bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy consumption and cooperation for optimal sensing
Authors: Ngampruetikorn Vudtiwat , Schwab David J. , Stephens Greg J.
Published: February 2020

The reliable detection of environmental molecules in the presence of noise is an important cellular function, yet the underlying computational mechanisms are not well understood. We introduce a model of two interacting sensors which allows for the principled exploration of signal statistics, cooperation strategies and the role of energy consumption in optimal sensing, quantified through the mutual information between the signal and the sensors. Here we report that in general the optimal sensing strategy depends both on the noise level and the statistics of the signals. For joint, correlated signals, energy consuming (nonequilibrium), asymmetric couplings result in maximum information gain in the low-noise, high-signal-correlation limit. Surprisingly we also find that energy consumption is not always required for optimal sensing. We generalise our model to incorporate time integration of the sensor state by a population of readout molecules, and demonstrate that sensor interaction and energy consumption remain important for optimal sensing.
Publisher Correction: Partial proteasomal degradation of Lola triggers the male-to-female switch of a dimorphic courtship circuit
Authors: Sato Kosei , Ito Hiroki , Yokoyama Atsushi , Toba Gakuta , Yamamoto Daisuke
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Physically-interpretable classification of biological network dynamics for complex collective motions
Authors: Fujii Keisuke , Takeishi Naoya , Hojo Motokazu , Inaba Yuki , Kawahara Yoshinobu
Published: February 2020

Understanding biological network dynamics is a fundamental issue in various scientific and engineering fields. Network theory is capable of revealing the relationship between elements and their propagation; however, for complex collective motions, the network properties often transiently and complexly change. A fundamental question addressed here pertains to the classification of collective motion network based on physically-interpretable dynamical properties. Here we apply a data-driven spectral analysis called graph dynamic mode decomposition, which obtains the dynamical properties for collective motion classification. Using a ballgame as an example, we classified the strategic collective motions in different global behaviours and discovered that, in addition to the physical properties, the contextual node information was critical for classification. Furthermore, we discovered the label-specific stronger spectra in the relationship among the nearest agents, providing physical and semantic interpretations. Our approach contributes to the understanding of principles of biological complex network dynamics from the perspective of nonlinear dynamical systems.
GHz Ultrasonic Chip-Scale Device Induces Ion Channel Stimulation in Human Neural Cells
Authors: Balasubramanian Priya S. , Singh Ankur , Xu Chris , Lal Amit
Published: February 2020

Emergent trends in the device development for neural prosthetics have focused on establishing stimulus localization, improving longevity through immune compatibility, reducing energy re-quirements, and embedding active control in the devices. Ultrasound stimulation can single-handedly address several of these challenges. Ultrasonic stimulus of neurons has been studied extensively from 100 kHz to 10 MHz, with high penetration but less localization. In this paper, a chip-scale device consisting of piezoelectric Aluminum Nitride ultrasonic transducers was engineered to deliver gigahertz (GHz) ultrasonic stimulus to the human neural cells. These devices provide a path towards complementary metal oxide semiconductor (CMOS) integration towards fully controllable neural devices. At GHz frequencies, ultrasonic wavelengths in water are a few microns and have an absorption depth of 10–20 µm. This confinement of energy can be used to control stimulation volume within a single neuron. This paper is the first proof-of-concept study to demonstrate that GHz ultrasound can stimulate neurons in vitro. By utilizing optical calcium imaging, which records calcium ion flux indicating occurrence of an action potential, this paper demonstrates that an application of a nontoxic dosage of GHz ultrasonic waves $$(\ge 0.05\frac{W}{c{m}^{2}})$$
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caused an average normalized fluorescence intensity recordings >1.40 for the calcium transients. Electrical effects due to chip-scale ultrasound delivery was discounted as the sole mechanism in stimulation, with effects tested at α = 0.01 statistical significance amongst all intensities and con-trol groups. Ionic transients recorded optically were confirmed to be mediated by ion channels and experimental data suggests an insignificant thermal contributions to stimulation, with a predicted increase of 0.03 oC for $$1.2\frac{W}{c{m}^{2}}\cdot $$
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This paper paves the experimental framework to further explore chip-scale axon and neuron specific neural stimulation, with future applications in neural prosthetics, chip scale neural engineering, and extensions to different tissue and cell types.
The impacts of Extra-tropical ENSO Precursors on Tropical Pacific Decadal-scale Variability
Authors: Zhao Yingying , Di Lorenzo Emanuele
Published: February 2020

Off-equatorial wind anomalies on seasonal timescales from both the North and South Pacific, known as “precursors” of the El Niño Southern Oscillation (ENSO), have been shown to independently trigger the ENSO feedbacks in the tropics and its teleconnections to the extra-tropics. However, the impacts of ENSO precursors on Tropical Pacific Decadal-scale Variability (TPDV) is still not well understood and quantified. We show that the dynamic sequence from extra-tropical ENSO precursors to ENSO (tropics) to extra-tropical ENSO teleconnections is not only important for ENSO, but acts as a primary mechanism to filter (e.g. reddening) the low-frequency variability of the seasonal precursors into the decadal-scale variance of the Pacific basin, accounting for the largest fraction of the TPDV (~65%) and its phase. This process, which contrasts previous theories advocating for a TPDV generated internally in the tropics (e.g. ENSO residuals), is inherently unpredictable and not well reproduced in climate models and raises challenges for understanding and predicting the role of internal TPDV in future climate change scenarios.
Mid age APOE ε4 carriers show memory-related functional differences and disrupted structure-function relationships in hippocampal regions
Authors: Evans Simon L. , Dowell Nicholas G. , Prowse Fenella , Tabet Naji , King Sarah L. , Rusted Jennifer M.
Published: February 2020

Carriers of the APOE e4 allele are at higher risk of age-related cognitive decline and Alzheimer’s disease (AD). The underlying neural mechanisms are uncertain, but genotype differences in medial temporal lobe (MTL) functional activity and structure at mid-age might contribute. We tested 16 non-e4 and 16 e4 carriers (aged 45–55) on a subsequent memory task in conjunction with MRI to assess how hippocampal volume (from T1 structural) and microstructure (neurite orientation-dispersion, from NODDI) differs by genotype and in relation to memory encoding. No previous study has investigated APOE effects on hippocampal microstructure using NODDI. Recall performance did not differ by genotype. A genotype by condition interaction in left parahippocampus indicated that in e4 carriers activity did not differentiate subsequently remembered from forgotten words. Hippocampal volumes and microstructure also did not differ by genotype but hippocampal volumes correlated positively with recognition performance in non-e4 carriers only. Similarly, greater hippocampal neurite orientation-dispersion was linked to better recall but only in non-e4s. Thus, we suggest that mid-age e4 carriers show a breakdown of normal MTL activation and structure-performance relationships. This could reflect an inability to utilise compensatory mechanisms, and contribute to higher risk of cognitive decline and AD in later life.
Metaphylogenetic analysis of global sewage reveals that bacterial strains associated with human disease show less degree of geographic clustering
Authors: Ahrenfeldt Johanne , Waisi Madina , Loft Isabella C. , Clausen Philip T. L. C. , Allesøe Rosa , Szarvas Judit , Hendriksen Rene S. , Aarestrup Frank M. , Lund Ole
Published: February 2020

Knowledge about the difference in the global distribution of pathogens and non-pathogens is limited. Here, we investigate it using a multi-sample metagenomics phylogeny approach based on short-read metagenomic sequencing of sewage from 79 sites around the world. For each metagenomic sample, bacterial template genomes were identified in a non-redundant database of whole genome sequences. Reads were mapped to the templates identified in each sample. Phylogenetic trees were constructed for each template identified in multiple samples. The countries from which the samples were taken were grouped according to different definitions of world regions. For each tree, the tendency for regional clustering was determined. Phylogenetic trees representing 95 unique bacterial templates were created covering 4 to 71 samples. Varying degrees of regional clustering could be observed. The clustering was most pronounced for environmental bacterial species and human commensals, and less for colonizing opportunistic pathogens, opportunistic pathogens and pathogens. No pattern of significant difference in clustering between any of the organism classifications and country groupings according to income were observed. Our study suggests that while the same bacterial species might be found globally, there is a geographical regional selection or barrier to spread for individual clones of environmental and human commensal bacteria, whereas this is to a lesser degree the case for strains and clones of human pathogens and opportunistic pathogens.
Influence of UV light irradiation on the corrosion behavior of electrodeposited Ni and Cu nanocrystalline foils
Authors: Deng Shu-hao , Lu Hao , Li D. Y.
Published: February 2020

Influence of ultraviolet (UV) light irradiation on the corrosion behavior of electrodeposited Ni and Cu nanocrystalline foils in 3.5% NaCl solution was studied by means of electrochemical methods, electron work function (EWF) analysis, and characterization with atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). It was demonstrated that the influence of solar light on corrosion of the metals was non-negligible, which could be very different for different materials. The UV light irradiation resulted in an increase in corrosion resistance of the Cu foil but showed an opposite influence on that of the Ni foil. Based on surface state analysis, it was concluded that the UV irradiation altered the surface oxide films. The UV light induced the formation of Cu2O on Cu, which is more stable and compacted than naturally formed CuO film. However, the UV light accelerated the formation of Ni2O3, which is loose, porous and brittle, compared to naturally formed NiO on Ni. The changes in oxide films were responsible for the opposite variations in the corrosion behavior of the Cu and Ni nanocrystalline foils caused by the UV light irradiation.
Slc20a1/Pit1 and Slc20a2/Pit2 are essential for normal skeletal myofiber function and survival
Authors: Chande Sampada , Caballero Daniel , Ho Bryan B. , Fetene Jonathan , Serna Juan , Pesta Dominik , Nasiri Ali , Jurczak Michael , Chavkin Nicholas W. , Hernando Nati , Giachelli Cecilia M. , Wagner Carsten A. , Zeiss Caroline , Shulman Gerald I. , Bergwitz Clemens
Published: February 2020

Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transporters are required and whether hormonal changes due to hypophosphatemia contribute to muscle function is unknown. To address these questions we generated a series of conditional knockout mice lacking one or both house-keeping Pi transporters Pit1 and Pit2 in skeletal muscle (sm), using the postnatally expressed human skeletal actin-cre. Simultaneous conditional deletion of both transporters caused skeletal muscle atrophy, resulting in death by postnatal day P13. smPit1−/−, smPit2−/− and three allele mutants are fertile and have normal body weights, suggesting a high degree of redundance for the two transporters in skeletal muscle. However, these mice show a gene-dose dependent reduction in running activity also seen in another hypophosphatemic model (Hyp mice). In contrast to Hyp mice, grip strength is preserved. Further evaluation of the mechanism shows reduced ERK1/2 activation and stimulation of AMP kinase in skeletal muscle from smPit1−/−; smPit2−/− mice consistent with energy-stress. Similarly, C2C12 myoblasts show a reduced oxygen consumption rate mediated by Pi transport-dependent and ERK1/2-dependent metabolic Pi sensing pathways. In conclusion, we here show that Pit1 and Pit2 are essential for normal myofiber function and survival, insights which may improve management of hypophosphatemic myopathy.
Intestinal Alkaline Phosphatase Exerts Anti-Inflammatory Effects Against Lipopolysaccharide by Inducing Autophagy
Authors: Singh Sudha B. , Carroll-Portillo Amanda , Coffman Cristina , Ritz Nathaniel L. , Lin Henry C.
Published: February 2020

Intestinal alkaline phosphatase (IAP) regulates bicarbonate secretion, detoxifies lipopolysaccharide (LPS), regulates gut microbes, and dephosphorylates proinflammatory nucleotides. IAP also exhibits anti-inflammatory effects in a Toll-like Receptor-4 (TLR-4) dependent manner. However, it is not known whether IAP induces autophagy. We tested the hypothesis that IAP may induce autophagy which may mediate the anti-inflammatory effects of IAP. We found that exogenous IAP induced autophagy in intestinal epithelial cells and in macrophages. TLR4INC34 (C34), a TLR4 signaling inhibitor, suppressed IAP-induced autophagy. IAP also inhibited LPS-induced IL-1β mRNA expression and activation of NF-κB. When autophagy was blocked by 3-methyladenine (3MA) or by Atg5 siRNA, IAP failed to block LPS-mediated effects. IAP also upregulated autophagy-related gene expression in small intestine in mice. We administered either vehicle or IAP (100 U/ml) in drinking water for 14 days in C57BL/6 mice. Mice were sacrificed and ileal tissues collected. Increased expression of Atg5, Atg16, Irgm1, Tlr4, and Lyz genes was observed in the IAP treated group compared to the vehicle treated group. Increase in Atg16 protein expression and fluorescence intensity of LC3 was also observed in IAP-treated tissues compared to the vehicle-treated tissues. Thus, our study lays the framework for investigating how IAP and autophagy may act together to control inflammatory conditions.
Scaling sports equipment for children promotes functional movement variability
Authors: Buszard Tim , Garofolini Alessandro , Reid Machar , Farrow Damian , Oppici Luca , Whiteside David
Published: February 2020

Scaling sports equipment to match the physical development of children allows motor skills to be performed with greater success and with more desirable movement patterns. It is unknown, however, how scaled equipment affects movement variability – a key factor associated with coordination. Our aim was to identify whether scaled sports equipment facilitates coordination and functional movement variability in children when performing a hitting for accuracy task in tennis. Twenty-five children were asked to execute a forehand stroke with the aim of hitting the ball to a target located 10 metres away. Participants performed the task in two conditions – a scaled equipment condition and a full-sized equipment condition. Scaled equipment led to superior hitting accuracy and greater temporal stability of the swing compared to full-sized equipment. Scaled equipment also afforded the emergence of a functional coupling between upper arm and forearm movement variability which helped regulate the distance between the shoulder and the racket. Comparatively there was a lack of coupling when full-sized equipment was used. Hence, scaled equipment promoted functional movement variability, whereas full-sized equipment resulted in the freezing of mechanical degrees of freedom. This suggests that children’s skill acquisition could be hindered and potentially regress when using inappropriately sized equipment.
An electronic alert system increases screening for hepatitis B and C and improves management of patients with haematological disorders
Authors: Riveiro-Barciela Mar , Gubern Paula , Roade Luisa , Abrisqueta Pau , Carreras María José , Farriols Anna , Bosch Francesc , Esteban Rafael , Buti María
Published: February 2020

Treatment of haematological disorders in patients with chronic hepatitis B or resolved infection (anti-HBc-positive) is associated with a risk of hepatitis B reactivation. Moreover, patients with chronic hepatitis C have a higher risk of haematological malignancies than general population. An electronic alert system was developed to promote screening of hepatitis B (HBV) and C (HCV) in patients starting haematological therapies. The system included screening and linkage to care and a request for testing in those without data. From March, 2017 to March, 2018 data from 420 consecutive patients with haematological diseases were included. At first prescription before the alerts, the HCV and HBV screening rate was 60.5%. Following the alerts, an additional 115 were screened, increasing the overall screening rate to 87.9%. Anti-HBc alone was detected in 57, anti-HCV in 13, and HBsAg in 2 patients. Overall, 68% of patients with any viral hepatitis markers were previously not know, and the impact was particularly important for anti-HBc detection (47/57 unknown). Nucleoside analogues were prescribed in 28 (49.1%) anti-HBc-positive and the 2 HBsAg-positive patients. Prospective follow-up with HBV DNA and HBsAg testing showed no cases of HBV reactivation. An estimated 1.2 HBV reactivations were avoided as consequence of the alert system. In summary, an electronic alert system increased viral hepatitis screening in patients receiving haematological treatment and led to improvements in the management of these patients, including avoided HBV reactivation.
Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers
Authors: Ogden Angela , Bhattarai Shristi , Sahoo Bikram , Mongan Nigel P. , Alsaleem Mansour , Green Andrew R. , Aleskandarany Mohammed , Ellis Ian O. , Pattni Sonal , Li Xiaoxian , Moreno Carlos S. , Krishnamurti Uma , Janssen Emiel A. , Jonsdottir Kristin , Rakha Emad , Rida Padmashree , Aneja Ritu
Published: February 2020

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) have been investigated as triple-negative breast cancer (TNBC) biomarkers. Reduced EGFR levels can be compensated by increases in HER3; thus, assaying EGFR and HER3 together may improve prognostic value. In a multi-institutional cohort of 510 TNBC patients, we analyzed the impact of HER3, EGFR, or combined HER3-EGFR protein expression in pre-treatment samples on breast cancer-specific and distant metastasis-free survival (BCSS and DMFS, respectively). A subset of 60 TNBC samples were RNA-sequenced using massive parallel sequencing. The combined HER3-EGFR score outperformed individual HER3 and EGFR scores, with high HER3-EGFR score independently predicting worse BCSS (Hazard Ratio [HR] = 2.30, p = 0.006) and DMFS (HR = 1.78, p = 0.041, respectively). TNBCs with high HER3-EGFR scores exhibited significantly suppressed ATM signaling and differential expression of a network predicted to be controlled by low TXN activity, resulting in activation of EGFR, PARP1, and caspases and inhibition of p53 and NFκB. Nuclear PARP1 protein levels were higher in HER3-EGFR-high TNBCs based on immunohistochemistry (p = 0.036). Assessing HER3 and EGFR protein expression in combination may identify which adjuvant chemotherapy-treated TNBC patients have a higher risk of treatment resistance and may benefit from a dual HER3-EGFR inhibitor and a PARP1 inhibitor.
EMG-Assisted Muscle Force Driven Finite Element Model of the Knee Joint with Fibril-Reinforced Poroelastic Cartilages and Menisci
Authors: Esrafilian A. , Stenroth L. , Mononen M. E. , Tanska P. , Avela J. , Korhonen R. K.
Published: February 2020

Abnormal mechanical loading is essential in the onset and progression of knee osteoarthritis. Combined musculoskeletal (MS) and finite element (FE) modeling is a typical method to estimate load distribution and tissue responses in the knee joint. However, earlier combined models mostly utilize static-optimization based MS models and muscle force driven FE models typically use elastic materials for soft tissues or analyze specific time points of gait. Therefore, here we develop an electromyography-assisted muscle force driven FE model with fibril-reinforced poro(visco)elastic cartilages and menisci to analyze knee joint loading during the stance phase of gait. Moreover, since ligament pre-strains are one of the important uncertainties in joint modeling, we conducted a sensitivity analysis on the pre-strains of anterior and posterior cruciate ligaments (ACL and PCL) as well as medial and lateral collateral ligaments (MCL and LCL). The model produced kinematics and kinetics consistent with previous experimental data. Joint contact forces and contact areas were highly sensitive to ACL and PCL pre-strains, while those changed less cartilage stresses, fibril strains, and fluid pressures. The presented workflow could be used in a wide range of applications related to the aetiology of cartilage degeneration, optimization of rehabilitation exercises, and simulation of knee surgeries.
IgG-Fc glycosylation before and after rituximab treatment in immune thrombocytopenia
Authors: Schmidt David E. , de Haan Noortje , Sonneveld Myrthe E. , Porcelijn Leendert , van der Schoot C. Ellen , de Haas Masja , Zwaginga Jaap-Jan , Wuhrer Manfred , Vidarsson Gestur
Published: February 2020

The interactions of antibodies with myeloid Fcγ receptors and the complement system are regulated by an Asn297-linked glycan in the Fc portion of IgG. Alterations of serum IgG-Fc glycosylation have been reported in various autoimmune diseases, and correlate with treatment response and disease activity. We hypothesized that IgG-Fc glycosylation is altered in immune thrombocytopenia (ITP) and associates with response to anti-CD20 monoclonal antibody treatment (rituximab). IgG-Fc glycosylation was analyzed by liquid chromatography-mass spectrometry. We found that IgG-Fc glycosylation was identical between refractory ITP patients (HOVON64 trial; N = 108) and healthy controls (N = 120). Two months after rituximab treatment, we observed a shift in Fc glycosylation, with a mean 1.7% reduction in galactosylation for IgG1 and IgG4 and a mean 1.5% increase for bisection in IgG1, IgG2/3 and IgG4 (adjusted p < 1.7 × 10−3 and p < 2 × 10−4, respectively). Neither baseline nor longitudinal changes in IgG-Fc glycosylation after rituximab were associated with clinical treatment response. We conclude that IgG-Fc glycosylation in refractory ITP is similar to healthy controls and does not predict treatment responses to rituximab. The observed changes two months after treatment suggest that rituximab may influence total serum IgG-Fc glycosylation. Overall, our study suggests that the pathophysiology of refractory ITP may differ from other autoimmune diseases.
Antibacterial effects of low-temperature plasma generated by atmospheric-pressure plasma jet are mediated by reactive oxygen species
Authors: Nicol McKayla J. , Brubaker Timothy R. , Honish Brian J. , Simmons Alyssa N. , Kazemi Ali , Geissel Madison A. , Whalen Connor T. , Siedlecki Christopher A. , Bilén Sven G. , Knecht Sean D. , Kirimanjeswara Girish S.
Published: February 2020

Emergence and spread of antibiotic resistance calls for development of non-chemical treatment options for bacterial infections. Plasma medicine applies low-temperature plasma (LTP) physics to address biomedical problems such as wound healing and tumor suppression. LTP has also been used for surface disinfection. However, there is still much to be learned regarding the effectiveness of LTP on bacteria in suspension in liquids, and especially on porous surfaces. We investigated the efficacy of LTP treatments against bacteria using an atmospheric-pressure plasma jet and show that LTP treatments have the ability to inhibit both gram-positive (S. aureus) and gram-negative (E. coli) bacteria on solid and porous surfaces. Additionally, both direct LTP treatment and plasma-activated media were effective against the bacteria suspended in liquid culture. Our data indicate that reactive oxygen species are the key mediators of the bactericidal effects of LTP and hydrogen peroxide is necessary but not sufficient for antibacterial effects. In addition, our data suggests that bacteria exposed to LTP do not develop resistance to further treatment with LTP. These findings suggest that this novel atmospheric-pressure plasma jet could be used as a potential alternative to antibiotic treatments in vivo.
The patterns of Non-communicable disease Multimorbidity in Iran: A Multilevel Analysis
Authors: Khorrami Zahra , Rezapour Maysam , Etemad Koorosh , Yarahmadi Shahin , Khodakarim Soheila , Mahdavi Hezaveh Alireza , Kameli Mohammadesmail , Khanjani Narges
Published: February 2020

The prevalence of non-communicable diseases is increasing worldwide. Multimorbidity and long-term medical conditions is common among these patients. This study aimed to investigate the patterns of non-communicable disease multimorbidity and their risk factors at the individual and aggregated level. Data was inquired from the nationwide survey performed in 2011, according to the WHO stepwise approach on NCD risk factors. A latent class analysis on multimorbidity components (11 chronic diseases) was performed and the association of some individual and aggregated risk factors (urbanization) with the latent subclasses was accessed using multilevel multinomial logistic regression. Latent class analysis revealed four distinct subclasses of multimorbidity among the Iranian population (10069 participants). Musculoskeletal diseases and asthma classes were seen in both genders. In males, the odds of membership in the diabetes class was 41% less by increasing physical activity; but with increased BMI, the odds of membership in the diabetes class was 1.90 times higher. Tobacco smoking increased the odds of membership in the musculoskeletal diseases class, 1.37 and 2.30 times for males and females, respectively. Increased BMI and low education increased the chances of females’ membership in all subclasses of multimorbidity. At the province level, with increase in urbanization, the odds of membership in the diabetes class was 1.28 times higher among males (P = 0.027). Increased age, higher BMI, tobacco smoking and low education are the most important risk factors associated with NCD multimorbidity among Iranians. Interventions and policies should be implemented to control these risk factors.
A quantitative study of stress fields ahead of a slip band blocked by a grain boundary in unalloyed magnesium
Authors: Andani Mohsen Taheri , Lakshmanan Aaditya , Karamooz-Ravari Mohammadreza , Sundararaghavan Veera , Allison John , Misra Amit
Published: February 2020

Stress localization ahead of a slip band blocked by a grain boundary is measured for three different grain boundaries in unalloyed Mg using high-resolution electron backscatter diffraction (HR-EBSD). The results are compared with a theoretical dislocation pile-up model, from which slip system resistance and micro-Hall–Petch coefficients for different grain boundary types are deduced. The results indicate that grain boundary character plays a crucial role in determining micro-Hall–Petch coefficients, which can be used to strengthen classical crystal plasticity constitutive models to make predictions linked to the effect of grain boundary strengthening.
Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen
Authors: Ou Li , Kong Wing-Pui , Chuang Gwo-Yu , Ghosh Mridul , Gulla Krishana , O’Dell Sijy , Varriale Joseph , Barefoot Nathan , Changela Anita , Chao Cara W. , Cheng Cheng , Druz Aliaksandr , Kong Rui , McKee Krisha , Rawi Reda , Sarfo Edward K. , Schön Arne , Shaddeau Andrew , Tsybovsky Yaroslav , Verardi Raffaello , Wang Shuishu , Wanninger Timothy G. , Xu Kai , Yang Gengcheng J. , Zhang Baoshan , Zhang Yaqiu , Zhou Tongqing ,   The VRC Production Program, Amharref Nadia , Barry Christopher , Boonyaratanakornkit Boonchai , Carey Elizabeth , Caringal Ria , Carlton Kevin , Chalamalsetty Naga , Charlton Adam , Chaudhuri Rajoshi , Chen Mingzhong , Chen Peifeng , Cibelli Nicole , Cooper Jonathan W. , Dahodwala Hussain , Fleischman Marianna , Frederick Julia C. , Fuller Haley , Gall Jason , Godfroy Isaac , Gollapudi Deepika , Gowetski Daniel , Horwitz Joe , Hussain Althaf , Ivleva Vera , Kueltzo Lisa , Li Yile , Mangalampalli Venkata , Moxey Gabriel , O’Connell Sarah , Patel Aakash , Rosales-Zavala Erwin , Scheideman Elizabeth , Schneck Nicole A. , Schneiderman Zachary , Shadrick William , Vinitsky Alison , Wang Xiangchun E. , Witter Sara , Yang Yanhong , Arnold Frank J. , Doria-Rose Nicole A. , Lei Q. Paula , Ryan Edward T. , Vann Willie F. , Mascola John R. , Kwong Peter D.
Published: February 2020

The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) – when conjugated to the carrier protein, keyhole limpet hemocyanin (KLH) – to be capable of inducing broadly neutralizing responses against HIV-1 in animal models. However, KLH is a multi-subunit particle derived from a natural source, and its manufacture as a clinical product remains a challenge. Here we report the preclinical development of recombinant tetanus toxoid heavy chain fragment (rTTHC) linked to FP8 (FP8-rTTHC) as a suitable FP-conjugate vaccine immunogen. We assessed 16 conjugates, made by coupling the 4 most prevalent FP8 sequences with 4 carrier proteins: the aforementioned KLH and rTTHC; theH. influenzaeprotein D (HiD); and the cross-reactive material from diphtheria toxin (CRM197). While each of the 16 FP8-carrier conjugates could elicit HIV-1-neutralizing responses, rTTHC conjugates induced higher FP-directed responses overall. A Sulfo-SIAB linker yielded superior results over an SM(PEG)2 linker but combinations of carriers, conjugation ratio of peptide to carrier, or choice of adjuvant (Adjuplex or Alum) did not significantly impact elicited FP-directed neutralizing responses in mice. Overall, SIAB-linked FP8-rTTHC appears to be a promising vaccine candidate for advancing to clinical assessment.
Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis
Authors: Zhou Yuqing , Fu Xiaofang , Liu Xiaoxiao , Huang Chenyang , Tian Guo , Ding Cheng , Wu Jie , Lan Lei , Yang Shigui
Published: February 2020

Influenza-related severe pneumonia and acute respiratory distress syndrome (ARDS) are severe threats to human health. The objective of this study was to assess the effects of systematic corticosteroid therapy in patients with pneumonia or ARDS. The PubMed, EMBASE, Web of Science and SCOPUS databases were searched up to July, 2019. Nineteen studies including 6637 individuals were identified, and fifteen studies (6427 patients) were included in the meta-analysis of mortality. Eighteen were observational studies and one was a randomized controlled trial (RCT). The meta-analysis results showed that corticosteroid therapy was associated with significantly higher mortality (OR 1.53, 95% CI [1.16, 2.01]) and incidence of nosocomial infection (OR 3.15, 95% CI [1.54, 6.45]). Subgroup analysis showed that among patients with unadjusted estimates, the odds of mortality were higher in patients receiving corticosteroid treatment (OR 1.98, 95% CI [1.23, 3.17]), however, among patients with adjusted estimates, the result showed no statistically significant difference between corticosteroid group and control group (OR 1.31, 95% CI [0.95, 1.80]). Current data do not support the routine use of corticosteroids in patients with influenza severe pneumonia or ARDS. RCTs are needed to provide more robust evidence.
Photosynthetic rate prediction model of newborn leaves verified by core fluorescence parameters
Authors: Zhang Pan , Zhang Zhongxiong , Li Bin , Zhang Haihui , Hu Jin , Zhao Juan
Published: February 2020

Due to the imperfect development of the photosynthetic apparatus of the newborn leaves of the canopy, the photosynthesis ability is insufficient, and the photosynthesis intensity is not only related to the external environmental factors, but also significantly related to the internal mechanism characteristics of the leaves. Light suppression and even light destruction are likely to occur when there is too much external light. Therefore, focus on the newborn leaves of the canopy, the accurate construction of photosynthetic rate prediction model based on environmental factor analysis and fluorescence mechanism characteristic analysis has become a key problem to be solved in facility agriculture. According to the above problems, a photosynthetic rate prediction model of newborn leaves in canopy of cucumber was proposed. The multi-factorial experiment was designed to obtain the multi-slice large-sample data of photosynthetic and fluorescence of newborn leaves. The correlation analysis method was used to obtain the main environmental impact factors as model inputs, and core chlorophyll fluorescence parameters was used for auxiliary verification. The best modeling method PSO-BP neural network was used to construct the newborn leaf photosynthetic rate prediction model. The validation results show that the net photosynthetic rate under different environmental factors of cucumber canopy leaves can be accurately predicted. The coefficient of determination between the measured values and the predicted values of photosynthetic rate was 0.9947 and the root mean square error was 0.8787. Meanwhile, combined with the core fluorescence parameters to assist the verification, it was found that the fluorescence parameters can accurately characterize crop photosynthesis. Therefore, this study is of great significance for improving the precision of light environment regulation for new leaf of facility crops.
NIPA2 regulates osteoblast function by modulating mitophagy in type 2 diabetes osteoporosis
Authors: Zhao Wei , Zhang Weilin , Ma Hongdong , Yang Maowei
Published: February 2020

The highly selective magnesium transporter non-imprinted in Prader-Willi/Angelman syndrome region protein 2 (NIPA2) has recently been associated with the development and progression of type 2 diabetes osteoporosis, but the mechanisms involved are still poorly understood. Because mitophagy is involved in the pathology of type 2 diabetes osteoporosis, the present study aimed to explore the relationship among NIPA2, mitophagy and osteoblast osteogenic capacity. NIPA2 expression was reduced in C57BKS background db/db mice and in vitro models of type 2 diabetes osteoporosis, and the activation of mitophagy in primary culture osteoblast-derived from db/db mice and in high glucose-treated human fetal osteoblastic cells (hFOB1.19) was observed. Knockdown, overexpression of NIPA2 and pharmacological inhibition of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) showed that NIPA2 increased osteoblast function, which was likely regulated by PTEN induced kinase 1 (PINK1)/E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy via the PGC-1α/forkhead box O3a(FoxO3a)/mitochondrial membrane potential (MMP) pathway. Furthermore, the negative effect of mitophagy on osteoblast function was confirmed by pharmacological regulation of mitophagy and knockdown of Parkin. Taken together, these results suggest that NIPA2 positively regulates the osteogenic capacity of osteoblasts via the mitophagy pathway in type 2 diabetes.
Resolving the positions of defects in superconducting quantum bits
Authors: Bilmes Alexander , Megrant Anthony , Klimov Paul , Weiss Georg , Martinis John M. , Ustinov Alexey V. , Lisenfeld Jürgen
Published: February 2020

Solid-state quantum coherent devices are quickly progressing. Superconducting circuits, for instance, have already been used to demonstrate prototype quantum processors comprising a few tens of quantum bits. This development also revealed that a major part of decoherence and energy loss in such devices originates from a bath of parasitic material defects. However, neither the microscopic structure of defects nor the mechanisms by which they emerge during sample fabrication are understood. Here, we present a technique to obtain information on locations of defects relative to the thin film edge of the qubit circuit. Resonance frequencies of defects are tuned by exposing the qubit sample to electric fields generated by electrodes surrounding the chip. By determining the defect’s coupling strength to each electrode and comparing it to a simulation of the field distribution, we obtain the probability at which location and at which interface the defect resides. This method is applicable to already existing samples of various qubit types, without further on-chip design changes. It provides a valuable tool for improving the material quality and nano-fabrication procedures towards more coherent quantum circuits.
Structural features in common of HBV and HIV-1 resistance against chirally-distinct nucleoside analogues entecavir and lamivudine
Authors: Yasutake Yoshiaki , Hattori Shin-ichiro , Tamura Noriko , Matsuda Kouki , Kohgo Satoru , Maeda Kenji , Mitsuya Hiroaki
Published: February 2020

Chronic hepatitis B virus (HBV) infection is a major public health problem that affects millions of people worldwide. Nucleoside analogue reverse transcriptase (RT) inhibitors, such as entecavir (ETV) and lamivudine (3TC), serve as crucial anti-HBV drugs. However, structural studies of HBV RT have been hampered due to its unexpectedly poor solubility. Here, we show that human immunodeficiency virus type-1 (HIV-1) with HBV-associated amino acid substitutions Y115F/F116Y/Q151M in its RT (HIVY115F/F116Y/Q151M) is highly susceptible to ETV and 3TC. Additionally, we experimentally simulated previously reported ETV/3TC resistance for HBV using HIVY115F/F116Y/Q151M with F160M/M184V (L180M/M204V in HBV RT) substituted. We determined crystal structures for HIV-1 RTY115F/F116Y/Q151M:DNA complexed with 3TC-triphosphate (3TC-TP)/ETV-triphosphate (ETV-TP)/dCTP/dGTP. These structures revealed an atypically tight binding conformation of 3TC-TP, where the Met184 side-chain is pushed away by the oxathiolane of 3TC-TP and exocyclic methylene of ETV-TP. Structural analysis of RTY115F/F116Y/Q151M/F160M/M184V:DNA:3TC-TP also demonstrated that the loosely bound 3TC-TP is misaligned at the active site to prevent a steric clash with the side chain γ-methyl of Val184. These findings shed light on the common structural mechanism of HBV and HIV-1 resistance to 3TC and ETV and should aid in the design of new agents to overcome drug resistance to 3TC and ETV.
Harmonia sedecimnotata (F.): Predatory potential, biology, life table, molecular characterization, and field evaluation against Aphis gossypii Glover
Authors: Boopathi T. , Singh S. B. , Dutta S. K. , Dayal V. , Singh A. R. , Chowdhury S. , Ramakrishna Y. , Aravintharaj R. , Shakuntala I. , Lalhruaipuii K.
Published: February 2020

The ladybird beetle,Harmonia sedecimnotata(F.) was studied in biology, life table, consumption rates, molecular characterization, and field evaluation. The net reproductive rate (R0), based on the age-stage and two-sex life table, was 43.2 eggs/individual. The female adults lived longer (68.1 d) than the male adults (62.9 d). The rate of consumption increased with progress in each stage of development. Compared to the other larval stages of the predator, the fourth stadium consumed most quantities ofAphis gossypiiGlover nymphs (Hemiptera: Aphididae) (200.4). Both female (2214.6) and male (1792.4) consumed more prey (nymphs) than larvae. The net rate of consumption was 1458.92 nymphs of melon aphids. There was no variation in the sequences of the two nucleotides out of 583 bp,H sedecimnotataChina (EU392410) and India (MG720024). Our investigations demonstrated that inoculative release of 30 or 40 or 50 adults per 100 m2attained high reduction of aphids (>90%). Thus, it may be recommended the release rate of 40 adults per 100 m2to suppress the eggplant aphid population.H. sedecimnotatais therefore one of the most promising biological control agents for cotton aphids that can be achieved for instant control through an inoculative release of adults.
Noise patterns in visceral surgical procedures: Analysis of second-by-second dBA data of 599 procedures over the course of one year
Authors: Baltin C. T. , Wilhelm H. , Wittland M. , Hoelscher A. H. , Stippel D. , Astvatsatourov A.
Published: February 2020

The objective of this study is to analyze noise patterns during 599 visceral surgical procedures. Considering work-safety regulations, we will identify immanent noise patterns during major visceral surgeries. Increased levels of noise are known to have negative health impacts. Based on a very fine-grained data collection over a year, this study will introduce a new procedure for visual representation of intra-surgery noise progression and pave new paths for future research on noise reduction in visceral surgery. Digital decibel sound-level meters were used to record the total noise in three operating theatres in one-second cycles over a year. These data were matched to archival data on surgery characteristics. Because surgeries inherently vary in length, we developed a new procedure to normalize surgery times to run cross-surgery comparisons. Based on this procedure, dBA values were adjusted to each normalized time point. Noise-level patterns are presented for surgeries contingent on important surgery characteristics: 16 different surgery types, operation method, day/night time point and operation complexity (complexity levels 1–3). This serves to cover a wide spectrum of day-to-day surgeries. The noise patterns reveal significant sound level differences of about 1 dBA, with the most-common noise level being spread between 55 and 60 dBA. This indicates a sound situation in many of the surgeries studied likely to cause stress in patients and staff. Absolute and relative risks of meeting or exceeding 60 dBA differ considerably across operation types. In conclusion, the study reveals that maximum noise levels of 55 dBA are frequently exceeded during visceral surgical procedures. Especially complex surgeries show, on average, a higher noise exposure. Our findings warrant active noise management for visceral surgery to reduce potential negative impacts of noise on surgical performance and outcome.
Integrative taxonomy, biogeography and conservation of freshwater mussels (Unionidae) in Russia
Authors: Bolotov Ivan N. , Kondakov Alexander V. , Konopleva Ekaterina S. , Vikhrev Ilya V. , Aksenova Olga V. , Aksenov Andrey S. , Bespalaya Yulia V. , Borovskoy Alexey V. , Danilov Petr P. , Dvoryankin Gennady A. , Gofarov Mikhail Y. , Kabakov Mikhail B. , Klishko Olga K. , Kolosova Yulia S. , Lyubas Artem A. , Novoselov Alexander P. , Palatov Dmitry M. , Savvinov Grigory N. , Solomonov Nikolay M. , Spitsyn Vitaly M. , Sokolova Svetlana E. , Tomilova Alena A. , Froufe Elsa , Bogan Arthur E. , Lopes-Lima Manuel , Makhrov Alexander A. , Vinarski Maxim V.
Published: February 2020

Freshwater mussels are ecosystem engineers and keystone species in aquatic environments. Unfortunately, due to dramatic declines this fauna is among the most threatened globally. Here, we clarify the taxonomy and biogeography of Russian Unionidae species based on the most comprehensive multi-locus dataset sampled to date. We revise the distribution and assess the conservation status for each species. This fauna comprises 16 native species from 11 genera and 4 tribes: Anodonta, Pseudanodonta (Anodontini); Amuranodonta, Beringiana, Buldowskia, Cristaria, Sinanodonta (Cristariini); Middendorffinaia, Nodularia, Unio (Unionini); and Lanceolaria (Lanceolariini). No country-level endemic species are known in Russia, except for Buldowskia suifunica that may also occur in China. Sinanodonta woodiana, a non-native species, was introduced from China. Russia comprises the northern parts of Western and Eastern Palearctic subregions. The first subregion with six species encompasses a huge area from the western boundary of Russia to the Lena Basin in Siberia. The second subregion with 10 species covers the Amur Basin, rivers east of the Lena Basin, coastal basins of the Japan Sea, and the North Pacific Islands. The fauna of Russia primarily includes widespread generalist species that are here considered Least Concern (LC). However, Buldowskia suifunica and Sinanodonta lauta have restricted distributions and are assessed here as Vulnerable (VU) and Endangered (EN), respectively.
Computational characterization of halogen vapor attachment, diffusion and desorption processes in zeolitic imidazolate framework-8
Authors: Li Dejie , Han Ying , Li Deqiang , Kang Qi , Shen Dazhong
Published: February 2020

Computational simulation methods are used for characterizing the detailed attachment, diffusion and desorption of halogen vapor molecules in zeolitic imidazolate framework-8 (ZIF-8). The attachment energies of Cl2, Br2 and I2 are −55.2, −48.5 and −43.0 kJ mol−1, respectively. The framework of ZIF-8 is disrupted by Cl2, which bonds with Zn either on the surface or by freely diffusing into the cage. A framework deformation on the surface of ZIF-8 can be caused by the attachment of Br2, but only reorientation of the 2-methylimidazolate linkers (mIms) for I2. In diffusion, the halogen molecules have a tendency to vertically permeate the apertures of cages followed with swing effect implemented by the mIms. Larger rotation angles of mIms are caused by Br2 because of its stronger interaction with mIms than I2. A maximum of 7 Br2 or 5 I2 molecules can be accommodated in one cage. Br2 are clinging to the mIms and I2 are arranged as crystal layout in the cages, therefore in desorption processes molecules attached to the surface and free inside are desorbed while some remained. These results are beneficial for better understanding the adsorption and desorption processes of halogen vapors in the porous materials.