Proper Morphology Research Articles

Importance of environmental signals for cardiac morphological development in Atlantic salmon.

The hearts of salmonids display remarkable plasticity, adapting to various environmental factors that influence cardiac function and demand. For instance, in response to cold temperature, the salmonid heart undergoes growth and remodeling to counterbalance the reduced contractile function associated with dropping temperatures. Alongside heart size, the distinct pyramidal shape of the wild salmonid heart is essential for optimal cardiac performance, yet the environmental drivers behind this optimal cardiac morphology remain to be fully understood. Intriguingly, farmed salmonids often have rounded, asymmetrical ventricles and misaligned bulbi from an early age. These deformities are noteworthy given that farmed salmon are often not exposed to natural cues, such as a gradual temperature increase and changing day lengths, during critical developmental stages. In this study, we investigated whether natural environmental conditions during early life stages are pivotal for proper cardiac morphology. Atlantic salmon were raised under simulated natural conditions (low temperature with a natural photoperiod; SimNat) and compared with those reared under simulated farming conditions (SimFarm). Our findings reveal that the ventricle shape and bulbus alignment in SimNat fish closely resemble those of wild salmon, while functional analyses indicate significant differences between SimNat and SimFarm hearts, suggesting diastolic dysfunction and higher cardiac workload in SimFarm hearts. These findings highlight the profound influence of environmental factors such as water temperature and photoperiod on the structural development of the salmonid heart, underscoring the importance of early environmental conditions for cardiac health.

Correlating Ultrastructural Changes in the Invasion Area of Colorectal Cancer with CT and MRI Imaging.

The cancer invasion of the large intestine, a destructive process that begins within the mucous membrane, causes cancer cells to gradually erode specific layers of the intestinal wall. The normal tissues of the intestine are progressively replaced by a tumour mass, leading to the impairment of the large intestine's proper morphology and function. At the ultrastructural level, the disintegration of the extracellular matrix (ECM) by cancer cells triggers the activation of inflammatory cells (macrophages) and connective tissue cells (myofibroblasts) in this area. This accumulation and the functional interactions between these cells form the tumour microenvironment (TM). The constant modulation of cancer cells and cancer-associated fibroblasts (CAFs) creates a specific milieu akin to non-healing wounds, which induces colon cancer cell proliferation and promotes their survival. This review focuses on the processes occurring at the "front of cancer invasion", with a particular focus on the role of the desmoplastic reaction in neoplasm development. It then correlates the findings from the microscopic observation of the cancer's ultrastructure with the potential of modern radiological imaging, such as computer tomography (CT) and magnetic resonance imaging (MRI), which visualizes the tumour, its boundaries, and the tissue reactions in the large intestine.

Astrocytic LRRK2 Controls Synaptic Connectivity via Regulation of ERM Phosphorylation.

Astrocytes, a major glial cell type of the brain, regulate synapse numbers and function. However, whether astrocyte dysfunction can cause synaptic pathologies in neurological disorders such as Parkinson's Disease (PD) is unknown. Here, we investigated the impact of the most common PD-linked mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (G2019S) on the synaptic functions of astrocytes. We found that both in human and mouse cortex, the LRRK2 G2019S mutation causes astrocyte morphology deficits and enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), which are important components of perisynaptic astrocyte processes. Reducing ERM phosphorylation in LRRK2 G2019S mouse astrocytes restored astrocyte morphology and corrected excitatory synaptic deficits. Using an in vivo BioID proteomic approach, we found Ezrin, the most abundant astrocytic ERM protein, interacts with the Autophagy-Related 7 (Atg7), a master regulator of catabolic processes. The Ezrin/Atg7 interaction is inhibited by Ezrin phosphorylation, thus diminished in the LRRK2 G2019S astrocytes. Importantly, Atg7 function is required to maintain proper astrocyte morphology. These studies reveal an astrocytic molecular mechanism that could serve as a therapeutic target in PD.

The association between patella alignment and morphology and knee osteoarthritis

ObjectiveThis study aims to quantitatively assess the relationship between the patella alignment and morphology and knee osteoarthritis (KOA), as well as the kinematics and kinetics of the knee, using gait analysis.MethodsEighty age-matched patients with KOA and control subjects were evaluated. Incident radiographic osteoarthritis (iROA) was identified using a Kellgren-Lawrence (KL) grade of ≥ 2. The modified Insall-Salvati ratio (Mod-ISR), patellar tilt angle (PTA), and patella index (PI) were utilized to evaluate the sagittal and transverse alignment of the patella and its morphology, respectively. Regression analyses were conducted to explore associations between patellar measurements and KOA, iROA, kinematics, and kinetics.ResultsSignificant differences were observed between the control and KOA groups in terms of KL grade, patella alta, abduction angle, and reaction force to the ground (P < 0.05, respectively). Following adjustment for covariates, a significant positive association was found between patella alta and KOA (OR = 0.307, 95%CI: 0.103 to 0.918, P = 0.035). Additionally, a significant negative association was observed between PTA and abduction angle (B = -0.376, 95%CI: -0.751 to -0.002; P = 0.049). The PI exhibited a statistically significant association with log-transformed vertical ground reaction force (B = 0.002, 95%CI: 0.001 to 0.003, P = 0.002). Furthermore, adjustment for covariates did not reveal any significant correlations with other indicators (P > 0.05, respectively).ConclusionThis study provides further evidence that proper alignment and morphology of the patella might be associated with maintaining normal biomechanical function. In addition, intervention measures targeting relevant patellar parameters, such as Mod-ISR, PTA, and PI, may positively impact KOA treatment outcomes.

Cellular transitions during cranial suture establishment in zebrafish

Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Human Enteroid Monolayers: A Novel, Functionally-Stable Model for Investigating Oral Drug Disposition.

To further the development of an in vitro model which faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from three donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell® inserts, and confirmed transformation into a largely enterocyte population via RNA-seq analysis and immunocytochemical (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins. Enteroid monolayer barrier integrity was demonstrated by elevated transepithelial electrical resistance (TEER) that stabilized after 10 days in culture and persisted for 42 days. These results were corroborated by low paracellular transport probe permeability at 7 and 21 days in culture. The activity of a prominent drug metabolizing enzyme, CYP3A, was confirmed at 7, 21, and 42 days culture under basal, 1α,25(OH)2 vitamin D3-induced, and 6',7'-dihydroxybergamottin-inhibited conditions. The duration of these experiments is particularly noteworthy, as this is the first study assessing drug metabolizing enzymes and transporters (DMET) expression/function for enteroids cultured for greater than 12 days. The sum of these results suggests enteroid monolayers are a promising ex vivo model to investigate and quantitatively predict an orally administered drug's intestinal absorption and/or metabolism. Significance Statement This study presents a novel ex vivo model of the human intestine, human intestinal organoid (enteroid) monolayers, that maintain barrier function and metabolic functionality for up to 42-days in culture. The incorporation of both barrier integrity and metabolic function over an extended period within the same model is an advancement over historically used in vitro systems, which either lack one or both of these attributes or have limited viability.

Composite hydrogels fabricated from CMC-PVA-GG incorporated with ZiF-8 for wound healing applications

The skin is at risk for injury to external factors since it serves as the body’s first line of defense against the external environment. Hydrogels have drawn much interest due to their intrinsic extracellular matrix (ECM) properties and their biomimetic, structural, and durable mechanical characteristics. Hydrogels have enormous potential use in skin wound healing due to their ability to deliver bioactive substances easily. In this study, composite hydrogels were developed by blending guar gum (GG), polyvinyl alcohol (PVA), and carboxymethyl cellulose (CMC) with crosslinker TEOS for skin wound treatment. The structural, surface morphology, surface roughness, and stability features of the composite hydrogels were characterized by several techniques, such as FTIR, SEM-EDX, AFM, and DSC. The increasing ZiF-8 causes more surface roughness, with decreased swelling in different media (Aqueous > PBS > NaCl). The increasing ZiF-8 amount causes less hydrophilic behavior and biodegradation with increasing gel fraction. The cytocompatibility of Zinc imidazolate framework-8 (ZiF-8) based composites was evaluated against fibroblast cell lines by cell viability, proliferation, and cell morphology. The increasing ZiF-8 caused more cell viability and proliferation with proper cell morphology. Hence, the results show that synthesized composite hydrogels may be a potential candidate for numerous wound repair applications.

Wnt5a Promotes Axon Elongation in Coordination with the Wnt-Planar Cell Polarity Pathway.

The establishment of neuronal polarity, involving axon specification and outgrowth, is critical to achieve the proper morphology of neurons, which is important for neuronal connectivity and cognitive functions. Extracellular factors, such as Wnts, modulate diverse aspects of neuronal morphology. In particular, non-canonical Wnt5a exhibits differential effects on neurite outgrowth depending upon the context. Thus, the role of Wnt5a in axon outgrowth and neuronal polarization is not completely understood. In this study, we demonstrate that Wnt5a, but not Wnt3a, promotes axon outgrowth in dissociated mouse embryonic cortical neurons and does so in coordination with the core PCP components, Prickle and Vangl. Unexpectedly, exogenous Wnt5a-induced axon outgrowth was dependent on endogenous, neuronal Wnts, as the chemical inhibition of Porcupine using the IWP2- and siRNA-mediated knockdown of either Porcupine or Wntless inhibited Wnt5a-induced elongation. Importantly, delayed treatment with IWP2 did not block Wnt5a-induced elongation, suggesting that endogenous Wnts and Wnt5a act during specific timeframes of neuronal polarization. Wnt5a in fibroblast-conditioned media can associate with small extracellular vesicles (sEVs), and we also show that these Wnt5a-containing sEVs are primarily responsible for inducing axon elongation.

The use of pulse transit time in diagnostics of sleep-disordered breathing in children

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Sleep is the physiological state of the body where proper morphology and duration are indispensable for human functions throughout both, physical and mental spheres. Disordered breathing during sleep impairs its morphology and results in major disorders in any age group. Adverse effects of Obstructive Sleep Apnea Syndrome in children and poor availability of centers offering children’s polysomnography call for a reliable and easily accessible screening method.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; The aim of the study were to evaluate the usefulness of pulse transit time in the diagnostics of disordered sleep breathing in children and to attempt to employ the parameter in screening tests. Pulse transit time is a physiological parameter determining the time needed for the pulse wave to travel between two measurement points.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Material and methods:&lt;/b&gt; Enrolled in the retrospective study were 153 patients (100 boys and 53 girls) suspected of obstructive sleep apnea syndrome who underwent polysomnography at I. Mościcki ENT Hospital in Chorzów.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; Statistically significant relations between apnea/hypopnea index and pulse transit time were observed in both, individual age groups and all of the patients. Pulse transit time results proved a negative correlation with apnea/hypopnea index values commonly accepted as a parameter concluding the polysomnography procedures.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; The results of the study indicate that pulse transit time measurements may find application in screening tests of sleep-disordered breathing in children.&lt;/br&gt;

Rice KORPOKKUR gene is expressed in mitotic cells and regulates pleiotropic features during vegetative phase.

Cell division is important for organisms to grow and repair damaged tissues. A mutant screen in rice has identified dwarf korpokkur (kor) mutants that code for a novel protein potentially involved in mitosis including cytokinesis in rice. The KOR gene is expressed during the mitotic phase and a defect in the KOR gene induces cells with two nuclei. Analysis of kor mutants suggests that the KOR gene promotes cell division in the rice leaf primordia for a period after initiation, and maintains proper cell morphology especially in non-meristematic tissues. Additionally, kor mutants showed a delayed transition from juvenile phase to adult phase. Future research will shed light on the relationship between the mitotic defect and other features observed in the kor mutants.

Perturbations in mitochondrial metabolism associated with defective cardiolipin biosynthesis: An in-organello real-time NMR study.

Mitochondria are central to cellular metabolism; hence, their dysfunction contributes to a wide array of human diseases including cancer, cardiopathy, neurodegeneration, and heritable pathologies such as Barth syndrome. Cardiolipin, the signature phospholipid of the mitochondrion promotes proper cristae morphology, bioenergetic functions, and directly affects metabolic reactions carried out in mitochondrial membranes. To match tissue-specific metabolic demands, cardiolipin typically undergoes an acyl tail remodeling process with the final step carried out by the phospholipid-lysophospholipid transacylase tafazzin. Mutations in the tafazzin gene are the primary cause of Barth syndrome. Here, we investigated how defects in cardiolipin biosynthesis and remodeling impact metabolic flux through the tricarboxylic acid cycle and associated pathways in yeast. Nuclear magnetic resonance was used to monitor in real-time the metabolic fate of 13C3-pyruvate in isolated mitochondria from three isogenic yeast strains. We compared mitochondria from a wild-type strain to mitochondria from a Δtaz1 strain that lacks tafazzin and contains lower amounts of unremodeled cardiolipin, and mitochondria from a Δcrd1 strain that lacks cardiolipin synthase and cannot synthesize cardiolipin. We found that the 13C-label from the pyruvate substrate was distributed through about twelve metabolites. Several of the identified metabolites were specific to yeast pathways, including branched chain amino acids and fusel alcohol synthesis. Most metabolites showed similar kinetics amongst the different strains but mevalonate and α-ketoglutarate, as well as the NAD+/NADH couple measured in separate nuclear magnetic resonance experiments, showed pronounced differences. Taken together, the results show that cardiolipin remodeling influences pyruvate metabolism, tricarboxylic acid cycle flux, and the levels of mitochondrial nucleotides.

Laser powder bed fusion of Nd2Fe14B+Nd70Cu30 hard magnetic material using double exposure scanning strategy

Combination of double exposure scanning strategy and low-melting Nd70Cu30 eutectic phase addition approaches was investigated to improve laser powder bed fusion of Nd2Fe14B-based hard magnetic material. Technological route of Nd2Fe14B + Nd70Cu30 powder mixture was developed to obtain initial material with proper morphology and characteristics for subsequent 3D-printing. Effect of the mentioned combination on structure of the formed material and its magnetic properties was studied. Improvement of printed material density up to 98.8 % and defectiveness reduction were shown. Three different types of areas were found in the structure of the synthesized material with variable neodymium, copper and iron content. Distribution of copper throughout the whole structure of the material showed the difference of the proposed approach with convenient grain boundary infiltration technique. More stable melting, quality of printed material and less deviations of magnetic properties were achieved due to the applied approach.

#2450 Alternative splicing in podocytes under mechanical stress: a new perspective for the pathogenic effect of glomerular hypertension

Abstract Background and Aims High blood pressure is considered one of the most important risk factors leading to chronic kidney disease. The pathogenesis of hypertension-induced damage to podocytes remains still elusive. Since recent reports have shown that alternative splicing (AS) has a significant impact on disease progression, we investigated alternative splicing of mechanically stretched podocytes, a well-established model for glomerular hypertension, in the Sys_CARE (Systems Medicine Investigation of AS in Cardiac and Renal Diseases) project. Our results provide new insights into the molecular mechanisms that might drive the progression of hypertensive nephropathy. Method Differentiated murine podocytes were exposed to mechanical stretch for 3 days under low and high stretch conditions. Subsequently, mRNA and proteins were analyzed by RNA-Seq and LC-MS/MS, respectively. Enrichment analysis identified transcripts which were classified according to the related biological processes, molecular function, and cellular components. Splicing and transcript expression were evaluated with bioinformatical tools such as MAJIQ, Multivariate Analysis of Transcript Splicing (rMATS), leafcutter, Whippet and IsoformSwitchAnalyzeR. Results Transcriptome analyses of mechanically stretched podocytes by RNA sequencing showed that mechanical stress leads to a high number of differentially expressed genes (1323 with log2 fc ± 1) compared to unstretched podocytes. Detailed gene set enrichment analysis for GO-Terms showed an enrichment among up-regulated transcripts related to mRNA processing and RNA splicing. In contrast, most transcripts with decreased expression upon stretch are associated with cytoskeleton function. To identify AS events, different AS tools were used. We found a wide variety of splice events. The most frequent event was exon skipping (between 63-82% of all AS events), followed by intron retention and alternative 5′ or 3′ splice site. 290 alternatively spliced genes were detected after mechanical stretch by three different splice analysis tools (rMATS, leafcutter, Whippet). Out of these candidates, the IsoformSwitchAnalyzeR identified 17 genes exhibiting significant isoform switches. To prioritize the candidates, we performed a screening that included only those genes that were identified by proteomic analysis and that are expressed in podocytes in vivo or showed an altered expression pattern in glomerular disease. This screening led to the two candidates Shroom3 and Myl6. Shroom3, an actin-binding protein, is crucial for podocyte morphology and function. Genetic variants of Shroom3 have been linked with chronic kidney disease by GWAS. Here we found that two of four Shroom3 isoforms showed significant expression changes due to mechanical stretch. Isoform 2 which showed the highest expression in cultured podocytes, significantly decreased, but the shorter isoform X1 was significantly up-regulated after mechanical stretch. Both changes were verified by qRT-PCR as well as by in situ hybridization in mouse tissue. Myosin light chain 6 (Myl6), a component of the myosin motor protein complex, has two isoforms which are detected in cultured podocytes as well as in vivo. We found an expression switch from isoform 1 to 2 due to mechanical stretch. Our analysis showed that this is accompanied by a change of the amino acid sequence AFVRHILS to ELVRMVLN, sequences that are well conserved in mice, rat, and human. The analysis of the protein structure by FoldX revealed that this change in the amino acid sequence could lead to an impairment of the binding of the motor protein complex to actin and might therefore influence the functionality of the actin cytoskeleton, which is highly important for proper podocyte foot process morphology. Conclusion Mechanical stretch of cultured mouse podocytes, which is an excellent model to simulate hypertensive nephropathy, leads to alterations in isoform expression due to alternative splicing. These changes in the expression of isoforms, such as Shroom 3 and Myl6, have the potential to play a key role in the pathophysiology of hypertension-induced nephropathy.

Numerical study on mixed lubrication performance of misaligned microgroove water-lubricated bearings considering cavitation and turbulence effects

This study presents a mixed lubrication model for misaligned microgroove water-lubricated bearings (WLBs). The model considers the effects of cavitation and turbulence to assess the mixed lubrication performance of WLBs with various microgroove morphologies. The equations are discretized using the control volume method (CVM) and solved by using the Fischer–Burmeister–Newton–Schur method for dealing with the constrained system. A comparison of the experimental data from the published literature demonstrates the model and methodology's validity. On this basis, the effects of rotational speed, load, and misalignment angle on the mixed lubrication performance of microgroove WLBs are investigated. The numerical results indicate that the left-triangular microgroove exhibits the best-mixed lubrication performance. Under elastohydrodynamic lubrication and mixed lubrication conditions, there are significant discrepancies in microgroove morphology. However, this discrepancy diminishes with increasing misalignment angles. The edge contact problem resulting from journal misalignment can be efficiently mitigated by selecting the proper microgroove morphology. This study provides useful guidance for the optimal design and mixed lubrication performance improvement of WLBs.

Multifunctional platform for future applications in cell and tissue engineering based on silicate phosphate hydroxyapatite co-doped with Li+, Eu3+ and Gd3+ ions

Although hydroxyapatite has established itself as a promising biomaterial for the simultaneous diagnosis and treatment of bone defects, several physicochemical properties can be further refined to achieve a specialized theranostic platform for cell and tissue engineering. In this context, we synthesized silicate-substituted hydroxyapatites co-doped with Li+, Eu3+, and Gd3+ ions (abbr. as Si-HAp-LEG) using a microwave-assisted hydrothermal method. The aim was to create a combination of dopants to stimulate bone regeneration (Li+ ion) while enabling bioimaging (Eu3+ and Gd3+ ions). Structural and morphological assessments included, e.g., XRPD (X-ray Powder Diffraction), HR-TEM (High-resolution Transmission Electron Microscopy) imaging, and BET (Brauner-Emmet-Teller) analysis. Unit-cell parameters were estimated via Rietveld refinement. The luminescence properties (emission, excitation spectra, and emission kinetics) were recorded depending on the varying Li+-ion concentration. The cytocompatibility of biomaterials was tested using hBMSCs (multipotent human bone-marrow mesenchymal stromal cells). In vitro assays evaluated biomaterials’ effects on morphology, metabolic activity (Alamar blue assay), and transcriptomic activity (RT-qPCR). The results indicate that co-doping with Li+, Eu3+, and Gd3+ ions introduces distortions while preserving the crystal structure of hydroxyapatite. Additionally, the cells maintained proper morphology and ultrastructure, internalizing biomaterials without significant cytotoxicity. The biomaterials also triggered the expression of key transcriptional factors. Si-HAp-LEG biomaterials, particularly LEG-222 and LEG-221, exhibit desired physicochemical and biological features, rendering them highly bioactive and promising for cell and tissue engineering applications.

Acceptor molecules with different central and terminal units for P3HT based solar cells: Effects of the molecular structures on their properties

The design strategy of acceptor materials matched with poly(3-hexylthiophene) (P3HT) is highly desired for the development of low-cost organic solar cells (OSCs). Herein, we introduced strong electron-donating central units and weak electron-withdrawing end groups to construct the acceptors with high HOMO and LUMO, modulated the molecular symmetry and conjugation length by changing the structures of central units, and synthesized six acceptor molecules, namely, TDTC-O2F, TTDTC-O2F, TTTDTC-O2F, TDTC-ThBr, TTDTC-ThBr and TTTDTC-ThBr. The high LUMO energy level of the acceptors endowed the P3HT based OSCs with relatively high Voc values. Molecular symmetry, conjugation length of central units and the terminal structure jointly affect the molecular crystallinity and miscibility of the blends. Owing to the proper film morphology, the P3HT:TTDTC-ThBr based devices achieved the champion power conversion efficiency of 6.15 %.

3D genomic alterations during development of skeletal muscle in chicken1

The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology, contractility, cell proliferation, differentiation, interactions, migration, and death. The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes. The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages. Hi-C was used to build a chromatin architectures during four representative stages. ChIP-seq was conducted to identify enhancers in these four stages, which are occupied by histone H3K27ac and H3K4me3 peaks. Results show that large-scale genome architecture changes are mostly unidirectional, and coupled by complex on/off dynamic patterns of gene expression. Specifically, we observed 258.30 Mb of the genome undergoing A/B compartment switching. Notable alterations (316.57 Mb) of interaction frequencies within TADs were observed. Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development. Some muscle-related gene promoters that interacted with active enhancers during development, and some myopathy/aging-associated genes that were activated in aging muscle were founded. These results provide key insights into skeletal muscle development in vivo, and offer a valuable resource that allows in-depth functional characterization of candidate genes.

Contrasting Energy Storage Systems for Small-Scale Isolated Grids

The goal of this article is to examine the best electricity storage methods, both in terms of technology and economics, for tiny, independent electrical grids that are integrated with power plants that generate renewable energy sources (RES). As case studies, three autonomous Greek is-lands—Symi, Astypalaia, and Kastelorizo—with yearly and approximately for our work is peak demand of 3.9 MW, 2.1 MW, and 0.889 MW, respectively, are examined. Every island under inves-tigation has exceptional solar and wind potential, and their locations are perfect for the installation of seawater PHS (pumped hydro storage). Regarding the energy storage facilities, two distinct strat-egies are examined: PHS systems (for the two largest islands) and electrochemical storage, which is another name for lead acid or lithium-ion batteries. Potential RES units include photovoltaic instal-lations and wind farms. The analysed plants' dimensioning is optimised with a shared goal in mind: achieving an annual percentage of RES penetration above 69.9% while keeping the selling price of energy below the current specific production cost. The analysis is combined with the systems under examination's economic assessment. It is demonstrated that wind-PHS is still a competitive alterna-tive for Symi and Astypalaia given the proper land morphology for PHS installations, while a wind-p/v-batteries features as the best choice for Kastelorizo. Only with PHS support can 99.9% annual RES penetration be attained; with electrochemical batteries, annual RES penetration can range from 79.9 to 91.1%. Electricity selling prices between 199 and 349 €/kWh, which result in payback periods between five and nine years, ensure the economic viability.

Temporal dynamics of genetic architecture governing leaf development in Populus.

Leaf development is a multifaceted and dynamic process orchestrated by a myriad of genes to shape the proper size and morphology. The dynamic genetic network underlying leaf development remains largely unknown. Utilizing a synergistic genetic approach encompassing dynamic genome-wide association study (GWAS), time-ordered gene co-expression network (TO-GCN) analyses and gene manipulation, we explored the temporal genetic architecture and regulatory network governing leaf development in Populus. We identified 42 time-specific and 18 consecutive genes that displayed different patterns of expression at various time points. We then constructed eight TO-GCNs that covered the cell proliferation, transition, and cell expansion stages of leaf development. Integrating GWAS and TO-GCN, we postulated the functions of 27 causative genes for GWAS and identified PtoGRF9 as a key player in leaf development. Genetic manipulation via overexpression and suppression of PtoGRF9 revealed its primary influence on leaf development by modulating cell proliferation. Furthermore, we elucidated that PtoGRF9 governs leaf development by activating PtoHB21 during the cell proliferation stage and attenuating PtoLD during the transition stage. Our study provides insights into the dynamic genetic underpinnings of leaf development and understanding the regulatory mechanism of PtoGRF9 in this dynamic process.

Structural insights into the formation of repulsive netrin guidance complexes.

Netrins dictate attractive and repulsive responses during axon growth and cell migration, where the presence of the receptor Uncoordinated-5 (UNC-5) on target cells results in repulsion. Here, we showed that UNC-5 is a heparin-binding protein, determined its structure bound to a heparin fragment, and could modulate UNC-5-heparin affinity using a directed evolution platform or structure-based rational design. We demonstrated that UNC-5 and UNC-6/netrin form a large, stable, and rigid complex in the presence of heparin, and heparin and UNC-5 exclude the attractive UNC-40/DCC receptor from binding to UNC-6/netrin to a large extent. Caenorhabditis elegans with a heparin-binding-deficient UNC-5 fail to establish proper gonad morphology due to abrogated cell migration, which relies on repulsive UNC-5 signaling in response to UNC-6. Combining UNC-5 mutations targeting heparin and UNC-6/netrin contacts results in complete cell migration and axon guidance defects. Our findings establish repulsive netrin responses to be mediated through a glycosaminoglycan-regulated macromolecular complex.