bluuebunny/crossref_metadata_2025 huggingface dataset:
발아 고단백 콩의 Lactobacillus brevis 젖산발효에 의한 가바와 이소플라본 함량 및 라디칼 소거활성의 비교
Authors: Hwang Chung Eun , Haque Md. Azizul , Lee Jin Hwan , Joo Ok Soo , Kim Su Cheol , Lee Hee Yul , Um Bong Sik , Park Kyung Sook , Cho Kye Man
Published: March 2020

In this study, soy-powder yogurt (SPY) with enhanced levels of γ-aminobutyric acid (GABA) and isoflavone aglycone was produced from sprouting high-protein soybeans (HPSs). The fermented steam-HPS sprouts (0 to 4 cm) were fermented (72 h) with Lactobacillus brevis, and the total free amino acids (FAAs) of the formed mixtures were determined to be 79.53, 489.93, 877.55, 780.53, and 979.97 mg/100 mL in the fermented HPS (FHPS), and the fermented steam-HPS with 0 cm (FSHPS-0), 1 cm (FSHPS-1), 2 cm (FSHPS-2), and 4 cm sprouting lengths (FSHPS-4), respectively. The levels of glutamic acid (GA) and GABA were observed to be the highest, 100.31 and 101.60 mg/100 mL, respectively, in the unfermented HPS (UFSHPS-1, 1 cm) and FSHPS-1 sprouts, respectively. Moreover, the total contents of the isoflavone glycoside form decreased proportionally to the increasing total levels of isoflavone aglycones after fermentation in FSHPS-0, FSHPS-1, FSHPS-2, and FSHPS-4. The levels of isoflavone aglycones were detected as 350.34, 289.15, 361.61, 445.05, and 491.25 μg/g in FHPS, FSHPS-0, FSHPS-1, FSHPS-2, and FSHPS-4, respectively. While FSHPS-1 exhibited the highest DPPH (63.28%) and ABTS (73.28%) radical scavenging activities, FSHPS-4 contained the highest isoflavone aglycone ratio (81.63%). All in all, the FSHPS-1 mixture prepared in this study exhibited high GABA content and functional prosperity, thereby making it suitable for potential applications in the soy-dairy industry.
Antioxidant and anti-inflammatory activities of water extracts and ethanol extracts from Portulaca oleracea L.
Authors: Kim Dong-Gyu , Shin Jung-Hye , Kang Min-Jung
Published: March 2020

Portulaca oleracea L., a species of Portulacaceae, is ubiquitous. It is a well-known traditional Chinese medicine for removing heat, counteracting toxicity, cooling blood, and maintaining hemostasia; it is also used as antidysentery agent. This study investigated the anti-oxidative and anti-inflammatory activities of water and ethanol extracts from P. oleracea. The total polyphenol content (21.08±0.03 mg GAE/g) and total flavonoid content (5.45±0.76 mg QE/g) of the ethanolic extracts were higher than those of the water extracts. The antioxidative activities were determined by evaluating the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2,2’-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and by the ferric reducing antioxidant potential (FRAP) assay. The ABTS radical scavenging activity of the water extract (75.53%) was higher in those of the water extract (67.03%) at concentration of 1,000 μg/mL. The DPPH radical scavenging activity and FRAP of the ethanol extract were higher than those of the water extract. We also investigated the anti-inflammatory activity of the P. oleracea extracts in LPS-stimulated Raw 264.7 cells. The production levels of nitric oxide (NO) and reactive oxygen species (ROS) significantly decreased with an increasing concentration of the extract. The expression levels of pro-inflammatory cytokines (tumor necrosis faction (TNF)-α, interleukin (IL)-1β, and IL-6) were significantly lower in the ethanol extract than in the LPS alone treatment group. Based on these results, ethanolic extract from P. oleracea could be an effective antioxidant and anti-inflammatory agent.
Effect of freezing pretreatment on the quality of osmotically extracted syrup from Citrus junos peel
Authors: Park Han-Sol , Kim Dong-Seob , Kim Han-Soo , Lee Young-Guen , Chung Hun-Sik
Published: March 2020

In this study, we assessed the effect of freezing pretreatment on the quality of osmotically extracted syrup from Citrus junos peels. Sliced peels were frozen for 7 days at −20°C or −70°C, mixed with sucrose and then stored for 40 days at 15°C. Syrups were prepared from these mixtures after osmotic treatment. Non-frozen fruits were used as control. The initial freezing point of C. junos peels was −4°C. Nominal freezing times were 42 and 13 min for −20°C and −70°C, respectively. The osmotically extracted syrup from the frozen peels was reddish brown while that of the untreated peels was yellow. The titratable acidity of the pretreated syrups was significantly higher than that of the untreated syrup, but clarity, vitamin C content, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were considerably lower. The pretreated syrups showed no notable difference in color, titratable acidity, clarity, and DPPH activity. Furthermore, contents of soluble solids, phenolic compounds, and flavonoids were unaffected. These results suggest that freezing before osmotic extraction affects the quality, producing syrups with higher acidity, reddish brown color, and lower antioxidant activity.
Quality characteristics and antioxidative activity of ‘Sulgidduk’ added with Elaeagnus multiflora powder
Authors: Hong Ju-Yeon , Oh Wang-Kyu
Published: March 2020

The purpose of this study was to evaluate the quality and functionality of Elaeagnus multiflora powder for developing a processed food using Elaeagnus multiflora powder. Elaeagnus multiflora ‘Sulgidduk’ was developed by adding 0, 3, 6, 9 and 12% Elaeagnus multiflora powder and the physicochemical characteristics of the ‘Sulgidduk’ were examined. Analysis of the general contents of the ‘Sulgidduk’ added with Elaeagnus multiflora powder showed that moisture, crude protein, crude lipids and crude ash increased, while the carbohydrate content decreased with increasing amount of added Elaeagnus multiflora powder the pH also decreased. The Brix value and soluble protein content increased as the amount of Elaeagnus multiflora was increased while the reducing sugar content decreased. The ‘Sulgidduk’ “L” value decreased, while its “a” and “b” values increased with increasing amount of Elaeagnus multiflora powder and the hardness, adhesiveness, cohesiveness, and chewiness decreased, the polyphenol contents and electron donating ability also increased. On the basis of these results, the preserved quality of ‘Sulgidduk’ added with Elaeagnus multiflora powder was higher than that of the control ‘Sulgidduk’.
Quality characteristics of Rehmannia glutinosa
dried at different drying temperature
Authors: Kim Yae Jin , Ma Kyung Ho , Han Jong Won , Lee Sang Hoon , Chang Jae Ki , Han Sin Hee
Published: March 2020

Rehmannia glutinosa (RG) is a widely cultivated medicinal crop
in Korea. Its rhizomes are commonly distributed in dried form as a food or
traditional medicine. However, very little research into the drying methods for
R. glutinosa has been conducted. This study was performed
to determine the effect of the drying temperature on the quality characteristics
of R. glutinosa. The famous domestic cultivar
‘Dagang’ was used for the study. The drying experiments were
carried out at 40, 50, 60, 70, and 80°C in a hot air dryer. All samples
were dried until their moisture content was less than 12%; the moisture
content of the raw root was 78.97±1.27%. Under the hot-air drying
conditions, the drying process required 288 h at 40°C, 144 h at
50°C, 45 h at 60°C, 22 h at 70°C, 12 h at 80°C. The
physical properties of RG were different for each drying temperature. When the
temperature was increased, the lightness color value decreased. Hardness which
is an important texture factor, was high for a drying temperature of
50–60°C and relatively low for 40°C, 70°C, and 80°C.
The catalpol content increased with increasing temperature up to 70°C,
and then decreased at higher temperature. Considering the overall
characteristics of the dried RG, hot-air drying at 60°C is optimal to
achieve desirable physical properties and high active content. These results
should provide useful information for the manufacture of high-quality dried
RG.
Quality characteristics of garlic peel according to processing
methods
Authors: Min Ji Hyun , Jeong Jae Hyun , Park Young Uk , Lee Jae Sun , Lee Seong Ju , Chang Who-Bong
Published: March 2020

Garlic peel has been found to have various beneficial effects including
antioxidant activities, antithrombosis activities and cancer inhibition. This
study was to analyze the quality characteristics and antioxidant activities of
garlic peel processed using different methods (control, roasting, steaming,
roasting after steaming and blanching) to determine the most appropriate
processing method for garlic peel to be used as a functional food ingredient.
The lightness color values was highest in the control group, redness was highest
in the roasting after steaming group, and yellowness was highest in the roasting
group. The total pyruvate content of the roasting after steaming group garlic
peel was 37.05 mg/100 g, which was higher than those of the other groups. The
total polyphenol and total flavonoid contents of garlic peel ranged 47.60 to
172.53 mg/100 g and 3.43 to 17.63 mg/100 g, respectively. The highest total
polyphenol content and total flavonoid content were observed for the roasting
after steaming group. 2,2-Diphenyl-1-picrylhydrazyl radical scavenging activity
was also the highest in the roasting after steaming group (81.28%). These
results indicate that the method used to process garlic peel affects its
quality, and that roasting after steaming is the most appropriate processing
method, as it achieves the highest antioxidant activity.
Analysis of mineral and ash contents in domestic commercial
sauces
Authors: Kim Hyun-Jeong , Kim Young-Eun , Kim Ji-Eun , Seo Dong Won , Kim Byung Hee , Lee Sam-Pin
Published: March 2020

To aid in the development of a food nutrient database, the ash and mineral
contents of 26 kinds of commercial sauces were analyzed. The contents of Na, Ca,
K, P, Mg, Fe, Mn, Zn, and Cu were analyzed using ICP-OES, while that of Se was
analyzed using ICP-MS. The reliability of the analytical method for the analysis
of minerals and ash was confirmed based on a control chart. The ash contents of
the sauces ranged from 1.08 to 12.79 g/100 g, with ‘Gondeulenamulbab
yangnyeomjang’ showing the highest Na, K, P, and ash contents. The Na
contents of the sauces differed greatly from 272.68 to 4,336.56 mg/100 g, with
‘Gondeulenamulbab yangnyeomjang’ (4,336.56±67.34 mg/100 g)
exhibiting the highest Na content. The mineral content ranges of the sauces were
5.93–108.36 mg/100 g for Ca, 51.74–448.76 mg/100 g for K, 7.81–115.95 mg/100 g
for P, and 2.69–74.45 mg/100 g for Mg. The sauces also contained 2.14–1,162.73
μg/100 g of Fe, 7.57–609.21 μg/100 g of Mn, 3.38–145.74
μg/100 g of Cu, and 1.51–156.78 μg/100 g of Se. These results can
be utilized as a basic database for the nutritional contents of commercial
sauces as well as for the development of new sauce products.
Potential biochemical markers to identify severe cases among COVID-19 patients
Authors: Xiang Jialin , Wen Jing , Yuan Xiaoqing , Xiong Shun , Zhou Xue , Liu Changjin , Min Xun
Published: March 2020

There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.
gapseq: Informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models
Authors: Zimmermann Johannes , Kaleta Christoph , Waschina Silvio
Published: March 2020

Microbial metabolic processes greatly impact ecosystem functioning and the physiology of multi-cellular host organisms. The inference of metabolic capabilities and phenotypes from genome sequences with the help of reference biomolecular knowledge stored in online databases remains a major challenge in systems biology. Here, we presentgapseq: a novel tool for automated pathway prediction and metabolic network reconstruction from microbial genome sequences.gapseqcombines databases of reference protein sequences (UniProt, TCDB), in tandem with pathway and reaction databases (MetaCyc, KEGG, ModelSEED). This enables the prediction of an organism’s metabolic capabilities from sequence homology and pathway topology criteria. By incorporating a novel LP-based gap-filling algorithm,gapseqfacilitates the construction of genome-scale metabolic models that are suitable for metabolic phenotype predictions by using constraint-based flux analysis. We validatedgapseqby comparing predictions to experimental data for more than 3, 000 bacterial organisms comprising 14, 895 phenotypic traits that include enzyme activity, energy sources, fermentation products, and gene essentiality. This large-scale phenotypic trait prediction test showed, thatgapseqyields an overall accuracy of 81% and thereby outperforms other commonly used reconstruction tools. Furthermore, we illustrate the application ofgapseq-reconstructed models to simulate biochemical interactions between microorganisms in multi-species communities. Altogether,gapseqis a new method that improves the predictive potential of automated metabolic network reconstructions and further increases their applicability in biotechnological, ecological, and medical research.gapseqis available athttps://github.com/jotech/gapseq.
Express saccades during a countermanding task
Authors: Errington Steven P. , Schall Jeffrey D.
Published: March 2020

Express saccades are unusually short latency, visually guided saccadic eye movements. They are most commonly observed when the fixation spot disappears at a consistent, short interval before a target spot appears at a repeated location. The saccade countermanding task includes no fixation-target gap, variable target presentation times, and the requirement to withhold saccades on some trials. These testing conditions should discourage production of express saccades. However, two macaque monkeys performing the saccade countermanding task produced consistent, multimodal distributions of saccadic latencies. These distributions consisted of a longer mode extending from 200 ms to as much as 600 ms after target presentation and another consistently less than 100 ms after target presentation. Simulations revealed that by varying express saccade production, monkeys could earn more reward. If express saccades were not rewarded, they were rarely produced. The distinct mechanisms producing express and longer saccade latencies were revealed further by the influence of regularities in the duration of the fixation interval preceding target presentation on saccade latency. Temporal expectancy systematically affected the latencies of regular but not of express saccades. This study highlights that cognitive control can integrate information across trials and strategically elicit intermittent very short latency saccades to acquire more reward.
Impact of library preparation-induced low GC sequencing bias onSalmonellaserotype prediction using SeqSero2
Authors: Li Shaoting , Zhang Shaokang , Deng Xiangyu
Published: March 2020

A recent study by Uezle et al. reported a lack of O antigen prediction by SeqSero2. We found that Nextera XT-prepared genomes in the study were abnormally challenging for O antigen prediction because of unusually high sequencing bias against low GC regions that was not seen in similarly prepared genomes from other laboratories. We recommend that SeqSero2 users be mindful of the GC-related sequencing bias when analyzing Nextera XT-prepared genomes. Although it is unusual for such biases to compromise serotype prediction by SeqSero2 per our knowledge and analysis, it is unknown whether they could affect subtyping and characterization of other low-GC regions, such asSalmonellapathogenicity islands, when genome assembly is affected by such biases.
In SilicoAnalysis ofB3GALTLGene Reveling 13 Novel Mutations Associated with Peters’-plus syndrome
Authors: Abdelmoneim Abdelrahman H. , Satti Arwa A. , Abdelmageed Miysaa I. , Murshed Naseem S. , Elfadol Nafisa M. , Mustafa Mujahed I. , Makhawi Abdelrafie M.
Published: March 2020

Background

Peters’-plus syndrome is a rare autosomal recessive disorder, which is characterized by a specific malformation of the eye that includes corneal opaqueness and iridocorneal adhesions (Peters’ anomaly) along with other systemic manifestations. Furthermore, various researches report the association between B3GALTL gene and Peters’-plus syndrome. In the current work we aim to analyze the deleterious SNPs in B3GALTL gene that predispose to Peters’-plus syndrome.

Method

the associated SNPs of the coding region of the B3GALTL gene was acquired from National Center for Biotechnology Information and then analyzed by eight softwares (SIFT, Polyphen2, Proven, SNAP2, SNP@GO, PMut, Imutant and Mupro). The physiochemical properties of the resulted SNPs were then analyzed by Hope project website and visualized by chimera software.

Result

Thirteen novel mutations (Y172C, A222V, C260R, C260Y, D349G, I354K, R377C, G379C, G393R, G393E, G395E, G425E, R445W) are discovered in B3GALTL gene to cause deleterious effects leading to the development of Peters’-plus syndrome.

Conclusion

Thirteen novel mutations in B3GALTL gene are predicted to cause Peters’-plus syndrome.
Identification of a plant kinase that phosphorylates the bacterial effector AvrPtoB
Authors: Lei Lei , Stevens Danielle M. , Coaker Gitta
Published: March 2020

A critical component controlling bacterial virulence is the delivery of pathogen effectors into plant cells during infection. Effectors alter host metabolism and immunity for pathogen benefit. Multiple effectors are phosphorylated by host kinases, and this posttranslational modification is important for their activity. We sought to identify host kinases involved in effector phosphorylation. Multiple phosphorylated effector residues matched the proposed consensus motif for the plant calcium-dependent protein kinase (CDPK) and Snf1-related kinase (SnRK) superfamily. The conservedPseudomonaseffector AvrPtoB acts as an E3 ubiquitin ligase and promotes bacterial virulence. We identified a member of the Arabidopsis SnRK family, SnRK2.8, which associated with AvrPtoB in yeast andin planta.SnRK2.8was required for AvrPtoB virulence functions, including facilitating bacterial colonization, suppression of callose deposition, and targeting the plant defense regulator NPR1 and flagellin receptor FLS2. Mass spectrometry revealed AvrPtoB phosphorylation at multiple serine residuesin planta, with S258 phosphorylation significantly reduced in thesnrk2.8knockout. AvrPtoB phospho-null mutants exhibited compromised virulence functions and were unable to suppress NPR1 accumulation, FLS2 accumulation, or inhibit FLS2-BAK1 complex formation upon flagellin perception. These data identify a conserved plant kinase utilized by a pathogen effector to promote disease.
A New, Simple Projection Model for COVID-19 Pandemic
Authors: Lu Jian
Published: March 2020

Background

With the worldwide outbreak of COVID-19, an accurate model to predict how the coronavirus pandemic will evolve in individual countries becomes important and urgent. Our goal is to provide a prediction model to help policy makers in different countries address the epidemic outbreak and adjust the control policies to contain the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) more effectively.

Methods

Unlike the classic public health and virus propagation models, this new projection model takes both government intervention and public response into account to generate reliable projections of the outbreak 10 days to 2 weeks in advance. This method is an observation based projection similar than the classic Moore’s Law in miroelectronics. The Moore’s law is not based on any physics law and yet has anticipated the development of microelectronics for decades. This work is an empirical relation to decribe the evolution of epidemic to pandemic situations in different countries. The country was selected as an observation unit because the regulation and political decision is an national decision for numerous measures such as the implementation of social distancing, the quarantine of suspected cases, and the closing of borders to achieve territorial containment.

Findings

This model has been successfully applied to predict the evolution of pendemic situation in China. Then the model was also validated by the South Korean data. With a reduction of cases calculated as reduction coefficient of the increase rate of daily cases Rc = 2% per day, we observed a very efficient policy with a strict systematic control in both China and South Korea. For the moment, the Canada, USA, Australia may have difficulties to limit the fast evolution of the epidemic. With a Rc<0.5%, it’s particularly important for the USA to consider escalating the control measures because the affected cases can reach more than one million very soon.

Interpertation

Due to the difference of national disciplines and historical culture, the national policy may be implemented and observed with different efficiency. The starting point where the government decided to apply total containment can also play a key role for the evolution of the pendemic situation. The model will allow each national government of the nations still affected by the pandemic to project the situation for the coming 10 to 14 days. It’s very important for the deployment of national and international efforts to stop the pandemic situation.

Funding

National Key R&D Program of China (Ministry of Science & Technology (MOST, China))
Tracking and forecasting milepost moments of the epidemic in the early-outbreak: framework and applications to the COVID-19
Authors: Wang Huiwen , Zhang Yanwen , Lu Shan , Wang Shanshan
Published: March 2020

Background

The outbreak of the 2019 novel coronavirus (COVID-19) has attracted global attention. In the early stage of the outbreak, the most important question concerns some meaningful milepost moments, including (1) the time when the number of daily confirmed cases decreases, (2) the time when the number of daily confirmed cases becomes smaller than that of the daily removed (recovered and death), (3) the time when the number of daily confirmed cases becomes zero, and (4) the time when the number of patients treated in hospital is zero, which indicates the end of the epidemic. Intuitively, the former two can be regarded as two important turning points which indicate the alleviation of epidemic to some extent, while the latter two as two “zero” points, respectively. Unfortunately, it is extremely difficult to make right and precise prediction due to the limited amount of available data at a early stage of the outbreak.

Method

To address it, in this paper, we propose a flexible framework incorporating the effectiveness of the government control to forecast the whole process of a new unknown infectious disease in its early-outbreak. Specially, we first establish the iconic indicators to characterize the extent of epidemic spread, yielding four periods of the whole process corresponding to the four meaningful milepost moments: two turning points and two “zero” points. Then we develop the tracking and forecasting procedure with mild and reasonable assumption. Finally we apply it to analyze and evaluate the COVID-19 using the public available data for mainland China beyond Hubei Province from the China Centers for Disease Control (CDC) during the period of Jan 29th, 2020, to Feb 29th, 2020, which shows the effectiveness of the proposed procedure.

Results

Results show that our model can clearly outline the development of the epidemic at a very early stage. The first prediction results on Jan 29th reveal that the first and second milepost moments for mainland China beyond Hubei Province would appear on Jan 31st and Feb 14th respectively, which are only one day and three days behind the real world situations. Forecasting results indicate that the number of newly confirmed cases will become zero in the mid-late March, and the number of patients treated in the hospital will become zero between mid-March and mid-April in mainland China beyond Hubei Province. The framework proposed in this paper can help people get a general understanding of the epidemic trends in counties where COVID-19 are raging as well as any other outbreaks of new and unknown infectious diseases in the future.
Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury
Authors: Kirita Yuhei , Wu Haojia , Uchimura Kohei , Wilson Parker C. , Humphreys Benjamin D.
Published: March 2020

After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this “failed-repair proximal tubule cell” or FR-PTC, state can be detected in other models of kidney injury, increasing in the aging rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.

Significance Statement

Single nucleus RNA sequencing revealed gene expression changes during repair after acute kidney injury. We describe a small population of proximal tubule cells that fail to repair (FR-PTC). Since this subpopulation expresses abundant pro-inflammatory and profibrotic genes, it may represent a new therapeutic target to improve repair and reduce fibrosis after AKI.
Topoisomerase 3B (TOP3B) DNA and RNA Cleavage Complexes and Pathway to Repair TOP3B-linked RNA and DNA Breaks
Authors: Saha Sourav , Sun Yilun , Huang Shar-Yin , Jo Ukhyun , Zhang Hongliang , Tse-Dinh Yuk-Ching , Pommier Yves
Published: March 2020

Genetic inactivation of TOP3B is linked with schizophrenia, autism, intellectual disability and cancer. The present study demonstrates thatin vivoTOP3B forms both RNA and DNA cleavage complexes (TOP3Bccs) and reveals a pathway for repairing TOP3Bccs. For detecting cellular TOP3Bccs, we engineered a “self-trapping” mutant of TOP3B (R338W TOP3B) and to determine how human cells repair TOP3Bccs, we depleted tyrosyl-DNA phosphodiesterases (TDP1 and TDP2). TDP2-deficient cells produced elevated TOP3Bccs both in DNA and RNA. Conversely, overexpression of TDP2 lowered cellular TOP3Bccs. Using recombinant human TDP2, we demonstrate that TDP2 cannot excise the native form of TOP3Bccs. Hypothesizing that TDP2 cannot access phosphotyrosyl linkage unless TOP3B is either proteolyzed or denatured, we found that cellular TOP3Bccs are ubiquitinated by the E3 Ubiquitin Ligase TRIM41 before undergoing proteasomal degradation and excision by TDP2.

HIGHLIGHTS

Method forin vivodetection of TOP3B cleavage complexes (TOP3Bccs) formed both in DNA and RNA, using a religation defective “self-trapping” R338W TOP3B mutant.

First evidence that TDP2 excises TOPccs produced by a type IA topoisomerase.

TDP2 processes both RNA and DNA TOP3Bccs following their ubiquitylation and proteasomal degradation inside cell.

TRIM41 is the first reported E3 ubiquitin ligase for TOP3Bcc ubiquitylation and proteasomal degradation.
First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naïve and Experienced COVID-19 Patients
Authors: Chen Hongyi , Zhang Zhicheng , Wang Li , Huang Zhihua , Gong Fanghua , Li Xiaodong , Chen Yahong , Wu Jinzi J.
Published: March 2020

As coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo®) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naïve and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naïve and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.
High risk of infection caused Posttraumatic Stress symptoms in individuals with poor sleep quality: A study on influence of Coronavirus disease (COVID-19) in China
Authors: Zhang Fan , Shang Zhilei , Ma Haiying , Jia Yanpu , Sun Luna , Guo Xin , Wu Lili , Sun Zhuoer , Zhou Yaoguang , Wang Yan , Liu Nianqi , Liu Weizhi
Published: March 2020

The influence of the outbreak of coronavirus disease (COVID-19) on mental health was poorly understood. The present study aimed to exam sleep problems and posttraumatic stress symptoms (PTSS) in Chinese immediately after the massive outbreak of COVID-19. A total of 2027 Chinese participated in the present study. Wuhan-expose history, sleep quality and PTSS were measured with self-rating scales. Results showed that there were significant differences of PCL-5 and of sleep quality scores in different data-collection dates (ps<0.05). There were significant differences of PCL-5 scores (t=-2.93, p<0.05) and latency onset of sleep (χ2=9.77, p<0.05) between participants with and without Wuhan-expose history. The interaction effect of Wuhan exposure history× sleep quality significantly influenced PCL-5 (ps<0.05). These results indicate that keeping good sleep quality in individuals with high infectious risk is a way to prevent PTSS.
The impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak - evidence from China
Authors: Shi Peng , Dong Yinqiao , Yan Huanchang , Li Xiaoyang , Zhao Chenkai , Liu Wei , He Miao , Tang Shixing , Xi Shuhua
Published: March 2020

OBJECTIVE

To investigate the impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak.

DESIGN

Ecological study.

SETTING

31 provincial-level regions in mainland China.

MAIN OUTCOME MEASURES

Data on COVID-19 incidence and climate between Jan 20 and Feb 29, 2020.

RESULTS

The number of new confirm COVID-19 cases in mainland China peaked on Feb 1, 2020. COVID-19 daily incidence were lowest at -10 °C and highest at 10 °C, while the maximum incidence was observed at the absolute humidity of approximately 7 g/m3. COVID-19 incidence changed with temperature as daily incidence decreased when the temperature rose. No significant association between COVID-19 incidence and absolute humidity was observed in distributed lag nonlinear models. Additionally, A modified susceptible-exposed-infectious-recovered (M-SEIR) model confirmed that transmission rate decreased with the increase of temperature, leading to further decrease of infection rate and outbreak scale.

CONCLUSION

Temperature is an environmental driver of the COVID-19 outbreak in China. Lower and higher temperatures might be positive to decrease the COVID-19 incidence. M-SEIR models help to better evaluate environmental and social impacts on COVID-19.

What is already known on this topic

Many infectious diseases present an environmental pattern in their incidence.

Environmental factors, such as climate and weather condition, could drive the space and time correlations of infectious diseases, including influenza.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted through aerosols, large droplets, or direct contact with secretions (or fomites) as influenza virus can.

Little is known about environmental pattern in COVID-19 incidence.

What this study adds

The significant association between COVID-19 daily incidence and temperature was confirmed, using 3 methods, based on the data on COVID-19 and weather from 31 provincial-level regions in mainland China.

Environmental factors were considered on the basis of SEIR model, and a modified susceptible-exposed-infectious-recovered (M-SEIR) model was developed.

Simulations of the COVID-19 outbreak in Wuhan presented similar effects of temperature on incidence as the incidence decrease with the increase of temperature.
Repurposing the yeast peroxisome to compartmentalize a toxic enzyme enables improved (S)-reticuline production
Authors: Grewal Parbir S. , Samson Jennifer A. , Baker Jordan J. , Choi Brian , Dueber John E.
Published: March 2020

Eukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with other factors in the cytosol. Increasingly, engineers are researching ways in which synthetic compartmentalization could be used to address challenges in metabolic engineering. Here, we identified that norcoclaurine synthase (NCS), the enzyme which catalyzes the first committed reaction in benzylisoquinoline alkaloid (BIA) biosynthesis, is toxic when expressed cytosolically inSaccharomyces cerevisiaeand, consequently, restricts (S)-reticuline production. We developed a compartmentalization strategy that alleviates NCS toxicity while promoting increased (S)-reticuline titer, achieved through efficient targeting of toxic NCS to the peroxisome while, crucially, taking advantage of the free flow of metabolite substrates and product across the peroxisome membrane. We identified that peroxisome protein capacity inS. cerevisiaebecomes a limiting factor for further improvement of BIA production and demonstrate that expression of engineered transcription factors can mimic the oleate response for larger peroxisomes, further increasing BIA titer without the requirement for peroxisome induction with fatty acids. This work specifically addresses the challenges associated with toxic NCS expression and, more broadly, highlights the potential for engineering organelles with desired characteristics for metabolic engineering.
Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth
Authors: Lloyd Colton J. , Monk Jonathan , Yang Laurence , Ebrahim Ali , Palsson Bernhard O.
Published: March 2020

Sustaining a robust metabolic network requires a balanced and fully functioning proteome. In addition to amino acids, many enzymes require cofactors (coenzymes and engrafted prosthetic groups) to function properly. Extensively validated genome-scale models of metabolism and gene expression (ME-models) have the unique ability to compute an optimal proteome composition underlying a metabolic phenotype, including the provision of all required cofactors. Here we use the ME-model forEscherichia coliK-12 MG1655 to computationally examine how environmental conditions change the proteome and its accompanying cofactor usage. We found that: (1) The cofactor requirements computed by the ME model mostly agree with the standard biomass objective function used in models of metabolism alone (M models); (2) ME-model computations reveal non-intuitive variability in cofactor use under different growth conditions; (3) An analysis of ME-model predicted protein use in aerobic and anaerobic conditions suggests an enrichment in the use of prebiotic amino acids in the proteins used to sustain anaerobic growth (4) The ME-model could describe how limitation in key protein components affect the metabolic state ofE. coli.Genome-scale models have thus reached a level of sophistication where they reveal intricate properties of functional proteomes and how they support differentE. colilifestyles.
Unsupervised manifold learning of collective behavior
Authors: Titus Mathew , Hagstrom George , Watson James R.
Published: March 2020

Collective behavior is an emergent property of numerous complex systems, from financial markets to cancer cells to predator-prey ecological systems. Characterizing modes of collective behavior is often done through human observation, training generative models, or other supervised learning techniques. Each of these cases requires knowledge of and a method for characterizing the macro-state(s) of the system. This presents a challenge for studying novel systems where there may be little prior knowledge. Here, we present a new unsupervised method of detecting emergent behavior in complex systems, and discerning between distinct collective behaviors. We require only metrics,d(1),d(2), defined on the set of agents,X, which measure agents’ nearness in variables of interest. We apply the method of diffusion maps to the systems (X, d(i)) to recover efficient embeddings of their interaction networks. Comparing these geometries, we formulate a measure of similarity between two networks, called the map alignment statistic (MAS). A large MAS is evidence that the two networks are codetermined in some fashion, indicating an emergent relationship between the metricsd(1)andd(2). Additionally, the form of the macro-scale organization is encoded in the covariances among the two sets of diffusion map components. Using these covariances we discern between different modes of collective behavior in a data-driven, unsupervised manner. This method is demonstrated on empirical fish schooling data. We show that our state classification subdivides the known behaviors of the school in a meaningful manner, leading to a finer description of the system’s behavior.

Author summary

Many complex systems in society and nature exhibit collective behavior where individuals’ local interactions lead to system-wide organization. One challenge we face today is to identify and characterize these emergent behaviors, and here we have developed a new method for analyzing data from individuals, to detect when a given complex system is exhibiting system-wide organization. Importantly, our approach requires no prior knowledge of the fashion in which the collective behavior arises, or the macro-scale variables in which it manifests. We apply the new method to an agent-based model and empirical observations of fish schooling. While we have demonstrated the utility of our approach to biological systems, it can be applied widely to financial, medical, and technological systems for example.
Potential role of theXcircular code in the regulation of gene expression
Authors: Thompson Julie D. , Ripp Raymond , Mayer Claudine , Poch Olivier , Michel Christian J.
Published: March 2020

TheXcircular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that theXcircular code has the important mathematical property of being an error-correcting code. Thus, motifs of theXcircular code, i.e. a series of codons belonging toX, which are significantly enriched in the genes, allow identification and maintenance of the reading frame in genes.Xmotifs have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role ofXmotifs as functional elements in the regulation of gene expression. Surprisingly, the definition of a simple parameter identifies several relations between theXcircular code and gene expression. First, we identify a correlation between the 20 codons of theXcircular code and the optimal codons/dicodons that have been shown to influence translation efficiency. Using previously published experimental data, we then demonstrate that the presence ofXmotifs in genes can be used to predict the level of gene expression. Based on these observations, we propose the hypothesis that theXmotifs represent a new genetic signal, contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.

Author Summary

The standard genetic code is used by (quasi-) all organisms to translate information in genes into proteins. Recently, other codes have been identified in genomes that increase the versatility of gene decoding. Here, we focus on the circular codes, an important class of genome codes, that have the ability to detect and maintain the reading frame during translation. Motifs of theXcircular code are enriched in protein-coding genes from most organisms from bacteria to eukaryotes, as well as in important molecules in the gene translation machinery, including transfer RNA (tRNA) and ribosomal RNA (rRNA). Based on these observations, it has been proposed that theXcircular code represents an ancestor of the standard genetic code, that was used in primordial systems to simultaneously decode a smaller set of amino acids and synchronize the reading frame. Using previously published experimental data, we highlight several links between the presence ofXmotifs in genes and more efficient gene expression, supporting the hypothesis that theXcircular code still contributes to the complex dynamics of gene regulation in extant genomes.
DrosophilaActivin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes
Authors: Kim Myung-Jun , O’Connor Michael B.
Published: March 2020

The Myostatin/Activin branch of the TGFβ superfamily acts as a negative regulator of mammalian skeletal muscle size, in part, through downregulation of insulin/IGF-1 signaling. Surprisingly, recent studies inDrosophilaindicate that Activin signaling acts as a positive regulator of muscle size. Here we demonstrate thatDrosophilaActivin signaling promotes growth of the muscle cells along all three axes; width, length and thickness. In addition, Activin signaling positively regulates the InR/dTORC1 pathway and the level of MHC, an essential sarcomeric protein, via promoting the transcription ofPdk1andAkt1. Enhancing InR/dTORC1 signaling in the muscle of Activin pathway mutants restores MHC levels close to wild-type, but only increased the width of muscle cells. In contrast, hyperactivation of the Activin pathway increases the length of muscle cells even when MHC levels were lowered by suppression of dTORC1. Together, these results indicate thatDrosophilaActivin pathway regulates larval muscle geometry via promoting InR/dTORC1-dependent MHC production and the differential assembly of sarcomeric components into either pre-existing (width) or new (length) sarcomeric units depending on the balance of InR/dTORC1 and Activin signals.
Deletion of FUNDC2 and CMC4 on chromosome Xq28 is sufficient to cause hypergonadotropic hypogonadism in men
Authors: Deng Xinxian , Fang He , Pathak Asha , Zou Angela M. , Neufeld-Kaiser Whitney , Malouf Emily A. , Failor R. Alan , Hisama Fuki M. , Liu Yajuan J.
Published: March 2020

Background

Hypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated.

Methods

Here, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Furthermore, expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion.

Results

Our patient’s Xq28 deletion is 44,806bp and contains only two genes FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier regulation, apoptosis, inflammatory response and gonadotropin-releasing regulation. Indeed, our patient has an elevated FSH level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation is skewed towards the deleted X, suggesting a mechanism to avoid FSH dysregulation.

Conclusion

Compared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and/or CMC4 results in dysregulation of apoptosis, inflammation and FSH, and is sufficient to cause Xq28-associated HH.
Testing structural models of psychopathology at the genomic level
Authors: Waldman Irwin D. , Poore Holly E. , Luningham Justin M. , Yang Jingjing
Published: March 2020

Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotypic levels. Despite recent efforts by collaborative consortia such as the Hierarchical Taxonomy of Psychopathology (HiTOP), this structure remains unclear. In this study, we tested multiple alternative structural models of psychopathology at the genomic level, using the genetic correlations among fourteen psychiatric disorders and related psychological traits estimated from GWAS summary statistics. The best-fitting model included four correlated higher-order factors – externalizing, internalizing, thought problems, and neurodevelopmental disorders – which showed distinct patterns of genetic correlations with external validity variables and accounted for substantial genetic variance in their constituent disorders. A bifactor model including a general factor of psychopathology as well as the four specific factors fit worse than the above model. Several model modifications were tested to explore the placement of some disorders – such as bipolar disorder, obsessive-compulsive disorder, and eating disorders – within the broader psychopathology structure. The best-fitting model indicated that eating disorders and obsessive-compulsive disorder, on the one hand, and bipolar disorder and schizophrenia, on the other, load together on the same thought problems factor. These findings provide support for several of the HiTOP higher-order dimensions and suggest a similar structure of psychopathology at the genomic and phenotypic levels.