bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypermobile Ehlers-Danlos Syndrome: Caregiver–Child Concordance Across Challenges, Readiness to Change, and Coping
Authors: Bieniak Keely H. , Koven Marissa L. , Bedree Helen , Tinkle Brad T. , Tran Susan T.
Published: October 2021

Objectives: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a heritable connective tissue disorder that results in physical symptoms, psychosocial challenges, and functional disability. Children with hEDS and their caregivers face challenges in managing the symptoms and associated impacts of the syndrome. Method: Mixed methods were utilized to allow children with hEDS and their caregivers to share challenges faced, effective coping strategies, and their readiness to engage in a self-management approach to treatment. As caregivers are frequently proxy reporters for their child’s experience, concordance between caregiver and child was assessed for each variable. Additionally, child outcomes were assessed in relation to caregiver–child concordance on readiness to engage in self-management. Results: Results suggest moderate concordance across dyads, with many dyads agreeing on the challenges presented by the physical consequences of hEDS but differing on beliefs regarding coping. There were small effect sizes indicating better child psychosocial functioning when dyads were concordant on readiness to engage in self-management. Conclusion: When making treatment recommendations, practitioners should consider differences and similarities between caregivers and children’s reported experiences with and beliefs about hEDS. Further, practitioner facilitation of family concordance on beliefs about hEDS may result in better outcomes for the child.

Implications for Impact Statement

This study suggests that youth with hypermobile Ehlers-Danlos Syndrome (hEDS) and their caregivers tend to agree on the challenges hEDS presents, and their readiness to change their coping approach. However, they differ slightly in their go-to coping strategies. Thus, practitioners are encouraged to recognize where similarities and differences exist across caregiver and child experiences with and beliefs about hEDS when making treatment recommendations and to facilitate family alignment on these beliefs.
Radiationless anapole states in on-chip photonics
Authors: Díaz-Escobar Evelyn , Bauer Thomas , Pinilla-Cienfuegos Elena , Barreda Ángela I. , Griol Amadeu , Kuipers L. , Martínez Alejandro
Published: October 2021

High-index nanoparticles are known to support radiationless states called anapoles, where dipolar and toroidal moments interfere to inhibit scattering to the far field. In order to exploit the striking properties arising from these interference conditions in photonic integrated circuits, the particles must be driven in-plane via integrated waveguides. Here, we address the excitation of electric anapole states in silicon disks when excited on-chip at telecom wavelengths. In contrast to normal illumination, we find that the anapole condition—identified by a strong reduction of the scattering—does not overlap with the near-field energy maximum, an observation attributed to retardation effects. We experimentally verify the two distinct spectral regions in individual disks illuminated in-plane from closely placed waveguide terminations via far-field and near-field measurements. Our finding has important consequences concerning the use of anapole states and interference effects of other Mie-type resonances in high-index nanoparticles for building complex photonic integrated circuitry.
Prediction of insulin treatment in women with gestational diabetes mellitus
Authors: Eleftheriades Makarios , Chatzakis Christos , Papachatzopoulou Eftychia , Papadopoulos Vassilis , Lambrinoudaki Irene , Dinas Konstantinos , Chrousos George , Sotiriadis Alexandros
Published: October 2021

Introduction

The identification of pregnant women with Gestational Diabetes Mellitus (GDM) who will require insulin therapy, may modify their management to closer monitoring and probable early interventions. The aim of the study was to develop a predictive model for the necessity of insulin treatment in women with GDM.

Materials and methods

This was a prospective cohort study. Data from 775 women diagnosed with GDM per the IADPSG criteria were analyzed using logistic regression and a machine learning algorithm, the Classification and Regression Trees (CART). Potential predictors routinely recorded at follow-up visits were tested and used for the development of the model. The resultant model was externally validated using the data from two different perinatology clinics.

Results

Preconceptional maternal BMI and morning fasting blood glucose levels at baseline and at 1 h during an Oral Glucose Tolerance Test (OGTT) were independent significant predictors for the treatment modality of GDM. Baseline blood glucose greater than 98 mg/dl and preconceptional maternal Body Mass Index (BMI) between 26 and 31 kg/height2 increased substantially the probability of insulin therapy (odds ratio [OR] 4.04, 95% confidence interval [CI] CI 2.65–6.17 and 2.21, 95%CI 1.42–3.43, respectively). The area under the curve (AUC) for the internal and external validation of the predictive model was 0.74 and 0.77, respectively.

Conclusions

A simple model based on maternal characteristics and the values of an OGTT can predict the need for insulin treatment with accuracy. Overweight women with an abnormal baseline blood glucose at OGTT are at high likelihood for insulin treatment.

Key message

Fifteen to 30% of women with Gestational Diabetes Mellitus (GDM) require insulin therapy. Overweight women with baseline blood glucose greater than 98 mg/dl at OGTT are at increased risk for insulin treatment and close monitoring and increased physical exercise are required.
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task
Authors: de Cates Angharad N. , Wright Lucy C. , Martens Marieke A. G. , Gibson Daisy , Türkmen Cagdas , Filippini Nicola , Cowen Philip J. , Harmer Catherine J. , Murphy Susannah E.
Published: October 2021

Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.
Mental health status and quality of life in close contacts of COVID-19 patients in the post-COVID-19 era: a comparative study
Authors: Zhao Yan-Jie , Zhang Shu-Fang , Li Wen , Zhang Ling , Cheung Teris , Tang Yi-Lang , Ng Chee H. , Yang Bing-Xiang , Xiang Yu-Tao
Published: October 2021

Close contacts of those with COVID-19 (CC) may experience distress and long-lasting mental health effects. However, the mental health status and quality of life (QOL) in CC have not been adequately examined. This study examined the mental health status and QOL in CC during the post-COVID-19 period. This cross-sectional study comprised 1169 CC and 1290 who were non-close contacts (non-CC). Demographic data were collected; depression, fatigue, post-traumatic stress symptoms (PTSS) and QOL were assessed using the Patient Health Questionnaire - 9 items (PHQ-9), fatigue numeric rating scale, Post-Traumatic Stress Disorder Checklist - 17 items (PCL-17), and the World Health Organization Quality of Life Questionnaire - brief version (WHOQOL-BREF), respectively. Analysis of covariance was used to compare depressive symptoms, QOL, fatigue, and PTSS between the CC and non-CC groups. Multiple logistic regression analyses were performed to determine the independent correlates for depression, fatigue, PTSS, and QOL in the CC group. Compared to the non-CC group, the CC group reported significantly more severe depression (F(1, 2458) = 5.58, p = 0.018) and fatigue (F(1, 2458) = 9.22, p = 0.002) in the post-COVID-19 period. No significant differences in PTSS and QOL between the CC and non-CC groups were found (F(1, 2458) = 2.93, p = 0.087 for PTSS; F(1, 2458) = 3.45, p = 0.064 for QOL). In the CC group, younger age, financial loss due to COVID-19, and perception of poor or fair health status were significantly associated with depression and fatigue, while frequent use of mass media was significantly associated with fatigue. In conclusion, close contacts of COVID-19 patients experienced high levels of depression and fatigue in the post-COVID-19 period. Due to the negative effects of depression and fatigue on daily functioning, early detection and timely interventions should be provided to this neglected population.
B-cell depletion abrogates immune mediated cytopenia and rejection of cord blood transplantation in Hurler syndrome
Authors: Nataraj R. , Hiwarkar P. , Bonney D. , Campbell H. , Jones S. , Deambrosis D. , Evans P. , Poulton K. , van Hasselt P. M. , Bierings MB. , Boelens J. J. , Lindemans C. A. , Wynn R.
Published: October 2021

Umbilical cord blood is the preferred donor cell source for children with Inherited Metabolic disorders undergoing Hematopoietic Cell Transplant (HCT), and its use has been associated with improved “engrafted survival” and higher donor chimerism compared to other cell sources. However, as in other pediatric cord blood transplants for non-malignant disease, immune-mediated cytopenia and primary graft failure limit its use, and the latter remains the commonest cause of death following cord blood transplant for non-malignant disease. We have previously shown an association between immune-mediated cytopenia and graft failure in inherited metabolic diseases suggesting that both immune-mediated cytopenia and graft failure could be mediated by antibodies from the residual recipient B cells. Since rituximab is effective in depletion of B cells and management of refractory immune-mediated cytopenia following HCT, we have added rituximab to the conditioning regimen. We studied 57 patients in 2 centers who received myeloablative conditioning for cord blood transplant in Hurler syndrome, and report a significant improvement in event-free survival with reduced incidence of graft failure and without any evidence of immune-mediated cytopenia in those patients that had received rituximab.
TGF-β-induced PLEK2 promotes metastasis and chemoresistance in oesophageal squamous cell carcinoma by regulating LCN2
Authors: Wang Feng , Zhang Chaoqi , Cheng Hong , Liu Chengming , Lu Zhiliang , Zheng Sufei , Wang Sihui , Sun Nan , He Jie
Published: October 2021

Oesophageal squamous cell carcinoma (ESCC) has a relatively unfavourable prognosis due to metastasis and chemoresistance. Our previous research established a comprehensive ESCC database (GSE53625). After analysing data from TCGA database and GSE53625, we found that PLEK2 predicted poor prognosis in ESCC. Moreover, PLEK2 expression was also related to the overall survival of ESCC patients undergoing chemotherapy. Repression of PLEK2 decreased the proliferation, migration, invasion and chemoresistance of ESCC cells in vitro and decreased tumorigenicity and distant metastasis in vivo. Mechanistically, luciferase reporter assay and chromatin immunoprecipitation assay suggested that TGF-β stimulated the process that Smad2/3 binds to the promoter sequences of PLEK2 and induced its expression. RNA-seq suggested LCN2 might a key molecular regulated by PLEK2. LCN2 overexpression in PLEK2 knockdown ESCC cells reversed the effects of decreased migration and invasion. In addition, TGF-β induced the expression of LCN2, but the effect disappeared when PLEK2 was knockdown. Moreover, AKT was phosphorylated in all regulatory processes. This study detected the major role of PLEK2 in driving metastasis and chemoresistance in ESCC by regulating LCN2, which indicates the potential use of PLEK2 as a biomarker to predict prognosis and as a therapeutic target for ESCC.
Metformin sensitises hepatocarcinoma cells to methotrexate by targeting dihydrofolate reductase
Authors: Wang Yinghui , Lu Hui , Sun Linchong , Chen Xin , Wei Haoran , Suo Caixia , Feng Junru , Yuan Mengqiu , Shen Shengqi , Jia Weidong , Wang Ying , Zhang Huafeng , Li Zijun , Zhong Xiuying , Gao Ping
Published: October 2021

Metformin, the first-line drug for type II diabetes, has recently been considered an anticancer agent. However, the molecular target and underlying mechanism of metformin’s anti-cancer effects remain largely unclear. Herein, we report that metformin treatment increases the sensitivity of hepatocarcinoma cells to methotrexate (MTX) by suppressing the expression of the one-carbon metabolism enzyme DHFR. We show that the combination of metformin and MTX blocks nucleotide metabolism and thus effectively inhibits cell cycle progression and tumorigenesis. Mechanistically, metformin not only transcriptionally represses DHFR via E2F4 but also promotes lysosomal degradation of the DHFR protein. Notably, metformin dramatically increases the response of patient-derived hepatocarcinoma organoids to MTX without obvious toxicity to organoids derived from normal liver tissue. Taken together, our findings identify an important role for DHFR in the suppressive effects of metformin on therapeutic resistance, thus revealing a therapeutically targetable potential vulnerability in hepatocarcinoma.
Severe cellular stress activates apoptosis independently of p53 in osteosarcoma
Authors: Ho Cheng-Jung , Ko Huey-Jiun , Liao Tzu-Shao , Zheng Xiang-Ren , Chou Po-Hsu , Wang Li-Ting , Lin Ru-Wei , Chen Chung-Hwan , Wang Chihuei
Published: October 2021

Apoptosis induced by doxorubicin, bortezomib, or paclitaxel, targeting DNA, 26S proteasome, and microtubules respectively, was assessed in two osteosarcoma cells, p53 wild-type U2OS and p53-null MG63 cells. Doxorubicin-induced apoptosis only occurred in U2OS, not in MG63. In contrast, bortezomib and paclitaxel could drive U2OS or MG63 toward apoptosis effectively, suggesting that apoptosis induced by bortezomib or paclitaxel is p53-independent. The expressions of Bcl2 family members such as Bcl2, Bcl-xl, and Puma could be seen in U2OS and MG63 cells with or without doxorubicin, bortezomib, or paclitaxel treatment. In contrast, another member, Bim, only could be observed in U2OS, not in MG63, under the same conditions. Bim knockdown did not affect the doxorubicin-induced apoptosis in U2OS, suggested that a BH3-only protein other than Bim might participate in apoptosis induced by doxorubicin. Using a BH3-mimetic, ABT-263, to inhibit Bcl2 or Bcl-xl produced a limited apoptotic response in U2OS and MG63 cells, suggesting that this BH3-mimetic cannot activate the Bax/Bak pathway efficiently. Significantly, ABT-263 enhanced doxorubicin- and bortezomib-induced apoptosis synergistically in U2OS and MG63 cells. These results implied that the severe cellular stress caused by doxorubicin or bortezomib might be mediated through a dual process to control apoptosis. Respectively, doxorubicin or bortezomib activates a BH3-only protein in one way and corresponding unknown factors in another way to affect mitochondrial outer membrane permeability, resulting in apoptosis. The combination of doxorubicin with ABT-263 could produce synergistic apoptosis in MG63 cells, which lack p53, suggesting that p53 has no role in doxorubicin-induced apoptosis in osteosarcoma. In addition, ABT-263 enhanced paclitaxel to induce moderate levels of apoptosis.
miR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE
Authors: Yang Yan , Lin Zeyang , Han Zhaopu , Wu Zhengxin , Hua Jianyu , Zhong Rui , Zhao Ruidan , Ran Honggang , Qu Kaiyong , Huang Hongfei , Tang Huamei , Huang Jiyi , Liu Zhongchen , Hong Xuehui , Peng Zhihai , Zhuang Guohong
Published: October 2021

Colorectal cancer (CRC) is a common tumor that harms human health with a high recurrence rate. It has been reported that the expression of microRNA-539 (miR-539) is low in several types of cancer, including CRC. Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) is highly expressed in CRC and promotes the proliferation, migration and angiogenesis of CRC. However, the relationship between miR-539 and TIPE and the mechanisms by which they regulate the proliferation of CRC remain to be explored. We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC.
ERRFI1 induces apoptosis of hepatocellular carcinoma cells in response to tryptophan deficiency
Authors: Cui Mingqing , Liu Dan , Xiong Wujun , Wang Yugang , Mi Jun
Published: October 2021

Tryptophan metabolism is an essential regulator of tumor immune evasion. However, the effect of tryptophan metabolism on cancer cells remains largely unknown. Here, we find that tumor cells have distinct responses to tryptophan deficiency in terms of cell growth, no matter hepatocellular carcinoma (HCC) cells, lung cancer cells, or breast cancer cells. Further study shows that ERRFI1 is upregulated in sensitive HCC cells, but not in resistant HCC cells, in response to tryptophan deficiency, and ERRFI1 expression level positively correlates with HCC patient overall survival. ERRFI1 knockdown recovers tryptophan deficiency-suppressed cell growth of sensitive HCC cells. In contrast, ERRFI1 overexpression sensitizes resistant HCC cells to tryptophan deficiency. Moreover, ERRFI1 induces apoptosis by binding PDCD2 in HCC cells, PDCD2 knockdown decreases the ERRFI1-induced apoptosis in HCC cells. Thus, we conclude that ERRFI1-induced apoptosis increases the sensitivity of HCC cells to tryptophan deficiency and ERRFI1 interacts with PDCD2 to induce apoptosis in HCC cells.
The ethical landscape(s) of non-invasive prenatal testing in England, France and Germany: findings from a comparative literature review
Authors: Perrot Adeline , Horn Ruth
Published: October 2021

Since 2019, England, France and Germany have started offering NIPT as a publicly funded second-tier test for common chromosomal aneuploidies (trisomy 21, 18 and/or 13). Despite these benefits, the introduction of NIPT into routine prenatal care also raises a number of ethical concerns. In this paper, we analyse how these issues are discussed differently across countries, echoing the different socio-political particularities and value-systems that shape the use and regulation of NIPT in a specific country. The international comparison between England, France and Germany shows how each country defines the principle of reproductive autonomy and weighs it against other principles and values, such as, human dignity, disability rights and the duty of care of health professionals. In terms of methodology, our literature review focuses on arguments and regulations of prenatal testing and reproductive choices (specifically on NIPT), through the investigation of regulatory, parliamentary, scientific, medical, association, institutional and media sources. The comparative review helps to better understand ethical questions discussed with regard to NIPT, and, more broadly, to prenatal genomic testing, and the limits associated with reproductive autonomy in the three countries studied. Whereas reproductive autonomy is valued in each country, it is understood and implemented differently depending on the socio-cultural context, and on what other principles are evoked and how they are defined.
A moisture-tolerant route to unprotected α/β-amino acid N-carboxyanhydrides and facile synthesis of hyperbranched polypeptides
Authors: Tian Zi-You , Zhang Zhengchu , Wang Shuo , Lu Hua
Published: October 2021

A great hurdle in the production of synthetic polypeptides lies in the access of N-carboxyanhydrides (NCA) monomers, which requires dry solvents, Schlenk line/gloveboxe, and protection of side-chain functional groups. Here we report a robust method for preparing unprotected NCA monomers in air and under moisture. The method employs epoxy compounds as ultra-fast scavengers of hydrogen chloride to allow assisted ring-closure and prevent NCA from acid-catalyzed decomposition under moist conditions. The broad scope and functional group tolerance of the method are demonstrated by the facile synthesis of over 30 different α/β-amino acid NCAs, including many otherwise inaccessible compounds with reactive functional groups, at high yield, high purity, and up to decagram scales. The utility of the method and the unprotected NCAs is demonstrated by the facile synthesis of two water-soluble polypeptides that are promising candidates for drug delivery and protein modification. Overall, our strategy holds great potential for facilitating the synthesis of NCA and expanding the industrial application of synthetic polypeptides.
Thermally active nanoparticle clusters enslaved by engineered domain wall traps
Authors: Tierno Pietro , Johansen Tom H. , Straube Arthur V.
Published: October 2021

The stable assembly of fluctuating nanoparticle clusters on a surface represents a technological challenge of widespread interest for both fundamental and applied research. Here we demonstrate a technique to stably confine in two dimensions clusters of interacting nanoparticles via size-tunable, virtual magnetic traps. We use cylindrical Bloch walls arranged to form a triangular lattice of ferromagnetic domains within an epitaxially grown ferrite garnet film. At each domain, the magnetic stray field generates an effective harmonic potential with a field tunable stiffness. The experiments are combined with theory to show that the magnetic confinement is effectively harmonic and pairwise interactions are of dipolar nature, leading to central, strictly repulsive forces. For clusters of magnetic nanoparticles, the stationary collective states arise from the competition between repulsion, confinement and the tendency to fill the central potential well. Using a numerical simulation model as a quantitative map between the experiments and theory we explore the field-induced crystallization process for larger clusters and unveil the existence of three different dynamical regimes. The present method provides a model platform for investigations of the collective phenomena emerging when strongly confined nanoparticle clusters are forced to move in an idealized, harmonic-like potential.
Orchestrating and sharing large multimodal data for transparent and reproducible research
Authors: Mammoliti Anthony , Smirnov Petr , Nakano Minoru , Safikhani Zhaleh , Eeles Christopher , Seo Heewon , Nair Sisira Kadambat , Mer Arvind S. , Smith Ian , Ho Chantal , Beri Gangesh , Kusko Rebecca ,   Massive Analysis Quality Control (MAQC) Society Board of Directors, Shraddha Thakkar , Sansone Susanna-Assunta , Tong Weida , Wolfinger Russ D. , Mason Christopher E. , Jones Wendell , Dopazo Joaquin , Furlanello Cesare , Lin Eva , Yu Yihong , Martin Scott , Hafner Marc , Haibe-Kains Benjamin
Published: October 2021

Reproducibility is essential to open science, as there is limited relevance for findings that can not be reproduced by independent research groups, regardless of its validity. It is therefore crucial for scientists to describe their experiments in sufficient detail so they can be reproduced, scrutinized, challenged, and built upon. However, the intrinsic complexity and continuous growth of biomedical data makes it increasingly difficult to process, analyze, and share with the community in a FAIR (findable, accessible, interoperable, and reusable) manner. To overcome these issues, we created a cloud-based platform called ORCESTRA (orcestra.ca), which provides a flexible framework for the reproducible processing of multimodal biomedical data. It enables processing of clinical, genomic and perturbation profiles of cancer samples through automated processing pipelines that are user-customizable. ORCESTRA creates integrated and fully documented data objects with persistent identifiers (DOI) and manages multiple dataset versions, which can be shared for future studies.
Phonon-induced disorder in dynamics of optically pumped metals from nonlinear electron-phonon coupling
Authors: Sous John , Kloss Benedikt , Kennes Dante M. , Reichman David R. , Millis Andrew J.
Published: October 2021

The non-equilibrium dynamics of matter excited by light may produce electronic phases, such as laser-induced high-transition-temperature superconductivity, that do not exist in equilibrium. Here we simulate the dynamics of a metal driven at initial time by a spatially uniform pump that excites dipole-active vibrational modes which couple nonlinearly to electrons. We provide evidence for rapid loss of spatial coherence, leading to emergent effective disorder in the dynamics, which arises in a system unitarily evolving under a translation-invariant Hamiltonian, and dominates the electronic behavior as the system evolves towards a correlated electron-phonon long-time state, possibly explaining why transient superconductivity is not observed. Our framework provides a basis within which to understand correlation dynamics in current pump-probe experiments of vibrationally coupled electrons, highlight the importance of the evolution of phase coherence, and demonstrate that pumped electron-phonon systems provide a means of realizing dynamically induced disorder in translation-invariant systems.
Urban mining by flash Joule heating
Authors: Deng Bing , Luong Duy Xuan , Wang Zhe , Kittrell Carter , McHugh Emily A. , Tour James M.
Published: October 2021

Precious metal recovery from electronic waste, termed urban mining, is important for a circular economy. Present methods for urban mining, mainly smelting and leaching, suffer from lengthy purification processes and negative environmental impacts. Here, a solvent-free and sustainable process by flash Joule heating is disclosed to recover precious metals and remove hazardous heavy metals in electronic waste within one second. The sample temperature ramps to ~3400 K in milliseconds by the ultrafast electrical thermal process. Such a high temperature enables the evaporative separation of precious metals from the supporting matrices, with the recovery yields >80% for Rh, Pd, Ag, and >60% for Au. The heavy metals in electronic waste, some of which are highly toxic including Cr, As, Cd, Hg, and Pb, are also removed, leaving a final waste with minimal metal content, acceptable even for agriculture soil levels. Urban mining by flash Joule heating would be 80× to 500× less energy consumptive than using traditional smelting furnaces for metal-component recovery and more environmentally friendly.
An energy-efficient pathway to turbulent drag reduction
Authors: Marusic Ivan , Chandran Dileep , Rouhi Amirreza , Fu Matt K. , Wine David , Holloway Brian , Chung Daniel , Smits Alexander J.
Published: October 2021

Simulations and experiments at low Reynolds numbers have suggested that skin-friction drag generated by turbulent fluid flow over a surface can be decreased by oscillatory motion in the surface, with the amount of drag reduction predicted to decline with increasing Reynolds number. Here, we report direct measurements of substantial drag reduction achieved by using spanwise surface oscillations at high friction Reynolds numbers ($${{{\mathrm{Re}}}_{\tau }}$$

Re

τ

) up to 12,800. The drag reduction occurs via two distinct physical pathways. The first pathway, as studied previously, involves actuating the surface at frequencies comparable to those of the small-scale eddies that dominate turbulence near the surface. We show that this strategy leads to drag reduction levels up to 25% at $${{{{{{{{\mathrm{Re}}}}}}}}}_{\tau }$$

Re

τ

= 6,000, but with a power cost that exceeds any drag-reduction savings. The second pathway is new, and it involves actuation at frequencies comparable to those of the large-scale eddies farther from the surface. This alternate pathway produces drag reduction of 13% at $${{{{{{{{\mathrm{Re}}}}}}}}}_{\tau }$$

Re

τ

= 12,800. It requires significantly less power and the drag reduction grows with Reynolds number, thereby opening up potential new avenues for reducing fuel consumption by transport vehicles and increasing power generation by wind turbines.
Designing small organic non-fullerene acceptor molecules with diflorobenzene or quinoline core and dithiophene donor moiety through density functional theory
Authors: Bary Ghulam , Ghani Lubna , Jamil Muhammad Imran , Arslan Muhammad , Ahmed Waqar , Ahmad Anees , Sajid Muhammad , Ahmad Riaz , Huang Duohui
Published: October 2021

The non-fullerene acceptors A1–A5 with diflourobenzene or quinoline core (bridge) unit, donor cyclopenta[1,2-b:3,4-b′]dithiophene unit and 2-(2-methylene-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile as acceptor unit with additional phenyl, fulvene or thieno[3,2-d]pyrimidinyl 5-oxide groups have been designed through DFT calculations. The optimization of molecular geometries were performed with density functional theory (DFT) at B3LYP 6-31G (d,p) level of theory. The frontier molecular orbital (FMO) energies, band gap energies and dipole moments (ground and excited state) have been calculated to probe the photovoltaic properties. The band gap (1.42–2.01 eV) and dipole moment values (5.5–18. Debye) showed that these designed acceptors are good candidates for organic solar cells. Time-Dependent Density Functional Theory (TD-DFT) results showed λmax (wave length at maximum absorption) value (611–837 nm), oscillator strength (f) and excitation energies (1.50–2.02 eV) in gas phase and in CHCl3 solvent (1.48–1.89 eV) using integral equation formalism variant (IEFPCM) model. The λmax in CHCl3 showed marginal red shift for all designed acceptors compared with gas phase absorption. The partial density of states (PDOS) has been plotted by using multiwfn which showed that all the designed molecules have more electronic distribution at the donor moiety and lowest at the central bridge. The reorganization energies of electron (λe) (0.0007 eV to 0.017 eV), and the hole reorganization energy values (0.0003 eV to − 0.0403 eV) were smaller which suggested that higher charged motilities. The blends of acceptors A1–A5 with donor polymer D1 provided open circuit voltage (Voc) and ∆HOMO off-set of the HOMO of donor and acceptors. These blends showed 1.04 to 1.5 eV values of Voc and 0 to 0.38 eV ∆HOMO off set values of the donor–acceptor bends which indicate improved performance of the cell. Finally, the blend of D1–A4 was used for the study of distribution of HOMO and LUMO. The HOMO were found distributed on the donor polymer (D1) while the A4 acceptor was found with LUMO distribution. Based on λmax values, and band gap energies (Eg), excitation energies (Ex), reorganization energies; the A3 and A4 will prove good acceptor molecules for the development of organic solar cells.
Enzyme modification using mutation site prediction method for enhancing the regioselectivity of substrate reaction sites
Authors: Ikebe Jinzen , Suzuki Munenori , Komori Aya , Kobayashi Kaito , Kameda Tomoshi
Published: October 2021

Enzymes with low regioselectivity of substrate reaction sites may produce multiple products from a single substrate. When a target product is produced industrially using these enzymes, the production of non-target products (byproducts) causes adverse effects such as increased processing costs for purification and the amount of raw material. Thus it is required the development of modified enzymes to reduce the amount of byproducts’ production. In this paper, we report a method called mutation site prediction for enhancing the regioselectivity of substrate reaction sites (MSPER). MSPER takes conformational data for docking poses of an enzyme and a substrate as input and automatically generates a ranked list of mutation sites to destabilize docking poses for byproducts while maintaining those for target products in silico. We applied MSPER to the enzyme cytochrome P450 CYP102A1 (BM3) and the two substrates to enhance the regioselectivity for four target products with different reaction sites. The 13 of the total 14 top-ranked mutation sites predicted by MSPER for the four target products succeeded in selectively enhancing the regioselectivity up to 6.4-fold. The results indicate that MSPER can distinguish differences of substrate structures and the reaction sites, and can accurately predict mutation sites to enhance regioselectivity without selection by directed evolution screening.
Sensory integration abilities for balance in glaucoma, a preliminary study
Authors: O’Connell Caitlin , Redfern Mark , Chan Kevin C. , Wollstein Gadi , Conner Ian P. , Cham Rakié
Published: October 2021

The goal of this study was to quantify the association between sensory integration abilities relevant for standing balance and disease stage in glaucoma. The disease stage was assessed using both functional (visual field deficit) and structural (retinal nerve fiber layer thickness) deficits in the better and worse eye. Balance was assessed using an adapted version of the well-established Sensory Organization Test (SOT). Eleven subjects diagnosed with mild to moderate glaucoma stood for 3 min in 6 sensory challenging postural conditions. Balance was assessed using sway magnitude and sway speed computed based on center-of-pressure data. Mixed linear regression analyses were used to investigate the associations between glaucoma severity and balance measures. Findings revealed that the visual field deficit severity in the better eye was associated with increased standing sway speed. This finding was confirmed in eyes open and closed conditions. Balance was not affected by the extent of the visual field deficit in the worse eye. Similarly, structural damage in either eye was not associated with the balance measures. In summary, this study found that postural control performance was associated with visual field deficit severity. The fact that this was found during eyes closed as well suggests that reduced postural control in glaucoma is not entirely attributed to impaired peripheral visual inputs. A larger study is needed to further investigate potential interactions between visual changes and central processing changes contributing to reduced balance function and increased incidence of falls in adults with glaucoma.
Spotlight onto surfactant–steam–bitumen interfacial behavior via molecular dynamics simulation
Authors: Ahmadi Mohammadali , Chen Zhangxin
Published: October 2021

Heavy oil and bitumen play a vital role in the global energy supply, and to unlock such resources, thermal methods, e.g., steam injection, are applied. To improve the performance of these methods, different additives, such as air, solvents, and chemicals, can be used. As a subset of chemicals, surfactants are one of the potential additives for steam-based bitumen recovery methods. Molecular interactions between surfactant/steam/bitumen have not been addressed in the literature. This paper investigates molecular interactions between anionic surfactants, steam, and bitumen in high-temperature and high-pressure conditions. For this purpose, a real Athabasca oil sand composition is employed to assess the phase behavior of surfactant/steam/bitumen under in-situ steam-based bitumen recovery. Two different asphaltene architectures, archipelago and Island, are used to examine the effect of asphaltene type on bitumen's interfacial behavior. The influence of having sulfur heteroatoms in a resin structure and a benzene ring's effect in an anionic surfactant structure on surfactant–steam–bitumen interactions are investigated systematically. The outputs are supported by different analyses, including radial distribution functions (RDFs), mean squared displacement (MSD), radius of gyration, self-diffusion coefficient, solvent accessible surface area (SASA), interfacial thickness, and interaction energies. According to MD outputs, adding surfactant molecules to the steam phase improved the interaction energy between steam and bitumen. Moreover, surfactants can significantly improve steam emulsification capability by decreasing the interfacial tension (IFT) between bitumen and the steam phase. Asphaltene architecture has a considerable effect on the interfacial behavior in such systems. This study provides a better and more in-depth understanding of surfactant–steam–bitumen systems and spotlights the interactions between bitumen fractions and surfactant molecules under thermal recovery conditions.
NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
Authors: Tomioka Keita , Miyamoto Tatsuo , Akutsu Silvia Natsuko , Yanagihara Hiromi , Fujita Kazumasa , Royba Ekaterina , Tauchi Hiroshi , Yamamoto Takashi , Koh Iemasa , Hirata Eiji , Kudo Yoshiki , Kobayashi Masao , Okada Satoshi , Matsuura Shinya
Published: October 2021

Genetic information is protected against a variety of genotoxins including ionizing radiation (IR) through the DNA double-strand break (DSB) repair machinery. Genome-wide association studies and clinical sequencing of cancer patients have suggested that a number of variants in the DNA DSB repair genes might underlie individual differences in chromosomal radiosensitivity within human populations. However, the number of established variants that directly affect radiosensitivity is still limited. In this study, we performed whole-exome sequencing of 29 Japanese ovarian cancer patients and detected the NBS1 I171V variant, which is estimated to exist at a rate of approximately 0.15% in healthy human populations, in one patient. To clarify whether this variant indeed contributes to chromosomal radiosensitivity, we generated NBS1 I171V variant homozygous knock-in HCT116 cells and mice using the CRISPR/Cas9 system. Radiation-induced micronucleus formation and chromosomal aberration frequency were significantly increased in both HCT116 cells and mouse embryonic fibroblasts (MEFs) with knock-in of the NBS1 I171V variant compared with the levels in wild-type cells. These results suggested that the NBS1 I171V variant might be a genetic factor underlying individual differences in chromosomal radiosensitivity.
Soil microbiota and microarthropod communities in oil contaminated sites in the European Subarctic
Authors: Melekhina E. N. , Belykh E. S. , Markarova M. Yu. , Taskaeva A. A. , Rasova E. E. , Baturina O. A. , Kabilov M. R. , Velegzhaninov I. O.
Published: October 2021

The present comprehensive study aimed to estimate the aftermath of oil contamination and the efficacy of removing the upper level of polluted soil under the conditions of the extreme northern taiga of northeastern European Russia. Soil samples from three sites were studied. Two sites were contaminated with the contents of a nearby sludge collector five years prior to sampling. The highly contaminated upper soil level was removed from one of them. The other was left for self-restoration. A chemical analysis of the soils was conducted, and changes in the composition of the soil zoocoenosis and bacterial and fungal microbiota were investigated. At both contaminated sites, a decrease in the abundance and taxonomic diversity of indicator groups of soil fauna, oribatid mites and collembolans compared to the background site were found. The pioneer eurytopic species Oppiella nova, Proisotoma minima and Xenyllodes armatus formed the basis of the microarthropod populations in the contaminated soil. A complete change in the composition of dominant taxonomic units was observed in the microbiota, both the bacterial and fungal communities. There was an increase in the proportion of representatives of Proteobacteria and Actinobacteria in polluted soils compared to the background community. Hydrocarbon-degrading bacteria—Alcanivorax, Rhodanobacter ginsengisoli, Acidobacterium capsulatum, and Acidocella—and fungi—Amorphotheca resinae abundances greatly increased in oil-contaminated soil. Moreover, among both bacteria and fungi, a sharp increase in the abundance of uncultivated organisms that deserve additional attention as potential oil degraders or organisms with a high resistance to oil contamination were observed. The removal of the upper soil level was partly effective in terms of decreasing the oil product concentration (from approximately 21 to 2.6 g/kg of soil) and preventing a decrease in taxonomic richness but did not prevent alterations in the composition of the microbiota or zoocoenosis.
Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections
Authors: Heemskerk M. T. , Korbee C. J. , Esselink J. J. , dos Santos C. Carvalho , van Veen S. , Gordijn I. F. , Vrieling F. , Walburg K. V. , Engele C. G. , Dijkman K. , Wilson L. , Verreck F. A. W. , Ottenhoff T. H. M. , Haks M. C.
Published: October 2021

The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria. Several active compounds were identified, including two drugs of the diphenylbutylpiperidine-class, Fluspirilene and Pimozide, commonly used as antipsychotics. Both molecules inhibited intracellular Mtb in pro- as well as anti-inflammatory primary human macrophages in a host-directed manner and synergized with conventional anti-bacterials. Importantly, these inhibitory effects extended to MDR-Mtb strains and the unrelated intracellular pathogen, Salmonella enterica serovar Typhimurium (Stm). Mechanistically Fluspirilene and Pimozide were shown to regulate autophagy and alter the lysosomal response, partly correlating with increased bacterial localization to autophago(lyso)somes. Pimozide’s and Fluspirilene’s efficacy was inhibited by antioxidants, suggesting involvement of the oxidative-stress response in Mtb growth control. Furthermore, Fluspirilene and especially Pimozide counteracted Mtb-induced STAT5 phosphorylation, thereby reducing Mtb phagosome-localized CISH that promotes phagosomal acidification. In conclusion, two approved antipsychotic drugs, Pimozide and Fluspirilene, constitute highly promising and rapidly translatable candidates for HDT against Mtb and Stm and act by modulating the autophagic/lysosomal response by multiple mechanisms.
Specialization of a mobile, apex predator affects trophic coupling among adjacent habitats
Authors: Cloyed Carl S. , Wilson Rachel M. , Balmer Brian C. , Hohn Aleta A. , Schwacke Lori H. , Zolman Eric S. , Tumlin Mandy C. , Wells Randall S. , Barleycorn Aaron A. , Allen Jason B. , Carmichael Ruth H.
Published: October 2021

Mobile, apex predators are commonly assumed to stabilize food webs through trophic coupling across spatially distinct habitats. The assumption that trophic coupling is common remains largely untested, despite evidence that individual behaviors might limit trophic coupling. We used stable isotope data from common bottlenose dolphins across the Gulf of Mexico to determine if these apex predators coupled estuarine and adjacent, nearshore marine habitats. δ13C values differed among the sites, likely driven by environmental factors that varied at each site, such as freshwater input and seagrass cover. Within most sites, δ13C values differed such that dolphins sampled in the upper reaches of embayments had values indicative of estuarine habitats while those sampled outside or in lower reaches of embayments had values indicative of marine habitats. δ15N values were more similar among and within sites than δ13C values. Data from multiple tissues within individuals corroborated that most dolphins consistently used a narrow range of habitats but fed at similar trophic levels in estuarine and marine habitats. Because these dolphins exhibited individual habitat specialization, they likely do not contribute to trophic coupling between estuarine and adjacent marine habitats at a regional scale, suggesting that not all mobile, apex predators trophically couple adjacent habitats.
Prediction of habitat suitability for Patrinia sibirica Juss. in the Southern Urals
Authors: Fedorov Nikolai , Kutueva Aliya , Muldashev Albert , Mikhaylenko Oksana , Martynenko Vasiliy , Fedorova Yulia
Published: October 2021

The paper presents the results of predictions of the habitat persistence for rare relict of the Pleistocene floristic complexPatrinia sibirica(L.) Juss. in the Southern Urals under various forecasted climate change scenarios. Climate variables from CHELSA BIOCLIM, elevation data (GMTED2010) and coarse fragment content in the top level of soil were used as predictors for modeling in the MaxEnt software. The impact of climate change onP. sibiricahabitats under the RCP4.5 and RCP8.5 scenarios calculated from an ensemble of four general circulation models has been analyzed. The modeling has shown that the changes in the habitat suitability depend on the altitude. Deterioration of the habitats could be attributed to a temperature increase in mountain forest locations, and to a precipitation of driest quarter increase in mountain forest-steppe locations. In both cases, this leads to the expansion of forest and shrub vegetation. Monitoring of the habitat persistence ofP. sibiricaand other relict species of the Pleistocene floristic complex can play a major role in predictions, as their massive decline would constitute that climatic changes exceed the ranges of their fluctuations in the Holocene.
Potential roles of 1,5-anhydro-d-fructose in modulating gut microbiome in mice
Authors: Ito Takashi , Totoki Takaaki , Takada Seiya , Otsuka Shotaro , Maruyama Ikuro
Published: October 2021

The gut microbiota has tremendous potential to affect the host’s health, in part by synthesizing vitamins and generating nutrients from food that is otherwise indigestible by the host. 1,5-Anhydro-d-fructose (1,5-AF) is a monosaccharide with a wide range of bioactive potentials, including anti-oxidant, anti-inflammatory, and anti-microbial effects. Based on its potential benefits and minimal toxicity, it is anticipated that 1,5-AF will be used as a dietary supplement to support general health. However, the effects of 1,5-AF on the gut microbiota are yet to be clarified. Here, using an unbiased metagenomic approach, we profiled the bacterial taxa and functional genes in the caecal microbiota of mice fed a diet containing either 2% 1,5-AF or a reference sweetener. Supplementation with 1,5-AF altered the composition of the gut microbiota, enriching the proportion of Faecalibacterium prausnitzii. 1,5-AF also altered the metabolomic profile of the gut microbiota, enriching genes associated with nicotinamide adenine dinucleotide biosynthesis. These findings support the potential benefits of 1,5-AF, but further studies are required to clarify the impact of 1,5-AF on health and disease.