bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating Horizontal Density Variations Into Large‐Scale Modeling of Ice Masses
Authors: Schelpe Camilla A. O. , Gudmundsson G. Hilmar
Published: January 2023

Gravity‐driven flow of large ice masses such as the Antarctic Ice Sheet (AIS) depends on both the geometry and the mass density of the ice sheet. The vertical density profile can be approximated as pure ice overlain by a firn layer of varying thickness, and for the AIS the firn thickness is not uncommonly 10%–20% of the total thickness, leading to not insignificant variation in horizontal density. Nevertheless, in most vertically integrated ice‐flow models today, the density is assumed constant, sometimes with an adjustment in thickness to compensate. In this study, we explore the treatment of horizontal density variations (HDVs) within vertically integrated ice‐sheet models. We assess the relative merits and shortcomings of previously proposed approaches and provide new formulations for including HDVs. We use perturbation analysis to derive analytical solutions that describe the impact of density variations on ice flow for both grounded ice and floating ice shelves, which reveal significant qualitative differences between each of the proposed density formulations. We recommend always including the horizontal gradient of the density in the body‐force term of the momentum equation, and in the mass‐conservationequation. Furthermore, by modeling the transient evolution of a large sector of the West Antarctic Ice Sheet (WAIS), we find that doing so leads to about a 10% correction in the estimated change in volume above flotation over 40 years. We conclude that including HDVs in flow modeling of the AIS is important for accurate predictions of mass loss.
Ubiquitous occurrence of a dimethylsulfoniopropionate ABC transporter in abundant marine bacteria
Authors: Li Chun-Yang , Mausz Michaela A , Murphy Andrew , Zhang Nan , Chen Xiu-Lan , Wang Shu-Yan , Gao Chao , Aguilo-Ferretjans María M , Silvano Eleonora , Lidbury Ian D E A , Fu Hui-Hui , Todd Jonathan D , Chen Yin , Zhang Yu-Zhong
Published: January 2023

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur compound in marine environments with important functions in both microorganisms and global biogeochemical carbon and sulfur cycling. The SAR11 clade and marine Roseobacter group (MRG) represent two major groups of heterotrophic bacteria in Earth’s surface oceans, which can accumulate DMSP to high millimolar intracellular concentrations. However, few studies have investigated how SAR11 and MRG bacteria import DMSP. Here, through comparative genomics analyses, genetic manipulations, and biochemical analyses, we identified an ABC (ATP-binding cassette)-type DMSP-specific transporter, DmpXWV, in Ruegeria pomeroyi DSS-3, a model strain of the MRG. Mutagenesis suggested that DmpXWV is a key transporter responsible for DMSP uptake in strain DSS-3. DmpX, the substrate binding protein of DmpXWV, had high specificity and binding affinity towards DMSP. Furthermore, the DmpX DMSP-binding mechanism was elucidated from structural analysis. DmpX proteins are prevalent in the numerous cosmopolitan marine bacteria outside the SAR11 clade and the MRG, and dmpX transcription was consistently high across Earth’s entire global ocean. Therefore, DmpXWV likely enables pelagic marine bacteria to efficiently import DMSP from seawater. This study offers a new understanding of DMSP transport into marine bacteria and provides novel insights into the environmental adaption of marine bacteria.
TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs
Authors: Wang Hongbo , Chu Fang , Zhang Xiao-feng , Zhang Peng , Li Li-xin , Zhuang Yun-long , Niu Xiao-feng , He Xi , Li Zhi-jie , Bai Ying , Mao Da , Liu Zhen-wen , Zhang Da-li , Li Bo-an
Published: January 2023

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR’s downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein–protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4’s promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.
Self-evolving photonic crystals for ultrafast photonics
Authors: Inoue Takuya , Morita Ryohei , Nigo Kazuki , Yoshida Masahiro , De Zoysa Menaka , Ishizaki Kenji , Noda Susumu
Published: January 2023

Ultrafast dynamics in nanophotonic materials is attracting increasing attention from the perspective of exploring new physics in fundamental science and expanding functionalities in various photonic devices. In general, such dynamics is induced by external stimuli such as optical pumping or voltage application, which becomes more difficult as the optical power to be controlled becomes larger owing to the increase in the energy required for the external control. Here, we demonstrate a concept of the self-evolving photonic crystal, where the spatial profile of the photonic band is dynamically changed through carrier-photon interactions only by injecting continuous uniform current. Based on this concept, we experimentally demonstrate short-pulse generation with a high peak power of 80 W and a pulse width of <30 ps in a 1-mm-diameter GaAs-based photonic crystal. Our findings on self-evolving carrier-photon dynamics will greatly expand the potential of nanophotonic materials and will open up various scientific and industrial applications.
Directing Min protein patterns with advective bulk flow
Authors: Meindlhumer Sabrina , Brauns Fridtjof , Finžgar Jernej Rudi , Kerssemakers Jacob , Dekker Cees , Frey Erwin
Published: January 2023

The Min proteins constitute the best-studied model system for pattern formation in cell biology. We theoretically predict and experimentally show that the propagation direction of in vitro Min protein patterns can be controlled by a hydrodynamic flow of the bulk solution. We find downstream propagation of Min wave patterns for low MinE:MinD concentration ratios, upstream propagation for large ratios, but multistability of both propagation directions in between. Whereas downstream propagation can be described by a minimal model that disregards MinE conformational switching, upstream propagation can be reproduced by a reduced switch model, where increased MinD bulk concentrations on the upstream side promote protein attachment. Our study demonstrates that a differential flow, where bulk flow advects protein concentrations in the bulk, but not on the surface, can control surface-pattern propagation. This suggests that flow can be used to probe molecular features and to constrain mathematical models for pattern-forming systems.
Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma
Authors: Salam Rana , Saliou Alexa , Bielle Franck , Bertrand Mathilde , Antoniewski Christophe , Carpentier Catherine , Alentorn Agusti , Capelle Laurent , Sanson Marc , Huillard Emmanuelle , Bellenger Léa , Guégan Justine , Le Roux Isabelle
Published: January 2023

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM.
Chromatin complex dependencies reveal targeting opportunities in leukemia
Authors: Najm Fadi J. , DeWeirdt Peter , Moore Molly M. , Bevill Samantha M. , El Farran Chadi A. , Macias Kevin A. , Hegde Mudra , Waterbury Amanda L. , Liau Brian B. , van Galen Peter , Doench John G. , Bernstein Bradley E.
Published: January 2023

Chromatin regulators are frequently mutated in human cancer and are attractive drug targets. They include diverse proteins that share functional domains and assemble into related multi-subunit complexes. To investigate functional relationships among these regulators, here we apply combinatorial CRISPR knockouts (KOs) to test over 35,000 gene-gene pairings in leukemia cells, using a library of over 300,000 constructs. Top pairs that demonstrate either compensatory non-lethal interactions or synergistic lethality enrich for paralogs and targets that occupy the same protein complex. The screen highlights protein complex dependencies not apparent in single KO screens, for example MCM histone exchange, the nucleosome remodeling and deacetylase (NuRD) complex, and HBO1 (KAT7) complex. We explore two approaches to NuRD complex inactivation. Paralog and non-paralog combinations of the KAT7 complex emerge as synergistic lethal and specifically nominate the ING5 PHD domain as a potential therapeutic target when paired with other KAT7 complex member losses. These findings highlight the power of combinatorial screening to provide mechanistic insight and identify therapeutic targets within redundant networks.
Accelerating ultrafast magnetization reversal by non-local spin transfer
Authors: Remy Quentin , Hohlfeld Julius , Vergès Maxime , Le Guen Yann , Gorchon Jon , Malinowski Grégory , Mangin Stéphane , Hehn Michel
Published: January 2023

When exciting a magnetic material with a femtosecond laser pulse, the amplitude of magnetization is no longer constant and can decrease within a time scale comparable to the duration of the optical excitation. This ultrafast demagnetization can even trigger an ultrafast, out of equilibrium, phase transition to a paramagnetic state. The reciprocal effect, namely an ultrafast remagnetization from the zero magnetization state, is a necessary ingredient to achieve a complete ultrafast reversal. However, the speed of remagnetization is limited by the universal critical slowing down which appears close to a phase transition. Here we demonstrate that magnetization can be reversed in a few hundreds of femtoseconds by overcoming the critical slowing down thanks to ultrafast spin cooling and spin heating mechanisms. We foresee that these results outline the potential of ultrafast spintronics for future ultrafast and energy efficient magnetic memory and storage devices. Furthermore, this should motivate further theoretical works in the field of femtosecond magnetization reversal.
The flavor-enhancing action of glutamate and its mechanism involving the notion of kokumi
Authors: Yamamoto Takashi , Inui-Yamamoto Chizuko
Published: January 2023

The sodium salt of glutamic acid, or monosodium glutamate (MSG), has two effects in foods: one is to induce a unique taste called umami, which is one of the five basic tastes, and the other is to make food palatable (i.e., flavor-enhancing or seasoning effects). However, the mechanism behind how MSG makes food more palatable remains poorly understood, although many food scientists seem to believe that the umami taste itself plays an important role. Here, we propose an alternative notion regarding this topic based on previous and recent studies. When added to complex food compositions, MSG facilitates the binding of existing kokumi substances to kokumi receptors. In turn, these bound kokumi substances enhance the intensity of umami, sweet, salty, and fatty tastes, resulting in increased palatability accompanied by kokumi flavor, such as thickness, mouthfulness, and continuity. The requisite for sufficient palatability and kokumi flavor is a good balance of umami and kokumi substances. This framework gives a scientifically useful background for providing newly developed foods, including cultured meat and plant-based meat substitutes, with good taste characteristics.
Virulence and antibiotic-resistance genes in Enterococcus faecalis associated with streptococcosis disease in fish
Authors: Akter Tasmina , Haque Md. Najmul , Ehsan Rakib , Paul Sulav Indra , Foysal Md. Javed , Tay Alfred Chin Yen , Islam Md. Tofazzal , Rahman Md. Mahbubur
Published: January 2023

Enterococcus faecalis is associated with streptococcosis like infection in fish. A whole-genome sequence study was conducted to investigate the virulence factor and antibiotic-resistance genes in three fish pathogenic E. faecalis. Genomic DNA was extracted from three strains of E. faecalis isolated from streptococcosis infected Nile tilapia (strains BF1B1 and BFFF11) and Thai sarpunti (strain BFPS6). The whole genome sequences of these three strains were performed using a MiSeq sequencer (Illumina, Inc.). All three strains conserved 69 virulence factor such as genes associated with protection against oxidative stress, bacterial cell wall synthesis, gelatinase toxin, multiple biofilm-associated genes and capsule producing genes. Moreover, 39 antibiotic-resistance genes against sixteen major groups of antibiotics were identified in the genome sequences of all three strains. The most commonly used antibiotic Tetracycline resistance genes were found only in BFPS6 strain, whereas, Bacteriocin synthesis genes were identified in both BFFF11 and BFPS6 strain. Phylogenetic analysis revealed that strains BF1B1 and BFFF1 form a different cluster than BFPS6. This is one of the first whole-genome sequence study of fish pathogenic E. faecalis, unfold new information on the virulence factor and Antibiotic resistance genes linked to pathogenicity in fish.
Training drives turnover rates in racehorse proximal sesamoid bones
Authors: Shaffer Sarah K. , Stover Susan M. , Fyhrie David P.
Published: January 2023

Focal bone lesions are often found prior to clinically relevant stress-fractures. Lesions are characterized by low bone volume fraction, low mineral density, and high levels of microdamage and are hypothesized to develop when bone tissue cannot sufficiently respond to damaging loading. It is difficult to determine how exercise drives the formation of these lesions because bone responds to mechanical loading and repairs damage. In this study, we derive steady-state rate constants for a compartment model of bone turnover using morphometric data from fractured and non-fractured racehorse proximal sesamoid bones (PSBs) and relate rate constants to racing-speed exercise data. Fractured PSBs had a subchondral focus of bone turnover and microdamage typical of lesions that develop prior to fracture. We determined steady-state model rate constants at the lesion site and an internal region without microdamage using bone volume fraction, tissue mineral density, and microdamage area fraction measurements. The derived undamaged bone resorption rate, damage formation rate, and osteoid formation rate had significant robust regression relationships to exercise intensity (rate) variables, layup (time out of exercise), and exercise 2–10 months before death. However, the direction of these relationships varied between the damaged (lesion) and non-damaged regions, reflecting that the biological response to damaging-loading differs from the response to non-damaging loading.
Duration between aneurysm rupture and treatment and its association with outcome in aneurysmal subarachnoid haemorrhage
Authors: Hostettler Isabel C. , Lange Nicole , Schwendinger Nina , Frangoulis Samira , Hirle Theresa , Trost Dominik , Gempt Jens , Kreiser Kornelia , Wostrack Maria , Meyer Bernhard
Published: January 2023

Timely treatment of aneurysmal subarachnoid haemorrhage (aSAH) is key to prevent further rupture and poor outcome. We evaluated complications and outcome adjusting for time from haemorrhage to treatment. Retrospective analysis of aSAH patients admitted between 2006 and 2020. Data was collected using standardized case report forms. We compared risk factors using multivariable logistic regression. We included 853 patients, 698 (81.8%) were treated within 24 h. Patients with higher Hunt and Hess grades were admitted and treated significantly faster than those with lower grades (overall p-value < 0.001). Fifteen patients (1.8%) rebled before intervention. In the multivariable logistic analysis adjusting for timing, Barrow Neurological Institute score and intracerebral haemorrhage were significantly associated with rebleeding (overall p-value 0.006; OR 3.12, 95%CI 1.09–8.92, p = 0.03, respectively) but timing was not. Treatment > 24 h was associated with higher mortality and cerebral infarction in only the subgroup of lower grades aSAH (OR 3.13, 1.02–9.58 95%CI, p-value = 0.05; OR 7.69, 2.44–25.00, p-value < 0.001, respectively). Therefore treatment > 24 h after rupture is associated with higher mortality and cerebral infarction rates in lower grades aSAH. Delay in treatment primarily affects lower grade aSAH patients. Patients with lower grade aSAH ought to be treated with the same urgency as higher-grade aSAH.
Correlations between COVID-19 and dengue obtained via the study of South America, Africa and Southeast Asia during the 2020s
Authors: Bergero Paula , Schaposnik Laura P. , Wang Grace
Published: January 2023

A dramatic increase in the number of outbreaks of dengue has recently been reported, and climate change is likely to extend the geographical spread of the disease. In this context, this paper shows how a neural network approach can incorporate dengue and COVID-19 data as well as external factors (such as social behaviour or climate variables), to develop predictive models that could improve our knowledge and provide useful tools for health policy makers. Through the use of neural networks with different social and natural parameters, in this paper we define a Correlation Model through which we show that the number of cases of COVID-19 and dengue have very similar trends. We then illustrate the relevance of our model by extending it to a Long short-term memory model (LSTM) that incorporates both diseases, and using this to estimate dengue infections via COVID-19 data in countries that lack sufficient dengue data.
Entropy analysis for a novel peristaltic flow in a curved heated endoscope: an application of applied sciences
Authors: Nadeem Sohail , Akhtar Salman , Saleem Anber , Akkurt Nevzat , Almutairi Shahah , Ghazwani Hassan Ali , Eldin Sayed M.
Published: January 2023

Entropy interpretation with a descriptive heat generation analysis is carried out for the heated flow between two homocentric and sinusoidally fluctuating curved tubes. A novel peristaltic endoscope is considered for the first time inside a curved tube with evaluation of heat transfer and entropy. This flexible and novel endoscope with peristaltic locomotion is more efficient for endoscopy of complex mechanical structures and it is more comfortable for patients undergoing the endoscopy of a human organs. A comprehensive mathematical model is developed that also completely evaluates the heat transfer analysis for this novel endoscope. Certain and systematic computations are performed with the help of Mathematica software and exact mathematical as well as graphical solutions are obtained. Entropy has a lower rate that is almost zero entropy in the central region of these two curved tubes, but maximum entropy is noted near the sinusoidally deformable walls of both the endoscope and channel.
Comparative proteomic analysis identified proteins and the phenylpropanoid biosynthesis pathway involved in the response to ABA treatment in cotton fiber development
Authors: Yang Yong , Lai Wenjie , Long Lu , Gao Wei , Xu Fuchun , Li Ping , Zhou Shihan , Ding Yuanhao , Hu Haiyan
Published: January 2023

Abscisic acid (ABA) is a plant hormone that plays an important role in cotton fiber development. In this study, the physiological changes and proteomic profiles of cotton (Gossypium hirsutum) ovules were analyzed after 20 days of ABA or ABA inhibitor (ABAI) treatment. The results showed that compared to the control (CK), the fiber length was significantly decreased under ABA treatment and increased under ABAI treatment. Using a tandem mass tags-based quantitative technique, the proteomes of cotton ovules were comprehensively analyzed. A total of 7321 proteins were identified, of which 365 and 69 differentially accumulated proteins (DAPs) were identified in ABA versus CK and ABAI versus CK, respectively. Specifically, 345 and 20 DAPs were up- and down-regulated in the ABA group, and 65 and 4 DAPs were up- and down-regulated in the ABAI group, respectively. The DAPs in the ABA group were mainly enriched in the biosynthesis of secondary metabolites, phenylpropanoid biosynthesis and flavonoid secondary metabolism, whereas the DAPs in the ABAI group were mainly enriched in the indole alkaloid biosynthesis and phenylpropanoid biosynthesis pathways. Moreover, 9 proteins involved in phenylpropanoid biosynthesis were upregulated after ABA treatment, suggesting that this pathway might play important roles in the response to ABA, and 3 auxin-related proteins were upregulated, indicating that auxin might participate in the regulation of fiber development under ABAI treatment.
Posttraumatic stress disorder and diabetes-related outcomes in patients with type 1 diabetes
Authors: Lunkenheimer Frederike , Eckert Alexander J. , Hilgard Dörte , Köth Daniel , Kulzer Bernhard , Lück Ursula , Lüdecke Blanca , Müller Antonia , Baumeister Harald , Holl Reinhard W.
Published: January 2023

Mental comorbidities in patients with type 1 diabetes mellitus (T1D) are common, and can have a negative impact on acute blood glucose levels and long-term metabolic control. Information on the association of T1D and comorbid posttraumatic stress disorder (PTSD) with diabetes-related outcomes is limited. The aim was to examine the associations between a clinical diagnosis of PTSD and diabetes-related outcomes in patients with T1D. Patients with T1D and comorbid documented PTSD from the DPV database (n = 179) were compared to a group with T1D without PTSD (n = 895), and compared to a group with T1D without comorbid mental disorder (n = 895) by matching demographics (age, gender, duration of diabetes, therapy and migration background) 1:5. Clinical diabetes-related outcomes {body mass index (BMI), hemoglobin A1c (hbA1c), daily insulin dose, diabetic ketoacidosis (DKA), hypoglycemia, number of hospital admissions, number of hospital days} were analyzed, stratified by age groups (≤ 25 years vs. > 25 years). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD or patients without mental disorders had significantly higher HbA1c (8.71 vs. 8.30 or 8.24%), higher number of hospital admissions (0.94 vs. 0.44 or 0.32 per year) and higher rates of DKA (0.10 vs. 0.02 or 0.01 events/year). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD had significantly higher BMI (0.85 vs. 0.59) and longer hospital stays (15.89 vs.11.58 days) than patients without PTSD. Patients with PTSD > 25 years compared with patients without PTSD or without any mental comorbidities had significantly fewer hospital admissions (0.49 vs. 0.77 or 0.69), but a longer hospital length of stay (20.35 vs. 11.58 or 1.09 days). We found that PTSD in younger patients with T1D is significantly related to diabetes outcome. In adult patients with T1D, comorbid PTSD is associated with fewer, but longer hospitalizations. Awareness of PTSD in the care of patients with T1D should be raised and psychological intervention should be provided when necessary.
Engineering of Chinese hamster ovary cells for co-overexpressing MYC and XBP1s increased cell proliferation and recombinant EPO production
Authors: Latorre Yesenia , Torres Mauro , Vergara Mauricio , Berrios Julio , Sampayo Maria Molina , Gödecke Natasha , Wirth Dagmar , Hauser Hansjörg , Dickson Alan J. , Altamirano Claudia
Published: January 2023

Improving the cellular capacity of Chinese hamster ovary (CHO) cells to produce large amounts of therapeutic proteins remains a major challenge for the biopharmaceutical industry. In previous studies, we observed strong correlations between the performance of CHO cells and expression of two transcription factors (TFs), MYC and XBP1s. Here, we have evaluated the effective of overexpression of these two TFs on CHO cell productivity. To address this goal, we generated an EPO-producing cell line (CHOEPO) using a targeted integration approach, and subsequently engineered it to co-overexpress MYC and XBP1s (a cell line referred to as CHOCXEPO). Cells overexpressing MYC and XBP1s increased simultaneously viable cell densities and EPO production, leading to an enhanced overall performance in cultures. These improvements resulted from the individual effect of each TF in the cell behaviour (i.e., MYC-growth and XBP1s-productivity). An evaluation of the CHOCXEPO cells under different environmental conditions (temperature and media glucose concentration) indicated that CHOCXEPO cells increased cell productivity in high glucose concentration. This study showed the potential of combining TF-based cell engineering and process optimisation for increasing CHO cell productivity.
Virtual screening and molecular dynamics simulations provide insight into repurposing drugs against SARS-CoV-2 variants Spike protein/ACE2 interface
Authors: Pirolli Davide , Righino Benedetta , Camponeschi Chiara , Ria Francesco , Di Sante Gabriele , De Rosa Maria Cristina
Published: January 2023

After over two years of living with Covid-19 and hundreds of million cases worldwide there is still an unmet need to find proper treatments for the novel coronavirus, due also to the rapid mutation of its genome. In this context, a drug repositioning study has been performed, using in silico tools targeting Delta Spike protein/ACE2 interface. To this aim, it has been virtually screened a library composed by 4388 approved drugs through a deep learning-based QSAR model to identify protein–protein interactions modulators for molecular docking against Spike receptor binding domain (RBD). Binding energies of predicted complexes were calculated by Molecular Mechanics/Generalized Born Surface Area from docking and molecular dynamics simulations. Four out of the top twenty ranking compounds showed stable binding modes on Delta Spike RBD and were evaluated also for their effectiveness against Omicron. Among them an antihistaminic drug, fexofenadine, revealed very low binding energy, stable complex, and interesting interactions with Delta Spike RBD. Several antihistaminic drugs were found to exhibit direct antiviral activity against SARS-CoV-2 in vitro, and their mechanisms of action is still debated. This study not only highlights the potential of our computational methodology for a rapid screening of variant-specific drugs, but also represents a further tool for investigating properties and mechanisms of selected drugs.
Arbuscular mycorrhizal fungi associated with maize plants during hydric deficit
Authors: Santana Letícia Rezende , da Silva Lais Noamy , Tavares Germanna Gouveia , Batista Priscila Ferreira , Cabral Juliana Silva Rodrigues , Souchie Edson Luiz
Published: January 2023

The objective of this study was to verify the physiological behavior and development of maize plants under hydric deficit inoculated with the AMF Rhizophagus clarus and Claroideoglomus etunicatum and the commercial inoculant ROOTELLA BR in nonsterilized soil as a strategy to mitigate the effects of drought in the crop. Corn seeds were grown and inoculated with R. clarus, C. etunicatum and the commercial inoculant ROOTELLA BR separately at sowing. The plants were grown in a greenhouse and submitted to water deficit in stage V3, keeping the pots at 20% field capacity for 10 days. The first analyses were performed, followed by reirrigation for 2 days, and the analyses were performed again. The experiment was a double factorial, with 2 water treatments (irrigated and water deficit) × 4 inoculation treatments (control, ROOTELLA BR, R. clarus, C. etunicatum) × 5 replicates per treatment, totaling 40 vessels. The results indicate that the plants were able to recover favorably according to the physiological data presented. It is noted that in inoculated plants, there was no damage to the photosynthetic apparatus. These data demonstrate that AMF contribute greatly to better plant recovery after a dry period and a new irrigation period. Inoculation with AMF favors postwater stress recovery in plants.
Hypoxia inducible factor-1α promotes trichogenic gene expression in human dermal papilla cells
Authors: Seo Jieun , Yan Lei , Kageyama Tatsuto , Nanmo Ayaka , Chun Yang-Sook , Fukuda Junji
Published: January 2023

Dermal papilla cells (DPCs) play critical roles in hair follicle development, but the underlying mechanisms that contribute to hair regeneration have yet to be fully elucidated, particularly in terms of alterations in androgenetic alopecia patients. In this study, we demonstrated that hypoxia-inducible factor-1α (HIF-1α) is suppressed in scalp tissues of androgenetic alopecia patients and potentially associated with hair follicle development. Using RT-qPCR and western blot, we found that mRNA and protein levels of trichogenic genes, LEF1 and versican (VCAN), were attenuated in HIF-1α knockdown DPCs. Under an in vivo mimicked environment in a three-dimensional spheroid culture, HIF-1α-suppressed DPCs downregulated the expression of hair induction-related genes. Finally, treatment with a HIF-1α activator resulted in the elevated expression of trichogenic genes in DPCs. This study highlights the importance of dermal HIF-1α expression in regulating trichogenic genes and provides a promising therapeutic target and a fundamental tissue engineering approach for hair loss treatment.
Tyrosine-targeted covalent inhibition of a tRNA synthetase aided by zinc ion
Authors: Qiao Hang , Xia Mingyu , Cheng Yiyuan , Zhou Jintong , Zheng Li , Li Wei , Wang Jing , Fang Pengfei
Published: January 2023

Aminoacyl-tRNA synthetases (AARSs), a family of essential protein synthesis enzymes, are attractive targets for drug development. Although several different types of AARS inhibitors have been identified, AARS covalent inhibitors have not been reported. Here we present five unusual crystal structures showing that threonyl-tRNA synthetase (ThrRS) is covalently inhibited by a natural product, obafluorin (OB). The residue forming a covalent bond with OB is a tyrosine in ThrRS active center, which is not commonly modified by covalent inhibitors. The two hydroxyl groups on the o-diphenol moiety of OB form two coordination bonds with the conserved zinc ion in the active center of ThrRS. Therefore, the β-lactone structure of OB can undergo ester exchange reaction with the phenolic group of the adjacent tyrosine to form a covalent bond between the compound and the enzyme, and allow its nitrobenzene structure to occupy the binding site of tRNA. In addition, when this tyrosine was replaced by a lysine or even a weakly nucleophilic arginine, similar bonds could also be formed. Our report of the mechanism of a class of AARS covalent inhibitor targeting multiple amino acid residues could facilitate approaches to drug discovery for cancer and infectious diseases.
Dynamic Vapour Sorption
Authors: Hunter Nicole
Published: January 2023

Dynamic vapour sorption (DVS) is a gravimetric technique used to measure the weight loss/gain of a material as a function of humidity. It is possible to use organic solvents on many commercially available instruments. The most common experiment carried out using DVS analysers is the construction of sorption isotherms for materials. The raw data are usually presented as normalised weight percentage versus time. Sorption isotherms are conventionally presented as equilibrium water content versus relative humidity. This chapter considers the principles of the technique and discusses its application to a wide range of samples, including food, pharmaceuticals, textiles, building materials and explosives.
Isothermal Microcalorimetry
Authors: Gaisford Simon
Published: January 2023

Isothermal calorimeters (IC) measure the power change for time-dependent phase transitions or processes. Instruments that are designed to measure power on a micro-Watt scale are termed isothermal microcalorimeters. They can study solids, liquids or heterogeneous mixtures and the design of the reaction vessel is critical. In this chapter, the principles, experimental arrangement and application of isothermal calorimetry are discussed.
Sample Controlled Thermal Analysis
Authors: Parkes G. M. B. , Charsley E. L.
Published: January 2023

Sample controlled thermal analysis (SCTA) methods, where the heating rate is governed by the sample itself, offer a significant number of benefits over conventional thermal analysis methods. The addition of SCTA software to many modern thermal analysis instruments means that it is now readily available. This chapter gives a broad overview of the different approaches to SCTA and their application to a wide range of thermal methods. The benefits of SCTA, which include enhanced resolution and improved kinetic data, are illustrated by applications to a range of materials.
Introduction to Forensic Toxicology and the Value of a Nationwide Database
Authors: Jones Alan Wayne
Published: January 2023

The creation of a nationwide forensic toxicology database (TOXBASE) furnishes a way to monitor trends and patterns of drug abuse in society, including the emergence of new designer drugs and their potential for toxicity. The demographics of people arrested for various drug-related crimes, such as drug-impaired driving, victims of drug-facilitated sexual assault (DFSA), etc., are also available by searching the database. One section of the database is devoted to the drugs encountered in post-mortem toxicology and their involvement in fatal poisonings and the potential for adverse drug–drug interactions. This chapter presents examples of some of the research projects undertaken with the help of a national forensic toxicology database available in Sweden.
Forensic Pharmacology
Authors: Langford Nigel J.
Published: January 2023

For substances to have an effect they are required to interact with some part of the body. This may be topically or systemically. The degree of effect the drug has is dependent on the amount of exposure. For most drugs this will require the substance to be absorbed into the systemic circulation and then distributed around the body and to its site of action. Once in the body, metabolic processes are in place to try and eliminate the drug from the body. This chapter considers these processes and looks at some of the circumstances where normal chemical pathways may be altered.
An Introduction to Heat Transfer
Authors: Elson Tim , Lettieri Paola
Published: January 2023

Heat is transferred from regions of high temperature to regions of low temperature and may take place by three different mechanisms or modes. This chapter takes the reader through the different modes, explaining key definitions and concepts and looks at the various types of heat exchanger used in industry.
An Introduction to Particle Systems
Authors: Lettieri Paola
Published: January 2023

The aim of this chapter is to provide a brief introductory guide to the characterization of solid materials (size analysis, shape and density), the interaction between particles and a fluid and the industrial process of fluidization. A number of relevant worked examples are provided to help the reader appreciate how theory relates to practice.
Forensic Toxicology
Authors: Torrance Hazel
Published: January 2023

Forensic toxicology is a subject that lies between science and medicine. This chapter explores the origins of toxicology and its application to legal proceedings. Different types of poisons are described and the many different factors that change their degree of effect on the body. Basic pharmacology terms are discussed with reference to more common drugs and their applications in forensic cases. The practical laboratory approach to forensic toxicological work is documented including details regarding instrumentation used and types of biological samples most commonly analysed and why. Suitable reports for court purposes are described with the importance of valid interpretation highlighted. The main themes of the chapter are discussed in more detail with the help of case studies including road traffic safety, alternative matrices and post-mortem toxicology. Differences in drug use trends are explored from local differences within a country to more obvious differences worldwide.
Review of Dielectric Elastomers (DEs) as Smart Materials
Authors: Shahinpoor Mohsen
Published: January 2023

Chapter 11 reviews dielectric elastomers (DEs). If rubbery elastomers like a silicone rubber sheet are sandwiched between two compliant electrodes, then any imposed electric field induces electrostatic forces (attraction) between the electrodes. Thus, the rubber sheet in between them can be compressed by the electrostatic forces, which then cause the rubbery sheet to expand sideways due to the Poisson's ratio effect and thus, actuation results. In 1880, Röntgen demonstrated this actuation by using two glasses as dielectrics, and once the opposing surfaces of these glasses were charged, small thickness changes were observed by Röntgen. Later electrostatically-induced pressures acting to compress dielectrics became known as the “Maxwell stress.” It was, however, Perline, Kornbluh, and Joseph in 1998 who introduced dielectric elastomer technology with compliant electrodes. They concluded that by deliberately choosing polymers with relatively low moduli of elasticity, the field-induced strain response due to Maxwell stress could be large. Polymer actuators designed to exploit Maxwell stress in this manner, became known as dielectric elastomers or DEs.
Review of Smart Materials for Controlled Drug Release
Authors: Alvarez-Lorenzo Carmen , Concheiro Angel
Published: January 2023

Chapter 15 reviews smart materials for controlled drug release. Systemically-administered controlled release systems allow fine-tuning of drug bioavailability, by regulating the amount and the rate at which the drug reaches the bloodstream, which is critical for the success of the therapy. Some drugs pose important problems in terms of efficacy and safety (e.g., antitumor drugs, antimicrobials) and suffer instability problems in the biological environment (e.g., gene materials), and thus the therapeutic performance of these drugs is improved when they are selectively directed (targeted) from the bloodstream to the site of action (tissues, cells or cellular structures). Both macro-dosage forms and nano-delivery systems may notably benefit from stimuli-responsive materials. Differently to pre-programmed drug release systems, formulations that provide discontinuous release as a function of specific signals (stimuli) are advantageous in many situations. Triggering drug release where, when, and how it is needed requires detailed knowledge of the changes that the illness causes in terms of physiological parameters. These changes can be characterized in terms of biomarkers (e.g., glucose, specific enzymes, or quorum sensing signals in the case of infection) and physicochemical parameters (pH, ions, temperature, glutathione) that may be exploited as internal stimuli. When the physio–pathological changes are too weak or poorly specific, the application of external stimuli may be an alternative. External sources of temperature, ultrasound, light, and magnetic or electric fields may allow for the focal switch on/off of drug release. This chapter provides an overview of the interest in activation-modulated and feedback-regulated controlled release systems, the mechanisms behind them, and some specific examples of responsive materials and their applications.
Why Is the Sunrise so Colourful?
Authors: Arridge Chris
Published: January 2023

Our star appearing above the horizon every morning, and descending again at dusk has been used to mark the daily cycles of humanity for millennia. And the colour of the sky at the beginning and end of the day can be as varied as the contents of the day itself. When the hues of a setting Sun are particularly spectacular, we may stop and wonder at the light show. But why can a sunset be so varied and colourful, when the Sun itself is largely unchanging?
How Can We See Inside You?
Authors: Burke Benjamin P.
Published: January 2023

Ever since the invention of fire we have used light as a technology to explore the world around us. Light in all its forms allows us to see places that were previously black. This chapter guides you through the history and uses of X- and γ-rays and how they can show us what cannot be seen easily.
Overview: Chemical Transformations
Authors: Scott Janet L.
Published: January 2023

This chapter provides a brief overview of the section of the book focused on chemical transformations. The context in which such processes should be considered is provided and some specific examples highlighted, while exclusions or omissions are briefly summarised.
Enzyme Biotransformations and Reactors
Authors: Leak David J. , Feng Xudong , Emanuelsson Emma A. C.
Published: January 2023

Enzyme-catalysed biotransformations, either using whole cells or free enzymes, are increasingly being exploited in industrial chemistry. They can offer remarkable reaction, stereo- and regio-selectivity, and work in benign aqueous systems. Some enzymes are remarkably robust, while others are relatively fragile, but may be stabilized by immobilization or used in whole cell systems. The use of purified (or partially purified) enzymes avoids the possibility of side reactions (of substrate or product), but incurs the additional cost of purification. This is why, historically, some of the most commonly used enzymes (e.g. lipases, proteases and glycoside hydrolases) are naturally extracellular. However, advances in molecular biology and protein engineering mean that production of any enzyme can be engineered into commonly used hosts (e.g. yeast or Escherichia coli). Methods are available to modify substrate recognition and reaction selectivity, allowing tuning of an enzyme to a novel substrate. Together with improvements in immobilization technology and enzyme reactor design, this is opening up new possibilities for single and multi-step biocatalytic processes.
Bioelectrochemical Systems
Authors: Schröder Uwe
Published: January 2023

By generating electricity from microbially catalysed anodic oxidation processes, the greatest potential lies in the use of wastewater as a fuel, which allows wastewater treatment and energy recovery to be combined. A recent development has expanded the scope of bioelectrochemical systems from power generation and wastewater treatment to an increasing number of applications such as bioelectrochemically driven desalination and microbial electrosynthesis. This chapter provides an overview of microbial bioelectrochemical systems, their fundamentals and potential applications.
Biofuels from Microalgae
Authors: Chuck Christopher J. , Wagner Jonathan L. , Jenkins Rhodri W.
Published: January 2023

The development of renewable liquid fuels is essential for reducing the impact of the transport sector on the environment. To achieve this, photosynthetic microalgae offer a credible source of biomass that could potentially meet the volume demand of this sector. While much research effort has been invested in developing microalgal biodiesel, an economic process remains elusive. A more promising route is the thermochemical conversion of whole algal biomass, especially by hydrothermal liquefaction. This creates a viscous bio-oil that can be further upgraded into suitable hydrocarbon fuels. Although a host of research challenges remain, these processes utilise the whole biomass and remove the costly de-watering and extraction stages. As such, the thermochemical transformation of algal biomass offers a credible route to an affordable renewable transport fuel. This chapter reviews the chemical processing considerations of producing algal biodiesel and fuels from the thermochemical valorisation of algal biomass and discusses the remaining research challenges in this area.
Overview of Separations, Purifications and Fractionations
Authors: Patterson Darrell Alec
Published: January 2023

An overview of the six separations chapters in the section of the book on chemical processing for a sustainable future is presented, contextualised within the general area of separations in chemical processing and the other separation techniques and unit operations that currently exist.
Nanocapillary sampling coupled to liquid chromatography mass spectrometry delivers single cell drug measurement and lipid fingerprints
Authors: Lewis Holly-May , Gupta Priyanka , Saunders Kyle D. G. , Briones Shazneil , von Gerichten Johanna , Townsend Paul A. , Velliou Eirini , Beste Dany J. V. , Cexus Olivier , Webb Roger , Bailey Melanie J.
Published: January 2023

This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living cells.
A primer to directed evolution: current methodologies and future directions
Authors: Sellés Vidal Lara , Isalan Mark , Heap John T. , Ledesma-Amaro Rodrigo
Published: January 2023

This review summarises the methods available for directed evolution, including mutagenesis and variant selection techniques. The advantages and disadvantages of each technique are presented, and future challenges in the field are discussed.
Ultrahigh-resolution quantum dot patterning for advanced optoelectronic devices
Authors: Nam Tae Won , Choi Min-Jae , Jung Yeon Sik
Published: January 2023

This review introduces recent advances in ultrahigh-resolution quantum dot patterning technologies, ranging from the single-particle to sub-micrometer scale, and provides guidance for selecting suitable strategies for specific applications.
Converting pH probes into “turn-on” fluorescent receptors for anions
Authors: Kataev Evgeny A.
Published: January 2023

The feature article outlines the design concept for the construction of “turn-on” fluorescent receptors for anions using fluorescent pH probes. Applications of this concept for the construction of fluorescent receptors for anions are described.
Cu/Cu2O nanocrystals for electrocatalytic carbon dioxide reduction to multi-carbon products
Authors: Yang Yisen , Tan Zhonghao , Wang Sha , Wang Yanyue , Hu Jingyang , Su Zhuizhui , Zhao Yingzhe , Tai Jing , Zhang Jianling
Published: January 2023

Cu/Cu2O nanocrystals were prepared for the efficient electrochemical conversion of carbon dioxide into multi-carbon products.