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Structures of α-galactosaminidases from the CAZy GH114 family and homologs defining a new GH191 family of glycosidases
Get PDFEndo-galactosaminidases are an underexplored family of enzymes involved in the degradation of galactosaminogalactan (GAG) and other galactosamine-containing cationic exopolysaccharides produced by fungi and bacteria. These exopolysaccharides are part of the cell wall and extracellular matrix of microbial communities. Currently, these galactosaminidases are found in three distinct CAZy families: GH114, GH135 and GH166. Despite the widespread occurrence of these enzymes in nearly all bacterial and fungal clades, only limited biochemical and structural data are available for these three groups. To expand our knowledge of endo-galactosaminidases, we selected several sequences predicted to encode endo-galactosaminidases and produced them recombinantly for structural and functional studies. Only very few predicted proteins could be produced in soluble form, and activity against bacterial Pel (pellicle) polysaccharide could only be confirmed for one enzyme. Here, we report the structures of two bacterial and one fungal enzyme. Whereas the fungal enzyme belongs to family GH114, the two bacterial enzymes do not lie in the current GH families but instead define a new family, GH191. During structure solution we realized that crystals of all three enzymes had various defects including twinning and partial disorder, which in the case of a more severe pathology in one of the structures required the design of a specialized refinement/model-building protocol. Comparison of the structures revealed several features that might be responsible for the described activity pattern and substrate specificity compared with other GAG-degrading enzymes
Magnetic interactions in CoFe2O4 / NiFe2O4 heterostructures
No full textFunctional oxides are a key class of materials that allows for epitaxial layering in order to combine different material properties. Epitaxial (111)-orientated CoFe2O4 / NiFe2O4 heterostructures were grown by pulsed laser deposition on Al2O3(0001) substrates and their structural and magnetic properties investigated. Whilst X-ray diffraction and electron microscopy demonstrate a single high quality coherent epitaxial film in the growth direction, chemical mapping by EDX and polarised neutron reflectivity analysis confirms chemical intermixing of Co and Ni ions across the interface. The chemical intermixing correlates to the strength of the exchange coupling at the interface that has implications for independent switching of layers in all-oxide spin filters
Genomic and transcriptomic analysis of ameloblastoma reveals distinct molecularly aggressive phenotypes
No full textAmeloblastoma (AM) is a benign but locally infiltrative epithelial odontogenic neoplasm of the jawbones that may reach grotesque proportions and be highly recurrent if inadequately removed. The BRAFV600E mutation has been demonstrated as a key molecular event in its development; nevertheless, there are many queries about its etiopathogenesis, which are yet to be answered. In this study, we aimed to integrate the results from whole-exome sequencing (WES) and RNA sequencing in AM samples to identify novel candidate genes that may be relevant to its pathogenesis. Thirteen-matched tumors were subjected to WES and RNA-seq, respectively, to detect gene mutations and gene expression profiles, along with the presence of gene fusions. Mutations were validated using Sanger sequencing, whereas transcriptome results were validated using qPCR. The results from both molecular techniques were merged in order to identify novel candidate genes that were biologically validated with immunohistochemistry. BRAFV600E mutation was present in 62% of the analyzed cases, and each AM presented at least 2 or 3 mutations affecting cancer-driver genes. RNA-seq showed different molecular subgroups associated with an aggressive and cancer-related phenotype (epithelial-mesenchymal transition and KRAS gene sets). No gene fusions were detected among the cases. CDH11 and TGM2, novel genes associated with epithelial-mesenchymal transition in AM, were selected and validated in tissues. Both WES and RNA-seq results showed gene alterations related to proliferation, cell differentiation, and metabolic processes. These results show that AM shares many of the hallmarks of cancer secondary to the presence of oncogenic mutations or activation of oncogenic signaling pathways
West Africa
No full textWest Africa is rarely included in standard studies of travel as a viable destination of medieval Europeans in its own right. It appears as a sideshow; part of a teleological narrative of exploration that had India as its target and modern imperialism as its long-term inevitable consequence. Perhaps as a result, pre-colonial Africa is often viewed through the lens of nineteenth- and twentieth-century British colonialism, something that is perpetuated today by continued Anglophone reliance on Hakluyt Society translations made during the colonial period. The texts to be discussed below originally involved layers of Castilian, Italian, French, Portuguese, or Latin; viewing them only from the British imperialistic perspective of these older translations can be very misleading. A result of this limited approach to West Africa is that several early accounts of European visits have been neglected. This chapter will explore some of accounts of West Africa, focusing on the vast coastlines of Upper and Lower Guinea (between modern Senegal and modern Ghana)
Disentangling social perspectives on the use of reclaimed water in agriculture using Q methodology
Get PDFReclaimed water is a promising alternative for irrigation in many water-stressed regions, but its expansion hinges on social acceptance. Previous studies have focused on the perceptions of consumers and farmers, overlooking the broader diversity of perspectives within the sector. This study seeks to address this gap by exploring the range of social perspectives on the use of reclaimed water for irrigation in Spain. Using Q methodology, we identified existing perspectives as well as synergies and frictions among them. We interviewed 23 stakeholders from environmental NGOs, food retailers, consumer and farmer organisations, public administrations, water treatment companies and associations, and water reuse experts. The results reveal three distinct perspectives: 1) reclaimed water must be promoted to secure agricultural production; 2) it has great potential, but needs technological improvement; and 3) it poses environmental risks, warranting cautious expansion. All perspectives agree that reclaimed water is a valuable resource for irrigation, but consumers lack sufficient information about its quality and benefits. Disagreements exist regarding its potential ecological impacts and who should bear the costs of reuse projects. Results suggest that avoiding negative environmental and socioeconomic impacts requires case by case consideration of reclamation technology and site-specific conditions. Additionally, awareness campaigns and stronger administrative support are crucial for promoting agricultural reclamation initiatives. This study underscores the importance of fostering stakeholder dialogue to promote sustainable and equitable reclaimed water use, ultimately supporting fair and effective water policies in Spain and other regions facing similar challenges
BPChAr—a Benzene Polycarboxylic Acid database to describe the molecular characteristics of laboratory-produced charcoal: Implications for soil science and archaeology
Get PDFThe benzene polycarboxylic acid (BPCA) method is a technique to characterise the aromaticity and aromatic condensation of pyrogenic carbon (PyC) in charred residues. As a molecular marker for polycondensed aromatic moieties, the analysis of BPCAs in archaeological contexts has great potential as a means of detecting and characterising charred residues where past fire traces are not evident. Despite the increased frequency of applications and significant developments since the method’s inception, no central database of BPCA results for modern charcoal pyrolysed under controlled laboratory conditions exists. Limited sample sizes in previous research have restricted the ability to precisely quantify the effects of combustion temperature, precursor feedstocks, pyrolysis parameters (e.g., oxygen availability), and methodological aspects (e.g., chromatography) on resultant BPCA profiles. To remedy this, we present the BPChAr database, which contains a total of 236 BPCA results on modern lab-produced charcoal. Through statistical analyses of the gathered data, we quantify the relationship between combustion temperature and resultant BPCA profiles, and construct random forest models to predict combustion temperature in unknown samples. Our findings show that additional variables hypothesised to play a role in shaping BPCA results — such as precursor feedstock type, oxygen availability during pyrolysis, and chromatographic separation method — have statistically significant implications for resultant BPCA profiles. Our analysis nuances these observations, highlighting at what charring temperatures and for what variables these concomitant parameters should be factored into the interpretation of BPCA results. Random forest models are also developed to predict precursor feedstock (hardwoods, softwoods, and grasses) in unknown samples, though further work is required to refine the accuracy of this model. The BPChAr database constitutes a fundamental tool for modern PyC research, and provides a baseline for future work aimed at employing the BPCA method in palaeoenvironmental and archaeological research
Association between walking and hip fracture in women aged 65 and older: 20-year follow-up from the study of osteoporotic fractures
Get PDFSummary
Hip fractures in elderly women pose significant healthcare challenges. Promoting walking for exercise as a cost-effective intervention may help reduce the risk of fractures in this population.
Purpose
This study aimed to examine the relationship between walking and hip fracture risk among women aged 65 years and older.
Methods
A 20-year prospective study (1986–2006) included 9704 women from the Study of Osteoporotic Fractures (SOF) in the USA. Participants were followed biennially, and walking exposure was assessed by the number of city blocks walked for exercise, routine activity, and total blocks walked daily. Cox regression models with time-varying covariates assessed associations, with competing risks addressed using Fine and Gray models. Penalized splines were used to explore dose–response relationships.
Results
In total, 1419 hip fractures were identified through the study period. The mean and median follow-up times for hip fractures or censoring were 15.0 and 15.8 years in the walking for exercise group, vs. 13.2 and 13.7 years in the not walking for exercise group. The hip fracture incidence rate was 10.0 cases per 1000 person-years (py) in the walking for exercise group compared to 10.9 per 1000 py in the not walking for exercise group. All-cause mortality was 37.1 per 1000 py in the walking for exercise group compared to 46.4 per 1000 py in the not walking for exercise group. Adjusted models showed that walking for exercise significantly reduced hip fracture risk (HR, 0.864; 95% CI, 0.762–0.980; P = 0.0230), with each additional block walked for exercise reducing risk (HR per block, 0.986; 95% CI, 0.978–0.995; P = 0.0022). Walking for routine activities showed no significant association. Spline analysis indicated walking 16 blocks (≈3200 steps) daily significantly lowered hip fracture risk.
Conclusion
Walking for exercise is linked to a reduced risk of hip fractures in elderly women. Walking the equivalent of 16 blocks or more (> 3200 steps) per day might be an effective way to reduce the risk of hip fractures in this vulnerable population
Managing lead times and backlogging in a resilient distribution network under demand uncertainty
Get PDFIn this work, we propose a novel multi-period location-inventory problem that assumes demand uncertainty, periodic review, backlogging, and lead times. The problem stems from the need to strategically manage distribution centers (DCs) to enhance the resilience of the supply chain, while providing a high service level to customers. A trade-off is sought between distribution resilience and stock-out risks on the one hand, and financial resources on the other hand. A progressive phase-in of the DCs is considered. The problem is cast as a two-stage decision-making process under uncertainty. A mixed-integer linear programming model is formulated. Two resilience indicators are adopted to access the results of a series of computational tests. Based on the experiments, it was found that the financial resources required to establish DCs throughout the planning horizon directly affect the long-term resilience of the supply chain. Nevertheless, the model proposed in this study can ensure that the supply chain resilience remains at a satisfactory level within the given financial resources
A Hybrid Γ-Model for Distribution Feeders: Linear Parameter Estimation Using Unsynchronized Terminal Measurements
Get PDFAccurate estimation of parameters for Distribution Network Feeders (DNFs) is crucial yet quite challenging, especially with limited synchronized measurements. This letter introduces a novel Hybrid Γ-Model (HGM) that leverages the circuit properties of DNFs to establish a linear relationship between unknown feeder parameters and unsynchronized terminal measurements. By combining two symmetrical Γ-models, the HGM effectively mitigates the inaccuracies and biases of simplified models. This model balances the accuracy of the equivalent П-model with the linearity of the short-line and Γ-models. An effective parameter estimation method is developed based on HGM, operating without requiring synchronized data. This method is applicable to both overhead lines and underground cables and is particularly useful in the latter case, where shunt susceptance is more significant. By avoiding iterative solutions, the proposed method ensures convergence and eliminates the risk of multiple outcomes
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