized horn tissue of the bovine hoof claw culminates ultimately in the development of solear ulceration. We have observed abnormal keratin distribution at the site of solear ulceration in the bovine claw that may be due to alteration of the positional cues of the keratinocytes. In this study we have characterized key cell biological changes associated with ulceration in the claw that may precipitate abnormal keratinization. Loss of basement membrane at sites of ulceration was found by immunofluorescent detection of laminin and integrins. In other tissues, basement membrane breakdown results from degradation by matrix metalloproteinases (MMPs). Similarly, elevated levels of MMPs 2 and 9 were observed in ulcerated bovine claw tissue both by zymography and, quantitatively, by assay of enzyme activity. In the sole of claws that contained an ulcer, tissue distal to the ulcer site also had elevated MMP 2 when compared with healthy sole tissue from the same animals, as did sole tissue of claws recovering from ulceration. Tissue inhibitor of metalloproteinase 2 (TIMP 2) was detected by ELISA in healthy tissue. TIMP 2 tended to be lower in diseased tissue distal to ulcer sites, and was significantly lower in ulcerated tissue. MMP 2 was located by immunofluorescence in the dermal and basal epidermal region of sole tissue, in the region of the basement membrane. Increased punctate staining of material in the dermis was associated with ulcerated material. ELISA of TIMP 2 in tissue extracts enriched for dermis or epidermis confirmed that the inhibitor was located predominantly in the dermis. To investigate a possible causal relationship between basement membrane anchorage and epidermal keratinization, the effect of function-blocking antibodies to laminins and integrins was tested in tissue explant cultures prepared from healthy sole tissue. Anti-integrin antibody treatment had no effect on either protein or DNA synthesis. In contrast, in the presence of anti-laminin antibody, protein synthesis was decreased in a concentration-dependent manner, a significant effect being observed at the highest concentration after treatment for 24 h. At this concentration, DNA synthesis was also decreased after 48 h of culture, an effect that may be relevant to a hibernal reduction in claw cell turnover, and the associated seasonal vulnerability of cows to claw damage. The results provide evidence for basement membrane disruption at ulcer sites, and an increased potential for disruption in the diseased claw, and a causal link between this and abnormal epidermal keratinization. Basement membrane disruption is in turn associated with reciprocal changes in MMPs and their inhibitors, favouring extracellular proteolysis. Whether MMP activation is the primary cause of dermal–epidermal deterioration and, if so, how MMP activation is triggered, remains to be determined.

The decline in milk yield after peak lactation in dairy animals has long been a biological conundrum for the mammary biologist, as well as a cause of considerable lost income for the dairy farmer. Recent advances in understanding the control of the mammary cell population now offer new insights on the former, and a potential means of alleviating the latter. The weight of evidence now indicates that a change in mammary cell number, the result of an imbalance between cell proliferation and cell removal, is a principal cause of declining production. Further, it suggests that the persistency of lactation, the rate of decline in milk yield with stage of lactation, is strongly influenced by the rate of cell death by apoptosis in the lactating gland. Mammary apoptosis was first demonstrated during tissue involution after lactation, but has now been detected during lactation, in mammary tissue of lactating mice, goats and cattle. Those factors that determine the rate of cell death by apoptosis are as yet poorly characterized, but include the frequency of milking in lactating goats. Initial evidence suggests that nutrition also is likely to influence cell survival after peak lactation, an important factor being the degree of oxidative stress imposed by feed and the tissue's ability to deal with, and prevent damage by, reactive oxygen species. Comparison of cows in calf or not pregnant during declining lactation also indicates a likely influence of reproductive hormones, with oestradiol and progesterone acting to preserve mammary ductal and alveolar integrity during the dry period, while allowing a degree of apoptosis and cell replacement. In each case, the molecular mechanisms controlling mammary cell survival (or otherwise) are as yet poorly defined. On the other hand, more persistent lactations are likely to benefit animal welfare through fewer calvings and by placing less emphasis on maximal production at peak lactation, and modelling of persistent lactation with longer calving intervals indicates their likely economic benefits. In these circumstances, there is considerable incentive to elucidate the determinants of mammary apoptosis, and the factors controlling the dynamic balance between cell proliferation and cell death in the lactating mammary gland.

Keratinization of the epidermal cells of the bovine claw generates the horn that gives the tissue its mechanical strength. Disruption of keratinization is likely to have a detrimental effect on the strength and integrity of the horn, and could lead to solar lesions and lameness. As part of a wider investigation of the cell biological causes of lameness in dairy animals, we have compared keratin synthesis and distribution in healthy bovine claw tissue with those in hooves with solar ulcers. Protein synthesis was measured by [35S]-labelled amino acid incorporation in claw tissue explant cultures. [35S]-labelled protein synthesis was higher in tissue from diseased claws than in healthy claws, and highest at the ulcer site. The identity of proteins synthesised in vitro did not differ between healthy and diseased tissue. DNA synthesis indicative of cell proliferation was also elevated in diseased tissue. Immunoblotting after one- or two-dimensional electrophoresis showed cytokeratins (CK) 4, 5/6, 10 and 14 to be amongst those expressed in healthy claw tissue. The relative abundance of these keratins was not altered in healthy regions of ulcerated hooves, nor at the ulcer site, but CK16, not usually found in healthy tissue, was detected in the sole of diseased claws. CK5/6 and CK14 were shown by immunohistochemistry to be present in the basal epidermis of healthy tissue, whereas CK10 was found in supra-basal layers. In healthy tissue from ulcerated claws, this distribution was unaltered, but at the site of solar ulcers, CK5/6 and CK14 were each found in both basal and supra-basal epidermis. The study suggests that solar ulceration of the bovine claw is not associated with gross alteration in the keratin composition of the tissue, but causes abnormal distribution of cytokeratins, perhaps as a result of loss of positional cues from the basement membrane. Ulceration did, however, stimulate cell repair involving epidermal protein synthesis (including keratins), and keratinocyte proliferation.

Chemically modified nucleotide analogs have gained widespread popularity for probing structure–function relationships. Among the modifications that were incorporated into RNAs for assessing the role of individual functional groups, the phenyl nucleotide has displayed surprising effects both in the contexts of the hammerhead ribozyme and pre-mRNA splicing. To examine the conformational properties of this hydrophobic base analog, we determined the crystal structure of an RNA double helix with incorporated phenyl ribonucleotides at 1.97 Å resolution. In the structure, phenyl residues are engaged in self-pairing and their arrangements suggest energetically favorable stacking interactions with 3′-adjacent guanines. The presence of the phenyl rings in the center of the duplex results in only moderate changes of the helical geometry. This finding is in line with those of earlier experiments that showed the phenyl analog to be a remarkably good mimetic of natural base function. Because the stacking interactions displayed by phenyl residues appear to be similar to those for natural bases, reduced conformational restriction due to the lack of hydrogen bonds with phenyl as well as alterations in its solvent structure may be the main causes of the activity changes with phenyl-modified RNAs.

Laminitis is a major cause of lameness in dairy cattle, and is widely attributed to a defect in the horny tissue that gives the hoof its mechanical strength. Defective horn is associated with, and may be preceded by, impaired keratin deposition in the hoof epidermis. The cause of abnormal keratin deposition is not easily identified but, like epidermal keratinization in other tissues, is likely to be controlled by hormones and the paracrine action of locally produced growth factors. The hormonal regulation of keratin synthesis and cell proliferation in the bovine hoof was studied using tissue explants in organ culture. As the highest incidence of laminitis is in early lactation, the study focused on insulin, cortisol and prolactin, three hormones implicated in lactogenesis and galactopoiesis. Incubation of tissue explants for 24 h in medium containing insulin (10–5000 ng/ml) stimulated protein synthesis measured by incorporation of 35 S-labelled amino acids. Histochemical examination showed that insulin binding co-localized with the site of protein synthesis. Insulin also stimulated DNA synthesis, an index of cell proliferation, which was measured by incorporation of [3H]methyl thymidine. Cortisol (10–5000 ng/ml) decreased protein synthesis, whereas prolactin (10–5000 ng/ml) had no significant effect on protein or DNA synthesis. Epidermal growth factor (10–200 ng/ml), a potent inhibitor of keratinization in other tissues, stimulated protein synthesis compared with untreated controls. Epidermal growth factor binding was located microscopically to the germinal and differentiating epidermal layers. SDS-PAGE and fluorography showed that the population of proteins synthesized in the presence of any hormone or growth factor combination did not differ from that in untreated controls and included the keratins involved in horn deposition. The results show that bovine hoof keratinization is under endocrine and growth factor control, and suggest that systemic changes in lactogenic hormones may act to inhibit keratin deposition.