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  • Bone-Marrow-Derived Mesenchymal Stem Cells, Their Conditioned Media, Protect against Cyclophosphamide-Induced Infertility in Rats

    Ibrabim, Dalia; Abozied, Nadia; Maboud, Samar Abdel; Alzamami, Ahmad; Alturki, Norah; Jaremko, Mariusz; Alanazi, Maram Khalil; Seddek, Asmaa (Frontiers in Pharmacology, Frontiers Media, 2023-03-22) [Article]
    Cancer is a deadly disease characterized by abnormal cell proliferation. Chemotherapy is one tech-nique of cancer treatment. Cyclophosphamide (CYP) is the most powerful chemotherapy medication, yet it has serious adverse effects. It is an antimitotic medicine that regulates cell proliferation and primarily targets quickly dividing cells, and it has been related to varying levels of infertility in hu-mans. In the current study, we assessed the biochemical, histological, and microscopic evaluations of testicular damage following CYP administration. Further, we have explored the potential protective impact of mesenchymal stem cell (MSCs) transplantation. The biochemical results revealed that ad-ministration of CYP increased serum concentrations of follicle-stimulating hormone (FSH) and lu-teinizing hormone (LH), while it decreased serum concentrations of free testosterone hormone (TH), testicular FSH, LH, and free TH concentrations, testicular total antioxidant capacity (TAC), and testicular activity of superoxide dismutase (SOD) enzyme. The histology and sperm examinations revealed that CYP induced destruction to the architectures of several tissues in the testes, which drastically reduced the Johnsen score as well as the spermatogenesis process. Surprisingly, trans-plantation of MSCs after CYP administration altered the deterioration effect of CYP injury on the testicular tissues, as demonstrated by biochemical and histological analysis. Our results indicated alleviation of serum and testicular sex hormones, as well as testicular oxidative stress markers (TAC and SOD activity), and nearly restored the normal appearance of the testicular tissues, Johnsen score, and spermatogenesis process. In conclusion, our work emphasizes the protective pharmacological use of MSCs to mitigate the effects of CYP on testicular tissues that impair the spermatogenesis process following chemotherapy. These findings indicate that transferring MSCs to chemotherapy patients could significantly improve spermatogenesis
  • Tuning anticancer properties and DNA-binding of Pt(ii) complexes via alteration of nitrogen softness/basicity of tridentate ligands

    Al-Rashdi, Kamelah S.; Babgi, Bandar A.; Ali, Ehab M. M.; Jedidi, Abdesslem; Emwas, Abdul-Hamid M.; Davaasuren, Bambar; Jaremko, Mariusz; Humphrey, Mark G. (RSC Advances, Royal Society of Chemistry (RSC), 2023-03-21) [Article]
    Nine tridentate Schiff base ligands of the type (N^N^O) were synthesized from reactions of primary amines {2-picolylamine (Py), N-phenyl-1,2-diaminobenzene (PhN), and N-phenyl-1,2-diaminoethane(EtN)} and salicylaldehyde derivatives {3-ethoxy (OEt), 4-diethylamine (NEt2) and 4-hydroxy (OH)}. Complexes with the general formula Pt(N^N^O)Cl were synthesized by reacting K2PtCl4 with the ligands in DMSO/ethanol mixtures. The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. The DNA-binding behaviours of the platinum(II) complexes were investigated by two techniques, indicating good binding affinities and a two-stage binding process for seven complexes: intercalation followed by switching to a covalent binding mode over time. The other two complexes covalently bond to ct-DNA without intercalation. Theoretical calculations were used to shed light on the electronic and steric factors that lead to the difference in DNA-binding behavior. The reactions of some platinum complexes with guanine were investigated experimentally and theoretically. The binding of the complexes with bovine serum albumin (BSA) indicated a static interaction with higher binding affinities for the ethoxy-containing complexes. The half maximal inhibitory concentration (IC50) values against MCF-7 and HepG2 cell lines suggest that platinum complexes with tridentate ligands of N-phenyl-o-phenylenediamine or pyridyl with 3-ethoxysalicylimine are good chemotherapeutic candidates. Pt-Py-OEt and Pt-PhN-OEt have IC50 values against MCF-7 of 13.27 and 10.97 μM, respectively, compared to 18.36 μM for cisplatin, while they have IC50 values against HepG2 of 6.99 and 10.15 μM, respectively, compared to 19.73 μM for cisplatin. The cell cycle interference behaviour with HepG2 of selected complexes is similar to that of cisplatin, suggesting apoptotic cell death. The current work highlights the impact of the tridentate ligand on the biological properties of platinum complexes.
  • 3D-Printed disposable nozzles for cost-efficient extrusion-based 3D bioprinting

    Albalawi, Hamed I.; Khan, Zainab N.; H. Rawas, Ranim; U. Valle-Pérez, Alexander; Abdelrahman, Sherin; Hauser, Charlotte (Materials Science in Additive Manufacturing, AccScience Publishing, 2023-03-21) [Article]
    3D bioprinting has significantly impacted tissue engineering with its capability to create intricate structures with complex geometries that were difficult to replicate through traditional manufacturing techniques. Extrusion-based 3D bioprinting methods tend to be limited when creating complex structures using bioinks of low viscosity. However, the capacity for creating multi-material structures that have distinct properties could be unlocked through the mixture of two solutions before extrusion. This could be used to generate architectures with varying levels of stiffness and hydrophobicity, which could be utilized for regenerative medicine applications. Moreover, it allows for combining proteins and other biological materials in a single 3D-bioprinted structure. This paper presents a standardized fabrication method of disposable nozzle connectors (DNC) for 3D bioprinting with hydrogel-based materials. This method entails 3D printing connectors with dual inlets and a single outlet to mix the material internally. The connectors are compatible with conventional Luer lock needles, offering an efficient solution for nozzle replacement. IVZK (Ac-Ile-Val-Cha-Lys-NH2) peptide-based hydrogel materials were used as a bioink with the 3D-printed DNCs. Extrusion-based 3D bioprinting was employed to print shapes of varying complexities, demonstrating potential in achieving high print resolution, shape fidelity, and biocompatibility. Post-printing of human neonatal dermal fibroblasts, cell viability, proliferation, and metabolic activity were observed, which demonstrated the effectiveness of the proposed design and process for 3D bioprinting using low-viscosity bioinks.
  • An overlooked soil carbon pool in vegetated coastal ecosystems: National-scale assessment of soil organic carbon stocks in coastal shelter forests of China.

    Li, Yuan; Fu, Chuancheng; Wang, Weiqi; Zeng, Lin; Tu, Chen; Luo, Yongming (The Science of the total environment, Elsevier BV, 2023-03-17) [Article]
    Protection and restoration of vegetated coastal ecosystems provide opportunities to mitigate climate change. Coastal shelter forests as one of vegetated coastal ecosystems play vital role on sandy coasts protection, but less attention is paid on their soil organic carbon (OC) sequestration potential. Here, we provide the first national-scale assessment of the soil OC stocks, fractions, sources and accumulation rates from 48 sites of shelter forests and 74 sites of sandy beaches across 22° of latitude in China. We find that, compared with sandy beaches, shelter forest plantation achieves an average soil desalination rate of 92.0 % and reduces the soil pH by 1.3 units. The improved soil quality can facilitate OC sequestration leading to an increase of soil OC stock of 11.8 (0.60–64.2) MgC ha−1 in shelter forests. Particulate OC (POC) is a dominant OC fraction in both sandy beaches and shelter forests, but most sites are >80 % in shelter forests. The low δ13C values and higher C:N ratios, which are more regulated by climate and tree species, together with high POC proportions suggest a substantial contribution of plant-derived OC. Bayesian mixing model indicates that 71.8 (33.5–91.6)% of the soil OC is derived from local plant biomass. We estimate that soil OC stocks in Chinese shelter forests are 20.5 (7.44–79.7) MgC ha−1 and 4.53 ± 0.71 TgC in the top meter, with an accumulation rate of 45.0 (6.90 to 194.1) gC m−2 year−1 and 99.5 ± 44.9 GgC year−1. According to coastal shelter forest afforestation plan, additional 1.72 ± 0.27 TgC with a rate of 37.9 ± 17.1 GgC year−1 can be sequestrated in the future. Our findings suggest that construction of coastal shelter forests can be an effective solution to sequester more soil carbon in coastal ecosystems.
  • Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.

    Larrayoz, Marta; Garcia-Barchino, Maria J; Celay, Jon; Etxebeste, Amaia; Jimenez, Maddalen; Perez, Cristina; Ordoñez, Raquel; Cobaleda, Cesar; Botta, Cirino; Fresquet, Vicente; Roa, Sergio; Goicoechea, Ibai; Maia, Catarina; Lasaga, Miren; Chesi, Marta; Bergsagel, P Leif; Larrayoz, Maria J; Calasanz, Maria J; Campos-Sanchez, Elena; Martinez-Cano, Jorge; Panizo, Carlos; Rodriguez-Otero, Paula; Vicent, Silvestre; Roncador, Giovanna; Gonzalez, Patricia; Takahashi, Satoru; Katz, Samuel G; Walensky, Loren D; Ruppert, Shannon M; Lasater, Elisabeth A; Amann, Maria; Lozano, Teresa; Llopiz, Diana; Sarobe, Pablo; Lasarte, Juan J; Planell, Nuria; Gomez-Cabrero, David; Kudryashova, Olga; Kurilovich, Anna; Revuelta, Maria V; Cerchietti, Leandro; Agirre, Xabier; San Miguel, Jesus; Paiva, Bruno; Prosper, Felipe; Martinez-Climent, Jose A (Nature medicine, Springer Science and Business Media LLC, 2023-03-16) [Article]
    The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.
  • Fouling of Polyalkylmethylsiloxane Composite Membranes during Pervaporation Separation of ABE-Fermentation Mixtures

    Rokhmanka, Tatyana N.; Grushevenko, Evgenia A.; Arapova, Olga V.; Bondarenko, Galina N.; Golubev, George S.; Borisov, Ilya L.; Volkov, Alexey V. (Applied Sciences, MDPI AG, 2023-03-16) [Article]
    Production of bio-alcohols is one of the approaches used in the development of alternative energy. Pervaporation is a promising option for the separation of bio-alcohols from the fermentation mixture. A serious problem in the process of continuous extraction of biobutanol from the fermentation broth is the contamination of the membrane, which leads to a decrease in its permeability over time. In this work, the transport properties of composite membranes based on polyheptylmethylsiloxane (PHeptMS), polydecylmethylsiloxane (PDecMS), and a commercial membrane MDK-3 were studied during separation of a real ABE-fermentation broth in vacuum pervaporation mode. The study was performed before and after continuous contact of the membranes with the fermentation broth for one month. Visually and by scanning electron spectroscopy, the presence of membrane surface residue and its effect on the wettability of the membrane selective layer by the components of the ABE broth were determined. The sediment composition was evaluated by energy dispersive analysis and infrared spectroscopy. According to the pervaporation separation of the ABE-broth using PHeptMS, PDecMS, and MDK-3 membranes, the butanol flux was 0.029, 0.012, and 0.054 kg/(m2·h), respectively. The butanol-water partition factor was 41, 22, and 13 for PHeptMS, PDecMS, and MDK-3, respectively. After one month of incubation of the membranes in ABE-fermentation broth during the separation of the model mixture, a decrease of 10 and 5% in permeate flux and separation factor, respectively, was observed for all membranes. Temperature dependences (30–60 °C) of permeate flux, permeability, and selectivity were obtained for the membranes after clogging. The most promising in terms of minimal negative changes as a result of fouling was demonstrated by the PHeptMS membrane. For it, the clogging dynamics during separation of the real fermentation broth for 216 h were investigated. Two characteristic steps of decrease in transport and separation properties were observed, after 28 and 150 h of the experiment. After 216 h of experiment, a 1.28-fold decrease in total flux through the membrane, a 9% decrease in butanol permeability, and a 10% decrease in n-butanol selectivity were found for PHeptMS.
  • Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens

    Chaudhary, Shahid; Ali, Zahir; Tehseen, Muhammad; Haney, Evan F.; Pantoja Angles, Aarón; Alshehri, Salwa; Wang, Tiannyu; Clancy, Gerard Jude; Ayach, Maya; Hauser, Charlotte; Hong, Pei-Ying; Hamdan, Samir; Hancock, Robert E. W.; Mahfouz, Magdy M. (Nature Communications, Springer Science and Business Media LLC, 2023-03-16) [Article]
    Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in AMP synthesis and their short plasma half-life render their clinical translation a challenge. To address these shortcomings, we report efficient production of bioactive amidated AMPs by transient expression of glycine-extended AMPs in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase (PAM). Cationic AMPs accumulate to substantial levels in PAM transgenic plants compare to nontransgenic N. benthamiana. Moreover, AMPs purified from plants exhibit robust killing activity against six highly virulent and antibiotic resistant ESKAPE pathogens, prevent their biofilm formation, analogous to their synthetic counterparts and synergize with antibiotics. We also perform a base case techno-economic analysis of our platform, demonstrating the potential economic advantages and scalability for industrial use. Taken together, our experimental data and techno-economic analysis demonstrate the potential use of plant chassis for large-scale production of clinical-grade AMPs.
  • The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain

    Alsanie, Walaa F.; Abdelrahman, Sherin; Felimban, Raed I.; Alkhatabi, Heba A.; Gaber, Ahmed; Alosimi, Ebtisam Abdulah; Alhomrani, Majid; Habeeballah, Hamza; Hauser, Charlotte; Alamri, Abdulhakeem S.; Althobaiti, Aiysha; Alsharif, Abdulaziz; Alzahrani, Ahmed S.; Al-Ghamdi, Mohammad S.; Raafat, Bassem M.; Alswat, Khaled A.; Althobaiti, Yusuf S.; Asiri, Yousif A. (International Journal of Molecular Sciences, MDPI AG, 2023-03-16) [Article]
    Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.
  • Fully Printed Dual-Layer Depolarizing Chipless RFID Tag for Wearable Applications

    Wang, Renqi; Akhter, Zubair; Li, Weiwei; Shamim, Atif (IEEE Journal of Radio Frequency Identification, Institute of Electrical and Electronics Engineers (IEEE), 2023-03-16) [Article]
    This work presents a cross-polar dual-layer chipless radio-frequency identification (RFID) tag based on a ladder-shaped resonator design. An integrated ground plane enables direct attachment to human skin without performance deterioration. Simulations show that the ladder-shaped resonator provides several advantages over traditional L-shaped and straight resonators, including a strong cross-polar radar cross section (-23.4 dBsm), third-order harmonics, orientation insensitivity, and compact size (0.062 λ2). The effects of the ground plane shape on the surface current distribution are investigated, and a circular tag of 20 mm radius is designed using ladder resonator groups and frequency shift encoding to provide an active area of 96.45 bits/λ2 and a unit frequency of 6.03 bits/GHz. The tag substrate is three-dimensionally (3D) printed with metallic resonator patterns that are subsequently screen-printed on the substrate. The maximum read range is measured at 40 mm using a cross-shaped, dual-polarized Vivaldi antenna connected to a network analyzer. The measured characteristics in free space are in good agreement with the simulation results, and practical on-body performance tests for the manufactured prototype using simulation and direct measurements indicate that the tag performance remains stable for both free space and on-body cases. The fully printed fabrication process makes the proposed tag design suitable for mass production at a low cost.
  • Molecular insights into the Darwin paradox of coral reefs from the sea anemone Aiptasia

    Cui, Guoxin; Konciute, Migle; Ling, Lorraine; Esau, Luke; Raina, Jean-Baptiste; Han, Baoda; Salazar Moya, Octavio Ruben; Presnell, Jason S.; Rädecker, Nils; Zhong, Huawen; Menzies, Jessica; Cleves, Phillip A.; Liew, Yi Jin; Krediet, Cory J.; Sawiccy, Val; Cziesielski, Maha Joana; Guagliardo, Paul; Bougoure, Jeremy; Pernice, Mathieu; Hirt, Heribert; Voolstra, Christian R.; Weis, Virginia M.; Pringle, John R.; Aranda, Manuel (Science Advances, American Association for the Advancement of Science (AAAS), 2023-03-15) [Article]
    Symbiotic cnidarians such as corals and anemones form highly productive and biodiverse coral reef ecosystems in nutrient-poor ocean environments, a phenomenon known as Darwin’s paradox. Resolving this paradox requires elucidating the molecular bases of efficient nutrient distribution and recycling in the cnidarian-dinoflagellate symbiosis. Using the sea anemone Aiptasia, we show that during symbiosis, the increased availability of glucose and the presence of the algae jointly induce the coordinated up-regulation and relocalization of glucose and ammonium transporters. These molecular responses are critical to support symbiont functioning and organism-wide nitrogen assimilation through glutamine synthetase/glutamate synthase–mediated amino acid biosynthesis. Our results reveal crucial aspects of the molecular mechanisms underlying nitrogen conservation and recycling in these organisms that allow them to thrive in the nitrogen-poor ocean environments.
  • LEP-AD: Language Embedding of Proteins and Attention to Drugs predicts drug target interactions

    Daga, Anuj; Khan, Sumeer Ahmad; Gomez-Cabrero, David; Hoehndorf, Robert; Kiani, Narsis A.; Tegner, Jesper (Cold Spring Harbor Laboratory, 2023-03-15) [Preprint]
    Predicting drug-target interactions is a tremendous challenge for drug development and lead optimization. Recent advances include training algorithms to learn drug-target interactions from data and molecular simulations. Here we utilize Evolutionary Scale Modeling (ESM-2) models to establish a Transformer protein language model for drug-target interaction predictions. Our architecture, LEP- AD, combines pre-trained ESM-2 and Transformer-GCN models predicting bind-ing affinity values. We report new best-in-class state-of-the-art results compared to competing methods such as SimBoost, DeepCPI, Attention-DTA, GraphDTA, and more using multiple datasets, including Davis, KIBA, DTC, Metz, ToxCast, and STITCH. Finally, we find that a pre-trained model with embedding of proteins (the LED-AD) outperforms a model using an explicit alpha-fold 3D representation of proteins (e.g., LEP-AD supervised by Alphafold). The LEP-AD model scales favorably in performance with the size of training data.
  • Assessing the Built Environment’s Reflectivity, Flexibility, Resourcefulness, and Rapidity Resilience Qualities against Climate Change Impacts from the Perspective of Different Stakeholders

    Al-Humaiqani, Mohammed M.; Al-Ghamdi, Sami (Sustainability, MDPI AG, 2023-03-13) [Article]
    The frequency and severity of climate change are projected to increase, leading to more disasters, increased built environment system (BES) vulnerability, and decreased coping capacity. Achieving resilience objectives in the built environment is challenging and requires the collaboration of all relevant sectors and professionals. In this study, various stakeholders were engaged, including governmental authorities, regulatory bodies, engineering firms, professionals, contractors, and non-governmental and non-profit organizations (NGOs and NPOs, respectively). The engagement was carried out through the answering of a questionnaire survey that reflects their perceptions about climate change adaptation, the built environment resilience qualities (RQs), and the degree of resilience of the existing built environment and their perceived capacities. The results were analyzed using several statistical tests. The results revealed that advancing public understanding and management tools, reducing economic losses, and developing necessary plans still require improvement. Additionally, the BESs were ranked concerning accepting the change and uncertainty inherited from the past or generated over time. This study emphasized the perception that the decision-making domain is crucial for delivering a reflective built environment. Additionally, features such as advancing public understanding and management tools, reducing economic losses, and developing necessary plans still require improvement. Furthermore, there is a belief in the importance of the task forces within the community as part of an emergency response plan, and a less reflective system would have less recovery speed. Therefore, the rapidity characteristic of a built environmental system to accept the change and uncertainty inherited from the past or generated over time is correlated to the system’s reflectivity quality. This study emphasizes the significant correlation between the different RQ traits. It also encourages researchers to formulate more objective methods to reach a set form for measuring RQs as an engineering standard.
  • Synthetic biology open language (SBOL) version 3.1.0

    Buecherl, Lukas; Mitchell, Thomas; Scott-Brown, James; Vaidyanathan, Prashant; Vidal, Gonzalo; Baig, Hasan; Bartley, Bryan; Beal, Jacob; Crowther, Matthew; Fontanarossa, Pedro; Gorochowski, Thomas; Grunberg, Raik; Kulkarni, Vishwesh; McLaughlin, James; Mısırlı, Göksel; Oberortner, Ernst; Wipat, Anil; Myers, Chris (Journal of Integrative Bioinformatics, Walter de Gruyter GmbH, 2023-03-13) [Article]
    Synthetic biology builds upon genetics, molecular biology, and metabolic engineering by applyingengineering principles to the design of biological systems. When designing a synthetic system, synthetic biolo-gists need to exchange information about multiple types of molecules, the intended behavior of the system, andactual experimental measurements. TheSynthetic Biology Open Language(SBOL) has been developed as a stan-dard to support the specification and exchange of biological design information in synthetic biology, followingan open community process involving both bench scientists and scientific modelers and software develop-ers, across academia, industry, and other institutions. This document describes SBOL 3.1.0, which improveson version 3.0.0 by including a number of corrections and clarifications as well as several other updates andenhancements. First, this version includes a complete set of validation rules for checking whether documentsare valid SBOL 3. Second, the best practices section has been moved to an online repository that allows formore rapid and interactive of sharing these conventions. Third, it includes updates based upon six commu-nity approved enhancement proposals. Two enhancement proposals are related to the representation of anobject’s namespace. In particular, theNamespaceclass has been removed and replaced with anamespaceproperty on each class. Another enhancement is the generalization of theCombinatorialDeriviationclass toallow direct use ofFeaturesandMeasures.Next,theParticipationclass now allowInteractionsto bepartic-ipantsto describe higher-order interactions. Another change is the use ofSequence Ontologyterms forFeatureorientation. Finally, this version of SBOL has generalized from using Unique Reference Identifiers (URIs) toInternationalized Resource Identifiers(IRIs) to support international character sets.
  • Abiotic selection of microbial genome size in the global ocean

    Ngugi, David; Acinas, Silvia G; Sanchez, Pablo; Gasol, Josep M.; Agusti, Susana; Karl, David M.; Duarte, Carlos M. (Nature Communications, Springer Science and Business Media LLC, 2023-03-13) [Article]
    Strong purifying selection is considered a major evolutionary force behind small microbial genomes in the resource-poor photic ocean. However, very little is currently known about how the size of prokaryotic genomes evolves in the global ocean and whether patterns reflect shifts in resource availability in the epipelagic and relatively stable deep-sea environmental conditions. Using 364 marine microbial metagenomes, we investigate how the average genome size of uncultured planktonic prokaryotes varies across the tropical and polar oceans to the hadal realm. We find that genome size is highest in the perennially cold polar ocean, reflecting elongation of coding genes and gene dosage effects due to duplications in the interior ocean microbiome. Moreover, the rate of change in genome size due to temperature is 16-fold higher than with depth up to 200 m. Our results demonstrate how environmental factors can influence marine microbial genome size selection and ecological strategies of the microbiome.
  • Differential susceptibility of Red Sea Pocilloporidae corals to UVB highlights photoacclimation potential

    Overmans, Sebastian; Agusti, Susana (Frontiers in Marine Science, Frontiers Media SA, 2023-03-13) [Article]
    Despite being exposed to extreme water temperatures and solar irradiances, Red Sea corals are relatively resistant to bleaching. While their thermal tolerance is well described, little is known about their resistance to ultraviolet-B radiation (UVB). Here, we performed a short-term (2 days) UVB-removal incubation with Stylophora pistillata, and in situ measurements with Pocillopora verrucosa complemented by a long-term (46 days) transplantation and UVB-removal experiment. Using a suite of physiological parameters (effective quantum yield (Fv’/Fm’), oxidative stress (lipid peroxidation, LPO), and primary production), we assessed the impacts of UVB on the physiology and acclimation capacity of Red Sea corals. Shielding S. pistillata from UVB did not change the gross primary production or Fv’/Fm’, and respiration and LPO in the host remained unaffected. In situ, P. verrucosa exhibited less varying and significantly higher Fv’/Fm’ in 8 m depth (0.61 ± 0.04) than in 4 m (0.52 ± 0.06), 2 m (0.51 ± 0.09), and 0.5 m (0.50 ± 0.11), where water temperatures ranged from 30.5–33.4, 30.6–34.0, 30.8–34.5, 30.6–37.3°C and daily UVB exposures averaged 0.9, 2.9, 11.8 and 21.4 kJ m-2, respectively. Fv’/Fm’ correlated the strongest with UVB (-0.57), followed by PAR (-0.54) and temperature (-0.40), suggesting that UVB is a key determinant of photosynthetic efficiency. Fv’/Fm’ of upward transplanted specimens (T 1m) was initially decreased but gradually increased and reached the same values as shallow corals (1 m) after 44 days. UVB removal significantly increased the Fv’/Fm’ of transplanted corals in the first 20 days. Oxidative stress was initially highest in T 1m samples under full sunlight but equalized with 1 m specimens by day 46, whereas oxidative stress was significantly reduced by day 4 in T 1m corals sheltered from UVB. Overall, UVB-removal generally had little impact on the physiology of shallow-water S. pistillata and P. verrucosa but considerably accelerated the acclimation of upward transplanted corals. Our study highlights that UVB is a crucial stressor governing the photoacclimation capacity of these Red Sea coral species.
  • Palidis: fast discovery of novel insertion sequences.

    Carr, Victoria R; Pissis, Solon P; Mullany, Peter; Shoaie, Saeed; Gomez-Cabrero, David; Moyes, David L (Microbial genomics, Cold Spring Harbor Laboratory, 2023-03-10) [Article]
    The diversity of microbial insertion sequences, crucial mobile genetic elements in generating diversity in microbial genomes, needs to be better represented in current microbial databases. Identification of these sequences in microbiome communities presents some significant problems that have led to their underrepresentation. Here, we present a bioinformatics pipeline called Palidis that recognizes insertion sequences in metagenomic sequence data rapidly by identifying inverted terminal repeat regions from mixed microbial community genomes. Applying Palidis to 264 human metagenomes identifies 879 unique insertion sequences, with 519 being novel and not previously characterized. Querying this catalogue against a large database of isolate genomes reveals evidence of horizontal gene transfer events across bacterial classes. We will continue to apply this tool more widely, building the Insertion Sequence Catalogue, a valuable resource for researchers wishing to query their microbial genomes for insertion sequences.
  • In vitro and in silico evaluations of actinomycin X2and actinomycin D as potent anti-tuberculosis agents

    Qureshi, Kamal Ahmad; Azam, Faizul; Fatmi, Muhammad Qaiser; Imtiaz, Mahrukh; Prajapati, Dinesh Kumar; Rai, Pankaj Kumar; Jaremko, Mariusz; Emwas, Abdul-Hamid M.; Elhassan, Gamal Osman (PeerJ, PeerJ, 2023-03-08) [Article]
    Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the world’s most devastating contagious diseases and is caused by the MDR-Mycobacterium tuberculosis (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, in vitro and in silico studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X2 (act-X2) and actinomycin-D (act-D), from the Streptomyces smyrnaeus strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia). Methods: The anti-TB activity of the isolated actinomycins was assessed in vitro using the Mtb H37Ra, Mycobacterium bovis (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. In silico molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands. Results: In vitro results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X2 had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The in silico molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-X2and act-D respectively. The molecular dynamics (MD) results demonstrated that act-X2 and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X2 was more potent than act-D. Conclusion: In conclusion, our results suggest that both actinomycins X2 and D are highly potent anti-TB drug candidates. We show that act-X2is better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.
  • Impact of electrochemically generated iron on the performance of an anaerobic wastewater treatment process.

    Hu, Zhetai; Hu, Shihu; Hong, Pei-Ying; Zhang, Xueqin; Prodanovic, Veljko; Zhang, Kefeng; Ye, Liu; Deletic, Ana; Yuan, Zhiguo; Zheng, Min (The Science of the total environment, Elsevier BV, 2023-03-07) [Article]
    Anaerobic treatment of domestic wastewater has the advantages of lower biomass yield, lower energy demand and higher energy recover over the conventional aerobic treatment process. However, the anaerobic process has the inherent issues of excessive phosphate and sulfide in effluent and superfluous H2S and CO2 in biogas. An electrochemical method allowing for in-situ generation of Fe2+ in the anode and hydroxide ion (OH−) and H2 in the cathode was proposed to overcome the challenges simultaneously. The effect of electrochemically generated iron (e‑iron) on the performance of anaerobic wastewater treatment process was explored with four different dosages in this work. The results showed that compared to control, the experimental system displayed an increase of 13.4–28.4 % in COD removal efficiency, 12.0–21.3 % in CH4 production rate, 79.8–98.5 % in dissolved sulfide reduction, 26.0–96.0 % in phosphate removal efficiency, depending on the e‑iron dosage between 40 and 200 mg Fe/L. Dosing of the e‑iron significantly upgraded the quality of produced biogas, showing a much lower CO2 and H2S contents in biogas in experimental reactor than that in control reactor. The results thus demonstrated that e‑iron can significantly improve the performance of anaerobic wastewater treatment process, bringing multiple benefits with the increase of its dosage regarding effluent and biogas quality.
  • Salts as Additives: A Route to Improve Performance and Stability of n-Type Organic Electrochemical Transistors

    Ohayon, David; Flagg, Lucas Q.; Giugni, Andrea; Wustoni, Shofarul; Li, Ruipeng; Hidalgo, Tania C.; Emwas, Abdul-Hamid M.; Sheelamanthula, Rajendar; McCulloch, Iain; Richter, Lee J.; Inal, Sahika (ACS Materials Au, American Chemical Society (ACS), 2023-03-06) [Article]
    Organic electrochemical transistors (OECTs) are becoming increasingly ubiquitous in various applications at the interface with biological systems. However, their widespread use is hampered by the scarcity of electron-conducting (n-type) backbones and the poor performance and stability of the existing n-OECTs. Here, we introduce organic salts as a solution additive to improve the transduction capability, shelf life, and operational stability of n-OECTs. We demonstrate that the salt-cast devices present a 10-fold increase in transconductance and achieve at least one year-long stability, while the pristine devices degrade within four months of storage. The salt-added films show improved backbone planarity and greater charge delocalization, leading to higher electronic charge carrier mobility. These films show a distinctly porous morphology where the interconnectivity is affected by the salt type, responsible for OECT speed. The salt-based films display limited changes in morphology and show lower water uptake upon electrochemical doping, a possible reason for the improved device cycling stability. Our work provides a new and easy route to improve n-type OECT performance and stability, which can be adapted for other electrochemical devices with n-type films operating at the aqueous electrolyte interface.
  • Perpetual Motion Electric Truck, Transporting Cargo with Zero Fuel Costs

    Hunt, Julian David; Tong, Wenxuan; Zakeri, Behnam; Jurasz, Jakub; Patro, Epari Ritesh; Durin, Bojan; Pacheco, Diego Augusto de Jesus; Leal Filho, Walter; Wada, Yoshihide (Elsevier BV, 2023-03-06) [Preprint]
    The transportation sector is going through a rapid transition to electric vehicles to minimize our reliance on fossil fuels and reduce CO2 emissions. This is also happening in the cargo transport sector, with a rapid deployment of electric trucks. This paper proposes that the replacement of diesel trucks with electric trucks should first happen on routes where cargo is delivered from a location with a higher altitude to a location with a lower altitude. This way, the regenerative braking system of the truck can completely recharge the truck’s battery. This paper investigates scenarios where electric trucks could operate indefinitely without grid electricity to charge their batteries. This concept was named perpetual motion electric truck (PMET). Results show that with an average road slope of 5%, 60 km/h speed, the weight of the cargo should be at least 1.32 times the weight of the truck, PMET can be achieved. PMET is an interesting alternative to reduce electricity demand and increase the sustainability of the transport sector.

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