### Recent Submissions

• #### Structural properties and stability of the Betaine-Urea natural deep eutectic solvent

(Journal of Molecular Liquids, Elsevier BV, 2021-09-25) [Article]
This work focuses on the stability and supramolecular structure of the betaine-urea-water (B:U:W) natural deep eutectic solvent. Solutions spanning a range of molar ratios of betaine, urea, and water were prepared, varying the temperature and preparation times, and were analyzed by attenuated total reflection Fourier-transform infrared spectroscopy and Nuclear Magnetic Resonance. Density Functional Theory and the Natural Bond Orbital analysis were employed to obtain the most stable conformations for each mixture. The experimental results show that, in non-anhydrous conditions, betaine:urea (1:1), a minimum of two moles of water are needed to form a metastable transparent liquid, and a minimum of three moles of water is required to have a stable NADES. Comparison of the 13C-NMR spectra of B:U:W 1:1:2 and 1:1:3 shows for the latter that the carbonyl groups of betaine and urea form stronger hydrogen bonds with water, and that the CH3 group of betaine becomes more deprotected by the addition of the extra water molecule, making 1:1:3 a more stable solution. Our experimental and computational results show that water is of crucial importance to the NADES supramolecular structure and stability. A better understanding of the structural characteristics of NADES can lead to better envisage applications for these green solvents.
• #### The long road to engineering durable disease resistance in wheat

(Current Opinion in Biotechnology, Elsevier BV, 2021-09-24) [Article]
A rich past of generating and configuring genetic structures in wheat (Triticum aestivum) combined with advances in DNA sequencing, bioinformatics and genome engineering has transformed the field of wheat functional genomics. Cloning a gene from the large and complex wheat genome is no longer unattainable; in the past 5 years alone, the molecular identity of 33 wheat disease resistance genes has been elucidated. The next 15 years will see the cloning of most of the 460 known wheat resistance genes and their corresponding effectors. Coupled with mechanistic insights into how resistance genes, effectors and pathogenicity targets interact and are affected by different genetic backgrounds, this will drive systems biology and synthetic engineering studies towards the alluring goal of generating durable disease resistance in wheat.
• #### A binary classifier based on a reconfigurable dense network of metallic nanojunctions

(Neuromorphic Computing and Engineering, IOP Publishing, 2021-09-24) [Article]
Major efforts to reproduce the brain performances in terms of classification and pattern recognition have been focused on the development of artificial neuromorphic systems based on top-down lithographic technologies typical of highly integrated components of digital computers. Unconventional computing has been proposed as an alternative exploiting the complexity and collective phenomena originating from various classes of physical substrates. Materials composed of a large number of non-linear nanoscale junctions are of particular interest: these systems, obtained by the self-assembling of nano-objects like nanoparticles and nanowires, results in non-linear conduction properties characterized by spatiotemporal correlation in their electrical activity. This appears particularly useful for classification of complex features: nonlinear projection into a high-dimensional space can make data linearly separable, providing classification solutions that are computationally very expensive with digital computers. Recently we reported that nanostructured Au films fabricated from the assembling of gold clusters by supersonic cluster beam deposition show a complex resistive switching behaviour. Their non-linear electric behaviour is remarkably stable and reproducible allowing the facile training of the devices on precise resistive states. Here we report about the fabrication and characterization of a device that allows the binary classification of Boolean functions by exploiting the properties of cluster-assembled Au films interconnecting a generic pattern of electrodes. This device, that constitutes a generalization of the perceptron, can receive inputs from different electrode configurations and generate a complete set of Boolean functions of n variables for classification tasks. We also show that the non-linear and non-local electrical conduction of cluster-assembled gold films, working at room temperature, allows the classification of non-linearly separable functions without previous training of the device.
• #### Clinically significant findings of high-risk mutations in human SLC29A4 gene associated with diabetes mellitus type 2 in Pakistani population

(Journal of Biomolecular Structure and Dynamics, Informa UK Limited, 2021-09-23) [Article]
This study conducted an in-depth analysis combining computational and experimental verifications of the deleterious missense mutations associated with the SLC29A4 protein. The functional annotation of the non-synonymous single nucleotide polymorphism (nsSNPs), followed by structure-function analysis, revealed 13 single nucleotide polymorphisms (SNP) as the most damaging. Among these, six mutants P429T/S, L144S, M108V, N86H, and V79E, were predicted as structurally and functionally damaging by protein stability analysis. Also, these variants are located at evolutionary conserved regions, either buried, contributing to the structural damage, or exposed, causing functional changes in the protein. These mutants were further taken for molecular docking studies. When verified via experimental analysis, the SNPs M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) showed an association with type 2 diabetes mellitus (T2DM). Minor allele frequency for rs149798710 (A > G) was 0.23 in controls, 0.29 in metformin responders, 0.37 in metformin non-responder, for rs151039853 (A > C) was 0.21 in controls, 0.28 in metformin responders, 0.36 in metformin non-responder and for rs17854505 (T > A) was 0.20 in controls, 0.25 in metformin responders, 0.37 in metformin non-responder. Hence, this study concludes that SLC29A4 M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) polymorphisms were associated with the increased risk of T2DM as well as with the increased risk towards the failure of metformin therapeutic response in T2DM patients of Pakistan. Communicated by Ramaswamy H. Sarma.
• #### NSD2 dimethylation at H3K36 promotes lung adenocarcinoma pathogenesis.

(Molecular cell, 2021-09-23) [Article]
The etiological role of NSD2 enzymatic activity in solid tumors is unclear. Here we show that NSD2, via H3K36me2 catalysis, cooperates with oncogenic KRAS signaling to drive lung adenocarcinoma (LUAD) pathogenesis. In vivo expression of NSD2$_{E1099K}$, a hyperactive variant detected in individuals with LUAD, rapidly accelerates malignant tumor progression while decreasing survival in KRAS-driven LUAD mouse models. Pathologic H3K36me2 generation by NSD2 amplifies transcriptional output of KRAS and several complementary oncogenic gene expression programs. We establish a versatile in vivo CRISPRi-based system to test gene functions in LUAD and find that NSD2 loss strongly attenuates tumor progression. NSD2 knockdown also blocks neoplastic growth of PDXs (patient-dervived xenografts) from primary LUAD. Finally, a treatment regimen combining NSD2 depletion with MEK1/2 inhibition causes nearly complete regression of LUAD tumors. Our work identifies NSD2 as a bona fide LUAD therapeutic target and suggests a pivotal epigenetic role of the NSD2-H3K36me2 axis in sustaining oncogenic signaling.
• #### Development of a gRNA-tRNA array of CRISPR/Cas9 in combination with grafting technique to improve gene-editing efficiency of sweet orange.

(Plant cell reports, Springer Science and Business Media LLC, 2021-09-23) [Article]
Key messageHere, we developed a reliable protocol for the fast and efficient gene-edited Anliu sweet orange plants production. The application of in vitro shoot grafting technology significantly reduced the growth cycle of transgenic seedlings, and the survival rate of cleft grafting was more than 90%. In addition, the mutation efficiency of the grafted geneedited sweet orange was significantly improved by short-term heat stress treatments. Thus, the combination strategy of grafting and heat stress treatments provided a reference for the fast and efficient multiplex gene editing of sweet orange.
• #### DTi2Vec: Drug–target interaction prediction using network embedding and ensemble learning

(Journal of Cheminformatics, Springer Science and Business Media LLC, 2021-09-22) [Article]
AbstractDrug–target interaction (DTI) prediction is a crucial step in drug discovery and repositioning as it reduces experimental validation costs if done right. Thus, developing in-silico methods to predict potential DTI has become a competitive research niche, with one of its main focuses being improving the prediction accuracy. Using machine learning (ML) models for this task, specifically network-based approaches, is effective and has shown great advantages over the other computational methods. However, ML model development involves upstream hand-crafted feature extraction and other processes that impact prediction accuracy. Thus, network-based representation learning techniques that provide automated feature extraction combined with traditional ML classifiers dealing with downstream link prediction tasks may be better-suited paradigms. Here, we present such a method, DTi2Vec, which identifies DTIs using network representation learning and ensemble learning techniques. DTi2Vec constructs the heterogeneous network, and then it automatically generates features for each drug and target using the nodes embedding technique. DTi2Vec demonstrated its ability in drug–target link prediction compared to several state-of-the-art network-based methods, using four benchmark datasets and large-scale data compiled from DrugBank. DTi2Vec showed a statistically significant increase in the prediction performances in terms of AUPR. We verified the "novel" predicted DTIs using several databases and scientific literature. DTi2Vec is a simple yet effective method that provides high DTI prediction performance while being scalable and efficient in computation, translating into a powerful drug repositioning tool.
• #### Genome sequencing and identification of cellulase genes in Bacillus paralicheniformis strains from the Red Sea

(BMC Microbiology, Springer Science and Business Media LLC, 2021-09-22) [Article]
Abstract Background Cellulolytic microorganisms are considered a key player in the degradation of plant biomass in various environments. These microorganisms can be isolated from various environments, such as soils, the insect gut, the mammalian rumen and oceans. The Red Sea exhibits a unique environment in terms of presenting a high seawater temperature, high salinity, low nutrient levels and high biodiversity. However, there is little information regarding cellulase genes in the Red Sea environment. This study aimed to examine whether the Red Sea can be a resource for the bioprospecting of microbial cellulases by isolating cellulase-producing microorganisms from the Red Sea environment and characterizing cellulase genes. Results Three bacterial strains were successfully isolated from the plankton fraction and the surface of seagrass. The isolated strains were identified as Bacillus paralicheniformis and showed strong cellulase activity. These results suggested that these three isolates secreted active cellulases. By whole genome sequencing, we found 10 cellulase genes from the three isolates. We compared the expression of these cellulase genes under cellulase-inducing and non-inducing conditions and found that most of the cellulase genes were generally upregulated during cellulolysis in the isolates. Our operon structure analysis also showed that cellulase genes form operons with genes involved in various kinds of cellular reactions, such as protein metabolism, which suggests the existence of crosstalk between cellulolysis and other metabolic pathways in the bacterial isolates. These results suggest that multiple cellulases are playing important roles in cellulolysis. Conclusions Our study reports the isolation and characterization of cellulase-producing bacteria from the Red Sea. Our whole-genome sequencing classified our three isolates as Bacillus paralicheniformis, and we revealed the presence of ten cellulase orthologues in each of three isolates’ genomes. Our comparative expression analysis also identified that most of the cellulase genes were upregulated under the inducing conditions in general. Although cellulases have been roughly classified into three enzyme groups of beta-glucosidase, endo-β-1,4-glucanase and exoglucanase, these findings suggest the importance to consider microbial cellulolysis as a more complex reaction with various kinds of cellulase enzymes.
• #### Strategies for engineering improved nitrogen use efficiency in crop plants via redistribution and recycling of organic nitrogen

(Current Opinion in Biotechnology, Elsevier BV, 2021-09-22) [Article]
Global use of nitrogen (N) fertilizers has increased sevenfold from 1960 to 1995 but much of the N applied is lost to the environment. Modifying the temporal and spatial distribution of organic N within the plant can lead to improved grain yield and/or grain protein content for the same or reduced N fertilizer inputs. Biotechnological approaches to modify whole plant distribution of amino acids and ureides has proven successful in several crop species. Manipulating selective autophagy pathways in crops has also improved N remobilization efficiency to sink tissues whilst the contribution of ribophagy, RNA and purine catabolism to N recycling in crops is still too early to foretell. Improved recycling and remobilization of N must exploit N-stress responsive transcriptional regulators, N-sensing or phloem-localized promotors and genetic variation for N-responsive traits.
• #### A Novel Miniature CRISPR-Cas13 System for SARS-CoV-2 Diagnostics

(ACS Synthetic Biology, American Chemical Society (ACS), 2021-09-21) [Article]
Rapid, point-of-care (POC) diagnostics are essential to mitigate the impacts of current (and future) epidemics; however, current methods for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require complicated laboratory tests that are generally conducted off-site and require substantial time. CRISPR-Cas systems have been harnessed to develop sensitive and specific platforms for nucleic acid detection. These detection platforms take advantage of CRISPR enzymes' RNA-guided specificity for RNA and DNA targets and collateral trans activities on single-stranded RNA and DNA reporters. Microbial genomes possess an extensive range of CRISPR enzymes with different specificities and levels of collateral activity; identifying new enzymes may improve CRISPR-based diagnostics. Here, we identified a new Cas13 variant, which we named as miniature Cas13 (mCas13), and characterized its catalytic activity. We then employed this system to design, build, and test a SARS-CoV-2 detection module coupling reverse transcription loop-mediated isothermal amplification (RT-LAMP) with the mCas13 system to detect SARS-CoV-2 in synthetic and clinical samples. Our system exhibits sensitivity and specificity comparable to other CRISPR systems. This work expands the repertoire and application of Cas13 enzymes in diagnostics and for potential <i>in vivo</i> applications, including RNA knockdown and editing. Importantly, our system can be potentially adapted and used in large-scale testing for diverse pathogens, including RNA and DNA viruses, and bacteria.
• #### A study on the synergetic effect of Bacillus amyloliquefaciens and dipotassium phosphate on Alternaria solani causing early blight disease of tomato

(European Journal of Plant Pathology, Springer Science and Business Media LLC, 2021-09-18) [Article]
A study of the effect of bioagents and dipotassium phosphate (DPP) and their combination on early blight disease reduction under greenhouse conditions was conducted. Native bacterial isolates as bio-control agents exhibited control against early blight. Five bacterial isolates were tested against the pathogen. All isolates exhibited significant antagonistic activity against Alternariasolani, isolate “bact-03” showed significant in vitro inhibition (42.6%) and later was identified as Bacillus amyloliquefaciensby 16S rDNA gene analysis. Tests conducted on dipotassium phosphate (DPP) at different concentrations (10 mM, 25 mM, and 50 mM) showed mycelial growth inhibition 14.2%, 27.4%, and 54.8%, respectively. In vitro synergetic study on seed germination showed that the combination of DPP and B. amyloliquefaciens antagonized the pathogen. Vigor index was also significant in the combination (343.0) as well as DPP (299.0), and bioagent (426.6) compared to control (170.0). In the in vivo application of B. amyloliquefaciens, DPP combination showed significant disease reduction. However, disease severity on the plants treated with DPP was 35%, and the plants treated with B. amyloliquefaciens was 30% while in combination of both showed the disease severity up to 42% that was significantly lower than control (82%). Application of these bioagents and DPP also sustained the plant weight by promoting the growth and development of plant. The results of this study indicate that naturally existing bioagents along with the slats of potassium phosphate may provide promising control of early blight disease. Due to their antagonistism, bacterial strains with the combination of salts can be used as bio-pesticides. Their applicationsimproves seed health and crop yield, but signaling relationship in pathogens, plants, and soil still needs to divulge to promote BCAs as encouraging bio-pesticides for the future.
• #### RNA-Sequencing And Mass-Spectrometry Proteomic Time-Series Analysis of T-Cell Differentiation Identified Multiple Splice Variants Models That Predicted Validated Protein Biomarkers In Inflammatory Diseases

(Research Square Platform LLC, 2021-09-17) [Preprint]
Background Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesized that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. Methods We characterized time-series of primary human naïve CD4+ T cells during early T-helper type 1 differentiation with RNA-sequencing and mass-spectrometry proteomics. We then performed computational time-series analysis in this system and in two other key human and murine immune cell types. Linear mathematical mixed time-delayed splice variant models were used to predict protein abundances, and the models were validated using out-of-sample predictions. Lastly, we re-analysed RNA-Seq datasets to evaluate biomarker discovery in five T-cell associated diseases, further validating the findings for multiple sclerosis (MS) and asthma.Results The new models significantly out-performing models not including the usage of multiple splice variants and time-delays, as shown in cross-validation tests. Our mathematical models provided more differentially expressed proteins between patients and controls in all five diseases. Moreover, analysis of these proteins in asthma and MS supported their relevance. One marker, sCD27, was clinically validated in MS using two independent cohorts, for treatment response and prognosis.Conclusion Our splice variant and time-delay models substantially improved the prediction of protein abundance from mRNA data in three immune cell-types. The models provided valuable biomarker candidates, which were validated in clinical studies of MS and asthma. We propose that our strategy is generally applicable for biomarker discovery.
• #### The Bouraké semi-enclosed lagoon (New Caledonia)- A natural laboratory to study the lifelong adaptation of a coral reef ecosystem to extreme environmental conditions

(Biogeosciences, Copernicus GmbH, 2021-09-17) [Article]
According to current experimental evidence, coral reefs could disappear within the century if CO2 emissions remain unabated. However, recent discoveries of diverse and high cover reefs that already live under extreme conditions suggest that some corals might thrive well under hot, high-pCO2, and deoxygenated seawater. Volcanic CO2 vents, semi-enclosed lagoons, and mangrove estuaries are unique study sites where one or more ecologically relevant parameters for life in the oceans are close to or even worse than currently projected for the year 2100. Although they do not perfectly mimic future conditions, these natural laboratories offer unique opportunities to explore the mechanisms that reef species could use to keep pace with climate change. To achieve this, it is essential to characterize their environment as a whole and accurately consider all possible environmental factors that may differ from what is expected in the future, possibly altering the ecosystem response. This study focuses on the semi-enclosed lagoon of Bouraké (New Caledonia, southwest Pacific Ocean) where a healthy reef ecosystem thrives in warm, acidified, and deoxygenated water. We used a multi-scale approach to characterize the main physical-chemical parameters and mapped the benthic community composition (i.e., corals, sponges, and macroalgae). The data revealed that most physical and chemical parameters are regulated by the tide, strongly fluctuate three to four times a day, and are entirely predictable. The seawater pH and dissolved oxygen decrease during falling tide and reach extreme low values at low tide (7.2 pHT and 1.9mgO2L-1 at Bouraké vs. 7.9 pHT and 5.5mgO2L-1 at reference reefs). Dissolved oxygen, temperature, and pH fluctuate according to the tide by up to 4.91mgO2L-1, 6.50 C, and 0.69pHT units on a single day. Furthermore, the concentration of most of the chemical parameters was 1 to 5 times higher at the Bouraké lagoon, particularly for organic and inorganic carbon and nitrogen but also for some nutrients, notably silicates. Surprisingly, despite extreme environmental conditions and altered seawater chemical composition measured at Bouraké, our results reveal a diverse and high cover community of macroalgae, sponges, and corals accounting for 28, 11, and 66 species, respectively. Both environmental variability and nutrient imbalance might contribute to their survival under such extreme environmental conditions. We describe the natural dynamics of the Bouraké ecosystem and its relevance as a natural laboratory to investigate the benthic organism's adaptive responses to multiple extreme environmental conditions.
• #### Malat-1-PRC2-EZH1 interaction supports adaptive oxidative stress dependent epigenome remodeling in skeletal myotubes

(Cell Death & Disease, Springer Science and Business Media LLC, 2021-09-16) [Article]
AbstractPRC2-mediated epigenetic function involves the interaction with long non-coding RNAs (lncRNAs). Although the identity of some of these RNAs has been elucidated in the context of developmental programs, their counterparts in postmitotic adult tissue homeostasis remain uncharacterized. To this aim, we used terminally differentiated postmitotic skeletal muscle cells in which oxidative stress induces the dynamic activation of PRC2-Ezh1 through Embryonic Ectoderm Develpment (EED) shuttling to the nucleus. We identify lncRNA Malat-1 as a necessary partner for PRC2-Ezh1-dependent response to oxidative stress. We show that in this pathway, PRC2-EZH1 dynamic assembly, and in turn stress induced skeletal muscle targeted genes repression, depends specifically on Malat-1. Our study reports about PRC2–RNA interactions in the physiological context of adaptive oxidative stress response and identifies the first lncRNA involved in PRC2-Ezh1 function.
• #### A novel hybrid adsorption heat transformer – multi-effect distillation (AHT-MED) system for improved performance and waste heat upgrade

(Applied Energy, Elsevier BV, 2021-09-16) [Article]
Multi-effect distillation (MED) systems are considered to be the most energy-efficient thermal desalination methods. This paper introduces the development of a novel thermal desalination system for performance superior to MED systems for the same operating temperature limits. Such an unprecedented achievement was attained by upgrading the heat source using the chemical potential of adsorption phenomena. The proposed Adsorption Heat Transformer (AHT) cycle hybridized with Multi-effect distillation system (AHT-MED) exhibits higher performance ratio and water production rate than a conventional MED system for the same heating source and sink. The heat generated by the heat of adsorption with the temperature higher than the heat source is supplied to the first effect of the MED system, thus, extending the temperature difference between the Top Brine Temperature (TBT) and Bottom Brine Temperature (BBT). The higher temperature difference offers more number of effects, with the equivalent temperature difference between the effects (ΔTe) as the design parameter. Using the low-temperature heat source (as low as 58 °C), the system can employ an increased number of effects (as high as 11) due to the supply of heat at an increased temperature of around 80 °C. The proposed system achieves a higher performance ratio (approximately 5.4) and water production rate (2 kg/s) compared to the standalone MED system (PR: 4.2, WPR: 1 kg/s) with the number of effects of the hybrid system as 10 at constant interstage temperature difference between the standalone and hybrid systems. This novel AHT-MED system opens up new possibilities for low-temperature heat source-driven thermal desalination with significantly improved performance.
• #### Comprehensive analytical approaches reveal species-specific search strategies in sympatric apex predatory sharks

(Ecography, Wiley, 2021-09-14) [Article]
Animals follow specific movement patterns and search strategies to maximize encounters with essential resources (e.g. prey, favourable habitat) while minimizing exposures to suboptimal conditions (e.g. competitors, predators). While describing spatiotemporal patterns in animal movement from tracking data is common, understanding the associated search strategies employed continues to be a key challenge in ecology. Moreover, studies in marine ecology commonly focus on singular aspects of species' movements, however using multiple analytical approaches can further enable researchers to identify ecological phenomena and resolve fundamental ecological questions relating to movement. Here, we used a set of statistical physics-based methods to analyze satellite tracking data from three co-occurring apex predators (tiger, great hammerhead and bull sharks) that predominantly inhabit productive coastal regions of the northwest Atlantic Ocean and Gulf of Mexico. We analyzed data from 96 sharks and calculated a range of metrics, including each species' displacements, turning angles, dispersion, space-use and community-wide movement patterns to characterize each species' movements and identify potential search strategies. Our comprehensive approach revealed high interspecific variability in shark movement patterns and search strategies. Tiger sharks displayed near-random movements consistent with a Brownian strategy commonly associated with movements through resource-rich habitats. Great hammerheads showed a mixed-movement strategy including Brownian and resident-type movements, suggesting adaptation to widespread and localized high resource availability. Bull sharks followed a resident movement strategy with restricted movements indicating localized high resource availability. We hypothesize that the species-specific search strategies identified here may help foster the co-existence of these sympatric apex predators. Following this comprehensive approach provided novel insights into spatial ecology and assisted with identifying unique movement and search strategies. Similar future studies of animal movement will help characterize movement patterns and also enable the identification of search strategies to help elucidate the ecological drivers of movement and to understand species' responses to environmental change.
• #### The time course of molecular acclimation to seawater in a euryhaline fish.

(Scientific reports, Springer Science and Business Media LLC, 2021-09-14) [Article]
The Arabian pupfish, Aphanius dispar, is a euryhaline fish inhabiting both inland nearly-freshwater desert ponds and highly saline Red Sea coastal lagoons of the Arabian Peninsula. Desert ponds and coastal lagoons, located respectively upstream and at the mouths of dry riverbeds ("wadies"), have been found to potentially become connected during periods of intense rainfall, which could allow the fish to migrate between these different habitats. Flash floods would therefore flush Arabian pupfish out to sea, requiring a rapid acclimation to a greater than 40 ppt change in salinity. To investigate the molecular pathways of salinity acclimation during such events, a Red Sea coastal lagoon and a desert pond population were sampled, with the latter exposed to a rapid increase in water salinity. Changes in branchial gene expression were investigated via genome-wide transcriptome measurements over time from 6 h to 21 days. The two natural populations displayed basal differences in genes related to ion transport, osmoregulation and immune system functions. These mechanisms were also differentially regulated in seawater transferred fish, revealing their crucial role in long-term adaptation. Other processes were only transiently activated shortly after the salinity exposure, including cellular stress response mechanisms, such as molecular chaperone synthesis and apoptosis. Tissue remodelling processes were also identified as transient, but took place later in the timeline, suggesting their importance to long-term acclimation as they likely equip the fish with lasting adaptations to their new environment. The alterations in branchial functional pathways displayed by Arabian pupfish in response to salinity increases are diverse. These reveal a large toolkit of molecular processes important for adaptation to hyperosmolarity that allow for successful colonization to a wide variety of different habitats.
• #### Naturally Extracted Hydrophobic Solvent and Self-Assembly in Interfacial Polymerization

(ACS Applied Materials & Interfaces, American Chemical Society (ACS), 2021-09-12) [Article]
Pharmaceutical, chemical, and food industries are actively implementing membrane nanofiltration modules in their processes to separate valuable products and recover solvents. Interfacial polymerization (IP) is the most widely used method to produce thin-film composite membranes for nanofiltration and reverse osmosis processes. Although membrane processes are considered green and environmentally friendly, membrane fabrication has still to be further developed in such direction. For instance, the emission of volatile solvents during membrane production in the industry has to be carefully controlled for health reasons. Greener solvents are being proposed for phase-separation membrane manufacture. For the IP organic phase, the proposition of greener alternatives is in an early stage. In this work, we demonstrate the preparation of a high-performing composite membrane employing zero vapor pressure and naturally extracted oleic acid as the IP organic phase. Its long hydrophobic chain ensures intrinsic low volatility and acid monomer dissolution, while the polar head induces a unique self-assembly structure during the film formation. Membranes prepared by this technique were selective for small molecules with a molecular weight cutoff of 650 g mol–1 and a high permeance of ∼57 L m–2 h–1 bar–1.
• #### Cancer-associated mutations in the p85α N-terminal SH2 domain activate a spectrum of receptor tyrosine kinases.

(Proceedings of the National Academy of Sciences of the United States of America, 2021-09-11) [Article]
The phosphoinositide 3-kinase regulatory subunit p85α is a key regulator of kinase signaling and is frequently mutated in cancers. In the present study, we showed that in addition to weakening the inhibitory interaction between p85α and p110α, a group of driver mutations in the p85α N-terminal SH2 domain activated EGFR, HER2, HER3, c-Met, and IGF-1R in a p110α-independent manner. Cancer cells expressing these mutations exhibited the activation of p110α and the AKT pathway. Interestingly, the activation of EGFR, HER2, and c-Met was attributed to the ability of driver mutations to inhibit HER3 ubiquitination and degradation. The resulting increase in HER3 protein levels promoted its heterodimerization with EGFR, HER2, and c-Met, as well as the allosteric activation of these dimerized partners; however, HER3 silencing abolished this transactivation. Accordingly, inhibitors of either AKT or the HER family reduced the oncogenicity of driver mutations. The combination of these inhibitors resulted in marked synergy. Taken together, our findings provide mechanistic insights and suggest therapeutic strategies targeting a class of recurrent p85α mutations.
• #### Symbiodinium microadriaticum (coral microalgal endosymbiont)

(Trends in Genetics, Elsevier BV, 2021-09-11) [Article]
Photosynthetic microalgae, from the family Symbiodiniaceae, engage in endosymbioses with marine invertebrates, including stony corals. More generally, dinoflagellates are ubiquitous protists and the main primary producers in the oceans. Despite their ecological and economic importance, their biology remains enigmatic. Here we assembled 94 chromosome-scale scaffolds of the ancestral Symbiodiniaceae species Symbiodinium microadriaticum. Contrary to the random order of genes typically found in eukaryotic cells, genes are enriched toward the ends of chromosomes in alternating unidirectional blocks that are sometimes enriched for genes of specific biological processes. These gene blocks are coexpressed and separated by structural boundaries where transcription converges. These structural domains, in turn, comprise the transcription-dependent basic building blocks of the chromosomes that fold as linear rods. Such a highly ordered structure linking gene orientation, transcription, and spatial organization of chromosomes is exceptional.