Macromolecular Structures Research Articles

Mechanotransduction in the pathogenesis of non-alcoholic fatty liver disease.

Mechanobiology is a domain of interdisciplinary research that aims to explore the impact of physical force, applied externally or internally, on cell and tissue function, including development, growth, and differentiation. Mechanotransduction is a term that describes how cells sense physical forces (such as compression, stretch, and shear stress), convert them into biochemical signals, and mount adaptive responses integrated by the nucleus. There is accumulating evidence that mechanical forces extensively inform the biological behaviour of liver cells in health and disease. Recent research has elucidated many cellular and molecular mechanisms involved in this process including the pleiotropic control and diverse effects of the paralogous transcription co-activators YAP/TAZ, which play a prominent role in mechanotransduction. The liver sinusoids represent a unique microenvironment in which cells are exposed to mechanical cues originating in the cytoskeleton and at interfaces with adjacent cells, the extracellular matrix, and vascular or interstitial fluids. In non-alcoholic fatty liver disease (NAFLD), hepatocellular lipid accumulation and ballooning, activation of inflammatory responses, dysfunction of liver sinusoidal endothelial cells, and transdifferentiation of hepatic stellate cells into a pro-contractile and pro-fibrotic phenotype have been associated with aberrant cycles of mechanosensing and mechanoresponses. The downstream consequences of disrupted mechanical homeostasis likely contribute to the progression of NAFLD and promote the development of portal hypertension, cirrhosis, and hepatocellular carcinoma. Identification of molecular targets involved in pathogenic mechanotransduction will allow for the development of novel strategies to prevent the progression of liver disease in NAFLD.

Antimicrobial and Gas Barrier Crustaceans and Fungal Chitin-Based Coatings on Biodegradable Bioplastic Films

Chitin nanofibrils (CN) can be obtained from crustaceans and fungal sources and can be used for preparing coatings for bioplastic films, that are fundamental for developing a safe and sustainable biodegradable food packaging. Coatings with different concentrations of CN from shrimps were applied on different bioplastic substrates, like Poly (butylene succinate-co-adipate)/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PBSA/PHBV) blend, Polybutylene succinate (PBS), and Polybutylene adipate terephthalate/Poly(lactic acid) (PBAT/PLA) blend, but the adhesion to the substrates was scarce. On the contrary, the fungal-based CN showed a better adhesion. Additionally, it was found that the use of an additive based on oligomeric lactic acid was useful to prepare a coating with an improved adhesion to bioplastics. The gas barrier properties to oxygen and water vapour of coated and un-coated films were measured, revealing an improvement of these properties thanks to applied coatings, especially towards the oxygen. Antimicrobial properties and biodegradation capacity were also evaluated revealing an antibacterial effect of the coatings that did not significantly interfere with their biodegradability. The results are discussed and interpreted considering the correlation between composition and macromolecular structures with the observed functional properties.

Unfolding the role of placental-derived Extracellular Vesicles in Pregnancy: From homeostasis to pathophysiology.

The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.

Photoinduced Side‐Chain Functionalization, Grafting, Cross‐Linking, and Chain Extension by Thiol‐Epoxide Click Reaction Using Photo Base Generator

AbstractIn this work, photoinduced thiol‐epoxy click reaction for side‐chain functionalization, chain‐extension, grafting, and cross‐linking of polymers prepared by atom transfer radical polymerization by using 1,5‐diazabicyclo[5.4.0]undec‐5‐ene thioxanthone acetate (Tx‐DBU) as a photo base generator (PBG) is described. Irradiation of Tx‐DBU at 365 nm leads to the generation of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in neutral form as a super base. DBU is capable of abstracting protons from thiols and thus formed thiolates are excellent nucleophiles that exhibit high affinity toward electrophiles such as epoxide rings. Appropriately selected thiols are successfully used for the desired reactions. The precursors and resulting polymers are characterized using 1H‐NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry measurements. This study shows that the use PBGs can further be extended to the synthesis of various complex macromolecular structures by the described post modification processes.

Structure of Waste Hemp Stalks and Their Sound Absorbing Properties.

To broaden the application fields of waste hemp stalks, the macromolecular, supramolecular, and morphological structures of waste hemp stalks were analyzed, and the relationship between these properties and the sound absorption properties of the hemp stalks was explored. Then, waste hemp stalk/polycaprolactone sound-absorbing composite materials were prepared by the hot pressing method. The influence of hemp stalk length and mass fraction, and the density and thickness of the composite materials on the sound absorption properties of composites prepared with the hot pressing temperature set to 140 °C, the pressure set to 8 MPa, and the pressing time set to 30 min was investigated. The results showed that, when the sound energy acts on the hemp stalk, the force between the chain segments, the unique hollow structure, and the large specific surface, act together to attenuate the sound energy and convert it into heat and mechanical energy in the process of propagation, to produce a good sound absorption effect. When the hemp stalk length and mass fraction were set to 6 mm and 50%, respectively, and the density and thickness of the material were set to 0.30 g/cm3 and 1.5 cm, respectively, the average sound absorption coefficient of the waste hemp stalk/polycaprolactone sound-absorbing composite material was 0.44, the noise reduction coefficient was 0.42, the maximum sound absorption coefficient was 1.00, and the sound-absorbing band was wide. The study provided an experimental and theoretical basis for the development of waste hemp stalk/polycaprolactone sound-absorbing composite materials, and provided a new idea for the recycling of the waste hemp stalk.

Organic molecules based palaeoenvironmental inferences and U mineralization in Palaeoproterozoic Bijawar basins of Central India

Palaeoproterozoic, siliclastic, intracratonic rocks of the Bijawar and Sonrai basins contain anomalous U concentration and abundant Organic Matter (OM), although, earlier studies documented rare data on commonality between high U content and closely associated OM. Moreover, OM contains several biomolecules of complex carbonaceous compounds with macro-molecular structures, but insignificant information is available on the origin and associated palaeoenvironmental conditions. Thus, present study on organo-uranyl-complexes is relevant and carried out to understand palaeoenvironmental reasons accountable for U mineralization. For this purpose, OM (isolated from each bulk sample) was analyzed for Total Organic Carbon (TOC), n-alkanes, n-fatty acids and Polycyclic Aromatic Hydrocarbon compounds (PAHs). Obtained TOC values range between 0.02 and 0.23 wt%. Mostly, calculated [(C/S)/12] and [(C/N)/12] values are low; indicate algal source and anoxic depositional conditions, but, Rohini carbonate, Bandai sandstone and Chloritic shale high values signify sub-oxic conditions. Also, low (<1.25) U/Th and high authigenic U data of mineralized Chloritic shale imply anoxic conditions and post-depositional enrichment of U ions (mostly as organo-uranyl-complexes), respectively.GC-MS data show high concentration of n-alkane, fatty acid methyl ester (FAME) and PAH molecules in the OM associated with the rocks signifying high U values. The predominance of Short Chain (SC) n-alkanes together with the SC n-fatty acids revealed derivation of OM from marine algae and bacteria. The Rohini carbonate and Chloritic shale show low isoprenoids, Pristane (Pr)/Phytane (Ph), CPI, OEP, Pr/n-C-17, Ph/n-C18, but high TC-/(Pr/Ph), TC/(Pr + Ph), MP, MPI, MPR and VR values, suggest biodegraded and thermally matured OM which has undergone hydrothermal alteration under anoxic to sub-anoxic conditions. Considerably, high degree of OM oxidization occurred synchronously with the reduction of U6+ to U4+ by sulfate-reducing bacteria. The consistent loss of diaromatic PAHs is also noticed from older to younger rock-units. Further, scanty appearance of PAHs in the lower Gorakalan shale and their disappearance in the upper Chloritic and black shale units, indicate progressive maturation of sediments. The Low Molecular Weight (LMW)-PAHs predominate over the High Molecular Weight (HMW)-PAHs. Comparatively, high phenanthrene abundance is also noticed in the Rohini carbonate, Chloritic shale and -black shale (with high U content). The high proportion of LMW-PAHs and absence of HMW-PAHs (>6 rings) is pointing towards the presence of hydrothermally derived bitumen. Moreover, partial combustion of OM (pyrogenic) contributed to the formation of PAHs. The Chloritic shale and Rohini carbonate are coeval with the Bijawars of the Sonrai basin, representing almost similar organo-molecular records. Organo-molecular abundance and their structural attributes when plotted across the stratigraphic successions, revealed alternate humid conditions facilitated U4+oxidation and formation of U6+ rich solutions, although arid/semiarid climatic conditions assisted precipitation, sorption and absorption of U4+. Almost, similar clay mineral attributes for both the basins lend support to cyclic humid to arid/semiarid palaeoenvironmental conditions. Moreover, majority of the OM derived from the algal mats has played critical role in U mineralization by trapping and adsorption of tiny uraninite grains as well as U ions onto the OM.

Anisotropic Microgels by Supramolecular Assembly and Precipitation Polymerization of Pyrazole-Modified Monomers.

Soft colloidal macromolecular structures with programmable chemical functionalities, size, and shape are important building blocks for the fabrication of catalyst systems and adaptive biomaterials for tissue engineering. However, the development of the easy upscalable and template-free synthesis methods to obtain such colloids lack in understanding of molecular interactions that occur in the formation mechanisms of polymer colloids. Herein, a computer simulation-driven experimental synthesis approach based on the supramolecular self-assembly followed by polymerization of tailored pyrazole-modified monomers is developed. Simulations for a series of pyrazole-modified monomers with different numbers of pyrazole groups, different length and polarity of spacers between pyrazole groups and the polymerizable group are first performed. Based on simulations, monomers able to undergo π-π stacking and guide the formation of supramolecular bonds between polymer segments are synthesized and these are used in precipitation polymerization to synthesize anisotropic microgels. This study demonstrates that microgel morphologies can be tuned from spherical, raspberry-like to dumbbell-like by the increase of the pyrazole-modified monomer loading, which is concentrated at periphery of growing microgels. Combining experimental and simulation results, this work provides a quantitative and predictive approach for guiding microgel design that can be further extended to a diversity of colloidal systems and soft materials with superior properties.

The structure and dynamics of bottlebrushes: Simulation and experimental studies combined

Bottlebrushes are complex macromolecular structures composed of polymer chains densely tethered to another polymer chain via a stable covalent bond linkage. Although numerous experimental techniques have been successfully applied for the characterization of bottlebrush polymers, some parameters still cannot be determined. Herein new simulation method using a dedicated machine was used to confront its applicability for complex macromolecules simulations. The bottlebrushes were synthesized by atom transfer radical polymerization (ATRP) with varied degree of polymerization (N) of the side chains, poly(methyl methacrylate) (PMMA). Poly(2-(2-bromoisobutyryloxy)ethyl methacrylate) (PBiBEM) was used as macroinitiator with a degree of polymerization Nbb = 102. Degree of polymerization of side chains (Nsc) changed from 28 to 113. The bottlebrushes were characterized by Gel Permeation Chromatography – Multiangle Laser Light Scattering (GPC-MALLS), Pulsed-field Gradient Spin Echo Nuclear Magnetic Resonance (PGSE NMR), and combined Static and Dynamic Light Scattering methods (SLS-DLS). A novel calculation strategy via the Monte Carlo-class Dynamic Lattice Liquid (DLL) algorithm executed on a dedicated machine ARUZ was applied for theoretical studies. The experimental values concerning the scaling behavior of polymer size and dynamics were compared and confronted with simulation results.

Effects of emulsifiers on heterocyclic amine formation and water distribution in roasted chicken patties

The present study aimed to investigate the effects of five emulsifiers, including DATEM, DMG, PL, SDS, and SPP, on HA formation in chemical models and roasted chicken patties. UPLC-MS analysis showed that DMG and SPP were the most promising among them. In particular, at 0.15–0.9% (w/w) in roasted chicken patties, they effectively reduced the contents of PhIP (21–43%), MeIQx (26–50%) and 4,8-DiMeIQx (16–43%) relative to the control, whereas DATEM, PL and SDS promoted their formation. Low-Field Nuclear Magnetic Resonance and Magnetic Resonance Imaging analysis revealed that the inhibitory effect of SPP and DMG was partly mediated through their capability to help retain water in the macromolecular structures of the muscle tissue. This favorable effect was also supported by the significantly improved adhesiveness of the SPP and DMG samples relative to other samples. These findings suggest that SPP and DMG are effective additives for attenuation of HA contents in meat-based products.

Factors Controlling Degradation of Biologically Relevant Synthetic Polymers in Solution and Solid State.

The field of biodegradable synthetic polymers, which is central for regenerative engineering and drug delivery applications, encompasses a multitude of hydrolytically sensitive macromolecular structures and diverse processing approaches. The ideal degradation behavior for a specific life science application must comply with a set of requirements, which include a clinically relevant kinetic profile, adequate biocompatibility, benign degradation products, and controlled structural evolution. Although significant advances have been made in tailoring materials characteristics to satisfy these requirements, the impacts of autocatalytic reactions and microenvironments are often overlooked resulting in uncontrollable and unpredictable outcomes. Therefore, roles of surface versus bulk erosion, in situ microenvironment, and autocatalytic mechanisms should be understood to enable rational design of degradable systems. In an attempt to individually evaluate the physical state and form factors influencing autocatalytic hydrolysis of degradable polymers, this Review follows a hierarchical analysis that starts with hydrolytic degradation of water-soluble polymers before building up to 2D-like materials, such as ultrathin coatings and capsules, and then to solid-state degradation. We argue that chemical reactivity largely governs solution degradation while diffusivity and geometry control the degradation of bulk materials, with thin "2D" materials remaining largely unexplored. Following this classification, this Review explores techniques to analyze degradation in vitro and in vivo and summarizes recent advances toward understanding degradation behavior for traditional and innovative polymer systems. Finally, we highlight challenges encountered in analytical methodology and standardization of results and provide perspective on the future trends in the development of biodegradable polymers.

A Novel Hyperthermostable Recombinant Protein Nanocage

Ferritin has an important role in iron storage in the cells, and due to its nanocage structure and self-assembly properties, it has wide application prospects in nanobiotechnology. The maize (Zea mays) ferritin gene ZmFer1 was cloned and expressed in Escherichia coli BL21 (DE3) for the first time. Change in macromolecular structure of ZmFer1 ferritin due to heat treatment was investigated using native PAGE electrophoresis, DLS, and TEM. Change in the secondary structures of the protein was evaluated using CD spectroscopy. Moreover, alteration in the conformation of the protein was evaluated using UV-absorption spectra and intrinsic fluorescence spectra. The Tm of ZmFer1 was obtained using DSC. Finally, the effect of heat on the function of ZmFer1 was assessed by iron loading ability. The purified ZmFer1 protein showed a homopolymer nanocage structure. The results of native PAGE electrophoresis, DLS, and TEM techniques showed that ZmFer1 protein nanocage is stable to heat treatment up to 90 °C, and some of the protein nanocages retain their macromolecular structures even at 100 °C in liquid aqueous solution. Based on the DSC results, ZmFer1 protein nanocage had a Tm of 81.9 °C. After treatment at 100 °C, stable ZmFer1 protein nanocages were able to store iron atoms. Recombinant ZmFer1 ferritin with a Tm > 80°C is a hyperthermostable protein nanocage. The results of this study are beneficial for the development of protein nanocages that are stable under extreme temperature conditions, as well as application of ZmFer1 in nanobiotechnology, biomaterials, and biomedical fields.

Neural representations of cryo-EM maps and a graph-based interpretation

BackgroundAdvances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a protein structure from the discrete voxel grid data of cryo-EM maps involves interpolation into the continuous spatial domain. We present a novel data format called the neural cryo-EM map, which is formed from a set of neural networks that accurately parameterize cryo-EM maps and provide native, spatially continuous data for density and gradient. As a case study of this data format, we create graph-based interpretations of high resolution experimental cryo-EM maps.ResultsNormalized cryo-EM map values interpolated using the non-linear neural cryo-EM format are more accurate, consistently scoring less than 0.01 mean absolute error, than a conventional tri-linear interpolation, which scores up to 0.12 mean absolute error. Our graph-based interpretations of 115 experimental cryo-EM maps from 1.15 to 4.0 Å resolution provide high coverage of the underlying amino acid residue locations, while accuracy of nodes is correlated with resolution. The nodes of graphs created from atomic resolution maps (higher than 1.6 Å) provide greater than 99% residue coverage as well as 85% full atomic coverage with a mean of 0.19 Å root mean squared deviation. Other graphs have a mean 84% residue coverage with less specificity of the nodes due to experimental noise and differences of density context at lower resolutions.ConclusionsThe fully continuous and differentiable nature of the neural cryo-EM map enables the adaptation of the voxel data to alternative data formats, such as a graph that characterizes the atomic locations of the underlying protein or macromolecular structure. Graphs created from atomic resolution maps are superior in finding atom locations and may serve as input to predictive residue classification and structure segmentation methods. This work may be generalized to transform any 3D grid-based data format into non-linear, continuous, and differentiable format for downstream geometric deep learning applications.

PDBe and PDBe-KB: Providing high-quality, up-to-date and integrated resources of macromolecular structures to support basic and applied research and education.

The archiving and dissemination of protein and nucleic acid structures as well as their structural, functional and biophysical annotations is an essential task that enables the broader scientific community to conduct impactful research in multiple fields of the life sciences. The Protein Data Bank in Europe (PDBe; pdbe.org) team develops and maintains several databases and web services to address this fundamental need. From data archiving as a member of the Worldwide PDB consortium (wwPDB; wwpdb.org), to the PDBe Knowledge Base (PDBe‐KB; pdbekb.org), we provide data, data‐access mechanisms, and visualizations that facilitate basic and applied research and education across the life sciences. Here, we provide an overview of the structural data and annotations that we integrate and make freely available. We describe the web services and data visualization tools we offer, and provide information on how to effectively use or even further develop them. Finally, we discuss the direction of our data services, and how we aim to tackle new challenges that arise from the recent, unprecedented advances in the field of structure determination and protein structure modeling.

Performance of Rejuvenated Asphalt and Mixtures with Waste Engine Oil Bottom and Liquid Styrene-Butadiene Rubber

To address the inadequate performance of rejuvenated asphalt when waste engine oil bottom (WEOB) is used as an asphalt rejuvenator, liquid styrene-butadiene rubber (liquid SBR) was used to enhance the performance of WEOB-rejuvenated asphalt. By testing the basic physical properties of asphalt and using the high- and low-temperature rheology, differential scanning calorimetry, Fourier infrared spectroscopy, and atomic force microscopy (AFM) tests, the index and microstructure changes of asphalt before and after aging and regeneration, from macrolevels and microlevels, were studied, along with the high- and low-temperature performance and water stability of the rejuvenated asphalt mixture. The WEOB decreased the glass transition temperature and low-temperature performance grade of aged asphalt and resulted in a significant effect on the recovery of penetration and softening point of aged asphalt; however, the recovery of low-temperature ductility was inadequate. Compared with WEOB, a rejuvenator comprising WEOB and liquid SBR (WEOB-S) further decreased the glass transition and continuous grading temperatures of aged asphalt, improved its low-temperature performance, and significantly influenced its ductility recovery. The AFM test showed that WEOB-S effectively dispersed the agglomerated bee-like wax crystals or macromolecular asphaltene structures in the aged asphalt, decreased the number and crests of the bee-like structures, and improved the microscopic uniformity, thus obtaining better macroscopic physical properties. Both WEOB and WEOB-S improved the low-temperature performance and water stability of rejuvenated asphalt mixtures; however, WEOB-S was more effective.

Revealed interactive association between macro-molecular structures and true nutrition supply in cool-season adapted CDC chickpeas and CDC barley using advanced vibrational molecular spectroscopic techniques

Recently, an interactive association between molecular structures and nutrition of protein could be used for evaluation of truly absorbable nutrient supply, nutrient utilization and availability. However, there was no study found in cool-season adapted chickpeas. The objectives of this study were to: (1) reveal an interactive association between macro-molecular structures and nutrition of protein in cool-season adapted CDC chickpeas; (2) Characterize macro-molecular structure features of cool-season adapted CDC chickpeas and their genotypic impact on nutrient profile, fractionation, bioenergy values and biodegradation function in comparison with CDC barley kernel. Macromolecular structures determination was carried out using molecular vibrational spectroscopy-ATR-FTIR. Results showed that with vibrational molecular spectroscopy, the macromolecular spectral characteristics could be revealed among the varieties and between types of CDC developed grain (Chickpea vs CDC barley). The molecular spectral characteristics had significant relationship (P < 0.05) with carbohydrate profiles, sub-fractions and degradation, bypassed, total digestible carbohydrate and protein. Multiple regression with model nutrient variable selection study showed that protein and carbohydrate-related macro-molecular structural parameters were associated with nutrient profiles and degradation characteristics. The results indicated that there was an interactive association between macro-molecular structures and nutrition of protein in cool-season chickpeas.

Extraordinary Temperature Dependence of Hierarchically Assembled Macromolecular Structures with Memory

Extraordinary Temperature Dependence of Hierarchically Assembled Macromolecular Structures with Memory

Extended investigation of Ficus religiosa based PVA electrospun nanofiber for cosmeceutical application

The compositionalcharacteristics, antibacterial, and antioxidant activity of polyvinyl alcohol (PVA)containing Ficus religiosaleaf extract (FR) at 5 % and10 wt%fabricated through electrospinning technique were examined. The mechanicaland water vapour permeability of PVA was enhanced by adding a 5 % loading of leaves extract, i.e., 80 % and 30 %, respectively. The nanofibers' antioxidant and antibacterial activities were improved by adding 5 %and 10 % loaded FR leaves extract. The colour of the nanofiberswas also marginally altered by adding more FR extract. The inclusion of extractincreased the thermal stability of films by 20 %. Improvements in the interfacial contacts between the leaves extract andPVA were carried about by the functional groups and binding characteristics of the PVA's extractedsurface and macromolecular structures. Increases in FR extractcontent impact the PVA matrix's distribution mechanism. This study demonstrated the advantages of adding Ficus religiosa leaves extractto PVA nanofibersand the possibilities for using them as the active material for cosmeceutical applications like skin enhancement or skin healing.

Abstract A28: BCL10 mutations define distinct dependencies guiding precision therapy for DLBCL

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and the activated B cell-like subtype (ABC-DLBCL) is the most aggressive form and harbors frequent mutations of immune signaling pathways that culminate in constitutive activation of CARD11-MALT1-BCL10 (CBM) complex and downstream NF-κB pathway. CBM complexes form large macromolecular structures due to signal-induced polymerization of the BCL10 subunit, which is affected by recurrent somatic mutations in ABC-DLBCLs. Through biochemical, structural and functional dissection of these mutations, we find that BCL10 mutations fall into two functionally distinct classes: missense mutations of the BCL10 CARD domain (hotspot R58Q) and truncation of its C-terminal tail (hotspot E140X). To explore the functional consequences of BCL10 mutations, we established reporter systems to evaluate their impact on MALT1 and NF-𝜅B activities which are BCL10 downstream signaling cascades. We found that almost all mutants induced aberrantly strong NF-𝜅B and MALT1 activities in lymphoma cells as compared to WT BCL10, indicating the gain-of-function effect of BCL10 mutations. By performing immunohistochemistry staining of p65 in a set of tumor tissue microarray from DLBCL patients (n=298), we revealed that BCL10 mutant tumors have significantly (Mann-Whitney p&amp;lt;0.0001) increased p65 nuclear staining score compared to BCL10 WT tumors, suggesting enhanced NF-𝜅B activity. To investigate the biochemical impact of BCL10 mutants on CBM complex formation, we performed fluorescence polarization and filamentation formation assays with purified WT and mutant BCL10 proteins and found that both BCL10R58Q and BCL10E140X manifested faster and more spontaneous polarization compared to BCL10WT. Surprisingly, through mapping the BCL10-MALT1 interaction, we found that truncating mutation (E140X) abrogated a novel protein interaction motif through which MALT1 inhibits BCL10 polymerization, thus unleashing spontaneous CBM filament formation and inducing addiction to MALT1 activity. In marked contrast, the CARD missense mutation (R58Q) on BCL10 filament interface not only does not disrupt but enhances filament formation and it also alters CBM complex kinetics forming glutamine network structures that stabilize BCL10 filaments, but this still may require the upstream signal to activate MALT1. Importantly, we found that BCL10 mutant cells were less dependent on upstream CARD11 activation in MALT1 activation, NF-𝜅B signaling and cell growth assays performed in ABC-DLBCL lines. Furthermore, in vitro and in vivo xenograft studies revealed that BCL10 mutant lymphomas are resistant to BTK inhibitors, whereas BCL10 truncating (E140X) but not missense CARD (R58Q) mutants were hypersensitive to MALT1 protease inhibitors. Therefore, BCL10 mutations are potential biomarkers for BTK inhibitor resistance in ABC-DLBCL and further precision can be achieved by tailoring therapy (e.g. MALT1 inhibitors that are currently being tested in clinical trials) according to specific biochemical effects of distinct mutation classes. Citation Format: Min Xia, Liron David, Matthew R Teater, Johana Gutierrez, Xiang Wang, Cem Meydan, Andrew Lytle, Graham Slack, David Scott, Ozlem Onder, Kojo Elenitoba-Johnson, Nahuel Zamponi, Leandro Cerchietti, Tianbao Lu, Ulrike Philippar, Lorena Fontan, Hao Wu, Ari Melnick. BCL10 mutations define distinct dependencies guiding precision therapy for DLBCL [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr A28.

Obtaining the best temperature parameters for co-carbonization of lignite (yatağan)-biomass (peach seed shell) by structural characterization

In this study, Yatağan lignite (YL) and peach kernel shells (PKS) were originally taken separately and in a 1: 1 ratio by weight. Experiments were carried out in a 3-zone heated cylindrical furnace in a steel reactor. Structural characterization of all the solid products obtained was made by FTIR, XRD, and SEM analysis. When the FTIR and XRD spectra of the raw samples are examined, it is seen that they are rich in functional groups. It is seen that the PKS has aliphatic and aromatic structures and cellulosic structure –OH stresses (3500 cm−1). The sharp peak around 2918 cm−1 in Yatağan lignite belongs to the aliphatic C–H stretch. In the XRD spectrum, it is seen that both structures are largely amorphous. The raw PKS contains 3 different amorphous macromolecular structures. Yatagan lignite, on the other hand, contains crystalline peaks of clay and inorganic structures, depending on the ash content, as well as the amorphous structure. As the temperature increases depending on the carbonization temperature, as seen in the FTIR spectrum, the peaks of the functional groups decrease and disappear with the disruption of small macromolecular structures. As a result of the structural adjustment with the temperature increase, M-O-M peaks around 1000 cm−1 remain due to the aromatic C–H stretching and ash content. The paper centers around test assurance of operating temperatures in the consuming layer during co-carbonization. It is obtained that 800 °C is the best temperature condition for the co-carbonization process. It has been concluded that the chars obtained as a result of pyrolysis will be used as a solid fuel in both environmental (the lowest sulfur content) and economic (400 °C) sense. However, the fact that it has a very low sulfur content with the increase in the liquid and gas efficiency obtained at high temperatures again proves the production of an environmentally friendly liquid fuel.

The macromolecular machinery of the nucleus in the senescence process

The different types of tissues of the human body age in different ways; Cells that undergo many divisions such epithelial and connective tissues if compared to neurons and muscle have different aging mechanisms. Thus, we propose a thesis that, cell nucleus is composed of a macrostructural machinery, whit mechanisms of control the number of mitotic divisions and chronological markers of cell age. So, the macro molecular proteins structures in telomeres called shelterin and proteins known as lamins that are core integrity conformational proteins of the nucleus would perform functions of cellular age as structural timers. Finally, in certain tissues an accumulation of a truncated lamin known as progerin and the shortening of telomeres in shelterin complex has a mechanical function in molecular machinery of the nucleus where they work a compression in the transcriptionally structure of active euchromatin, with advancing of age this compression would decrease the rate of transcription of many genes, and causing the aging of organism.