Renewing approaches to understanding the minerals and waters at alkaline waste sites

Highly alkaline (pH 9-12) waters can arise from a range of natural and anthropogenic processes. The latter include drainage waters from a range of globally significant anthropogenic by-products such as lime, cement and steel wastes, bauxite processing residue and combustion ashes. Such waste storage sites are often characterised by extreme geochemical conditions that can be hazardous to aquatic life, but are equally an increasing focus for resource recovery and carbon capture initiatives. The very high rates of mineral precipitation at these sites can give rise to the formation of transient minerals that are not currently well understood. As such our estimates of carbon budgets and understanding of trace metal dynamics at highly alkaline sites is currently limited. This thesis aimed to improve the basis for characterising hyperalkaline carbonate systems by (1) understanding the dominant carbonate fabrics found in secondary deposits and their formation processes, (2) identifying transient minerals forming at hyperalkaline sites, and (3) improving methods for characterising dissolved inorganic carbon and secondary mineral phases at high pH sites.Petrographic analysis showed distinctive shrubby carbonates forming in hyperalkaline (pH 9–12) and moderate conductivity (conductivity 425–3200μS) solutions at ambient temperature (12.5–13°C) at two disposal sites in the UK. Microfabrics in anthropogenic sites are comparable to travertines but lack the sub-surface facies and at extreme pH exhibit sparry crusts without clear equivalents in travertines. Despite the highly alkaline conditions, significant diatomaceous and cyanobacterial biofilms were reported growing in the presence of these carbonates, suggesting a bio-influence on their formation. This sedimentology of anthropogenic carbonates shows that calcite mineral formation is complex and not homogeneous or purely driven by thermodynamic processes.Whilst most of the secondary deposits at the study sites appear to be dominated by calcite, this study provides the first account internationally of ikaite (CaCO3.6H2O) crystallization within steel-slag leachate through novel field (Fourier Transform Infra-Red) and laboratory (X-Ray Diffraction) validation. This study suggests that ikaite is a secondary mineral with a primary phase being amorphous calcium carbonate (ACC). The ikaite forming in steel-slag leachate affected waters is incorporating large inventories of potentially harmful metals (e.g. lead and cadmium) which could be of environmental concern given ikaite is not thermally stable and could release a pulse of contamination in short duration warming events. The final component of the study develops a new protocol for assessing dissolved inorganic carbon (DIC) in alkaline waters via strontium carbonate precipitation. This method is compared to established methods for DIC using field and laboratory titration. The strontium method appears to perform much better than the existing methods and is likely to provide more robust estimates of alkalinity and saturation index of carbonate minerals.The combined findings provide an improved understanding of carbonate precipitation processes at highly alkaline sites which in turn should assist future research endeavours around mineral carbonation, trace metal dynamics and environmental remediation at these sites

What are the different styles of calcite precipitation within a hyperalkaline leachate? A sedimentological Anthropocene case study

This study aims to compare the fabrics of anthropogenic carbonates downstream of lime and steel disposal sites with models of carbonate precipitation from natural systems to elucidate potential drivers, precipitation mechanisms, morphological similarities, predictability in 3D facies distributions and depositional models of these systems. For this purpose, a combination of sedimentological, mineralogical and geochemical approaches is conducted including the analysis of microfacies (petrographic microscope and electron microscopy), X-ray diffraction and hydrochemistry. The data show that both anthropogenic and natural systems exhibit clear proximal, middle and distal zones of carbonate precipitation. The main macroscopic differences are the dominance of swamp environments in the proximal zone and the prevalence of tufa-like barrage-and-pool sequences in the middle and distal zones. Microfabrics in anthropogenic sites are comparable to travertines but lack the sub-surface facies and at extreme pH exhibit sparry crusts without clear equivalents in travertines. This sedimentology of anthropogenic carbonates shows that calcite mineral formation is complex and not homogeneous or purely driven by thermodynamic processes. Considering the sedimentology of these human-induced systems will help us understand precipitation mechanisms which will aid both efforts to utilise anthropogenic alkaline wastes for carbon capture and manage their environmental impacts

What Causes Carbonates to Form “Shrubby” Morphologies? An Anthropocene Limestone Case Study

The South Atlantic Aptian “Pre-Salt” shrubby carbonate successions offshore Brazil and Angola are of major interest due to their potential hydrocarbon accumulations. Although the general sedimentology of these deposits is widely recognized to be within saline, alkaline lakes in rift volcanic settings, the specific genesis of shrubby carbonate morphologies remains unclear. This study reports the first petrographically comparable shrubby carbonates amongst other carbonate microfacies from an Anthropocene limestone formed under hyperalkaline (pH 9–12) and hypersaline (conductivity 425–3200 μS) conditions at ambient temperature (12.5–13°C) (Consett, United Kingdom). This discovery allows us to capitalize on exceptional long-term hydrochemical monitoring efforts from the site, demonstrating that shrubby carbonates occur uniquely within the waters richest in calcium (∼240 mg/L) and with highest pH (∼12) and consequently with very high levels of supersaturation. However, the physical distribution of shrubs is more comparable with estimated local kinetic precipitation rate than it is to thermodynamic saturation, indicating that the fundamental control on shrub formation arises from crystal surface processes. The shrubby carbonate we report grows in the presence of significant diatomaceous and cyanobacterial biofilms, despite the highly alkaline conditions. These biofilms are lost from the deposited material early due to the high solubility of organic and silica within hyperalkaline settings, and this loss contributes to very high intercrystalline porosity. Despite the presence of these microbes, few if any of the fabrics we report would be considered as “boundstones” despite it being clear that most fabrics are being deposited in the presence of abundant extra-cellular polymeric substances. We are aware of no previous petrographic work on anthropogenic carbonates of this type, and recommend further investigation to capitalize on what can be learned from these “accidental laboratories.”

Heterozygous CDKL5 Knockout Female Mice Are a Valuable Animal Model for CDKL5 Disorder

CDKL5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked CDKL5 (cyclin-dependent kinase-like five) gene. CDKL5 disorder primarily affects girls and is characterized by early-onset epileptic seizures, gross motor impairment, intellectual disability, and autistic features. Although all CDKL5 female patients are heterozygous, the most valid disease-related model, the heterozygous female Cdkl5 knockout (Cdkl5 +/-) mouse, has been little characterized. The lack of detailed behavioral profiling of this model remains a crucial gap that must be addressed in order to advance preclinical studies. Here, we provide a behavioral and molecular characterization of heterozygous Cdkl5 +/- mice. We found that Cdkl5 +/- mice reliably recapitulate several aspects of CDKL5 disorder, including autistic-like behaviors, defects in motor coordination and memory performance, and breathing abnormalities. These defects are associated with neuroanatomical alterations, such as reduced dendritic arborization and spine density of hippocampal neurons. Interestingly, Cdkl5 +/- mice show age-related alterations in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling, two crucial signaling pathways involved in many neurodevelopmental processes. In conclusion, our study provides a comprehensive overview of neurobehavioral phenotypes of heterozygous female Cdkl5 +/- mice and demonstrates that the heterozygous female might be a valuable animal model in preclinical studies on CDKL5 disorder

Cardiac Functional and Structural Abnormalities in a Mouse Model of CDKL5 Deficiency Disorder

CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a severe neurodevelopmental disease that mostly affects girls, who are heterozygous for mutations in the X-linked CDKL5 gene. Mutations in the CDKL5 gene lead to a lack of CDKL5 protein expression or function and cause numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, gastrointestinal problems, and severe neurodevelopmental impairment. Mouse models of CDD recapitulate several aspects of CDD symptomology, including cognitive impairments, motor deficits, and autistic-like features, and have been useful to dissect the role of CDKL5 in brain development and function. However, our current knowledge of the function of CDKL5 in other organs/tissues besides the brain is still quite limited, reducing the possibility of broad-spectrum interventions. Here, for the first time, we report the presence of cardiac function/structure alterations in heterozygous Cdkl5 +/- female mice. We found a prolonged QT interval (corrected for the heart rate, QTc) and increased heart rate in Cdkl5 +/- mice. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Interestingly, Cdkl5 +/- hearts showed increased fibrosis, altered gap junction organization and connexin-43 expression, mitochondrial dysfunction, and increased ROS production. Together, these findings not only contribute to our understanding of the role of CDKL5 in heart structure/function but also document a novel preclinical phenotype for future therapeutic investigation

Expression of a Secretable, Cell-Penetrating CDKL5 Protein Enhances the Efficacy of Gene Therapy for CDKL5 Deficiency Disorder

Although delivery of a wild-type copy of the mutated gene to cells represents the most effective approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for treatment of brain disorders. Herein, we develop a cross-correction-based strategy to enhance the efficiency of a gene therapy for CDKL5 deficiency disorder, a severe neurodevelopmental disorder caused by CDKL5 gene mutations. We created a gene therapy vector that produces an Igk-TATk-CDKL5 fusion protein that can be secreted via constitutive secretory pathways and, due to the cell-penetration property of the TATk peptide, internalized by cells. We found that, although AAVPHP.B_Igk-TATk-CDKL5 and AAVPHP.B_CDKL5 vectors had similar brain infection efficiency, the AAVPHP.B_Igk-TATk-CDKL5 vector led to higher CDKL5 protein replacement due to secretion and penetration of the TATk-CDKL5 protein into the neighboring cells. Importantly, Cdkl5 KO mice treated with the AAVPHP.B_Igk-TATk-CDKL5 vector showed a behavioral and neuroanatomical improvement in comparison with vehicle or AAVPHP.B_CDKL5 vector-treated Cdkl5 KO mice. In conclusion, we provide the first evidence that a gene therapy based on a cross-correction approach is more effective at compensating Cdkl5-null brain defects than gene therapy based on the expression of the native CDKL5, opening avenues for the development of this innovative approach for other monogenic diseases

Dinoflagellate resting cysts from surface sediments of the Adriatic Ports: distribution and potential spreading patterns

The ability of microalgae to preserve viable in coastal sediments as resting forms provides a reservoir of biodiversity and a useful tool to determine species spreadings. This study represents the first port baseline survey on dinoflagellate cysts, investigated in nine Adriatic ports during a cross border project. 40 dinoflagellate taxa were detected. The assemblages resulted in all ports dominated by Lingulodinium polyedra and Alexandrium minutum/affine/tamutum group. General separation to the western and eastern side of the Adriatic regarding cysts assemblage composition, partially abundance, was observed. Seven taxa were detected as non-indigenous species for the Adriatic. Two taxa are included in the list of harmful aquatic organisms, indicating the potential threat of ballast waters in the Adriatic. Potential spreading of taxa by general circulation and ballast waters, intra- and extra-Adriatic was investigated. The entering in to force of the ballast waters management regulations should enhance prospects to minimize future harmful impacts

Ikaite formation in streams affected by steel waste leachate: First report and potential impact on contaminant dynamics

Highly alkaline (pH 9–12) waters can arise from a range of globally significant and environmentally impactful industrial processes such as lime, steel and cement production, alumina refining and energy generation (e.g. combustion ashes). Such residue storage sites are often characterized by extreme geochemical conditions that can be hazardous to aquatic life but are quickly becoming a critical focus for resource recovery and carbon capture initiatives. The very high rates of mineral precipitation at these sites can give rise to the formation of transient minerals that are not currently well understood. As such our estimates of carbon budgets and understanding of trace metal dynamics at highly alkaline sites is currently limited. This study provides a significant advancement in the basis for characterising hyperalkaline carbonate systems through identification and chemical analysis of transient minerals forming in sites receiving high pH (>11) steel slag leachate in northern England. Whilst most of the secondary deposits at the study sites appear to be dominated by calcite, this study provides the first account of ikaite (CaCO3.6H2O) crystallization within steel-slag leachate, using novel field (Fourier Transform Infra-Red) supported by rapid laboratory (X-Ray Diffraction) validation. This study suggests that ikaite is a secondary mineral with a primary phase being amorphous calcium carbonate (ACC). Trace element analysis of ikaite forming in these steel-slag leachate affected waters is demonstrates its strong affinity to incorporate relatively large inventories of potentially harmful metals (e.g. lead and cadmium). Importantly, ikaite is only stable at low temperatures (−4 to 8 °C) and thus is of significant concern given its potential to release hazardous pulses of contamination during warming events in the spring. The findings provide an improved understanding of carbonate precipitation processes at highly alkaline sites which in turn should influence future research endeavours around mineral carbonation, trace metal dynamics and environmental remediation at these sites globally

Pilot Study of the Effects of Chronic Intracerebroventricular Infusion of Human Anti-IgLON5 Disease Antibodies in Mice

Background: Anti-IgLON5 disease is a rare late-onset neurological disease associated with autoantibodies against IgLON5, neuronal accumulation of phosphorylated Tau protein (p-Tau), and sleep, respiratory, and motor alterations. Purpose: We performed a pilot study of whether the neuropathological and clinical features of anti-IgLON5 disease may be recapitulated in mice with chronic intracerebroventricular infusion of human anti-IgLON5 disease IgG (Pt-IgG). Methods: Humanized transgenic hTau mice expressing human Tau protein and wild-type (WT) control mice were infused intracerebroventricularly with Pt-IgG or with antibodies from a control subject for 14 days. The sleep, respiratory, and motor phenotype was evaluated at the end of the antibody infusion and at least 30 days thereafter, followed by immunohistochemical assessment of p-Tau deposition. Results: In female hTau and WT mice infused with Pt-IgG, we found reproducible trends of diffuse neuronal cytoplasmic p-Tau deposits in the brainstem and hippocampus, increased ventilatory period during sleep, and decreased inter-lick interval during wakefulness. These findings were not replicated on male hTau mice. Conclusion: The results of our pilot study suggest, but do not prove, that chronic ICV infusion of mice with Pt-IgG may elicit neuropathological, respiratory, and motor alterations. These results should be considered as preliminary until replicated in larger studies taking account of potential sex differences in mice

PERPASSANDO A TEMÁTICA FAMÍLIA NAS TESES DE DOUTORADO DE 2004 A 2013 NA UNIVERSIDADE ESTADUAL JÚLIO MESQUITA - CÂMPUS DE FRANCA

O presente artigo apresenta dados da pesquisa realizada no primeiro semestrede 2014, como instrumento de avaliação da aula integrada das disciplinas Seminários de Dissertação e Famílias e Relações de Gênero como Construções Sociais. O objetivo da pesquisa foi de identificar e analisar as teses de doutorado defendidas no Programa de Pós Graduação em Serviço Social da Universidade Estadual Paulista “Júlio de Mesquita Filho” – Faculdade de Ciências Humanas e Sociais Câmpus de Franca, entre os anos de 2004 e 2013 com a temática família. Os dados coletados considerados foram: o ano de defesa, os objetivos gerais e específicos, os aspectos teóricos e conceituais e os procedimentos metodológicos utilizados pelos autores