bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct synthesis of nanostructured silver antimony sulfide powders from metal xanthate precursors
Authors: Alharbi Yasser T. , Alam Firoz , Salhi Abdelmajid , Missous Mohamed , Lewis David J.
Published: February 2021

Silver(I) ethylxanthate [AgS2COEt] (1) and antimony(III) ethylxanthate [Sb(S2COEt)3] (2) have been synthesised, characterised and used as precursors for the preparation of AgSbS2 powders and thin films using a solvent-free melt method and spin coating technique, respectively. The as-synthesized AgSbS2 powders were characterized by powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. The crystalline AgSbS2 powder was investigated using XRD, which shows that AgSbS2 has cuboargyrite as the dominant phase, which was also confirmed by Raman spectroscopy. SEM was also used to study the morphology of the resulting material which is potentially nanostructured. EDX spectra gives a clear indication of the presence of silver (Ag), antimony (Sb) and sulfur (S) in material, suggesting that decomposition is clean and produces high quality AgSbS2 crystalline powder, which is consistent with the XRD and Raman data. Electronic properties of AgSbS2 thin films deposited by spin coating show a p-type conductivity with measured carrier mobility of 81 cm2 V−1 s−1 and carrier concentration of 1.9 × 1015 cm−3. The findings of this study reveal a new bottom-up route to these compounds, which have potential application as absorber layers in solar cells.
C. elegans electrotaxis behavior is modulated by heat shock response and unfolded protein response signaling pathways
Authors: Taylor Shane K. B. , Minhas Muhammad H. , Tong Justin , Selvaganapathy P. Ravi , Mishra Ram K. , Gupta Bhagwati P.
Published: February 2021

The nematodeC. elegansis a leading model to investigate the mechanisms of stress-induced behavioral changes coupled with biochemical mechanisms. Our group has previously characterizedC. elegansbehavior using a microfluidic-based electrotaxis device, and showed that worms display directional motion in the presence of a mild electric field. In this study, we describe the effects of various forms of genetic and environmental stress on the electrotactic movement of animals. Using exposure to chemicals, such as paraquat and tunicamycin, as well as mitochondrial and endoplasmic reticulum (ER) unfolded protein response (UPR) mutants, we demonstrate that chronic stress causes abnormal movement.Additionally, we report thatpqe-1(human RNA exonuclease 1 homolog) is necessary for the maintenance of multiple stress response signaling and electrotaxis behavior of animals. Further, exposure ofC. elegansto several environmental stress-inducing conditions revealed that while chronic heat and dietary restriction caused electrotaxis speed deficits due to prolonged stress, daily exercise had a beneficial effect on the animals, likely due to improved muscle health and transient activation of UPR. Overall, these data demonstrate that the electrotaxis behavior of worms is susceptible to cytosolic, mitochondrial, and ER stress, and that multiple stress response pathways contribute to its preservation in the face of stressful stimuli.
Macroporous chitosan/methoxypoly(ethylene glycol) based cryosponges with unique morphology for tissue engineering applications
Authors: Kumar Pradeep , Pillay Viness , Choonara Yahya E.
Published: February 2021

Three-dimensional porous scaffolds are widely employed in tissue engineering and regenerative medicine for their ability to carry bioactives and cells; and for their platform properties to allow for bridging-the-gap within an injured tissue. This study describes the effect of various methoxypolyethylene glycol (mPEG) derivatives (mPEG (-OCH3 functionality), mPEG-aldehyde (mPEG-CHO) and mPEG-acetic acid (mPEG-COOH)) on the morphology and physical properties of chemically crosslinked, semi-interpenetrating polymer network (IPN), chitosan (CHT)/mPEG blend cryosponges. Physicochemical and molecular characterization revealed that the –CHO and –COOH functional groups in mPEG derivatives interacted with the –NH2 functionality of the chitosan chain. The distinguishing feature of the cryosponges was their unique morphological features such as fringe thread-, pebble-, curved quartz crystal-, crystal flower-; and canyon-like structures. The morphological data was well corroborated by the image processing data and physisorption curves corresponding to Type II isotherm with open hysteresis loops. Functionalization of mPEG had no evident influence on the macro-mechanical properties of the cryosponges but increased the matrix strength as determined by the rheomechanical analyses. The cryosponges were able to deliver bioactives (dexamethasone and curcumin) over 10 days, showed varied matrix degradation profiles, and supported neuronal cells on the matrix surface. In addition, in silico simulations confirmed the compatibility and molecular stability of the CHT/mPEG blend compositions. In conclusion, the study confirmed that significant morphological variations may be induced by minimal functionalization and crosslinking of biomaterials.
The power of community science to quantify ecological interactions in cities
Authors: Putman Breanna J. , Williams Riley , Li Enjie , Pauly Gregory B.
Published: February 2021

Studying animals in urban environments is especially challenging because much of the area is private property not easily accessible to professional scientists. In addition, collecting data on animals that are cryptic, secretive, or rare is also challenging due to the time and resources needed to amass an adequate dataset. Here, we show that community science can be a powerful tool to overcome these challenges. We used observations submitted to the community science platform iNaturalist to assess predation and parasitism across urbanization gradients in a secretive, ‘hard-to-study’ species, the Southern Alligator Lizard (Elgaria multicarinata). From photographs, we quantified predation risk by assessing tail injuries and quantified parasitism by counting tick loads on lizards. We found that tail injuries increased with age and with urbanization, suggesting that urban areas are risky habitats. Conversely, parasitism decreased with urbanization likely due to a loss of hosts and anti-tick medications used on human companion animals. This community science approach generated a large dataset on a secretive species rapidly and at an immense spatial scale that facilitated quantitative measures of urbanization (e.g. percent impervious surface cover) as opposed to qualitative measures (e.g. urban vs. rural). We therefore demonstrate that community science can help resolve ecological questions that otherwise would be difficult to address.
Microbial degradation of Procion Red by Pseudomonas stutzeri
Authors: Bera Sweta Parimita , Tank S. K.
Published: February 2021

The bacterium Pseudomonas stutzeri SPM-1, obtained from textile wastewater dumping sites of Surat, Gujarat was studied for the degradation of the textile azo dye Procion Red—H3B. The optimization was carried on the phenanthrene enrichment medium followed by exposing it to variable environmental factors and nutritional sources. The complete decolorization of dye (50 mg/L) happened within 20 h of incubation at pH 8 and temperature 32 ± 0.2 °C under microaerophilic conditions. Decolourization was monitored with the shifting of absorbance peak in UV–Vis spectrophotometry and HPLC analysis. The physicochemical studies of effluent before and after the treatment revealed 85%, 90%, and 65% decline in BOD, COD, and TOC levels. The strain showed significant activities of azoreductase (95%), laccase (76%), and NADH-DCIP reductase (88%) at 12 h, 10 h, and 8 h of growth respectively indicating evidence for reductive cleavage of the dye. The changes in the functional groups were confirmed by the presence of new peaks in FT-IR data. GC–MS analysis helped in recognizing the degraded dye compounds thus elucidating the proposed pathway for degradation of Procion Red—H3B. The potential of the bioremediation process was concluded by a phytotoxicity test using two plants, Vigna radiata and Cicer arietinum. Our study demonstrates that the strain Pseudomonas stutzeri SPM-1 has rapid decolorization efficiency and holds a noteworthy perspective in industrial application for textile wastewater treatment.
DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice
Authors: Szurgot Inga , Hanke Leo , Sheward Daniel J. , Vidakovics Laura Perez , Murrell Ben , McInerney Gerald M. , Liljeström Peter
Published: February 2021

The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.
Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method
Authors: Charoenkwan Phasit , Chiangjong Wararat , Lee Vannajan Sanghiran , Nantasenamat Chanin , Hasan Md. Mehedi , Shoombuatong Watshara
Published: February 2021

As anticancer peptides (ACPs) have attracted great interest for cancer treatment, several approaches based on machine learning have been proposed for ACP identification. Although existing methods have afforded high prediction accuracies, however such models are using a large number of descriptors together with complex ensemble approaches that consequently leads to low interpretability and thus poses a challenge for biologists and biochemists. Therefore, it is desirable to develop a simple, interpretable and efficient predictor for accurate ACP identification as well as providing the means for the rational design of new anticancer peptides with promising potential for clinical application. Herein, we propose a novel flexible scoring card method (FSCM) making use of propensity scores of local and global sequential information for the development of a sequence-based ACP predictor (named iACP-FSCM) for improving the prediction accuracy and model interpretability. To the best of our knowledge, iACP-FSCM represents the first sequence-based ACP predictor for rationalizing an in-depth understanding into the molecular basis for the enhancement of anticancer activities of peptides via the use of FSCM-derived propensity scores. The independent testing results showed that the iACP-FSCM provided accuracies of 0.825 and 0.910 as evaluated on the main and alternative datasets, respectively. Results from comparative benchmarking demonstrated that iACP-FSCM could outperform seven other existing ACP predictors with marked improvements of 7% and 17% for accuracy and MCC, respectively, on the main dataset. Furthermore, the iACP-FSCM (0.910) achieved very comparable results to that of the state-of-the-art ensemble model AntiCP2.0 (0.920) as evaluated on the alternative dataset. Comparative results demonstrated that iACP-FSCM was the most suitable choice for ACP identification and characterization considering its simplicity, interpretability and generalizability. It is highly anticipated that the iACP-FSCM may be a robust tool for the rapid screening and identification of promising ACPs for clinical use.
Revealing noncollinear magnetic ordering at the atomic scale via XMCD
Authors: Kielgast Fridtjof , Baev Ivan , Beeck Torben , Pressacco Federico , Martins Michael
Published: February 2021

Mass-selected V and Fe monomers, as well as the heterodimer$${\text{Fe}}_1{\text{V}}_1$$Fe1V1, were deposited on a Cu(001) surface. Their electronic and magnetic properties were investigated via X-ray absorption (XAS) and X-ray magnetic circular dichroism (XMCD) spectroscopy. Anisotropies in the magnetic moments of the deposited species could be examined by means of angle resolving XMCD, i.e. changing the X-ray angle of incidence. A weak adatom-substrate-coupling was found for both elements and, using group theoretical arguments, the ground state symmetries of the adatoms were determined. For the dimer, a switching from antiparallel to parallel orientation of the respective magnetic moments was observed. We show that this is due to the existence of a noncollinear spin-flop phase in the deposited dimers, which could be observed for the first time in such a small system. Making use of the two magnetic sublattices model, we were able to find the relative orientations for the dimer magnetic moments for different incidence angles.
The dynamics of explore–exploit decisions reveal a signal-to-noise mechanism for random exploration
Authors: Feng Samuel F. , Wang Siyu , Zarnescu Sylvia , Wilson Robert C.
Published: February 2021

Growing evidence suggests that behavioral variability plays a critical role in how humans manage the tradeoff between exploration and exploitation. In these decisions a little variability can help us to overcome the desire to exploit known rewards by encouraging us to randomly explore something else. Here we investigate how such ‘random exploration’ could be controlled using a drift-diffusion model of the explore–exploit choice. In this model, variability is controlled by either the signal-to-noise ratio with which reward is encoded (the ‘drift rate’), or the amount of information required before a decision is made (the ‘threshold’). By fitting this model to behavior, we find that while, statistically, both drift and threshold change when people randomly explore, numerically, the change in drift rate has by far the largest effect. This suggests that random exploration is primarily driven by changes in the signal-to-noise ratio with which reward information is represented in the brain.
GNSS total variometric approach: first demonstration of a tool for real-time tsunami genesis estimation
Authors: Ravanelli Michela , Occhipinti Giovanni , Savastano Giorgio , Komjathy Attila , Shume Esayas B. , Crespi Mattia
Published: February 2021

Global Navigation Satellite System (GNSS) is used in seismology to study the ground displacements as well as to monitor the ionospheric total electron content (TEC) perturbations following seismic events. The aim of this work is to combine these two observations in one real-time method based on the Total Variometric Approach (TVA) to include the GNSS real-time data stream in future warning systems and tsunami genesis estimation observing both, ground motion and TEC. Our TVA couples together the Variometric Approach for Displacement Analysis Stand-alone Engine (VADASE) with the Variometric Approach for Real-Time Ionosphere Observation (VARION) algorithms. We apply the TVA to the Mw 8.3 Illapel earthquake, that occurred in Chile on September 16, 2015, and we demonstrate the coherence of the earthquake ground shaking and the TEC perturbation by using the same GNSS data stream in a real-time scenario. Nominally, we also highlight a stronger kinetic energy released in the north of the epicenter and visible in both, the ground motion and the TEC perturbation detect at 30 s and around 9.5 min after the rupture respectively. The high spatial resolution of ionospheric TEC measurement seems to match with the extent of the seismic source. The GNSS data stream by TVA of both the ground and ionospheric measurement opens today new perspectives to real-time warning systems for tsunami genesis estimation.
Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
Authors: Halsall John A. , Andrews Simon , Krueger Felix , Rutledge Charlotte E. , Ficz Gabriella , Reik Wolf , Turner Bryan M.
Published: February 2021

Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.
Freely scalable and reconfigurable optical hardware for deep learning
Authors: Bernstein Liane , Sludds Alexander , Hamerly Ryan , Sze Vivienne , Emer Joel , Englund Dirk
Published: February 2021

As deep neural network (DNN) models grow ever-larger, they can achieve higher accuracy and solve more complex problems. This trend has been enabled by an increase in available compute power; however, efforts to continue to scale electronic processors are impeded by the costs of communication, thermal management, power delivery and clocking. To improve scalability, we propose a digital optical neural network (DONN) with intralayer optical interconnects and reconfigurable input values. The path-length-independence of optical energy consumption enables information locality between a transmitter and a large number of arbitrarily arranged receivers, which allows greater flexibility in architecture design to circumvent scaling limitations. In a proof-of-concept experiment, we demonstrate optical multicast in the classification of 500 MNIST images with a 3-layer, fully-connected network. We also analyze the energy consumption of the DONN and find that digital optical data transfer is beneficial over electronics when the spacing of computational units is on the order of $$>10\,\upmu $$

>
10

μ

m.
Deformation of the Fermi surface of a spinless two-dimensional electron gas in presence of an anisotropic Coulomb interaction potential
Authors: Ciftja Orion
Published: February 2021

We consider the stability of the circular Fermi surface of a two-dimensional electron gas system against an elliptical deformation induced by an anisotropic Coulomb interaction potential. We use the jellium approximation for the neutralizing background and treat the electrons as fully spin-polarized (spinless) particles with a constant isotropic (effective) mass. The anisotropic Coulomb interaction potential considered in this work is inspired from studies of two-dimensional electron gas systems in the quantum Hall regime. We use a Hartree–Fock procedure to obtain analytical results for two special Fermi liquid quantum electronic phases. The first one corresponds to a system with circular Fermi surface while the second one corresponds to a liquid anisotropic phase with a specific elliptical deformation of the Fermi surface that gives rise to the lowest possible potential energy of the system. The results obtained suggest that, for the most general situations, neither of these two Fermi liquid phases represent the lowest energy state of the system within the framework of the family of states considered in this work. The lowest energy phase is one with an optimal elliptical deformation whose specific value is determined by a complex interplay of many factors including the density of the system.
Pruritus is common in patients with chronic liver disease and is improved by nalfurafine hydrochloride
Authors: Yoshikawa Shuhei , Asano Takeharu , Morino Mina , Matsumoto Keita , Kashima Hitomi , Koito Yudai , Miura Takaya , Takahashi Yuko , Tsuboi Rumiko , Ishii Takehiro , Otake Haruka , Fujiwara Junichi , Sekine Masanari , Uehara Takeshi , Yuhashi Kazuhito , Matsumoto Satohiro , Asabe Shinichi , Miyatani Hiroyuki , Mashima Hirosato
Published: February 2021

Pruritus is known to be a common complication in hepatitis patients, but the exact frequency and degree are not fully elucidated. Thus, we evaluated pruritus of 450 patients with chronic liver disease at our hospital. Pruritus was observed in 240 (53%) of the patients. Pruritus was significantly associated with males (OR = 1.51, P = 0.038) and patients with alkaline phosphatase (ALP) ≥ 200 U/L (OR = 1.56, P = 0.0495) and was significantly less in HBsAg-positive patients (OR = 0.449, P = 0.004). Seasonally, there was no difference in the frequency of pruritus between summer and winter. Of the 24 refractory pruritus patients treated with nalfurafine, 17 (71%) indicated improvement of itch, which is defined as a decrease in the visual analog scale score ≥ 30 mm. Pruritus was improved by nalfurafine both during daytime and nighttime in the Kawashima’s scores evaluation. All patients who received nalfurafine exhibited improved Kawashima’s scores ≥ 1 point during the daytime or nighttime. In conclusion, pruritus occurred in > 50% of patients with chronic liver disease, and predictors of pruritus were males and ALP ≥ 200 U/L. Nalfurafine may be useful for pruritus, regardless of whether daytime or nighttime.
Risk compensation and face mask mandates during the COVID-19 pandemic
Authors: Yan Youpei , Bayham Jude , Richter Aaron , Fenichel Eli P.
Published: February 2021

Face masks are an important component in controlling COVID-19, and policy orders to wear masks are common. However, behavioral responses are seldom additive, and exchanging one protective behavior for another could undermine the COVID-19 policy response. We use SafeGraph smart device location data and variation in the date that US states and counties issued face mask mandates as a set of natural experiments to investigate risk compensation behavior. We compare time at home and the number of visits to public locations before and after face mask orders conditional on multiple statistical controls. We find that face mask orders lead to risk compensation behavior. Americans subject to the mask orders spend 11–24 fewer minutes at home on average and increase visits to some commercial locations—most notably restaurants, which are a high-risk location. It is unclear if this would lead to a net increase or decrease in transmission. However, it is clear that mask orders would be an important part of an economic recovery if people otherwise overestimate the risk of visiting public places.
Theta-modulated oscillatory transcranial direct current stimulation over posterior parietal cortex improves associative memory
Authors: Vulić Katarina , Bjekić Jovana , Paunović Dunja , Jovanović Miloš , Milanović Slađan , Filipović Saša R.
Published: February 2021

Associative memory (AM) reflects the ability to remember and retrieve multiple pieces of information bound together thus enabling complex episodic experiences. Despite growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of AM, there are inconsistent evidence regarding its benefits. An alternative to standard constant tDCS could be the application of frequency-modulated tDCS protocols, that mimic natural function-relevant brain rhythms. Here, we show the effects of anodal tDCS oscillating in theta rhythm (5 Hz; 1.5 ± 0.1 mA)versusconstant anodal tDCS and sham over left posterior parietal cortex on cued recall of face-word associations. In a crossover design, each participant completed AM assessment immediately following 20-min theta-oscillatory, constant, and sham tDCS, as well as 1 and 5 days after. Theta oscillatory tDCS increased initial AM performance in comparison to sham, and so did constant tDCS. On the group level, no differences between oscillatory and constant tDCS were observed, but individual-level analysis revealed that some participants responded to theta-oscillatory but not to constant tDCS, and vice versa,which could be attributed to their different physiological modes of action. This study shows the potential of oscillatory tDCS protocols for memory enhancement to produce strong and reliable memory-modulating effects which deserve to be investigated further.
Visual outcomes of lens subluxation surgery with Cionni modified capsular tension rings in Marfan syndrome
Authors: Chen Tianhui , Deng Michael , Zhang Min , Chen Jiahui , Chen Zexu , Jiang Yongxiang
Published: February 2021

Marfan syndrome (MFS) is a hereditary disease with an incidence of 0.3% in the general population. Approximately 60% of MFS patients with FBN1 gene mutation will suffer ectopia lentis (EL) from the age of 3. With the development of EL, severe loss of vision will accrue because of lens tilt and glaucoma. Cionni modified capsular tension rings (MCTR) has been applied in the surgery for EL in MFS patients. To evaluate visual acuity and safety of using MCTR during lens subluxation surgery in MFS patients, 66 MFS patients (110 eyes) were included in our study, with the mean duration of follow-up of 4.7 months (SD 1.76 months). The capsular bags were preserved in 101 eyes (91.81%) with MCTR implantation. There was an overall significant improvement in BCVA at 1-month follow-up which was maintained at 3 months. Multivariable linear regression revealed that older age at first visit was associated with greater postoperative BCVA at the 1-month follow-up (P = 0.007). A significant difference was found between different degrees of lens subluxation and the length of surgical time and complications. At follow-up, only two eyes (1.98%) were identified to have developed retinal detachments. In conclusion, better visual outcomes can be achieved when patients received an early operation with MCTR implantation.
White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling
Authors: Sarma Manoj K. , Pal Amrita , Keller Margaret A. , Welikson Tamara , Ventura Joseph , Michalik David E. , Nielsen-Saines Karin , Deville Jaime , Kovacs Andrea , Operskalski Eva , Church Joseph A. , Macey Paul M. , Biswal Bharat , Thomas M. Albert
Published: February 2021

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.
Body mass index trajectories and the risk for Alzheimer’s disease among older adults
Authors: Kang Seo Young , Kim Ye-Jee , Jang Wooyoung , Son Ki Young , Park Hye Soon , Kim Young Sik
Published: February 2021

The effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.
Comprehensive characterization and quantification of adeno associated vectors by size exclusion chromatography and multi angle light scattering
Authors: McIntosh Nicole L. , Berguig Geoffrey Y. , Karim Omair A. , Cortesio Christa L. , De Angelis Rolando , Khan Ayesha A. , Gold Daniel , Maga John A. , Bhat Vikas S.
Published: February 2021

Adeno associated virus (AAV) capsids are a leading modality for in vivo gene delivery. Complete and precise characterization of capsid particles, including capsid and vector genome concentration, is necessary to safely and efficaciously dose patients. Size exclusion chromatography (SEC) coupled to multiangle light scattering (MALS) offers a straightforward approach to comprehensively characterize AAV capsids. The current study demonstrates that this method provides detailed AAV characterization information, including but not limited to aggregation profile, size-distribution, capsid content, capsid molar mass, encapsidated DNA molar mass, and total capsid and vector genome titer. Currently, multiple techniques are required to generate this information, with varying accuracy and precision. In the current study, a new series of equations for SEC-MALS are used in tandem with intrinsic properties of the capsids and encapsidated DNA to quantify multiple physical AAV attributes in one 20-min run with minimal sample manipulation, high accuracy, and high precision. These novel applications designate this well-established method as a powerful tool for product development and process analytics in future gene therapy programs.
The role of inflammatory cytokines in anemia and gastrointestinal mucosal injury induced by foot electric stimulation
Authors: Fan Fangcheng , Ai Yangwen , Sun Ting , Li Shuran , Liu Hua , Shi Xiaojie , Zhang Ziqian , Liu Qingshan , Cheng Yong
Published: February 2021

Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.
Obstructive sleep apnoea syndrome (OSAS) as a risk factor for secondary osteoporosis in children
Authors: Sies Nur Syazwin , Zaini Azriyanti Anuar , de Bruyne Jessie Anne , Jalaludin Muhammad Yazid , Nathan Anna Marie , Han Ng Yit , Thavagnanam Surendran
Published: February 2021

Repetitive hypoxia seen in obstructive sleep apnoea syndrome (OSAS) may affect bone metabolism increasing the risk for secondary osteoporosis. This study investigates the association between OSAS in children and secondary osteoporosis. This cross-sectional study included 150 children aged 10–17 years: 86 with OSAS and 64 with no OSAS. OSAS was confirmed by polysomnography. Quantitative ultrasound (QUS) of calcaneum measuring speed of sound (SoS) and broadband ultrasound attenuation (BUA) were collected. Other parameters collected including bone profile, vitamin D levels, physical activity scoring and dietary calcium intake. Majority were male and Malay ethnicity. OSAS children were mostly obese (84%) and 57% had moderate to severe OSAS. Most had lower physical activities scores. Mean (SD) phosphate and Alkaline phosphatase were lower in OSA children compared to controls: PO4, p = 0.039 and ALP, p < 0.001. Using both single and multivariate analysis, children with OSAS had a lower mean SoS value, p < 0.001 and p = 0.004 respectively after adjusting for age, BMI and bone profile. Children with OSAS had lower SoS suggesting risk for secondary osteoporosis. QUS calcaneus is a non-invasive, feasible tool and can be used to screen risk of osteoporosis in children. Further bone mineral density assessment is needed in these groups of children to confirm diagnosis of osteoporosis.
The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study
Authors: Kesarwani Ashwani , Sahu Parul , Jain Kshama , Sinha Prakriti , Mohan K. Varsha , Nagpal Puja S. , Singh Surender , Zaidi Rana , Nagarajan Perumal , Upadhyay Pramod
Published: February 2021

Due to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.
In vivo measurement of pH and CO2 levels in the uterus of sows through the estrous cycle and after insemination
Authors: López-Albors Octavio , Llamas-López Pedro José , Ortuño Joaquín Ángel , Latorre Rafael , García-Vázquez Francisco Alberto
Published: February 2021

The pH–CO2–HCO3− system is a ubiquitous biological regulator with important functional implications for reproduction. Knowledge of the physiological values of its components is relevant for reproductive biology and the optimization of Assisted Reproductive Technologies (ARTs). However, in situ measurements of these parameters in the uterus are scarce or null. This study describes a non-invasive method for in situ time-lapse recording of pH and CO2 within the uterus of non-anesthetized sows. Animals were at three different reproductive conditions, estrous with no insemination and two hours after insemination, and diestrous. From pH and CO2 data, HCO3− concentration was estimated. The non-invasive approach to the porcine uterus with novel optical probes allowed the obtaining of in situ physiological values of pH, CO2, and HCO3−. Variable oscillatory patterns of pH, CO2 and HCO3− were found independently of the estrous condition. Insemination did not immediately change the levels of uterine pH, CO2 (%) and HCO3− concentration, but all the values were affected by the estrous cycle decreasing significantly at diestrous condition. This study contributes to a better understanding of the in vivo regulation of the pH-CO2-HCO3− system in the uterus and may help to optimize the protocols of sperm treatment for in vitro fertilization.
Photons detected in the active nerve by photographic technique
Authors: Zangari Andrea , Micheli Davide , Galeazzi Roberta , Tozzi Antonio , Balzano Vittoria , Bellavia Gabriella , Caristo Maria Emiliana
Published: February 2021

The nervous system is one of the most complex expressions of biological evolution. Its high performance mostly relies on the basic principle of the action potential, a sequential activation of local ionic currents along the neural fiber. The implications of this essentially electrical phenomenon subsequently emerged in a more comprehensive electromagnetic perspective of neurotransmission. Several studies focused on the possible role of photons in neural communication and provided evidence of the transfer of photons through myelinated axons. A hypothesis is that myelin sheath would behave as an optical waveguide, although the source of photons is controversial. In a previous work, we proposed a model describing how photons would arise at the node of Ranvier. In this study we experimentally detected photons in the node of Ranvier by Ag+photoreduction measurement technique, during electrically induced nerve activity. Our results suggest that in association to the action potential a photonic radiation takes place in the node.
Self-assembling thermostable chimeras as new platform for arsenic biosensing
Authors: Puopolo Rosanna , Sorrentino Ilaria , Gallo Giovanni , Piscitelli Alessandra , Giardina Paola , Le Goff Alan , Fiorentino Gabriella
Published: February 2021

The correct immobilization and orientation of enzymes on nanosurfaces is a crucial step either for the realization of biosensors, as well as to guarantee the efficacy of the developed biomaterials. In this work we produced two versions of a chimeric protein, namely ArsC-Vmh2 and Vmh2-ArsC, which combined the self-assembling properties of Vmh2, a hydrophobin from Pleurotus ostreatus, with that of TtArsC, a thermophilic arsenate reductase from Thermus thermophilus; both chimeras were heterologously expressed in Escherichia coli and purified from inclusion bodies. They were characterized for their enzymatic capability to reduce As(V) into As(III), as well as for their immobilization properties on polystyrene and gold in comparison to the native TtArsC. The chimeric proteins immobilized on polystyrene can be reused up to three times and stored for 15 days with 50% of activity loss. Immobilization on gold electrodes showed that both chimeras follow a classic Langmuir isotherm model towards As(III) recognition, with an association constant (KAsIII) between As(III) and the immobilized enzyme, equal to 650 (± 100) L mol−1 for ArsC-Vmh2 and to 1200 (± 300) L mol−1 for Vmh2-ArsC. The results demonstrate that gold-immobilized ArsC-Vmh2 and Vmh2-ArsC can be exploited as electrochemical biosensors to detect As(III).
Intrinsic disorder in protein domains contributes to both organism complexity and clade-specific functions
Authors: Gao Chao , Ma Chong , Wang Huqiang , Zhong Haolin , Zang Jiayin , Zhong Rugang , He Fuchu , Yang Dong
Published: February 2021

Interestingly, some protein domains are intrinsically disordered (abbreviated as IDD), and the disorder degree of same domains may differ in different contexts. However, the evolutionary causes and biological significance of these phenomena are unclear. Here, we address these issues by genome-wide analyses of the evolutionary and functional features of IDDs in 1,870 species across the three superkingdoms. As the result, there is a significant positive correlation between the proportion of IDDs and organism complexity with some interesting exceptions. These phenomena may be due to the high disorder of clade-specific domains and the different disorder degrees of the domains shared in different clades. The functions of IDDs are clade-specific and the higher proportion of post-translational modification sites may contribute to their complex functions. Compared with metazoans, fungi have more IDDs with a consecutive disorder region but a low disorder ratio, which reflects their different functional requirements. As for disorder variation, it’s greater for domains among different proteins than those within the same proteins. Some clade-specific ‘no-variation’ or ‘high-variation’ domains are involved in clade-specific functions. In sum, intrinsic domain disorder is related to both the organism complexity and clade-specific functions. These results deepen the understanding of the evolution and function of IDDs.
Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists
Authors: Zeug Matthias , Markovic Nebojsa , Iancu Cristina V. , Tripp Joanna , Oreb Mislav , Choe Jun-yong
Published: February 2021

Hydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids’ non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5–1.9 Å) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid–base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a β-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.
Estimated seroprevalence of SARS-CoV-2 antibodies among adults in Orange County, California
Authors: Bruckner Tim A. , Parker Daniel M. , Bartell Scott M. , Vieira Veronica M. , Khan Saahir , Noymer Andrew , Drum Emily , Albala Bruce , Zahn Matthew , Boden-Albala Bernadette
Published: February 2021

Clinic-based estimates of SARS-CoV-2 may considerably underestimate the total number of infections. Access to testing in the US has been heterogeneous and symptoms vary widely in infected persons. Public health surveillance efforts and metrics are therefore hampered by underreporting. We set out to provide a minimally biased estimate of SARS-CoV-2 seroprevalence among adults for a large and diverse county (Orange County, CA, population 3.2 million). We implemented a surveillance study that minimizes response bias by recruiting adults to answer a survey without knowledge of later being offered SARS-CoV-2 test. Several methodologies were used to retrieve a population-representative sample. Participants (n = 2979) visited one of 11 drive-thru test sites from July 10th to August 16th, 2020 (or received an in-home visit) to provide a finger pin-prick sample. We applied a robust SARS-CoV-2 Antigen Microarray technology, which has superior measurement validity relative to FDA-approved tests. Participants include a broad age, gender, racial/ethnic, and income representation. Adjusted seroprevalence of SARS-CoV-2 infection was 11.5% (95% CI: 10.5–12.4%). Formal bias analyses produced similar results. Prevalence was elevated among Hispanics (vs. other non-Hispanic: prevalence ratio [PR] = 1.47, 95% CI 1.22–1.78) and household income < $50,000 (vs. > $100,000: PR = 1.42, 95% CI: 1.14 to 1.79). Results from a diverse population using a highly specific and sensitive microarray indicate a SARS-CoV-2 seroprevalence of ~ 12 percent. This population-based seroprevalence is seven-fold greater than that using official County statistics. In this region, SARS-CoV-2 also disproportionately affects Hispanic and low-income adults.