bluuebunny/crossref_metadata_2025 huggingface dataset:
Bcl-2-dependent autophagy disruption during aging impairs amino acid utilization that is restored by hochuekkito
Authors: Nahata Miwa , Mogami Sachiko , Sekine Hitomi , Iizuka Seiichi , Okubo Naoto , Fujitsuka Naoki , Takeda Hiroshi
Published: July 2021

Chronic undernutrition contributes to the increase in frailty observed among elderly adults, which is a pressing issue in the sector of health care for older people worldwide. Autophagy, an intracellular recycling system, is closely associated with age-related pathologies. Therefore, decreased autophagy in aging could be involved in the disruption of energy homeostasis that occurs during undernutrition; however, the physiological mechanisms underlying this process remain unknown. Here, we showed that 70% daily food restriction (FR) induced fatal hypoglycemia in 23–26-month-old (aged) mice, which exhibited significantly lower hepatic autophagy than 9-week-old (young) mice. The liver expressions of Bcl-2, an autophagy-negative regulator, and Beclin1–Bcl-2 binding, were increased in aged mice compared with young mice. The autophagy inducer Tat-Beclin1 D11, not the mTOR inhibitor rapamycin, decreased the plasma levels of the glucogenic amino acid and restored the blood glucose levels in aged FR mice. Decreased liver gluconeogenesis, body temperature, physical activity, amino acid metabolism, and hepatic mitochondrial dynamics were observed in the aged FR mice. These changes were restored by treatment with hochuekkito that is a herbal formula containing several autophagy-activating ingredients. Our results indicate that Bcl-2 upregulation in the liver during the aging process disturbs autophagy activation, which increases the vulnerability to undernutrition. The promotion of liver autophagy may offer clinical therapeutic benefits to frail elderly patients.
Genetic discrimination: introducing the Asian perspective to the debate
Authors: Kim Hannah , Ho Calvin W. L. , Ho Chih-Hsing , Athira P. S. , Kato Kazuto , De Castro Leonardo , Kang Hui , Huxtable Richard , Zwart Hub , Ives Jonathan , Lee Ilhak , Joly Yann , Kim So Yoon
Published: July 2021

Our article aims to provide a comprehensive portrayal of how seven Asian jurisdictions have sought to address the challenge of genetic discrimination (GD) by presenting an analysis of the relevant legislation, policies, and practices. Based on our findings, policy discussion and action on preventing or mitigating GD have been narrowly framed in terms of employment, insurance, disability, marriage, and family planning. Except for South Korea, none of the jurisdictions we examined has adopted specific legislation to prevent GD. However, for Asia to truly benefit from its recent scientific and technological progress in genomics, we highlight the need for these jurisdictions to engage more proactively with the challenges of GD through a coordinated regulatory and governance mechanism.
A method for gaining a deeper insight into the aroma profile of olive oil
Authors: Suzuki Daisuke , Sato Yuko , Mori Akane , Tamura Hirotoshi
Published: July 2021

Volatile compounds in food play a crucial role in affecting food quality and consumer preference, but the volatile compounds in olive oil are not fully understood due to the matrix effect of oil. The oiling-out assisted liquid–liquid extraction (OA-LLE), which we previously reported, is an effective method for isolating volatile compounds from edible oils with a strong matrix effect. However, when we apply OA-LLE to extra virgin olive oil (EVOO), the aromatic extracts contain non-volatile compounds such as pigments because of solvent-based extraction. Solvent-assisted flavor evaporation (SAFE) can remove such non-volatiles from extracts, but SAFE is affected by a matrix effect during distillation, resulting in a decrease in performance. By combining the advantages of OA-LLE and SAFE, we propose an effective approach, OA-LLE followed by SAFE (OA-LLE + SAFE), for extracting aroma compounds from EVOO. The “two assists” should help to better understand the native aroma profile of EVOO.
Nanopore sequencing of single-cell transcriptomes with scCOLOR-seq
Authors: Philpott Martin , Watson Jonathan , Thakurta Anjan , Brown Tom , Brown Tom , Oppermann Udo , Cribbs Adam P.
Published: July 2021

Here we describe single-cell corrected long-read sequencing (scCOLOR-seq), which enables error correction of barcode and unique molecular identifier oligonucleotide sequences and permits standalone cDNA nanopore sequencing of single cells. Barcodes and unique molecular identifiers are synthesized using dimeric nucleotide building blocks that allow error detection. We illustrate the use of the method for evaluating barcode assignment accuracy, differential isoform usage in myeloma cell lines, and fusion transcript detection in a sarcoma cell line.
Microbial metagenomic approach uncovers the first rabbit haemorrhagic disease virus genome in Sub-Saharan Africa
Authors: Happi Anise N. , Ogunsanya Olusola A. , Oguzie Judith U. , Oluniyi Paul E. , Olono Alhaji S. , Heeney Jonathan L. , Happi Christian T.
Published: July 2021

Rabbit Haemorrhagic Disease (RHD) causes high morbidity and mortality in rabbits and hares. Here, we report the first genomic characterization of lagovirus GI.2 virus in domestic rabbits from sub-Saharan Africa. We used an unbiased microbial metagenomic Next Generation Sequencing (mNGS) approach to diagnose the pathogen causing the suspected outbreak of RHD in Ibadan, Nigeria. The liver, spleen, and lung samples of five rabbits from an outbreak in 2 farms were analyzed. The mNGS revealed one full and two partial RHDV2 genomes on both farms. Phylogenetic analysis showed close clustering with RHDV2 lineages from Europe (98.6% similarity with RHDV2 in the Netherlands, and 99.1 to 100% identity with RHDV2 in Germany), suggesting potential importation. Subsequently, all the samples were confirmed by RHDV virus-specific RT-PCR targeting the VP60 gene with the expected band size of 398 bp for the five rabbits sampled. Our findings highlight the need for increased genomic surveillance of RHDV2 to track its origin, understand its diversity and to inform public health policy in Nigeria, and Sub-Saharan Africa.
Gender differences in BaYaka forager sleep-wake patterns in forest and village contexts
Authors: Kilius Erica , Samson David R. , Lew-Levy Sheina , Sarma Mallika S. , Patel Ujas A. , Ouamba Yann R. , Miegakanda Valchy , Gettler Lee T. , Boyette Adam H.
Published: July 2021

Sleep studies in small-scale subsistence societies have broadened our understanding of cross-cultural sleep patterns, revealing the flexibility of human sleep. We examined sleep biology among BaYaka foragers from the Republic of Congo who move between environmentally similar but socio-ecologically distinct locations to access seasonal resources. We analyzed the sleep–wake patterns of 51 individuals as they resided in a village location (n = 39) and a forest camp (n = 23) (362 nights total). Overall, BaYaka exhibited high sleep fragmentation (50.5) and short total sleep time (5.94 h), suggestive of segmented sleep patterns. Sleep duration did not differ between locations, although poorer sleep quality was exhibited in the village. Linear mixed effect models demonstrated that women’s sleep differed significantly from men’s in the forest, with longer total sleep time (β ± SE =  − 0.22 ± 0.09, confidence interval (CI) = [− 0.4, − 0.03]), and higher sleep quality (efficiency; β ± SE =  − 0.24 ± 0.09, CI = [− 0.42, − 0.05]). These findings may be due to gender-specific social and economic activities. Circadian rhythms were consistent between locations, with women exhibiting stronger circadian stability. We highlight the importance of considering intra-cultural variation in sleep–wake patterns when taking sleep research into the field.
Communication breakdown: Limits of spectro-temporal resolution for the perception of bat communication calls
Authors: Hörpel Stephen Gareth , Baier A. Leonie , Peremans Herbert , Reijniers Jonas , Wiegrebe Lutz , Firzlaff Uwe
Published: July 2021

During vocal communication, the spectro-temporal structure of vocalizations conveys important contextual information. Bats excel in the use of sounds for echolocation by meticulous encoding of signals in the temporal domain. We therefore hypothesized that for social communication as well, bats would excel at detecting minute distortions in the spectro-temporal structure of calls. To test this hypothesis, we systematically introduced spectro-temporal distortion to communication calls of Phyllostomus discolor bats. We broke down each call into windows of the same length and randomized the phase spectrum inside each window. The overall degree of spectro-temporal distortion in communication calls increased with window length. Modelling the bat auditory periphery revealed that cochlear mechanisms allow discrimination of fast spectro-temporal envelopes. We evaluated model predictions with experimental psychophysical and neurophysiological data. We first assessed bats’ performance in discriminating original versions of calls from increasingly distorted versions of the same calls. We further examined cortical responses to determine additional specializations for call discrimination at the cortical level. Psychophysical and cortical responses concurred with model predictions, revealing discrimination thresholds in the range of 8–15 ms randomization-window length. Our data suggest that specialized cortical areas are not necessary to impart psychophysical resilience to temporal distortion in communication calls.
Mosquito species identification using convolutional neural networks with a multitiered ensemble model for novel species detection
Authors: Goodwin Autumn , Padmanabhan Sanket , Hira Sanchit , Glancey Margaret , Slinowsky Monet , Immidisetti Rakhil , Scavo Laura , Brey Jewell , Sai Sudhakar Bala Murali Manoghar , Ford Tristan , Heier Collyn , Linton Yvonne-Marie , Pecor David B. , Caicedo-Quiroga Laura , Acharya Soumyadipta
Published: July 2021

With over 3500 mosquito species described, accurate species identification of the few implicated in disease transmission is critical to mosquito borne disease mitigation. Yet this task is hindered by limited global taxonomic expertise and specimen damage consistent across common capture methods. Convolutional neural networks (CNNs) are promising with limited sets of species, but image database requirements restrict practical implementation. Using an image database of 2696 specimens from 67 mosquito species, we address the practical open-set problem with a detection algorithm for novel species. Closed-set classification of 16 known species achieved 97.04 ± 0.87% accuracy independently, and 89.07 ± 5.58% when cascaded with novelty detection. Closed-set classification of 39 species produces a macro F1-score of 86.07 ± 1.81%. This demonstrates an accurate, scalable, and practical computer vision solution to identify wild-caught mosquitoes for implementation in biosurveillance and targeted vector control programs, without the need for extensive image database development for each new target region.
Positive evidence for clinical pharmacist interventions during interdisciplinary rounding at a psychiatric hospital
Authors: Stuhec Matej , Tement Valentina
Published: July 2021

Clinical pharmacists have not yet become an integral part of interdisciplinary ward rounds in most psychiatric hospitals across the European Union. This retrospective observational pre-post study examined the impact of clinical pharmacist recommendations in an interdisciplinary medical team during psychiatric hospital rounding. The study included all patients in a Slovenian psychiatric hospital who were hospitalized 2019–2020. The clinical pharmacist made 315 recommendations for a total of 224 participants (average age M = 59.4, median = 56). Psychiatrists accepted 295 (93.7%) of the recommendations. After the recommendations, the number of expressed and potential drug-related problems decreased in 166 (93.8%) and 129 (93.8%) interventions, respectively. Three months after discharge, 222 accepted recommendations were continued (70.5%). The most common recommendations were related to antipsychotics (19.4%, N = 61) followed by antidepressants (16.8%, N = 53). Including a clinical pharmacist in the interdisciplinary ward rounds at a psychiatric hospital reduced the number of expressed and potential drug-related problems with a very high recommendation acceptance rate. These results are the first in Central Europe to explore the benefits of including a clinical pharmacist in ward rounding.
Novel mumps virus epitopes reveal robust cytotoxic T cell responses after natural infection but not after vaccination
Authors: Kaaijk Patricia , Emmelot Maarten E. , Meiring Hugo D. , van Els Cécile A. C. M. , de Wit Jelle
Published: July 2021

Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-B*07:02- and HLA-A*01:01-restricted MuV T cell epitopes from this set of peptides. High frequencies of T cells against these five MuV epitopes could be detected ex vivo in all tested mumps patients. Moreover, these epitope-specific T cells derived from mumps patients displayed strong cytotoxic activity. In contrast, only marginal T cell responses against these novel MuV epitopes could be detected in recently vaccinated persons, corroborating earlier findings. Identifying which MuV epitopes are dominantly targeted in the mumps-specific CD8+ T- response is an important step towards better understanding in the discrepancies between natural infection or vaccination-induced cell-mediated immune protection.
Earthquakes and very deep groundwater perturbation mutually induced
Authors: Kaown Dugin , Lee Kang-Kun , Kim Jaeyeon , Woo Jeong-Ung , Lee Sanghoon , Park In-Woo , Lee Daeha , Lee Jin-Yong , Kim Heejung , Ge Shemin , Yeo In-Wook
Published: July 2021

We report unique observations from drilling and hydraulic stimulation at a depth of approximately 4.3 km in two Enhanced Geothermal System (EGS) wells at the Pohang EGS site, South Korea. We surveyed drilling logs and hydraulic stimulation data, simulated pore pressure diffusion around the fault delineated by seismic and drilling log analyses, conducted acoustic image logging through the EGS wells, observed significant water level drops (740 m) in one of the two EGS wells, and obtained hydrochemical and isotopic variation data in conjunction with the microbial community characteristics of the two EGS wells. We discuss the hydraulic and hydrochemical responses of formation pore water to a few key seismic events near the hypocenter. We focused on how the geochemistry of water that flowed back from the geothermal wells changed in association with key seismic events. These were (1) a swarm of small earthquakes that occurred when a significant circulation mud loss occurred during well drilling, (2) the MW 3.2 earthquake during hydraulic stimulation, and (3) the MW 5.5 main shock two months after the end of hydraulic stimulation. This study highlights the value of real-time monitoring and water chemistry analysis, in addition to seismic monitoring during EGS operation.
A novel strategy for site selective spin-labeling to investigate bioactive entities by DNP and EPR spectroscopy
Authors: Herr Kevin , Fleckenstein Max , Brodrecht Martin , Höfler Mark V. , Heise Henrike , Aussenac Fabien , Gutmann Torsten , Reggelin Michael , Buntkowsky Gerd
Published: July 2021

A novel specific spin-labeling strategy for bioactive molecules is presented for eptifibatide (integrilin) an antiplatelet aggregation inhibitor, which derives from the venom of certain rattlesnakes. By specifically labeling the disulfide bridge this molecule becomes accessible for analytical techniques such as Electron Paramagnetic Resonance (EPR) and solid state Dynamic Nuclear Polarization (DNP). The necessary spin-label was synthesized and inserted into the disulfide bridge of eptifibatide via reductive followed by insertion by a double Michael addition under physiological conditions. This procedure is universally applicable for disulfide containing biomolecules and is expected to preserve their tertiary structure with minimal change due to the small size of the label and restoring of the previous disulfide connection. HPLC and MS analysis show the successful introduction of the spin label and EPR spectroscopy confirms its activity. DNP-enhanced solid state NMR experiments show signal enhancement factors of up to 19 in13C CP MAS experiments which corresponds to time saving factors of up to 361. This clearly shows the high potential of our new spin labeling strategy for the introduction of site selective radical spin labels into biomolecules and biosolids without compromising its conformational integrity for structural investigations employing solid-state DNP or advanced EPR techniques.
Extraction of apex beat waveform from acoustic pulse wave by sound sensing system using stochastic resonance
Authors: Fujita Etsunori , Horikawa Masahiro , Nobuhiro Yoshika , Maeda Shinichiro , Kojima Shigeyuki , Ogura Yumi , Murata Kohji , Kisaka Tomohiko , Taoda Kazushi , Kaneko Shigehiko , Yoshizumi Masao
Published: July 2021

With a sound sensing system using stochastic resonance (4SR), it became possible to obtain an acoustic pulse wave (APW)—a waveform created via a mixture of apex beat and heart sound. We examined 50 subjects who were healthy, with no underlying cardiovascular diseases. We could determine boundary frequency (BF) using APW and phonocardiogram signals. APW data was divided into two bands, one from 0.5 Hz to BF, and a second one from BF to 50 Hz. This permitted the extraction of cardiac apex beat (CAB) and cardiac acoustic sound (CAS), respectively. BF could be expressed by a quadratic function of heart rate, and made it possible to collect CAB and CAS in real time. According to heart rate variability analysis, the fluctuation was 1/f, which indicated an efficient cardiac movement when heart rate was 70 to 80/min. In the frequency band between 0.5 Hz and BF, CAB readings collected from the precordial region resembled apex cardiogram data. The waveforms were classified into five types. Therefore, the new 4SR sensing system can be used as a physical diagnostic tool to obtain biological pulse wave data non-invasively and repeatedly over a long period, and it shows promise for broader applications, including AI analysis.
Long-term efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease
Authors: Mo Guo-ye , Zhou Teng-peng , Guo Hui-zhi , Li Yong-xian , Tang Yong-chao , Guo Dan-qing , Luo Pei-jie , Li Dong-xiao , Yuan Kai , Mo Ling , Zhang Shun-cong
Published: July 2021

This study aimed to evaluate the efficacy and safety of bone cement-augmented pedicle screw fixation for stage III Kümmell disease. Twenty-five patients with stage III Kümmell disease who received bone cement-augmented pedicle screw fixation at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2009 and December 2015 were enrolled. All patients were females with a history of osteoporosis. The vertebral Cobb angle (V-Cobb angle), the fixed segment Cobb Angle (S-Cobb angle), pelvic parameters, visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI) were assessed preoperatively, postoperatively and at the final follow-up. Complications, loosening rate, operation time, and intraoperative bleeding were recorded. The average lumbar vertebral density T-value was − 3.68 ± 0.71 SD, and the average age was 71.84 ± 5.39. The V-Cobb angle, S-Cobb angle, and Sagittal Vertical Axis (SVA) were significantly smaller postoperatively compared to the preoperative values. The VAS and ODI at 1 month after surgery were 3.60 ± 1.00 and 36.04 ± 6.12%, respectively, which were both significantly lower than before surgery (VAS: 8.56 ± 1.04, ODI: 77.80 ± 6.57%). Bone cement-augmented pedicle screw fixation is a safe and effective treatment for stage III Kümmell disease. It can effectively correct kyphosis, restore and maintain sagittal balance, and maintain spinal stability.
Optimizing the catalytic activities of methanol and thermotolerant Kocuria flava lipases for biodiesel production from cooking oil wastes
Authors: Najjar Azhar , Hassan Elhagag Ahmed , Zabermawi Nidal , Saber Saber H. , Bajrai Leena H. , Almuhayawi Mohammed S. , Abujamel Turki S. , Almasaudi Saad B. , Azhar Leena E. , Moulay Mohammed , Harakeh Steve
Published: July 2021

In this study, two highly thermotolerant and methanol-tolerant lipase-producing bacteria were isolated from cooking oil and they exhibited a high number of catalytic lipase activities recording 18.65 ± 0.68 U/mL and 13.14 ± 0.03 U/mL, respectively. Bacterial isolates were identified according to phenotypic and genotypic 16S rRNA characterization as Kocuria flava ASU5 (MT919305) and Bacillus circulans ASU11 (MT919306). Lipases produced from Kocuria flava ASU5 showed the highest methanol tolerance, recording 98.4% relative activity as well as exhibited high thermostability and alkaline stability. Under the optimum conditions obtained from 3D plots of response surface methodology design, the Kocuria flava ASU5 biocatalyst exhibited an 83.08% yield of biodiesel at optimized reaction variables of, 60 ○C, pH value 8 and 1:2 oil/alcohol molar ratios in the reaction mixture. As well as, the obtained results showed the interactions of temperature/methanol were significant effects, whereas this was not noted in the case of temperature/pH and pH/methanol interactions. The obtained amount of biodiesel from cooking oil was 83.08%, which was analyzed by a GC/Ms profile. The produced biodiesel was confirmed by Fourier-transform infrared spectroscopy (FTIR) approaches showing an absorption band at 1743 cm−1, which is recognized for its absorption in the carbonyl group (C=O) which is characteristic of ester absorption. The energy content generated from biodiesel synthesized was estimated as 12,628.5 kJ/mol. Consequently, Kocuria flava MT919305 may provide promising thermostable, methanol-tolerant lipases, which may improve the economic feasibility and biotechnology of enzyme biocatalysis in the synthesis of value-added green chemicals.
Novel silicon bipodal cylinders with controlled resonances and their use as beam steering metasurfaces
Authors: Fawzy Samar M. , Mahmoud Ahmed M. , Ismail Yehea I. , Allam Nageh K.
Published: July 2021

Metasurfaces have paved the way for high performance wavefront shaping and beam steering applications. Phase-gradient metasurfaces (PGM) are of high importance owing to the powerful and relatively systematic tool they offer for manipulating electromagnetic wave fronts and achieving various functionalities. Herein, we numerically present a novel unit cell known as bipodal cylinders (BPC), made of Silicon (Si) and placed on a Silicon dioxide (SiO2) substrate to be compatible with CMOS fabrication techniques and to avoid field leakage into a high index substrate. Owing to its geometrical structure, the BPC structure provides a promising unit cell for electromagnetic wave manipulation. We show that BPC offers a way to shift the electric dipole mode to a frequency higher than that of the magnetic dipole mode. We investigate the effect of varying different geometrical parameters on the performance of such unit cell. Building on that, a metasurface is then presented that can achieve efficient electromagnetic beam steering with high transmission of 0.84 and steering angle of 15.2°; with very good agreement with the theoretically predicted angle covering the whole phase range from 0 to 2$$\pi$$
π
.
Underrecognition and undertreatment of thirst among hospitalized patients with restricted oral feeding and drinking
Authors: Ho Vanda , Goh Gordon , Tang Xuan Rong , See Kay Choong
Published: July 2021

Thirst is distressing but overlooked by healthcare professionals. Patients experience thirst due to comorbidities, physical or cognitive limitations, and iatrogenesis. Nasogastric tube (NGT) use and nil-by-mouth(NBM) orders are common practices that can lead to thirst. However, thirst in these populations has never been formally studied. We aim to examine prevalence of recognition and treatment of thirst among NGT + NBM and NBM patients. Our descriptive study was conducted intermittently over 25 weeks, across 1.5 years, in 12 adult general medicine wards of a tertiary hospital. Cognitively intact NGT + NBM or NBM inpatients, defined as Abbreviated Mental Test score ≥ 8, were studied. One-time questionnaire was administered. Variables included: demography, co-morbidities, clinical condition, feeding route, thirst defined by thirst distress and/or intensity ≥ 3, pain, hunger and volume status. 88 NGT + NBM and NBM patients were studied. 69.3% suffered from thirst. Thirsty patients experienced significant thirst-related distress (mean score ± SD: 5.7 ± 2.5). Subjects with previous stroke and who were euvolemic tended towards thirst. 13.6% were asked about thirst by doctors or nurses. Thirst was a major source of patient distress in our study. We suggest that thirst needs to be actively identified and targeted to achieve person-centred care.
Strain and ligand effects in Pt-Ni alloys studied by valence-to-core X-ray emission spectroscopy
Authors: Chen Jiatang , Finfrock Y. Zou , Wang Zhiqiang , Sham Tsun-Kong
Published: July 2021

Experimental detection of the Pt 5d densities of states in the valence band is conducted on a series of Pt-Ni alloys by high energy resolution valence-to-core X-ray emission spectroscopy (VTC-XES) at the Pt L3-edge. VTC-XES measurements reveal that the Pt d-band centroid shifts away from the Fermi level upon dilution, accompanied by concentration-dependent Pt d-band width. The competition between the strain effect and ligand effect is observed experimentally for the first time. It is found that the d-band widths in Pt3Ni and PtNi are broader than that of Pt metal due to compressive strain which overcompensates the effect of dilution, while it is narrower in PtNi3 where the ligand effect dominates. VTC-XES is demonstrated to be a powerful tool to study the Pt d-band contribution to the valence band of Pt-based bimetallic. The implication for the enhanced activity of Pt-Ni catalysts in oxygen reduction reaction is discussed.
Patch antenna sensor for wireless ice and frost detection
Authors: Kozak Ryan , Khorsand Kasra , Zarifi Telnaz , Golovin Kevin , Zarifi Mohammad H.
Published: July 2021

A patch antenna sensor with T-shaped slots operating at 2.378 GHz was developed and investigated for wireless ice and frost detection applications. Detection was performed by monitoring the resonant amplitude and resonant frequency of the transmission coefficient between the antenna sensor and a wide band receiver. This sensor was capable of distinguishing between frost, ice, and water with total shifts in resonant frequency of 32 MHz and 36 MHz in the presence of frost and ice, respectively, when compared to the bare sensor. Additionally, the antenna was sensitive to both ice thickness and the surface area covered in ice displaying resonant frequency shifts of 2 MHz and 8 MHz respectively between 80 and 160 μL of ice. By fitting an exponential function to the recorded data, the freezing rate was also extracted. The analysis within this work distinguishes the antenna sensor as a highly accurate and robust method for wireless ice accretion detection and monitoring. This technology has applications in a variety of industries including the energy sector for detection of ice on wind turbines and power lines.
Acetaldehyde exposure underlies functional defects in monocytes induced by excessive alcohol consumption
Authors: Shiba Shunsuke , Nakamoto Nobuhiro , Chu Po-Sung , Ojiro Keisuke , Taniki Nobuhito , Yamaguchi Akihiro , Morikawa Rei , Katayama Tadashi , Yoshida Aya , Aoki Ryo , Teratani Toshiaki , Suzuki Takahiro , Miyamoto Takeshi , Hara Sachiko , Yokoyama Akira , Kanai Takanori
Published: July 2021

Increased intestinal permeability and hepatic macrophage activation by endotoxins are involved in alcohol-induced liver injury pathogenesis. Long-term alcohol exposure conversely induces endotoxin immune tolerance; however, the precise mechanism and reversibility are unclear. Seventy-two alcohol-dependent patients withalcohol dehydrogenase-1B(ADH1B, rs1229984) andaldehyde dehydrogenase-2(ALDH2, rs671) gene polymorphisms admitted for alcohol abstinence were enrolled. Blood and fecal samples were collected on admission and 4 weeks after alcohol cessation and were sequentially analyzed. Wild-type andALDH2*2transgenic mice were used to examine the effect of acetaldehyde exposure on liver immune responses. The productivity of inflammatory cytokines of peripheral CD14+monocytes in response to LPS stimulation was significantly suppressed in alcohol dependent patients on admission relative to that in healthy controls, which was partially restored by alcohol abstinence with little impact on the gut microbiota composition. Notably, immune suppression was associated withALDH2/ADH1Bgene polymorphisms, and patients with a combination ofALDH2*1/*2andADH1B*2genotypes, the most acetaldehyde-exposed group, demonstrated a deeply suppressed phenotype, suggesting a direct role of acetaldehyde. In vitro LPS and malondialdehyde-acetaldehyde adducted protein stimulation induced direct cytotoxicity on monocytes derived from healthy controls, and a second LPS stimulation suppressed the inflammatory cytokines production. Consistently, hepatic macrophages of ethanol-administeredALDH2*2transgenic mice exhibited suppressed inflammatory cytokines production in response to LPS compared to that in wild-type mice, reinforcing the contribution of acetaldehyde to liver macrophage function. These results collectively provide new perspectives on the systemic influence of excessive alcohol consumption based on alcohol-metabolizing enzyme genetic polymorphisms.
Introducing the novel Cytoscape app TimeNexus to analyze time-series data using temporal MultiLayer Networks (tMLNs)
Authors: Pierrelée Michaël , Reynders Ana , Lopez Fabrice , Moqrich Aziz , Tichit Laurent , Habermann Bianca H.
Published: July 2021

Integrating -omics data with biological networks such as protein–protein interaction networks is a popular and useful approach to interpret expression changes of genes in changing conditions, and to identify relevant cellular pathways, active subnetworks or network communities. Yet, most -omics data integration tools are restricted to static networks and therefore cannot easily be used for analyzing time-series data. Determining regulations or exploring the network structure over time requires time-dependent networks which incorporate time as one component in their structure. Here, we present a method to project time-series data on sequential layers of a multilayer network, thus creating atemporal multilayer network(tMLN). We implemented this method as a Cytoscape app we named TimeNexus. TimeNexus allows to easily create, manage and visualize temporal multilayer networks starting from a combination of node and edge tables carrying the information on the temporal network structure. To allow further analysis of the tMLN, TimeNexus creates and passes on regular Cytoscape networks in form of static versions of the tMLN in three different ways: (i) over the entire set of layers, (ii) over two consecutive layers at a time, (iii) or on one single layer at a time. We combined TimeNexus with the Cytoscape apps PathLinker and AnatApp/ANAT to extract active subnetworks from tMLNs. To test the usability of our app, we applied TimeNexus together with PathLinker or ANAT on temporal expression data of the yeast cell cycle and were able to identify active subnetworks relevant for different cell cycle phases. We furthermore used TimeNexus on our own temporal expression data from a mouse pain assay inducing hindpaw inflammation and detected active subnetworks relevant for an inflammatory response to injury, including immune response, cell stress response and regulation of apoptosis. TimeNexus is freely available from the Cytoscape app store athttps://apps.cytoscape.org/apps/TimeNexus.
On the phenomena of partial crystallization of highly undercooled magnesium silicate molten droplets
Authors: Shete Ganesh , Mishra Sushil , Karagadde Shyamprasad , Srivastava Atul
Published: July 2021

The present work reports real-time observations of the phenomena of partial crystallization of one of the glass-forming materials, namely enstatite (MgSiO3) from its supercooled liquid droplet. Initially, the molten droplet has been held under purely non-contact conditions using the aerodynamic levitation technique. The desired levels of undercooling have been achieved by deliberately making the levitated molten droplet touch a thin molybdenum wire and hence to initiate heterogeneous nucleation from the point of contact. Influence of thermal parameters like undercooling, cooling rates and recalescence on the process of crystallization is investigated. To understand and report the morphological properties and extent of crystallinity, the solidified enstatite samples have been characterized using optical/scanning electron microscopy (SEM) and X-ray diffraction (XRD) respectively, which confirmed the formation of partially crystallized enstatite spherules and fully glass spherules. XRD showed sharp peaks of enstatite, which confirm crystallinity and a halo profile confirms the amorphous phase of enstatite. Based on the observations of several experiments, we propose the effect of thermal parameters such as levels of undercooling and recalescence on the partial crystallization, as well as partial glass formation from the initially molten droplets of enstatite composition.
Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia
Authors: Al-Hassi Hafid O. , Ng Oliver , Evstatiev Rayko , Mangalika Manel , Worton Natalie , Jambrich Manuela , Khare Vineeta , Phipps Oliver , Keeler Barrie , Gasche Christoph , Acheson Austin G. , Brookes Matthew J.
Published: July 2021

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.
Prevalence of UL97 gene mutations and polymorphisms in cytomegalovirus infection in the colon associated with or without ulcerative colitis
Authors: Tamura Satoshi , Osawa Satoshi , Ishida Natsuki , Miyazu Takahiro , Tani Shinya , Yamade Mihoko , Iwaizumi Moriya , Hamaya Yasushi , Kosugi Isao , Furuta Takahisa , Sugimoto Ken
Published: July 2021

Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV infection in the colon remains unknown. We investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing was performed. In comparison with AD169 reference strain, natural polymorphisms were frequently detected in codons N68D (100%), I244V (100%), and D605E (86.4%). Seven polymorphisms were detected infrequently (< 10%) outside the kinase domain. However, no known GCV resistance mutations were found. There seemed to be no difference between the ratio of polymorphisms in patients with and without UC. In conclusions, we did not detect UL97 gene mutations associated with GCV resistance in GCV-naive patients with or without UC. Consistent with previous reports, D605E polymorphism may be used as a genetic marker for CMV in East Asian countries.
The origin and radiation of the phosphoprotein phosphatase (PPP) enzymes of Eukaryotes
Authors: Kerk David , Mattice Jordan F. , Valdés-Tresanco Mario E. , Noskov Sergei Yu , Ng Kenneth K.-S. , Moorhead Greg B.
Published: July 2021

Phosphoprotein phosphatase (PPP) enzymes are ubiquitous proteins involved in cellular signaling pathways and other functions. Here we have traced the origin of the PPP sequences of Eukaryotes and their radiation. Using a bacterial PPP Hidden Markov Model (HMM) we uncovered “BacterialPPP-Like” sequences in Archaea. A HMM derived from eukaryotic PPP enzymes revealed additional, unique sequences in Archaea and Bacteria that were more like the eukaryotic PPP enzymes then the bacterial PPPs. These sequences formed the basis of phylogenetic tree inference and sequence structural analysis allowing the history of these sequence types to be elucidated. Our phylogenetic tree data strongly suggest that eukaryotic PPPs ultimately arose from ancestors in the Asgard archaea. We have clarified the radiation of PPPs within Eukaryotes, substantially expanding the range of known organisms with PPP subtypes (Bsu1, PP7, PPEF/RdgC) previously thought to have a more restricted distribution. Surprisingly, sequences from the Methanosarcinaceae (Euryarchaeota) form a strongly supported sister group to eukaryotic PPPs in our phylogenetic analysis. This strongly suggests an intimate association between an Asgard ancestor and that of the Methanosarcinaceae. This is highly reminiscent of the syntrophic association recently demonstrated between the cultured Lokiarchaeal species Prometheoarchaeum and a methanogenic bacterial species.
Genetic diversity for drought and low-phosphorus tolerance in rice (Oryza sativa L.) varieties and donors adapted to rainfed drought-prone ecologies
Authors: Roy Somnath , Verma B. C. , Banerjee Amrita , Kumar J. , Ray Uday Sankar , Mandal N. P.
Published: July 2021

Drought and phosphate availability are two major abiotic factors limiting productivity of rice in rainfed upland areas. There has been a constant need for new improved donor with tolerance to multiple abiotic stress conditions for rainfed rice breeding. In the present study, a set of 32 popular rice varieties and landraces were evaluated for drought and low-phosphorus (P) tolerance, and also characterized using grain yield under reproductive drought QTLs (DTY QTLs) and Pup1 linked/specific molecular markers. Twenty-seven genotypes were identified as tolerant to moderately tolerant to drought. The SSR markers linked to ten DTY QTLs classified the genotypes into two groups corresponding to aus and indica. The tolerant genotypes were distributed under both groups. Based on the core markers of Pup1 locus, complete tolerant haplotype was recorded in nine genotypes other than the tolerant check Dular. Nine more genotypes showed the incomplete tolerant haplotypes. The rice genotypes showed significantly high genetic variability for low-P tolerance in hydroponic study. A few genotypes revealed non-Pup1 type tolerance which needs further confirmation.
Early prediction of diagnostic-related groups and estimation of hospital cost by processing clinical notes
Authors: Liu Jinghui , Capurro Daniel , Nguyen Anthony , Verspoor Karin
Published: July 2021

As healthcare providers receive fixed amounts of reimbursement for given services under DRG (Diagnosis-Related Groups) payment, DRG codes are valuable for cost monitoring and resource allocation. However, coding is typically performed retrospectively post-discharge. We seek to predict DRGs and DRG-based case mix index (CMI) at early inpatient admission using routine clinical text to estimate hospital cost in an acute setting. We examined a deep learning-based natural language processing (NLP) model to automatically predict per-episode DRGs and corresponding cost-reflecting weights on two cohorts (paid under Medicare Severity (MS) DRG or All Patient Refined (APR) DRG), without human coding efforts. It achieved macro-averaged area under the receiver operating characteristic curve (AUC) scores of 0·871 (SD 0·011) on MS-DRG and 0·884 (0·003) on APR-DRG in fivefold cross-validation experiments on the first day of ICU admission. When extended to simulated patient populations to estimate average cost-reflecting weights, the model increased its accuracy over time and obtained absolute CMI error of 2·40 (1·07%) and 12·79% (2·31%), respectively on the first day. As the model could adapt to variations in admission time, cohort size, and requires no extra manual coding efforts, it shows potential to help estimating costs for active patients to support better operational decision-making in hospitals.
Synthetic polarization-sensitive optical coherence tomography by deep learning
Authors: Sun Yi , Wang Jianfeng , Shi Jindou , Boppart Stephen A.
Published: July 2021

Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution label-free optical biomedical imaging modality that is sensitive to the microstructural architecture in tissue that gives rise to form birefringence, such as collagen or muscle fibers. To enable polarization sensitivity in an OCT system, however, requires additional hardware and complexity. We developed a deep-learning method to synthesize PS-OCT images by training a generative adversarial network (GAN) on OCT intensity and PS-OCT images. The synthesis accuracy was first evaluated by the structural similarity index (SSIM) between the synthetic and real PS-OCT images. Furthermore, the effectiveness of the computational PS-OCT images was validated by separately training two image classifiers using the real and synthetic PS-OCT images for cancer/normal classification. The similar classification results of the two trained classifiers demonstrate that the predicted PS-OCT images can be potentially used interchangeably in cancer diagnosis applications. In addition, we applied the trained GAN models on OCT images collected from a separate OCT imaging system, and the synthetic PS-OCT images correlate well with the real PS-OCT image collected from the same sample sites using the PS-OCT imaging system. This computational PS-OCT imaging method has the potential to reduce the cost, complexity, and need for hardware-based PS-OCT imaging systems.
Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance
Authors: Schumann Tina , König Jörg , von Loeffelholz Christian , Vatner Daniel F. , Zhang Dongyan , Perry Rachel J. , Bernier Michel , Chami Jason , Henke Christine , Kurzbach Anica , El-Agroudy Nermeen N. , Willmes Diana M. , Pesta Dominik , de Cabo Rafael , O´Sullivan John F. , Simon Eric , Shulman Gerald I. , Hamilton Bradford S. , Birkenfeld Andreas L.
Published: July 2021

Genome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that loss of Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.
Evolution of tissue and developmental specificity of transcription start sites in Bos taurus indicus
Authors: Forutan Mehrnush , Ross Elizabeth , Chamberlain Amanda J. , Nguyen Loan , Mason Brett , Moore Stephen , Garner Josie B. , Xiang Ruidong , Hayes Ben J.
Published: July 2021

To further the understanding of the evolution of transcriptional regulation, we profiled genome-wide transcriptional start sites (TSSs) in two sub-species,Bos taurus taurusandBos taurus indicus, that diverged approximately 500,000 years ago. Evolutionary and developmental-stage differences in TSSs were detected across the sub-species, including translocation of dominant TSS and changes in TSS distribution. The 16% of all SNPs located in significant differentially used TSS clusters across sub-species had significant shifts in allele frequency (472 SNPs), indicating they may have been subject to selection. In spleen and muscle, a higher relative TSS expression was observed inBos indicusthanBos taurusfor all heat shock protein genes, which may be responsible for the tropical adaptation ofBos indicus.
An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum
Authors: O’Keefe Sarah , Zong Guanghui , Duah Kwabena B. , Andrews Lauren E. , Shi Wei Q. , High Stephen
Published: July 2021

The heterotrimeric Sec61 complex is a major site for the biogenesis of transmembrane proteins (TMPs), accepting nascent TMP precursors that are targeted to the endoplasmic reticulum (ER) by the signal recognition particle (SRP). Unlike most single-spanning membrane proteins, the integration of type III TMPs is completely resistant to small molecule inhibitors of the Sec61 translocon. Using siRNA-mediated depletion of specific ER components, in combination with the potent Sec61 inhibitor ipomoeassin F (Ipom-F), we show that type III TMPs utilise a distinct pathway for membrane integration at the ER. Hence, following SRP-mediated delivery to the ER, type III TMPs can uniquely access the membrane insertase activity of the ER membrane complex (EMC) via a mechanism that is facilitated by the Sec61 translocon. This alternative EMC-mediated insertion pathway allows type III TMPs to bypass the Ipom-F-mediated blockade of membrane integration that is seen with obligate Sec61 clients.