bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAL62 overexpression enhances uridine diphosphoglucose-dependent trehalose synthesis and glycerol metabolism for cryoprotection of baker’s yeast in lean dough
Authors: Sun Xi , Zhang Jun , Fan Hua Zhi , Xiao Ping , Li Feng , Liu Qing Hai , Zhu Bi Wen 
Published: July 2020

Abstract
Background: In Saccharomyces cerevisiae, the alpha-glucosidase (maltase) is a key enzyme in maltose metabolism. Overexpression of the alpha-glucosidase-encoding gene MAL62 has been shown to increase the freezing tolerance of yeast in lean dough. However, its cryoprotection mechanism is still not clear.Results: RNA sequencing (RNA-seq) revealed that MAL62 overexpression increased transcription of uridine diphosphoglucose (UDPG)-dependent trehalose synthesis. The changes in transcript abundance were confirmed by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and enzyme activity assays. When the UDPG-dependent trehalose synthase activity was abolished, MAL62 overexpression failed to promote the synthesis of intracellular trehalose. Moreover, in strains lacking trehalose synthesis, cell viability in the late phase of prefermentation freezing coupled with MAL62 overexpression was slightly reduced, which can be explained by the increase in intracellular glycerol concentration which was consistent with the elevated transcription of glycerol synthesis pathways. Conclusions: The increased freezing tolerance by MAL62 overexpression is mainly achieved by the increased trehalose content via the UDPG-dependent pathway, and glycerol plays a secondary role. These findings shed new light to the mechanism of yeast response to freezing in lean bread dough and can help the improvement of industrial yeast strains.
A combination of genome reduction and promoter engineering can enhance surfactin production by Bacillus amyloliquefaciens LL3
Authors: Zhang Fang , Huo Kaiyue , Song Xingyi , Quan Yufen , Gao Weixia , Wang Shufang , Yang Chao 
Published: July 2020

Abstract
Background: Genome reduction and metabolic engineering have emerged as intensive research hotspots for constructing the optimal functional chassis and various microbial cell factories. Surfactin, a lipopeptide-type biosurfactant with broad spectrum antibiotic activity, has wide application prospects in anticancer therapy, biocontrol and bioremediation. Bacillus amyloliquefaciens LL3, previously isolated by our lab, contains an intact srfA operon in the genome for surfactin biosynthesis.Results: In this study, a genome-reduced strain GR167 lacking ~4.18% of the B. amyloliquefaciens LL3 genome was constructed by deleting some unnecessary genomic regions. Compared with the strain NK-1 (LL3 derivative, ΔuppΔpMC1), GR167 harbored faster growth rate, higher transformation efficiency, increased intracellular reducing power level and higher heterologous protein productivity. Furthermore, the optimal chassis GR167 was engineered for enhanced surfactin production. Firstly, the iturin and fengycin biosynthetic gene clusters were deleted from GR167 to generate GR167ID. Subsequently, two strong promoters PRsuc and PRtpxi from LL3 were obtained by RNA-seq and promoter strength characterization, and then they were individually substituted for the native srfA promoter in GR167ID to generate GR167IDS and GR167IDT. The best mutant GR167IDS showed a 678-fold improvement in the transcriptional level of the srfA operon relative to GR167ID, and it produced 311.35 mg/L surfactin, with a 10.4-fold increase relative to GR167.Conclusions: The genome-reduced strain GR167 was advantageous over the parental strain in several industrially relevant physiological traits assessed and it was highlighted as an optimum chassis for enhanced surfactin production. In future studies, further reduction of the LL3 genome can be expected to create high-performance chassis for synthetic biology applications.
Geographic access and maternal health services utilization in Sélingué Health District, Mali.
Authors: TOUNKARA Moctar , Sangho Oumar , Beebe Madeleine , Whiting-Collins Lillian Joyce , Goins Rebecca R. , Marker Hannah C. , Winch Peter J. , Doumbia Seydou 
Published: July 2020

Abstract
Introduction. Maternal mortality is one of the main causes of death for women of childbearing age in Mali, and improving this outcome is slow, even in high geographic-access regions. Disparities in maternal health services utilization can constitute a major obstacle in the reduction of maternal mortality and denotes a lack of equity in the Malian health system.Literature on maternal health inequity has explored structural and individual factors influencing outcomes but has not examined inequities in health facility distribution within moderate geographic access districts in Mali. The purpose of this article is to examine disparities in education and geographic distance and how they affect utilization of maternal care within the Sélingué health district, a district with moderate geographic access to care, near Bamako, Mali.Methods. We conducted a cross sectional survey with cluster sampling in the Sélingué health district. Maternal health services characteristics and indicators were described. Association between dependent and independent variables was verified using Kendall’s tau-b correlation, Chi square, logistic regression with odds ratio and 95% confidence interval. Gini index and concentration curve were used to measure inequity.Results. The majority of the participants were 20 to 24 years old. Over 68% of our sample had some education, 65% completed at least four ANC visits, and 60.8% delivered at a health facility. Despite this evidence of healthcare access in Sélingué, disparities within the health district impede the other roughly 40% of our sample from utilizing maternal healthcare. The concentration index demonstrated the impact of inequity in geographic access comparing women residing near and far from the referral care facility.Conclusion. Maternal health services underutilization, within a district with moderate geographic access, indicates that deliberate attention should be paid to addressing geographic access even in such a district.
Interleukin-35 inhibited production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells
Authors: Chen Tao , Fu Lixin , Sun Qiaomei , Zhou Peimei , Guo Zai-pei 
Published: July 2020

Abstract
Background: IL-35 is a newly anti-inflammatory cytokine which belong to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, play important roles in the pathogenesis of chronic spontaneous urticarial (CSU). The aim of our study is to explore the inhibited role of IL-35 in HMC-1. Methods: The effects of IL-35 on cell proliferation, cytokine expression and histamine release in human mast cell line (HMC­1) were investigated by CCK8, ELISA or RT-PCR. The phosphorylation of ERK1/2, p38 and JNK1/2, in PMA and A23187 induced HMC-1 cells were detected by Western Blot.Results: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the released of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation of ERK1/2, p38 and JNK1/2, in PMA and A23187 induced HMC-1 cells. Conclusions: This study provides first observations on the inhibitory and anti-inflammtory effect of IL-35 on activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.
The expression of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110 is dependent on the growth phase
Authors: Droste Julian , Ortseifen Vera , Schaffert Lena , Persicke Marcus , Schneiker-Bekel Susanne , Pühler Alfred , Kalinowski Jörn 
Published: July 2020

Abstract
Background: Actinoplanes sp. SE50/110 is the natural producer of the diabetes mellitus drug acarbose, which is highly produced during the growth phase and ceases during the stationary phase. In previous works, the growth-dependency of acarbose formation was assumed to be caused by a decreasing transcription of the acarbose biosynthesis genes during transition and stationary growth phase.Results: In this study, transcriptomic data using RNA-seq and state-of-the-art proteomic data from seven time points of controlled bioreactor cultivations were used to analyze expression dynamics during growth of Actinoplanes sp. SE50/110. A hierarchical cluster analysis revealed co-regulated genes, which display similar transcription dynamics over the cultivation time. Aside from the expected metabolic switch from primary to secondary metabolism during transition phase, we observed a significantly decreasing transcript abundance of all acarbose biosynthetic genes, with the strongest decrease for the monocistronically transcribed genes acbA, acbB, acbD and acbE. Our data confirm a similar trend for acb gene transcription and acarbose formation rate.Surprisingly, the proteome dynamics does not follow the respective transcription for all acb genes. This suggests different protein stabilities or post-transcriptional regulation of the Acb proteins, which in turn could indicate bottlenecks in the acarbose biosynthesis. Furthermore, several genes are co-expressed with the acb gene cluster over the course of the cultivation, including eleven transcriptional regulators (e.g. ACSP50_0424), two sigma factors (ACSP50_0644, ACSP50_6006) and further genes, which have not previously been in focus of acarbose research in Actinoplanes sp. SE50/110.Conclusion: In conclusion, we have demonstrated, that a genome wide transcriptome and proteome analysis in a high temporal resolution is well suited to study the acarbose biosynthesis and the transcriptional and post-transcriptional regulation thereof.
Identification of key pathways and hub genes in the myogenic process of pluripotent stem cell: A bioinformatics study
Authors: Fei Wenyong , Liu Mingsheng , Zhang Yao , Cao Shichao , Wang Xuanqi , Xie Bin , Wang Jingcheng 
Published: July 2020

Abstract
Purpose: The study aims to determine the process of myoginc differentiation in human pluripotent stem cells and to figure out that the key pathways and hub genes in the process, which do helpful for the further research of muscular regeneration.Method: Three gene expression profiles, GSE131125, GSE148994, GSE149055, about the comparisons of pluripotent stem cells and myogenic stem cells from the Gene Expression Omnibus (GEO) data base. Common differentially expressed genes (DEGs) were obtained and for the further analysis as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analysis and protein‑protein interaction (PPI) network. In vitro cell research to verify the hub genes and key pathways.Result:824 DEGs were co-expressed in the three GSEs. 19 hub genes were identified from the PPI network. The GO and KEGG pathway analysis were performed to determine the functions of DEGs. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis.Conclusion: Our research revealed the main hub genes and modules in the myogeinc process of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration. Paving a way for more accurate treatment for muscle dysfunction.
Long-term Outcomes of the R3™ Delta Ceramic Acetabular System in Total Hip Arthroplasty
Authors: Davis Edward Thomas , Remes Ville , Virolainen Petri , Gebuhr Peter , Backlé Bart Van , Revell Matthew P. , Kopjar Branko 
Published: July 2020

Abstract
Background: Whilst bony fixation of hip replacement has stable solutions, there remains controversy over which bearing best optimizes longevity and function. Ceramic-on-ceramic (CoC) bearing combinations are associated with lower risk of revision due to aseptic loosening and dislocation. Evidence for long-term functional outcomes of modern, 4th generation CoC bearings is limited. The aim of this study was to analyze outcomes and complications of the R3™ Acetabular System (Smith & Nephew, Inc., Cordova, TN, USA) in combination with BIOLOX® Delta ceramic femoral head in patients undergoing primary total hip arthroplasty (THA).Methods: Between June 2009 and May 2011, 175 patients (178 hips) were enrolled into a prospective, study at 6 sites in Europe and prospectively followed-up at 3 months and 1, 3, 5, and 7 years postoperative. Results: Total WOMAC score improved from 63 (range, 22-91) preoperative to 8 (range, 0- 8) at 1-year follow-up and remained unchanged at 7-year follow-up. Modified Harris Hip Score improved from 45 (range, 10-87) preoperative to 83 (range, 25-100) at 3 months, 91 (range, 42-100) at 1 year, and 92 (range, 46, 100) at 7 years. UCLA Activity Rating Scale score improved from 3.3 (range, 1-8) preoperative to 6.2 (range, 2-8) at 1 year; it marginally declined to 5.8 (range, 3-8) at 7-year follow-up. There were 4 trochanteric fractures and 5 patients died of unrelated reasons. Three hips were revised (2 periprosthetic fractures and 1 subluxation). The 7-year cumulative survival rate was 98.3%. Conclusion: Clinical and functional improvements of THA with CoC bearing are maintained at 7 years postoperative.
Intraventricular haemorrhage in a Ugandan cohort of low birth weight neonates: The IVHU study
Authors: MacLeod Rachael , Paulson Joseph N , Okalany Noella , Okello Francis , Acom Linda , Ikiror Juliet , Cowan Frances M , Tann Cally J , Dyet Leigh E , Hagmann Cornelia F , Burgoine Kathy 
Published: July 2020

Abstract
Background Globally, 15 million neonates are born prematurely every year, over half in low income countries (LICs). Premature and low birth weight neonates have a higher risk of intraventricular haemorrhage (IVH). There are minimal data regarding IVH in sub-Saharan Africa. This study aimed to examine the incidence, severity and timing of and modifiable risk factors for IVH amongst low-birth-weight neonates in Uganda.Methods This is a prospective cohort study of neonates with birthweights of ≤2000g admitted to a neonatal unit (NNU) in a regional referral hospital in eastern Uganda. Maternal data were collected from interviews and medical records. Neonates had cranial ultrasound (cUS) scans on the day of recruitment and days 3, 7 and 28 after birth. Risk factors were tabulated and are presented alongside odds ratios (ORs) and adjusted odds ratios (aORs) for IVH incidence. Outcomes included incidence, timing and severity of IVH and 28-day survival. Results Overall, 120 neonates were recruited. IVH was reported in 34.2% of neonates; 19.2% had low grade (Papile grades 1-2) and 15% had high grade (Papile grades 3-4). Almost all IVH (90.2%) occurred by day 7, including 88.9% of high grade IVH. Of those with known outcomes, 70.4% (81/115) were alive on day 28 and survival was not associated with IVH. We found that vaginal delivery, gestational age (GA) <32 weeks, resuscitation in the NNU and being small for gestational age (SGA, <10th centile) increased the odds of IVH. Of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. Conclusion In this resource limited NNU in eastern Uganda, more than a third of neonates born weighing ≤2000g had an IVH and the majority of these occurred by day 7. We found that vaginal birth, earlier gestation, being SGA and need for resuscitation after admission to the NNU increased the risk of IVH. This study had a high rate of SGA neonates and the risk factors and relationship of these factors with IVH in this setting needs further investigation. The role of antenatal steroids in the prevention of IVH in LICs also needs urgent exploration.
Recent Advances in the Development of Casein Kinase 1 Inhibitors
Authors: Li Sha-Sha , Dong Yue-Hui , Liu Zhao-Peng 
Published: July 2020

Background:
The casein kinase 1 (CK1) family is involved in regulating many cellular
processes, including membrane trafficking, DNA damage repair, cytoskeleton dynamics,
cytoskeleton maintenance and apoptosis. CK1 isoforms, especially CK1δ and CK1ε have
emerged as important therapeutic targets for severe disorders such as Alzheimer’s disease
(AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer.
Due to the importance of CK1 for the pathogenesis of disorders, there are great interests
in the development of CK1 inhibitors.

Method:
Using SciFinder® as a tool, the publications about the biology of CK1 and the recent
developments of CK1 inhibitors were surveyed with an exclusion of those published as
patents.

Results:
This review presents the current state of knowledge on the development of CK1 inhibitors,
including both synthetic small molecular inhibitors that were divided into 7 categories
according to structural features, and the natural compounds. An overview of the advancement
of CK1 inhibitors was given, with the introduction of various existing CK1 inhibitors,
their inhibitory activities, and the structure-activity relationships.

Conclusion:
Through physicochemical characterization and biological investigations, it is
possible to understand the structure-activity relationship of CK1 inhibitors, which will contribute
to better design and discovery of potent and selective CK1 inhibitors as potential
agents for severe disorders such as AD, ALS and cancer.
The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients
Authors: Okay Gülay , Koc Meliha Meric , Guler Eray Metin , Yabaci Ayşegül , Kocyigit Abdürrahim , Akkoyunlu Yasemin 
Published: July 2020

Background:
Serum cytokine levels over the course of HIV infection usually increase
with immunosuppression and decrease after antiretroviral treatment (ART).

Objectives:
The aim of the study is to compare cytokine levels between HIV-infected patients (HIP)
and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine
levels.

Methods:
The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and
sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples
of HIP at the beginning and at month 6 of ART and in controls.

Results:
The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the
study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive
(p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was
lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002).
There was a positive correlation between the CD4+T cell count and serum concentration of IFN-
γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA
level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive
correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p>0.00).

Conclusions:
Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease
after ART, they were still significantly higher than the controls. IFN-γ responded differently
to ART compared to the other cytokines, indicating that it may play a distinct and important role in
the pathogenesis of HIV infection.
In Silico Investigation of the SARS CoV2 Protease with Thymoquinone, the Major Constituent of Nigella Sativa
Authors: Kadil Youness , Mouhcine Mohammed , Filali Houda 
Published: July 2020

Introduction:
The COVID-19 caused by a new type of coronavirus has emerged from
China and led to thousands of deaths globally. Despite many groups engaged in studying the newly
emerged virus and searching for the treatment, the understanding of the SARS-CoV2 target ligand
interactions represents a key challenge. Several studies are being conducted to identify potential
treatment. Alternatively, the results of numerous studies have shown that protease inhibitors
can be a genuine leader in research. The antiviral activity and beneficial effect against respiratory
disorders of thymoquinone have been largely demonstrated.

Aim:
The aim of this study is to evaluate in silico the inhibition of the replication of SARS CoV2
by thymoquinone.

Methods:
This is a molecular simulation study using SARS CoV2 protease and thymoquinone
structures provided by Protein Data Bank.

Results:
The preliminary results have shown that thymoquinone may have inhibitory activities
against SARS CoV2 protease.

Conclusion:
Furthermore, given the demonstrated results of thymoquinone, we can conclude that
it may be considered as an effective or adjuvant treatment for SARS CoV2 infection.
The Interaction of Isoflavone Phytoestrogens with ERα and ERβ by Molecular Docking and Molecular Dynamics Simulations
Authors: Wang Ting , Liu Yaquan , Zhuang Xuming , Luan Feng , Zhao Chunyan 
Published: July 2020

Aim and Objective:
Isoflavone phytoestrogens, commonly present in natural plants, are
closely related to human health. The combination of them with estrogen receptors in the body can
play an important role in the prevention and treatment of cardiovascular diseases, cancer, and menopausal
diseases. This research is conducted for the wider application of isoflavone phytoestrogens
in various fields.

Methods:
In this study, molecular docking studies and molecular dynamics simulations were performed
to explore the affinities and interaction between three typical isoflavone phytoestrogens and
estrogen receptors (ERα and ERβ), respectively.

Results:
Molecular docking results showed that the affinity of genistein, daidzein, and formononetin
was different, and the ligand structures and hydrogen bonds force were the main factors affecting
the binding abilities.

Conclusion:
The calculation of the binding free energy shows the stability of the complex and the
contribution of various interactions to the binding free energy. The decomposition of binding free
energy indicates that van der Waals interaction and electrostatic interaction promote the binding of
the complex, which are in agreement with the docking studies.
Anticancer Potential of Aguerin B, a Sesquiterpene Lactone Isolated from Centaurea behen in Metastatic Breast Cancer Cells
Authors: Amini Elaheh , Nabiuni Mohammad , Behzad Seyed Bahram , Seyfi Danial , Eisvand Farhad , Sahebkar Amirhossein , Shakeri Abolfazl 
Published: July 2020

Background:
Breast carcinoma is a malignant disease that represents the most common
non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the
use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor
cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident
from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide.

Objective:
In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects
of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of
metastatic-related genes (Pak-1, Rac-1 and HIF-1α).

Methods:
Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using
MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying
molecular basis, the mRNA expressions were evaluated by real time PCR.

Results:
It was found that aguerin B significantly inhibited human breast cancer cell growth in
vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis.
Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α
and Zeb-1 transcriptional levels.

Conclusion:
Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic
effect, suggesting that it may consider as a potential multi target bio compound for treatment
of breast metastatic carcinoma.