bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective rational humanization of a PASylated anti-galectin-3 Fab for the sensitive PET imaging of thyroid cancer in vivo
Authors: Peplau Emanuel , De Rose Francesco , Eichinger Andreas , Reder Sybille , Mittelhäuser Markus , Scafetta Giorgia , Schwaiger Markus , Weber Wolfgang A. , Bartolazzi Armando , D’Alessandria Calogero , Skerra Arne
Published: April 2021

The lack of a non-invasive test for malignant thyroid nodules makes the diagnosis of thyroid cancer (TC) challenging. Human galectin-3 (hGal3) has emerged as a promising target for medical TC imaging and diagnosis because of its exclusive overexpression in malignant thyroid tissues. We previously developed a human-chimeric αhGal3 Fab fragment derived from the rat monoclonal antibody (mAb) M3/38 with optimized clearance characteristics using PASylation technology. Here, we describe the elucidation of the hGal3 epitope recognized by mAb M3/38, X-ray crystallographic analysis of its complex with the chimeric Fab and, based on the three-dimensional structure, the rational humanization of the Fab by CDR grafting. Four CDR-grafted versions were designed using structurally most closely related fully human immunoglobulin VH/VL regions of which one—employing the acceptor framework regions of the HIV-1 neutralizing human antibody m66—showed the highest antigen affinity. By introducing two additional back-mutations to the rodent donor sequence, an affinity toward hGal3 indistinguishable from the chimeric Fab was achieved (KD = 0.34 ± 0.02 nM in SPR). The PASylated humanized Fab was site-specifically labelled with the fluorescent dye Cy7 and applied for the immuno-histochemical staining of human tissue sections representative for different TCs. The same protein was conjugated with the metal chelator Dfo, followed by radiolabelling with 89Zr(IV). The resulting protein tracer allowed the highly sensitive and specific PET/CT imaging of orthotopic tumors in mice, which was confirmed by quantitative analysis of radiotracer accumulation. Thus, the PASylated humanized αhGal3 Fab offers clinical potential for the diagnostic imaging of TC.
Magmatic karst reveals dynamics of crystallization and differentiation in basaltic magma chambers
Authors: Kruger Willem , Latypov Rais
Published: April 2021

An understanding of magma chamber dynamics relies on answering three important yet highly controversial questions: where, why, and how magma chambers crystallize and differentiate. Here we report on a new natural phenomenon—the undercut-embayed chamber floor in the Bushveld Complex—which allows us to address these questions. The undercut-embayed floor is produced by magmatic karstification (i.e. erosion by dissolution) of the underlying cumulates by replenishing magmas that form basal flows on the chamber floor. This results in a few metres thick three-dimensional framework of spatially interconnected erosional remnants that separate the floor cumulates from the overlying resident melt. The basal flow in this environment is effectively cooled through the floor, inducing heterogeneous nucleation and in situ growth against much of its three-dimensional framework. The solidification front thus propagates in multiple directions from the surfaces of erosional remnants. Fractional crystallization may occur within this environment by convective removal of a compositional boundary layer from in situ growing crystals and is remarkably efficient even in very confined spaces. We propose that the way magma crystallizes and differentiates in the undercut-embayed chamber floor is likely common for the evolution of many basaltic magma chambers.
Interim and end-treatment 18F-Fluorocholine PET/CT and bone scan in prostate cancer patients treated with Radium 223 dichloride
Authors: García Vicente Ana María , Amo-Salas Mariano , Cassinello Espinosa Javier , Gómez Díaz Roberto , Soriano Castrejón Ángel
Published: April 2021

To assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis. Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p = 0.004). No agreement was observed between end-treatment diagnostic studies. Interim and end-treatment FCH PET/CT were related to PFS (p = 0.011 and p < 0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p < 0.001, p = 0.037 and p = 0.008, respectively). Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.
Neurodevelopment correlates with gut microbiota in a cross-sectional analysis of children at 3 years of age in rural China
Authors: Rothenberg Sarah E. , Chen Qiurong , Shen Jian , Nong Yanfen , Nong Hua , Trinh Eva P. , Biasini Fred J. , Liu Jihong , Zeng Xiaoyun , Zou Yunfeng , Ouyang Fengxiu , Korrick Susan A.
Published: April 2021

We investigated cross-sectional associations between children’s neurodevelopment and their gut microbiota composition. Study children (36 months of age) lived in rural China (n = 46). Neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd Edition, yielding the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Children's gut microbiota was assessed using 16S rRNA gene profiling. Microbial diversity was characterized using alpha diversity patterns. Additionally, 3 coabundance factors were determined for the 25 most abundant taxa. Multivariable linear regression models were constructed to examine the relationships between Bayley scores (MDI and PDI) and children's gut microbiota. In adjusted models, MDI and PDI scores were not associated with alpha diversity indices. However, in adjusted models, MDI and PDI scores were positively associated with the first coabundance factor, which captured positive loadings for the genera Faecalibacterium, Sutterella, and Clostridium cluster XIVa. For an interquartile range increase in the first coabundance factor, MDI scores increased by 3.9 points [95% confidence interval (CI): 0, 7.7], while PDI scores increased by 8.6 points (95% CI 3.1, 14). Our results highlight the potential for gut microbial compositional characteristics to be important correlates of children's Bayley Scales performance at 36 months of age.
Low dose of zearalenone elevated colon cancer cell growth through G protein-coupled estrogenic receptor
Authors: Lo Emily Kwun Kwan , Lee Jetty Chung-Yung , Turner Paul C. , El-Nezami Hani
Published: April 2021

Colon cancer is one of the leading causes of cancer death worldwide. It is widely believed that environmental factors contribute to colon cancer development. Zearalenone (ZEA) is non-steroidal estrogenic mycotoxin that is widely found in the human diet and animal feeds. Most cancer studies of ZEA focused on estrogen sensitive cancers, while few focused on other types, such as colon cancer; despite the gastrointestinal tract being the first barrier exposed to food contaminants. This study investigated the stimulatory effects of ZEA on colon cancer cell lines and their underlying molecular mechanisms. ZEA promoted anchorage independent cell growth and cell cycle progression through promoting G1-to-S phase transition. Proliferative marker, cyclin D1 and Ki67 were found to be upregulated upon ZEA treatment. G protein-coupled estrogenic receptor 1 (GPER) protein expression was promoted upon ZEA treatment suggesting the involvement of GPER. The growth promoting effect mediated through GPER were suppressed by its antagonist G15. ZEA were found to promote the downstream parallel pathway, MAPK signaling pathway and Hippo pathway effector YAP1. Altogether, our observations suggest a novel mechanism by which ZEA could promote cancer growth and provide a new perspective on the carcinogenicity of ZEA.
Topographical transition of submicron pillar array of azo molecular glass induced by circularly polarized light
Authors: Wang Zenan , Hsu Chungen , Wang Xiaogong
Published: April 2021

The well-aligned submicron patterns on surfaces have attracted wide attention from scientific curiosity to practical applications. Understanding their formation and transition is highly desirable for efficient manufacture of the patterns for many usages. Here, we report a unique observation on self-organized topographical transition of submicron pillar array of an azo molecular glass, induced by irradiation with circularly polarized light. During gradual erasure of the patterns upon exposure to the light, which is a property of this material, a new set of pillars unexpectedly emerge with new one in middle of each triangle cell of the original array. The highly regular pillar array with triple area density is formed and finally stabilized in the process, as revealed by thorough investigation reported here. This unusual observation and its rationalization will be of benefit for deep understanding of the light–matter interaction and can be expected to be applied in different areas.
Female mice are more prone to develop an addictive-like phenotype for sugar consumption
Authors: Wei Shoupeng , Hertle Sarah , Spanagel Rainer , Bilbao Ainhoa
Published: April 2021

The concept of “sugar addiction” is gaining increasing attention in both the lay media and scientific literature. However, the concept of sugar addiction is controversial and only a few studies to date have attempted to determine the “addictive” properties of sugar using rigorous scientific criteria. Here we set out to systematically test the addictive properties of sugar in male and female mice using established paradigms and models from the drug addiction field. Male and female C57BL/6N (8–10 weeks old) were evaluated in 4 experimental procedures to study the addictive properties of sugar: (i) a drinking in the dark (DID) procedure to model sugar binging; (ii) a long-term free choice home cage drinking procedure measuring the sugar deprivation effect (SDE) following an abstinence phase; (iii) a long-term operant sugar self-administration with persistence, motivation and compulsivity measures and (iv) intracranial self-stimulation (ICSS). Female mice were more vulnerable to the addictive properties of sugar than male mice, showing higher binge and long-term, excessive drinking, a more pronounced relapse-like drinking following deprivation, and higher persistence and motivation for sugar. No sex differences were seen in a compulsivity test or reward sensitivity measured using ICSS following extended sugar consumption. This study demonstrates the occurrence of an addictive-like phenotype for sugar in male and female mice, similar to drugs of abuse, and suggests sex-dependent differences in the development of sugar addiction.
High insecticide resistance mediated by different mechanisms in Culex quinquefasciatus populations from the city of Yaoundé, Cameroon
Authors: Talipouo Abdou , Mavridis Konstantinos , Nchoutpouen Elysée , Djiappi-Tchamen Borel , Fotakis Emmanouil Alexandros , Kopya Edmond , Bamou Roland , Kekeunou Sévilor , Awono-Ambene Parfait , Balabanidou Vasileia , Balaska Sofia , Wondji Charles Sinclair , Vontas John , Antonio-Nkondjio Christophe
Published: April 2021

Culex mosquitoes particularly Culex quinquefasciatus are important arboviral and filariasis vectors, however despite this important epidemiological role, there is still a paucity of data on their bionomics. The present study was undertaken to assess the insecticide resistance status of Cx. quinquefasciatus populations from four districts of Yaoundé (Cameroon). All Culex quinquefasciatus populations except one displayed high resistance to bendiocarb and malathion with mortalities ranging from 0 to 89% while high resistance intensity against both permethrin and deltamethrin was recorded. Molecular analyses revealed high frequencies of the ACE-1 G119S mutation (ranging from 0 to 33%) and kdr L1014F allele (ranging from 55 to 74%) in all Cx. quinquefasciatus populations. Significant overexpression was detected for cytochrome P450s genes CYP6AA7 and CYP6Z10, as well as for Esterase A and Esterase B genes. The total cuticular hydrocarbon content, a proxy of cuticular resistance, was significantly increased (compared to the S-lab strain) in one population. The study confirms strong insecticide resistance mediated by different mechanisms in Cx. quinquefasciatus populations from the city of Yaoundé. The expansion of insecticide resistance in Culex populations could affect the effectiveness of current vector control measures and stress the need for the implementation of integrated vector control strategies in urban settings.
The orthopedic characterization of cfap298tm304 mutants validate zebrafish to faithfully model human AIS
Authors: Marie-Hardy Laura , Cantaut-Belarif Yasmine , Pietton Raphaël , Slimani Lotfi , Pascal-Moussellard Hugues
Published: April 2021

Cerebrospinal fluid (CSF) circulation relies on the beating of motile cilia projecting in the lumen of the brain and spinal cord cavities Mutations in genes involved in cilia motility disturb cerebrospinal fluid circulation and result in scoliosis-like deformities of the spine in juvenile zebrafish. However, these defects in spine alignment have not been validated with clinical criteria used to diagnose adolescent idiopathic scoliosis (AIS). The aim of this study was to describe, using orthopaedic criteria the spinal deformities of a zebrafish mutant model of AIS targeting a gene involved in cilia polarity and motility, cfap298tm304. The zebrafish mutant line cfap298tm304, exhibiting alteration of CSF flow due to defective cilia motility, was raised to the juvenile stage. The analysis of mutant animals was based on micro-computed tomography (micro-CT), which was conducted in a QUANTUM FX CALIPER, with a 59 µm-30 mm protocol. 63% of the cfap298tm304 zebrafish analyzed presented a three-dimensional deformity of the spine, that was evolutive during the juvenile phase, more frequent in females, with a right convexity, a rotational component and involving at least one dislocation. We confirm here that cfap298tm304 scoliotic individuals display a typical AIS phenotype, with orthopedic criteria mirroring patient’s diagnosis.
Systematic prediction of drug resistance caused by transporter genes in cancer cells
Authors: Shen Yao , Yan Zhipeng
Published: April 2021

To study the drug resistance problem caused by transporters, we leveraged multiple large-scale public data sets of drug sensitivity, cell line genetic and transcriptional profiles, and gene silencing experiments. Through systematic integration of these data sets, we built various machine learning models to predict the difference between cell viability upon drug treatment and the silencing of its target across the same cell lines. More than 50% of the models built with the same data set or with independent data sets successfully predicted the testing set with significant correlation to the ground truth data. Features selected by our models were also significantly enriched in known drug transporters annotated in DrugBank for more than 60% of the models. Novel drug-transporter interactions were discovered, such as lapatinib and gefitinib with ABCA1, olaparib and NVPADW742 with ABCC3, and gefitinib and AZ628 with SLC4A4. Furthermore, we identified ABCC3, SLC12A7, SLCO4A1, SERPINA1, and SLC22A3 as potential transporters for erlotinib, three of which are also significantly more highly expressed in patients who were resistant to therapy in a clinical trial.
Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab
Authors: Trilla-Fuertes Lucía , Gámez-Pozo Angelo , Maurel Joan , Garcia-Carbonero Rocio , Capdevila Jaume , G-Pastrián Laura , Mendiola Marta , Peña Cristina , López-Vacas Rocío , Cuatrecasas Miriam , García-Alfonso Pilar , Ramos-Ruiz Ricardo , Llorens Carlos , Ghanem Ismael , Conill Carles , Heredia-Soto Victoria , Campos-Barros Ángel , Fresno Vara Juan Ángel , Feliu Jaime
Published: April 2021

Squamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.
Fate of 14C-labeled few-layer graphene in natural soils: competitive roles of ferric oxides
Authors: Dong Shipeng , Wang Tingting , Lu Kun , Zhao Jian , Tong Yang , Mao Liang
Published: April 2021

Ferric oxides were identified as the predominant component governing the fate of FLG in natural soils by restricting the mobility or facilitating the transformative release of graphene.
Creating and testing an activity with interdisciplinary connections: entropy to osmosis
Authors: Martinez Brianna L. , Kararo Alex T. , Parent Kristin N. , Underwood Sonia M. , Matz Rebecca L.
Published: April 2021

Students often struggle to make interdisciplinary connections and cite a lack of opportunity to make such connections. To address this issue, we are developing activities aligned with the framework of three-dimensional learning that provide students with opportunities to make connections between chemistry concepts and biological phenomena. Here, we focus on an activity that asks students to incorporate the concept of entropy in explaining the biological phenomenon of osmosis across a cell membrane. This activity was administered in both introductory cell and molecular biology and second-semester general chemistry courses. We found that after completing carefully scaffolded questions within the activity, students were better able to correctly use the concept of entropy in explaining osmosis than they were before the scaffolding questions. Additionally, we found that students’ course history appeared to impact their explanations of this phenomenon in that students who had taken second-semester general chemistry (i.e., the semester in which entropy is discussed for these students) provided more sophisticated responses and were less likely to include scientifically inaccurate ideas than their peers who had not taken second-semester general chemistry.
Computational and photophysical characterization of a Laurdan malononitrile derivative
Authors: Hornum Mick , Kongsted Jacob , Reinholdt Peter
Published: April 2021

The ketone group of the traditional push–pull dye Laurdan is replaced with a malononitrile group. The new probe is less bright than Laurdan due to a large drop in the fluorescence quantum yield but functions well as a molecular rotor.
Near-infrared C-term MCD spectroscopy of octahedral uranium(v) complexes
Authors: Curran Daniel J. , Ganguly Gaurab , Heit Yonaton N. , Wolford Nikki J. , Minasian Stefan G. , Löble Matthias W. , Cary Samantha K. , Kozimor Stosh A. , Autschbach Jochen , Neidig Michael L.
Published: April 2021

Experimental and theoretical near-infrared C-term MCD spectroscopy as a tool to enable broader insight into electronic structure in U(v) Oh complexes.
Luminescence from open-shell, first-row transition metal dipyrrin complexes
Authors: Scharf Austin B. , Zheng Shao-Liang , Betley Theodore A.
Published: April 2021

Several first-row transition metal complexes of the 1,9-bis(2′,4′,6′-triphenylphenyl)-5-mesityl dipyrrinato ligand and its tetrahalogenated analogues have been synthesized and their luminescence spectra obtained.
Exposure to nano-polystyrene induces metabolic alteration in lipid homeostasis in Caco-2
Authors: Kim Sun Jo , Long Nguyen Phuoc , Jung Cheol Woon , Anh Nguyen Hoang , Min Jung Eun , Kim Hyung Min , Kwon Sung Won
Published: April 2021

Disturbance in lipid homeostasis was revealed by global metabolic profiling following acute and prolonged exposure to 50 nm polystyrene.
Balancing the mechanical, electronic, and self-healing properties in conductive self-healing hydrogel for wearable sensor applications
Authors: Su Gehong , Yin Shuya , Guo Youhong , Zhao Fei , Guo Quanquan , Zhang Xinxing , Zhou Tao , Yu Guihua
Published: April 2021

Dynamic interfacial interactions between the HAPAA and PANI hydrogels are favorable for self-healing; thus, the PANI network can enhance the mechanical and electronic properties of HAPAA hydrogel without compromising its self-healing performance.
A new strategy for large-scale synthesis of Na0.5Bi0.5TiO3 nanowires and their application in piezocatalytic degradation
Authors: Huang Rui , Wu Jiang , Lin Enzhu , Kang Zihan , Qin Ni , Bao Dinghua
Published: April 2021

Na0.5Bi0.5TiO3 nanowires prepared by the template hydrothermal method exhibited excellent piezocatalytic activity in the degradation of organic pollutants.
Step-wise and one-pot synthesis of highly substituted conjugated trienes from 2-oxobenzo[h]chromenes/2H-pyran-2-ones
Authors: Elagamy Amr , Althagafi Ismail , Pratap Ramendra
Published: April 2021

The synthesis of conjugated trienes by ring contraction of 2-oxobenzo[h]chromenes/2H-pyran-2-ones followed by decarboxylative rearrangement has been developed.
Cobalt single atom catalysts for the efficient electrosynthesis of hydrogen peroxide
Authors: Xu Hui , Zhang Shengbo , Geng Jing , Wang Guozhong , Zhang Haimin
Published: April 2021

Cobalt single atoms anchored on N-doped graphitic carbon were successfully synthesised and exhibited superior two-electron oxygen reduction reaction activity with a H2O2 selectivity of ∼76.0% at 0.5 V (vs. RHE).
The improvement in hole-transporting and electroluminescent properties of diketopyrrolopyrrole pigment by grafting with carbazole dendrons
Authors: Kitisriworaphan Wipaporn , Chawanpunyawat Thanyarat , Manyum Thanaporn , Chasing Pongsakorn , Namuangruk Supawadee , Sudyoadsuk Taweesak , Promarak Vinich
Published: April 2021

Diketopyrrolopyrrole pigments grafted with carbazole dendrons in OLEDs exhibit strong and stable yellow emissions with brightness of 3060 cd m−2, luminous efficiency of 9.24 cd A−1 and EQE of 3.11%.
Ring-opening hydrolysis of spiro-epoxyoxindoles using a reusable sulfonic acid functionalized nitrogen rich carbon catalyst
Authors: Patel Parth , Tak Raj Kumar , Parmar Bhavesh , Dabas Shilpa , Patel Brijesh , Suresh Eringathodi , Khan Noor-ul H. , Subramanian Saravanan
Published: April 2021

Catalytic synthesis of vicinal diols via ring-opening hydrolysis of spiro-epoxyoxindoles.
A novel energy efficient path for nitrogen fixation using a non-thermal arc
Authors: Muzammil Iqbal , Lee Dae Hoon , Dinh Duy Khoe , Kang Hongjae , Roh Seon Ah , Kim You-Na , Choi Seongil , Jung Chanmi , Song Young-Hoon
Published: April 2021

The studied process offers high NO selectivity with low energy consumption, which is much lower than the previously reported value of plasma-assisted atmospheric nitrogen fixation and is close to that of the Haber–Bosch process.
Electrorotation of particle-coated droplets: from fundamentals to applications
Authors: Rozynek Z. , Banaszak J. , Mikkelsen A. , Khobaib K. , Magdziarz A.
Published: April 2021

In this work we provide the basic features of electric field-induced rotation of particle-covered droplets and demonstrate new application of such electrorotation.
A sulfamethoxazole molecularly imprinted two-dimensional photonic crystal hydrogel sensor
Authors: Cao Yunlei , Liu Genqi , Zheng Bingqing , Wang Xinlong , Li Huanhuan , Wang Gang , Zhao Lingli , Wang Yue
Published: April 2021

We have prepared an SMZ–MIPCH sensor for the efficient detection of SMZ. This sensor can realize the visual detection of SMZ through changes in the diameter of the Debye ring and sensor color.
Novel NIR-II semiconducting molecule incorporating sorafenib for imaging guided synergetic cancer phototherapy and anti-angiogenic therapy
Authors: Zou Huihui , Wei Zheng , Song Chuanhui , Ran Jianchuan , Cao Zichen , Tang Chuanchao , Zhang Guorong , Cai Yu , Lu Mingxing , Han Wei
Published: April 2021

With the addition of sorafenib into organic semiconducting molecule T8IC, TS nanoparticles (NPs) were formed by nanoprecipitation with synergetic anti-angiogenic and phototheranostic effects.
The induction of half-metallicity and enhanced ferromagnetism in a Cr2Ge2Te6 monolayer via electron doping and alkali metal adsorption
Authors: Ilyas Asif , Wu Haifei , Usman Tariq , Khan Salman Ali , Deng Renren
Published: April 2021

Exploring the phenomenon of half-metallicity in Cr2Ge2Te6 monolayer via electron-doping or adsorption makes it a promising for spintronic devices. Moreover, experimentally adsorption is viable for achieving half-metallicity in CGT systems.
The variation of intrinsic defects in XTe (X = Ge, Sn, and Pb) induced by the energy positions of valence band maxima
Authors: Huo Haiyang , Wang Yuxiang , Xi Lili , Yang Jiong , Zhang Wenqing
Published: April 2021

The difference of vacancy formation energy between PbTe and Ge (Sn)Te can be understood by the relative position of valence band maximum (VBM) energy levels. The higher the VBM, the lower the formation energy of acceptor defect (such as Vx).
Genetic and epigenetic regulation of the non-muscle myosin light chain kinase isoform by lung inflammatory factors and mechanical stress
Authors: Sun Xiaoguang , Sun Belinda L. , Sammani Saad , Bermudez Tadeo , Dudek Steven M. , Camp Sara M. , Garcia Joe G.N.
Published: April 2021

Rationale: The myosin light chain kinase gene, MYLK, encodes three proteins via unique promoters, including the non-muscle isoform of myosin light chain kinase (nmMLCK), a cytoskeletal protein centrally involved in regulation of vascular integrity. As MYLK coding SNPs are associated with severe inflammatory disorders (asthma, acute respiratory distress syndrome (ARDS)), we explored clinically relevant inflammatory stimuli and promoter SNPs in nmMLCK promoter regulation. Methods: Full-length or serially deleted MYLK luciferase reporter promoter activities were measured in human lung endothelial cells (ECs). SNP-containing non-muscle MYLK (nmMYLK) DNA fragments were generated and nmMYLK promoter binding by transcription factors (TFs) detected by protein–DNA electrophoretic mobility shift assay (EMSA). Promoter demethylation was evaluated by 5-aza-2′-deoxycytidine (5-Aza). A preclinical mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) was utilized for nmMLCK validation. Results: Lung EC levels of nmMLCK were significantly increased in LPS-challenged mice and LPS, tumor necrosis factor-α (TNF-α), 18% cyclic stretch (CS) and 5-Aza each significantly up-regulated EC nmMYLK promoter activities. EC exposure to FG-4592, a prolyl hydroxylase inhibitor that increases hypoxia-inducible factor (HIF) expression, increased nmMYLK promoter activity, confirmed by HIF1α/HIF2α silencing. nmMYLK promoter deletion studies identified distal inhibitory and proximal enhancing promoter regions as well as mechanical stretch-, LPS- and TNFα-inducible regions. Insertion of ARDS-associated SNPs (rs2700408, rs11714297) significantly increased nmMYLK promoter activity via increased transcription binding (glial cells missing homolog 1 (GCM1) and intestine-specific homeobox (ISX), respectively). Finally, the MYLK rs78755744 SNP (−261G/A), residing within a nmMYLK CpG island, significantly attenuated 5-Aza-induced promoter activity. Conclusion: These findings indicate nmMYLK transcriptional regulation by clinically relevant inflammatory factors and ARDS-associated nmMYLK promoter variants are consistent with nmMLCK as a therapeutic target in severe inflammatory disorders.
Spoken Vocabulary Outcomes of Toddlers With Developmental Delay After Parent-Implemented Augmented Language Intervention
Authors: Walters Casy , Sevcik Rose A. , Romski MaryAnn
Published: April 2021

Purpose

Early intervention using augmentative and alternative communication (AAC) supports both receptive and expressive language skills. However, many parents and clinicians still worry that augmented language intervention might delay or impair speech development. This study aimed to (a) characterize and analyze the speech sound development of toddlers with developmental delay who participated in a parent-implemented language intervention; (b) examine the accuracy of speech sounds among toddlers who participated in an augmented language intervention using speech-generating devices and toddlers who participated in a traditional, spoken language intervention; and (c) examine the relationship between baseline factors (i.e., receptive and expressive language skills, vocal imitation, and number of unintelligible utterances) and the number of spoken target vocabulary words after intervention.

Method

This study used extant data from two randomized control trials of parent-implemented language interventions using AAC or spoken language. Out of 109 children who completed the intervention, 45 children produced spoken target vocabulary words at the end of the intervention. We identified and phonetically transcribed spoken target vocabulary words for each child and then classified them based on Shriberg and Kwiatkowski's (1982) developmental sound classes.

Results

Children's speech sound accuracy was not significantly different across intervention groups. Overall, children who produced more words had more speech sound errors and higher baseline language scores. Intervention group and baseline receptive and expressive language skills significantly predicted the number of spoken target vocabulary words produced at the end of intervention.

Conclusions

Participation in AAC intervention resulted in significantly more spoken target vocabulary words and no statistically significant differences in speech sound errors when compared to children who received spoken language intervention without AAC. Results support using AAC interventions for very young children without the fear that it will delay speech or spoken language development.

Supplemental Material

https://doi.org/10.23641/asha.14265365
The turnpike property in semilinear control
Authors: Pighin Dario
Published: April 2021

An exponential turnpike property for a semilinear control problem is proved. The state-target is assumed to be small, whereas the initial datum can be arbitrary. Turnpike results are also obtained for large targets, requiring that the control acts everywhere. In this case, we prove the convergence of the infimum of the averaged time-evolution functional towards the steady one. Numerical simulations are performed.
Neuropsychiatrische Folgen der COVID-19-Pandemie
Authors: Dreßing Andrea , Hosp Jonas , Kuehner Christine , Dreßing Harald , Meyer-Lindenberg Andreas
Published: April 2021

Die COVID-19-Pandemie hat erhebliche Auswirkungen auf die psychische Gesundheit. Neben Ängsten um die ökonomische Situation, die eigene Gesundheit und die Gesundheit anderer Menschen können auch Maßnahmen der Pandemiekontrolle wie Distanzierung und die dadurch bedingte Isolation psychosoziale Folgen haben. Schließlich kann die Infektion selbst im Rahmen einer systemischen Manifestation zu psychiatrischen und neuropsychiatrischen Symptomen führen. In dieser Arbeit werden unterschiedliche Mechanismen dargestellt, die mittelbar oder unmittelbar zu neuropsychologischen und psychopathologischen Symptomen im Kontext der COVID-19-Pandemie führen können.
Mathematical Interpretation of the Pharmacodynamics of Homoeopathic Medicines
Authors: Warner John Michel
Published: April 2021

According to Hahnemann, homoeopathic medicines must be great immune responses inducers. In crude states, these medicines pose severe threats to the immune system. So, the immune-system of an organism backfires against the molecules of the medicinal substances. The complex immune response mechanism activated by the medicinal molecules can handle any threats which are similar to the threats posed by the medicinal molecules. The intersectional operation of the two sets, medicine-induced immune responses and immune responses necessary to cure diseases, shows that any effective homoeopathic medicine, which is effective against any disease, can induce immune responses which are necessary to cure the specific disease. In this article, this mechanism has been exemplified by the action of Silicea in human body. Also, a neuroimmunological assessment of the route of medicine administration shows that the oral cavity and the nasal cavity are two administration-routes where the smallest doses (sometimes even few molecules) of a particular homoeopathic medicine induce the most effective and sufficient (in amount) purgatory immune responses. Administering the smallest unitary doses of Silicea in the oral route can make significant changes in the vital force line on the dose–response relationship graph. The dose–response relationship graph further implicates that the most effective dose of a medicine must be below the lethality threshold. If multiple doses of any medicine are administered at same intervals, the immune-system primarily engages with the medicinal molecules; but along the passage of time, the engagement line splits into two: one engages with the medicinal molecules and another engages with diseases. The immune system's engagement with the diseases increases along the passage of time, though the engagement with the medicinal molecules gradually falls with the administration of descending doses. Necessarily, I have shown through mathematical logic that the descending doses, though they seem to be funny, can effectively induce the most effective immune responses.
Heparan Sulfate Proteoglycans in Diabetes
Authors: Hiebert Linda M.
Published: April 2021

Diabetes is a complex disorder responsible for the mortality and morbidity of millions of individuals worldwide. Although many approaches have been used to understand and treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans (HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly negatively charged, and are found in all cells primarily attached to the plasma membrane or present in the extracellular matrix (ECM). HSPGs are involved in development, cell migration, signal transduction, hemostasis, inflammation, and antiviral activity, and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying diabetes, increases reactive oxygen species and upregulates the enzyme heparanase that degrades HSPGs or affects the synthesis of the HSPGs altering their structure. The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides the blood vessel, other cells and tissues in the heart, kidney, and eye are affected by diabetes. Although not well understood, the adipose tissue, intestine, and brain also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly involved in protecting the β cells of the pancreas from autoimmune destruction and could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may contribute to the pathology of the disease. Understanding the role of HSPGs and how they are modified by diabetes may lead to new treatments as well as preventative measures to reduce the morbidity and mortality associated with this complex condition.
Endothelial Heparan Sulfate Proteoglycans in Sepsis: The Role of the Glycocalyx
Authors: Oshima Kaori , King Samantha I. , McMurtry Sarah A. , Schmidt Eric P.
Published: April 2021

There is increasing recognition of the importance of the endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer, in vascular homeostasis. Heparan sulfate proteoglycans (HSPGs) are a major structural constituent of the endothelial glycocalyx and serve to regulate vascular permeability, microcirculatory tone, leukocyte and platelet adhesion, and hemostasis. During sepsis, endothelial HSPGs are shed through the induction of “sheddases” such as heparanase and matrix metalloproteinases, leading to loss of glycocalyx integrity and consequent vascular dysfunction. Less well recognized is that glycocalyx degradation releases HSPG fragments into the circulation, which can shape the systemic consequences of sepsis. In this review, we will discuss (1) the normal, homeostatic functions of HSPGs within the endothelial glycocalyx, (2) the pathological changes in HSPGs during sepsis and their consequences on the local vascular bed, and (3) the systemic consequences of HSPG degradation. In doing so, we will identify potential therapeutic targets to improve vascular function during sepsis as well as highlight key areas of uncertainty that require further mechanistic investigation.
Synthesis and Solvatochromic Behavior of Zwitterionic Donor–Bridge–Acceptor Systems with Oligo(p-phenylene) Spacers
Authors: Zharinova Irina , Saker Neto Nicolau , Owyong Tze Cin , White Jonathan M. , Wong Wallace W. H.
Published: April 2021

Oligo(p-phenylene)s with a donor phenol group and an acceptor pyridinium moiety separated by one and two p-phenylene units were synthesized by the linear iterative Suzuki–Miyaura coupling method using aryl nonaflates as effective coupling reagents. Zwitterionic forms of these push–pull molecules were generated upon deprotonation of the phenol leading to large redshifts in absorbance maxima. UV-vis absorbance studies also revealed strong dependence of the band position on solvent polarity: a smooth bathochromic shift can be observed with the decrease of the solvent polarity. The molecule with one p-phenylene bridging unit showed the strongest solvatochromic characteristics in the series, spanning the range of 167 nm while moving from polar water to less polar N,N-dimethylformamide. The magnitude of this shift was close to Reichardt's dye — one of the most solvatochromic organic dyes known.
Congenital Perineal Groove Defect in Monozygotic Twin Infants: A Literature Review
Authors: Harsono Mimily , Yanishevski David , Pourcyrous Massroor
Published: April 2021

Perineal groove is a rare benign congenital anomaly with lesion that resembles perforation of mid-perineum or perineal raphe area. Most reported cases of congenital perineal groove presented as an isolated defect in term or early-term singleton female infants. Thus far, there is no reported case of this anomaly in monozygotic twins. Embryo pathogenesis of this female predominance congenital defect remains controversial. Many clinicians are unfamiliar with this congenital anomaly. This congenital defect tends to get self-resolved at around 2 year of age. Nevertheless, the exposed nonepithelized mucous membrane can carry risk of local infection or irritation with the possibility of requiring early surgical correction. The defect can be infrequently associated with other ano-urogenital malformations that required immediate surgical intervention. Most isolated cases tend to be asymptomatic and self-healed with expectant management. Surgical correction may be considered if not healed after 2 years of age. Early diagnosis at birth is important to avoid misdiagnoses at later age for trauma, dermatitis, sexual abuse, and risk of unnecessary aggressive intervention. Early parental counseling for providing good hygiene and close follow-up is important to prevent infection or inflammation. Presentation of this anomaly in both monozygotic twins may support the hypothesis of potential disruption during embryo morphogenesis stages.
Levitating a sphere similar in size to the acoustic wavelength
Authors: Frank Jodi Ackerman
Published: April 2021

Single-beam acoustic levitation technique employs a computationally fast sound field model to produce a twin tuning forks trap.
Progress towards lower-cost proton exchange membrane fuel cells
Authors: Kim Meeri
Published: April 2021

A research update reviews the latest strategies to reduce the amount of expensive platinum group metals in proton exchange membrane fuel cells.
Effect of noise on the collective dynamics of a heterogeneous population of active rotators
Authors: Klinshov V. V. , Zlobin D. A. , Maryshev B. S. , Goldobin D. S.
Published: April 2021

We study the collective dynamics of a heterogeneous population of globally coupled active rotators subject to intrinsic noise. The theory is constructed on the basis of the circular cumulant approach, which yields a low-dimensional model reduction for the macroscopic collective dynamics in the thermodynamic limit of an infinitely large population. With numerical simulation, we confirm a decent accuracy of the model reduction for a moderate noise strength; in particular, it correctly predicts the location of the bistability domains in the parameter space.
Evidence of surface and bulk magnetic ordering in Fe and Mn doped Bi2(SeS)3 topological insulator
Authors: Singh Mahima , Kumar Shiv , Alam Mohd , Gangwar Vinod K. , Ghosh Labanya , Pal Debarati , Singh Rahul , Shahi P. , Chaudhary P. , Shimada Kenya , Chatterjee Sandip
Published: April 2021

The magneto-transport, angle resolved photoemission spectroscopy (ARPES), and magnetization of Bi2-xMx(SeS)3 (with M = Fe, Mn) have been investigated. In Fe-doped Bi2(SeS)3, the presence of both electron-mediated Ruderman–Kittel–Kasuya–Yosida (RKKY) coupling and carrier-independent van Vleck magnetism has been demonstrated. Interestingly, by varying the Fe content and temperature, the interplay between the two mechanisms for magnetic ordering has been revealed. On the other hand, in the Mn-doped sample, hole-mediated RKKY coupling is observed. Thus, a particular mechanism can be used to induce magnetic ordering in the topological insulator. Furthermore, both ARPES and magnetic studies indicate that surface magnetic ordering may or may not break the time reversal symmetry (TRS), whereas bulk magnetic ordering breaks the TRS, suggesting the potentiality of these materials for spintronic application.
Recent advancements in enzyme-mediated crosslinkable hydrogels: In vivo-mimicking strategies
Authors: Song Wonmoon , Ko Junghyeon , Choi Young Hwan , Hwang Nathaniel S.
Published: April 2021

Enzymes play a central role in fundamental biological processes and have been traditionally used to trigger various processes. In recent years, enzymes have been used to tune biomaterial responses and modify the chemical structures at desired sites. These chemical modifications have allowed the fabrication of various hydrogels for tissue engineering and therapeutic applications. This review provides a comprehensive overview of recent advancements in the use of enzymes for hydrogel fabrication. Strategies to enhance the enzyme function and improve biocompatibility are described. In addition, we describe future opportunities and challenges for the production of enzyme-mediated crosslinkable hydrogels.
Glass polyamorphism in gallium: Two amorphous solid states and their transformation on the potential energy landscape
Authors: Liu Yizhi , Sun Gang , Xu Limei
Published: April 2021

Using the potential energy landscape (PEL) formalism and molecular dynamics simulations, we investigate a phase transformation between two amorphous solid states of gallium, namely, a low-density amorphous solid (LDA) and a high-density amorphous solid (HDA), and compare with its equilibrium counterpart, the liquid–liquid phase transition (LLPT). It is found that on the PEL, the signatures of the out-of-equilibrium LDA–HDA transition are reminiscent of those of the equilibrium LLPT in terms of pressure, inherent structure pressure, inherent structure energy, and shape function, indicating that the LDA–HDA transformation is a first-order-like transition. However, differences are also found between the out-of-equilibrium phase transition and the equilibrium one, for example, the path from LDA to HDA on the PEL cannot be accessed by the path from LDL to HDL. Our results also suggest that the signatures of the out-of-equilibrium transition in gallium are rather general features of systems with an accessible LLPT—not only systems with pairwise interactions but also those with many-body interactions. This finding is of crucial importance for obtaining a deeper understanding of the nature of transitions in the polyamorphic family.
Nonlinear dynamical behavior of an SEIR mathematical model: Effect of information and saturated treatment
Authors: Das Tanuja , Srivastava Prashant K. , Kumar Anuj
Published: April 2021

When a disease spreads in a population, individuals tend to change their behavior due to the presence of information about disease prevalence. Therefore, the infection rate is affected and incidence term in the model should be appropriately modified. In addition, a limitation of medical resources has its impact on the dynamics of the disease. In this work, we propose and analyze an Susceptible-Exposed-Infected-Recovered (SEIR) model, which accounts for the information-induced non-monotonic incidence function and saturated treatment function. The model analysis is carried out, and it is found that when R0 is below one, the disease may or may not die out due to the saturated treatment (i.e., a backward bifurcation may exist and cause multi-stability). Further, we note that in this case, disease eradication is possible if medical resources are available for all. When R0 exceeds one, there is a possibility of the existence of multiple endemic equilibria. These multiple equilibria give rise to rich and complex dynamics by showing various bifurcations and oscillations (via Hopf bifurcation). A global asymptotic stability of a unique endemic equilibrium (when it exists) is established under certain conditions. An impact of information is shown and also a sensitivity analysis of model parameters is performed. Various cases are considered numerically to provide the insight of model behavior mathematically and epidemiologically. We found that the model shows hysteresis. Our study underlines that a limitation of medical resources may cause bi(multi)-stability in the model system. Also, information plays a significant role and gives rise to a rich and complex dynamical behavior of the model.