Galactose protects against cell damage in mouse models of acute pancreatitis

Acute pancreatitis (AP), a human disease in which the pancreas digests itself, has substantial mortality with no specific therapy. The major causes of AP are alcohol abuse and gallstone complications, but it also occurs as an important side effect of the standard asparaginase-based therapy for childhood acute lymphoblastic leukemia. Previous investigations into the mechanisms underlying pancreatic acinar cell death induced by alcohol metabolites, bile acids, or asparaginase indicated that loss of intracellular ATP generation is an important factor. We now report that, in isolated mouse pancreatic acinar cells or cell clusters, removal of extracellular glucose had little effect on this ATP loss, suggesting that glucose metabolism was severely inhibited under these conditions. Surprisingly, we show that replacing glucose with galactose prevented or markedly reduced the loss of ATP and any subsequent necrosis. Addition of pyruvate had a similar protective effect. We also studied the effect of galactose in vivo in mouse models of AP induced either by a combination of fatty acids and ethanol or asparaginase. In both cases, galactose markedly reduced acinar necrosis and inflammation. Based on these data, we suggest that galactose feeding may be used to protect against AP

Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis

A Simulation-Based Study of Classroom IAQ and Thermal Comfort Performance Across New Zealand’s Six Climate Zones: The Avalon Typology

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Density-Dependent Variations of Vegetation Dynamics in the Horton Plains National Park as Indicators of the Possible Long-Term Impacts of Forest Dieback and Recovery

Forest dieback in the Horton Plains (HNP) has been documented since the 1970s.  However, its impact on the current vegetation composition has not been studied.  Our objective was to determine the possible impacts of forest dieback on vegetation diversity and taxonomic composition in HNP.  Here, we carried out a complete vegetation census of all trees ≥ 5 cm diameter at breast height in 24 sub-plots of 25 m × 25 m within four main plots (3750 m2 each) having six sub-plots each.  Two of the main plots (A and B) were on the eastern slope of HNP towards Ohiya while the other two (C and D) were on the western slope towards ‘World’s End’.  Tree density at the sub-plot and main plot levels varied significantly (p(χ2) <0.0001) with main plots A and C having lower tree densities (1,363 and 1,824 ha-1) than B and D (3,253 and 2,712 ha-1), possibly as a long-term (over 50 years since the 1970s) consequence of dieback-related phenomena. Shannon-Wiener and Simpson diversity indices, species richness and Shannon-Wiener and Simpson evenness indices varied significantly (p<0.05) among main plots while showing negative linear relationships with tree density at the main plot level.  Accordingly, all five indices were higher in the two lower-density plots (A and C) in comparison to the respective higher-density plots (B and D). We recorded 42 tree species in the overall study area, with Syzygium revolutum (IVI=27.97), Symplocos bractealis (IVI=23.08) and Neolitsea fuscata (IVI=20.45) being the three most-influential, based on the Importance Value Index (IVI).  We identified tree species sensitive or resilient to density reduction, possibly due to dieback-related phenomena, by quantifying the plot-wise variation of IVI of each species.  Accordingly, Syzygium revolutum and Symplocos bractealis showed substantial reductions in IVI due to density reduction on both slopes of HNP, which shows that they are sensitive species.  In contrast, Calophyllum walkeri is identified as resilient as its IVI showed little variation with density reduction on both slopes.  The IVI of Neolitsea fuscata decreased with decreased tree density on the western slope, but increased on the eastern slope, thus showing differential sensitivity to dieback-related processes, probably due to environmental variations on the two slopes. Increasing trends in species richness, evenness and diversity indices with decreased tree density indicate that processes of recovery from tree dieback are occurring via colonization and re-growth.  These results reveal important underlying trends of vegetation dynamics in HNP. Keywords: Horton Plains, Forest dieback, IVI, Diversity, Tree densit

Assessment of Forest Health in the Horton Plains National Park in Relation to Possible Forest Dieback and Recovery

Dieback of the upper montane forest in the Horton Plains (HNP) has been reported since 1970s.  While some visual patches of dieback are observed, there have been limited systematic assessments on the underlying status of the forest, especially in areas which do not show widespread tree death.  Here, our objective was to quantify the current health status of the forest in HNP via a comprehensive tree-level assessment scheme.  For this purpose, we developed a ‘dieback index (DBI)’ based on visual assessment of, (a) percentage of defoliation and (b) presence of abnormalities (disease symptoms, physical damage, yellowing etc.) in the foliage canopy plus (c) the extent of stem damage in each individual tree of DBH≥5 cm in 24 sampling plots (25 m×25 m) within four main plots of 3750 m2, distributed equally on eastern and western slopes of HNP.  Based on defoliation and leaf abnormalities, the health status of the foliage canopy of each tree was ranked from 1 (healthy) to 6 (dead).  Similarly, health status of each tree stem was ranked on a 1 (<10% of surface area below 1.5 m height damaged) to 6 (>75% damaged) scale.  For each tree, a combined rank on a 1-6 scale was given based on the combination of leaf and stem ranks.  A dieback score for each tree was given based on the combined rank as: rank 1-0%; 2-20%; 3-40%; 4-60%; 5-80% and 6-100%. Finally, a dieback index (DBI) for each 25 m×25 m plot was computed as the sum of dieback scores of its trees weighed by the fraction of trees within each combined rank.  A vegetation survey during August-October 2023 showed that plot-wise DBI, which could range from 0 (healthy) to 100 (dead), varied significantly (p<0.001) among the four main plots. The two main plots on the eastern slope of HNP showed significantly (p<0.05) higher mean DBI (51.40 and 45.43) than the two plots on the western slope (35.57 and 37.91). At the plot level, DBI varied from 28.82 to 54.40 and showed a significant (p<0.05) negative linear relationship with canopy leaf area index as measured by hemispherical photography in each plot.  Canopy openness, measured as the visible sky fraction of each hemispheric image, showed a significant (p<0.05) positive linear relationship with DBI.  These relationships validated DBI as a measure of health status of the forest, which can be used in future assessments of forest health and dieback status at HNP.   Keywords: Horton Plains, Dieback index, Forest health, Leaf area inde

Clinical Utility of Radiologic Disease Reassessment in the Management of Pediatric B-Cell Non-Hodgkin Lymphoma

Although outcomes for children with B-cell non-Hodgkin lymphoma are excellent, between 20% and 40% demonstrate residual radiologic abnormalities at disease assessment during consolidation therapy, the significance of which remains uncertain. The authors report the outcomes for all children treated for B-cell non-Hodgkin lymphoma at our center over an 11-year period. Twenty-four of 64 (38%) children had residual radiologic abnormalities at disease remission assessment. Seven (29%) underwent histologic biopsies that were normal. No children with residual radiologic abnormalities experienced disease relapse or death, suggesting that imaging at this time point creates clinical uncertainty without indicating residual disease or predicting relapse

Women and citizenship post-trafficking : the case of Nepal

The research for this paper was funded by the Economic and Social Research Council – ESRC Res-062-23-1490: ‘Post Trafficking in Nepal: Sexuality and Citizenship in Livelihood Strategies’. Diane Richardson would like to acknowledge the support provided by the award of a Leverhulme TrustMajor Research Fellowship, ‘Transforming Citizenship: Sexuality, Gender and Citizenship Struggles’ [award MRF-2012-106].This article analyses the relationship between gender, sexuality and citizenship embedded in models of citizenship in the Global South, specifically in South Asia, and the meanings associated with having - or not having - citizenship. It does this through an examination of women's access to citizenship in Nepal in the context of the construction of the emergent nation state in the 'new' Nepal 'post-conflict'. Our analysis explores gendered and sexualized constructions of citizenship in this context through a specific focus on women who have experienced trafficking, and are beginning to organize around rights to sustainable livelihoods and actively lobby for changes in citizenship rules which discriminate against women. Building from this, in the final section we consider important implications of this analysis of post-trafficking experiences for debates about gender, sexuality and citizenship more broadly.Publisher PDFPeer reviewe