Objective
Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis ...(CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function.
Methods
Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell‐based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples.
Results
Patients with KCTD7 mutations can exhibit movement disorders or developmental regression before seizure onset, and are distinguished from similar disorders by an earlier age of onset. Although most published KCTD7 patient variants were excluded from a genome sequence database of normal human variations, most newly identified patient variants are present in this database, potentially challenging disease causality. However, genetic analysis and impaired biochemical interactions with cullin 3 support a causal role for patient KCTD7 variants, suggesting deleterious alleles of KCTD7 and other rare disease variants may be underestimated. Both patient‐derived fibroblasts and yeast lacking Whi2 with sequence similarity to KCTD7 have impaired autophagy consistent with brain pathology.
Interpretation
Biallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7 deficiency appears to cause an underlying autophagy‐lysosome defect conserved in yeast, thereby assigning a biological role for KCTD7. Ann Neurol 2018;84:774–788
Abstract
The article examines the assessment of ecological and economic competitiveness of regions using factor analysis. Ecological and economic competitiveness of the territory is formed from ...groups of components, some of which will determine its basic potential, others - the potential of possible development trajectories. The ratio of these components is different for each region and in each period of time when competitiveness is determined. Ecological and economic competitiveness of the region is determined by the ratio of several areas that interact and interdependent: social, economic, environmental. It is proposed to introduce the amount of atmospheric rent into the indicators of assessing the competitiveness of regions. Atmospheric rent is a fiscal lever of influence and a stimulus for the formation of ecological and economic competitiveness of the region. The factor analysis confirmed that the value of atmospheric rent is a significant indicator that belongs to the first, most important group of indicators, and therefore should be taken into account when conducting environmental and economic assessment. To study the ecological and economic competitiveness, there were built two models and compared by the results modeling. The most accurate model turned out to be additive, which is explained by a more balanced consideration of the load of indicators and the share of explained variation of data by each of the factors. The assessment of ecological and economic competitiveness was carried out on the example of regions of Ukraine and the ranks of these regions were determined.
Abstract
The article analyzes modern scientific approaches to sustainable finance and features of the transition of national financial systems, markets, financial flows in the direction from ...unsustainable to innovative sustainable technologies. The latest practice of implementing investment and financial activities in accordance with the goals of sustainable development is systematized. In the context of building a system of sustainable finance in Ukraine, the parity of two vectors of its functioning should be taken into account: ensuring both the sustainability of the financial sector itself and the sustainable functioning of the economy as a whole. That is, the development of the national system of sustainable finance in Ukraine is based on the generally recognized world practice in the field of sustainable finance and the decisions of the United Nations Organization, which relate to the financial aspects of sustainable development. In the context of this transformational process, Ukraine joined the Paris Agreement and received the Second Nationally Determined Contribution, which is a concept of state development to achieve ecologically and economically expedient transformations in all sectors of the economy. Financing of the Second Nationally Determined Contribution by 2030 should include a combination of domestic budget allocations, the private sector (domestic and foreign), bilateral and multilateral financial mechanisms, and international assistance. The article focuses on the need to understand the concepts and tools for ensuring financial stability, to determine the differentiated characteristics of the main directions of the transformation of the financial system and typologies of its transition. The authors single out the basic characteristics of transitions to sustainability and innovation processes: rethinking the achievement of new economic, environmental and social goals; time limit; creation of new socially inclusive, fair, ecologically sustainable economic systems; rejuvenation of the economic system through constant innovation; ensuring support for the financial orientation of transitions to sustainable development, which require integration and coordination of financial flows.
Abstract
This article is devoted to the implementation of scientific achievements into the educational process of physics specialties students in the framework of study course “Solid State Physics”. ...In this work, based on our previous scientific results, we present a quantum-mechanical approach that can adequately describe the temperature dependences of the dielectric crystals thermal conductivity. The basic provisions of quantum-mechanical approach are studied by students in the framework of university study course “Solid State Physics” and are based on Einstein and Debye classical models. This approach is based on the assumption that in dielectric crystals heat is transferred due to the phonons (Debye model) and thermal diffusion between the thermally activated neighboring quantum mechanical oscillators directly from site to site on a time scale of one-half of the oscillation period (Einstein model). In term of this consideration the thermal conductivity of molecular crystals are simulated in the framework of thermal conductivity model where heat is transferred by low-frequency phonons with taking into account phonon–rotation coupling, and above the phonon mobility edge by “diffusive” modes. For this purpose the theoretical temperature dependences of the isochoric thermal conductivity have been calculated numerically in the interval near or over the Debye temperature and compared with experimental results for solid
C
6
H
12
, CHCl
3
and
CH
2
Cl
2
.
Using simple molecular crystals as an example it is shows the dualism of the nature of heat transfer processes in the temperature region of the order of the Debye temperature and above. The obtained results will be useful for implementation in the educational process in the study course “Solid State Physics” in particular for understanding the features of heat transfer in the high-temperature range of dielectric crystals existence.
Abstract
This paper presents the preface of the proceedings for the 4th International Conference on Sustainable Futures: Environmental, Technological, Social, and Economic Matters (ICSF 2023), a ...multidisciplinary event that explores the challenges and opportunities of sustainability in various domains. The preface outlines the conference’s objectives, themes, workshops, and topics, as well as its contribution to advancing sustainable development and global dialogue. It also acknowledges the efforts and inputs of various stakeholders who have made the conference possible, especially in light of the pandemic situation. Furthermore, it thanks IOP Publishing for its support and flexibility in facilitating open access publishing. The paper concludes by looking forward to future editions of ICSF and the ongoing quest for a more sustainable and interconnected world. The paper invites readers to delve into the rich and diverse content that shapes this influential conference.
Abstract
This paper represents a preface to the Proceedings of the 3rd International Conference on Sustainable Futures: Environmental, Technological, Social, and Economic Matters (ICSF 2022) held at ...the Kryvyi Rih, Ukraine, 24–27 May 2022. Background information and the organizational structure of the meeting, program committee, and acknowledgments of the contributions of the many people who made the conference a success are presented.
PIGT-CDG, an autosomal recessive syndromic intellectual disability disorder of glycosylphosphatidylinositol (GPI) anchors, was recently described in two independent kindreds Multiple Congenital ...Anomalies-Hypotonia-Seizures Syndrome 3 (OMIM, #615398). PIGT encodes phosphatidylinositol-glycan biosynthesis class T, a subunit of the heteropentameric transamidase complex that facilitates the transfer of GPI to proteins. GPI facilitates attachment (anchoring) of proteins to cell membranes. We describe, at ages 7 and 6years, two children of non-consanguineous parents; they had hypotonia, severe global developmental delay, and intractable seizures along with endocrine, ophthalmologic, skeletal, hearing, and cardiac anomalies. Exome sequencing revealed that both siblings had compound heterozygous variants in PIGT (NM_015937.5), i.e., c.918dupC, a novel duplication leading to a frameshift, and c.1342C>T encoding a previously described missense variant. Flow cytometry studies showed decreased surface expression of GPI-anchored proteins on granulocytes, consistent with findings in previous cases. These siblings further delineate the clinical spectrum of PIGT-CDG, reemphasize the neuro-ophthalmologic presentation, clarify the endocrine features, and add hypermobility, low CSF albumin quotient, and hearing loss to the phenotypic spectrum. Our results emphasize that GPI anchor-related congenital disorders of glycosylation (CDGs) should be considered in subjects with early onset severe seizure disorders and dysmorphic facial features, even in the presence of a normal carbohydrate-deficient transferrin pattern and N-glycan profiling. Currently available screening for CDGs will not reliably detect this family of disorders, and our case reaffirms that the use of flow cytometry and genetic testing is essential for diagnosis in this group of disorders.
•We describe the third kindred of PIGT-CDG caused by biallelic variants in PIGT.•We clarify and expand clinical phenotype of PIGT-CDG.•We identify a novel mutation, c.918dupC predictive of p.Val307Argfs*13, in PIGT.•We emphasize current screening methods for CDGs cannot detect PIGT-CDG.•We explore flow cytometry as a possible screening test in GPI anchor disorders.
Marine fish movement plays a critical role in ecosystem functioning and is increasingly studied with acoustic telemetry. Traditionally, this research has focused on single species and small spatial ...scales. However, integrated tracking networks, such as the Integrated Tracking of Aquatic Animals in the Gulf of Mexico (iTAG) network, are building the capacity to monitor multiple species over larger spatial scales. We conducted a synthesis of passive acoustic monitoring data for 29 species (889 transmitters), ranging from large top predators to small consumers, monitored along the west coast of Florida, USA, over 3 yr (2016-2018). Space use was highly variable, with some groups using all monitored areas and others using only the area where they were tagged. The most extensive space use was found for Atlantic tarpon
Megalops atlanticus
and bull sharks
Carcharhinus leucas
. Individual detection patterns clustered into 4 groups, ranging from occasionally detected long-distance movers to frequently detected juvenile or adult residents. Synchronized, alongshore, long-distance movements were found for Atlantic tarpon, cobia
Rachycentron canadum
, and several elasmobranch species. These movements were predominantly northbound in spring and southbound in fall. Detections of top predators were highest in summer, except for nearshore Tampa Bay where the most detections occurred in fall, coinciding with large red drum
Sciaenops ocellatus
spawning aggregations. We discuss the future of collaborative telemetry research, including current limitations and potential solutions to maximize its impact for understanding movement ecology, conducting ecosystem monitoring, and supporting fisheries management.
Reconstruction of major proximal femoral segmental defects is one of the most difficult challenges in revision total hip arthroplasty (THA). One technique that has been successful is the use of a ...modular, long-stemmed prosthesis, cemented to an allograft proximal femur and press-fit to the host bone. Since July 1989, the authors have used this technique in 30 hips (29 patients). The trochanteric slide approach was used in all cases. Sixty pounds of weight bearing was encouraged for six weeks, then full weight bearing as tolerated. The mean follow-up period was 22 months (range, two to 46 months). All but two grafts united to the host bone clinically and radiographically. Complications included five dislocations, one graft-host nonunion, one graft resorption, and one deep infection requiring resection arthroplasty. The latter patient was subsequently reconstructed successfully using the same technique. Although the follow-up period is short, the authors have been encouraged by the early success of these allograft-prosthetic composites. Advantages of this approach include rapid return to weight bearing, physiologic loading of the distal femur, and reconstitution of vital proximal bone stock.
The use of an intramedullary alignment rod in the distal part of the femur is an important step in performing total knee-replacement arthroplasty. On the basis of our observation of a sudden decrease ...in oxygen saturation in some patients after insertion of the rod, a prospective study was done of the circulatory and blood-gas changes that were associated with insertion in thirty-five patients. We examined the effects of the use of an eight-millimeter solid alignment rod, with and without venting; an eight-millimeter fluted alignment rod, with venting; and an eight-millimeter fluted or solid alignment rod, inserted through a 12.7-millimeter drill-hole, but without other venting. A statistically significant reduction in oxygen saturation, arterial oxygen tension (PaO2), and end-tidal carbon-dioxide tension (PETCO2) occurred after insertion of both solid and fluted eight-millimeter alignment rods through an eight-millimeter hold in both vented and unvented femoral canals, in association with a significant increase (p less than 0.01) in intramedullary pressure. Bone-marrow contents and fat were retrieved from samples of blood from the right atrium, indicating that embolization of marrow contents had occurred during insertion of the alignment rod. A small decrease in systemic blood pressure and heart rate also occurred. These changes were completely eliminated by the use of a 12.7-millimeter drill-hole as the entry site of the eight-millimeter fluted rod. We concluded that insertion of an intramedullary alignment rod in the femur causes embolization of marrow contents, which decreases arterial oxygen tension, oxygen saturation, end-tidal carbon-dioxide tension, arterial blood pressure, and heart rate.
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