bluuebunny/crossref_metadata_2025 huggingface dataset:
FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis
Authors: Khanehzad Maryam , Abbaszadeh Roya , Holakuyee Marzieh , Modarressi Mohammad Hossein , Nourashrafeddin Seyed Mehdi
Published: January 2021

Background

Spermatogenesis is a complex process that is controlled by interactions between germ cells and somatic cells. The commitment of undifferentiated spermatogonia to differentiating spermatogonia and normal spermatogenesis requires the action of gonadotropins. Additionally, numerous studies revealed the role of retinoic acid signaling in induction of germ cell differentiation and meiosis entry.

Main text

Recent studies have shown that expression of several RA signaling molecules including Rdh10, Aldh1a2, Crabp1/2 are influenced by changes in gonadotropin levels. Components of signaling pathways that are regulated by FSH signaling such as GDNF, Sohlh1/2, c-Kit, DMRT, BMP4 and NRGs along with transcription factors that are important for proliferation and differentiation of spermatogonia are also affected by retinoic acid signaling.

Conclusion

According to all studies that demonstrate the interface between FSH and RA signaling, we suggest that RA may trigger spermatogonia differentiation and initiation of meiosis through regulation by FSH signaling in testis. Therefore, to the best of our knowledge, this is the first time that the correlation between FSH and RA signaling in spermatogenesis is highlighted.
Designing provider-focused implementation trials with purpose and intent: introducing the PRECIS-2-PS tool
Authors: Norton Wynne E. , Loudon Kirsty , Chambers David A. , Zwarenstein Merrick
Published: January 2021

Background

First articulated by Schwartz and Lellouch (1967), randomized controlled trials (RCTs) can be conceptualized along a continuum from more explanatory to more pragmatic. The purpose and intent of the former is to test interventions under ideal contexts, and the purpose and intent of the latter is to test interventions in real-world contexts. The PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) is a validated tool that helps researchers make decisions about the elements of the trial to match the overall purpose and intent of the trial along the continuum. The PRECIS-2 tool has guided the design of hundreds of RCTs. However, a few aspects of the tool would benefit from greater clarity, including its application to provider-focused implementation trials rather than patient-focused intervention trials.

Main text

We describe the newly developed PRECIS-2-Provider Strategies (PRECIS-2-PS) tool, an extension of the PRECIS-2 tool, which has been adapted for trials testing provider-focused strategies. We elaborate on nine domains that can make a provider-focused trial more explanatory or more pragmatic, including eligibility, recruitment, setting, implementation resources, flexibility of provider strategies, flexibility of intervention, data collection, primary outcome, and primary analysis. We detail the complementary roles that researchers and stakeholders play in the trial design phase, with implications for generalizability of trial results to the contexts in which they are intended to be applied.

Conclusions

The PRECIS-2-PS tool is designed to help research and practice teams plan for provider-focused trials that reflect the overall intent and purpose of the trial. The tool has potential to help advance the science of provider-focused strategies across a range of trials, with the ultimate goal of facilitating the adoption, integration, and sustainability of provider-focused strategies outside the context of trials.
Exosomal miR-186 derived from BMSCs promote osteogenesis through hippo signaling pathway in postmenopausal osteoporosis
Authors: Li Lu , Zhou Xin , Zhang Jun-tao , Liu Ai-feng , Zhang Chao , Han Jin-chang , Zhang Xiao-qing , Wu Si , Zhang Xiao-yu , Lv Fu-quan
Published: January 2021

Background

Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited.

Methods

We used real-time polymerase chain reaction (qPCR), Western blotting, and RNA pull down to investigate the relationship between miR-186 and MOB Kinase Activator 1A (Mob1). Also, we investigated the effect of exosome in osteogenesis using alkaline phosphatase (ALP) staining. And hematoxylin eosin (HE) staining was used to verify the osteogenesis in PMO model.

Results

Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO + Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis.

Conclusions

We concluded that exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.
Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study
Authors: Levy Bruno , Fritz Caroline , Piona Caroline , Duarte Kevin , Morelli Andrea , Guerci Philippe , Kimmoun Antoine , Girerd Nicolas
Published: January 2021

Background

Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns.

Methods

Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1–H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases.

Results

Esmolol was infused 9 (6.4–11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34–0.83) to 0.78 (0.3–1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110–125) to 100 (92–103) beats/min and a decrease in cardiac index from 4.2 (3.1–4.4) to 2.9 (2.5–3.7) l/min/m−2. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients.

Conclusion

In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).
NRG1 fusions in breast cancer
Authors: Howarth Karen D. , Mirza Tashfina , Cooke Susanna L. , Chin Suet-Feung , Pole Jessica C. , Turro Ernest , Eldridge Matthew D. , Garcia Raquel Manzano , Rueda Oscar M. , Boursnell Chris , Abraham Jean E. , Caldas Carlos , Edwards Paul A. W.
Published: January 2021

Background

NRG1gene fusions may be clinically actionable, since cancers carrying the fusion transcripts can be sensitive to tyrosine kinase inhibitors. TheNRG1gene encodes ligands for the HER2(ERBB2)-ERBB3 heterodimeric receptor tyrosine kinase, and the gene fusions are thought to lead to autocrine stimulation of the receptor. TheNRG1fusion expressed in the breast cancer cell line MDA-MB-175 serves as a model example of such fusions, showing the proposed autocrine loop and exceptional drug sensitivity. However, its structure has not been properly characterised, its oncogenic activity has not been fully explained, and there is limited data on such fusions in breast cancer.

Methods

We analysed genomic rearrangements and transcripts ofNRG1in MDA-MB-175 and a panel of 571 breast cancers.

Results

We found that the MDA-MB-175 fusion—originally reported as aDOC4(TENM4)-NRG1fusion, lacking the cytoplasmic tail ofNRG1—is in reality a double fusion,PPP6R3-TENM4-NRG1, producing multiple transcripts, some of which include the cytoplasmic tail. We hypothesise that manyNRG1fusions may be oncogenic not for lacking the cytoplasmic domain but because they do not encode NRG1’s nuclear-localised form. The fusion in MDA-MB-175 is the result of a very complex genomic rearrangement, which we partially characterised, that creates additional expressed gene fusions,RSF1-TENM4,TPCN2-RSF1, andMRPL48-GAB2.

We searched forNRG1rearrangements in 571 breast cancers subjected to genome sequencing and transcriptome sequencing and found four cases (0.7%) with fusions,WRN-NRG1,FAM91A1-NRG1,ARHGEF39-NRG1, andZNF704-NRG1, all splicing intoNRG1at the same exon as in MDA-MB-175. However, theWRN-NRG1andARHGEF39-NRG1fusions were out of frame. We identified rearrangements ofNRG1in many more (8% of) cases that seemed more likely to inactivate than to create activating fusions, or whose outcome could not be predicted because they were complex, or both. This is not surprising becauseNRG1can be pro-apoptotic and isinactivated in some breast cancers.

Conclusions

Our results highlight the complexity of rearrangements ofNRG1in breast cancers and confirm that some do not activate but inactivate. Careful interpretation ofNRG1rearrangements will therefore be necessary for appropriate patient management.
Description of a rat model of polymicrobial abdominal sepsis mimicking human colon perforation
Authors: Utiger Julia M. , Glas Michael , Levis Anja , Prazak Josef , Haenggi Matthias
Published: January 2021

Objective

Standard rodent sepsis models as cecal ligation and puncture models (CLP) or cecal ligation and incision models (CLI) are frequently not suited experiments, mainly because they lack surgical repair, and they are difficult to control for severity. The colon ascendens stent peritonitis model (CASP) overcomes some of these limitations.

Result

Here we present our modification of the rodent CASP model, where severity of sepsis can be controlled by timing of surgical repair and treatment, and by diameter of the stent. Further, basic hemodynamic monitoring (blood pressure and heart rate) and frequent blood sampling can be achieved, which might guide further treatment.
Biochemical and molecular changes of the zosteric acid-treated Escherichia coli biofilm on a mineral surface
Authors: Villa Federica , Secundo Francesco , Forlani Fabio , Cattò Cristina , Cappitelli Francesca
Published: January 2021

Purpose

The main goal of the present work was to assess the effectiveness of zosteric acid (ZA) in hindering Escherichia coli biofilm formation on a mineral surface.

Methods

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) flow system was used to probe in situ the biochemical changes induced by ZA on E. coli sessile cells growing on the zinc selenide ATR plate. Comparative proteome analysis was conducted on the sessile cells to better understand the principal molecular changes that occur on ZA-treated biofilms.

Results

The ZA treatment modified the kinetics of the biofilm development. After the ZA exposure, dramatic changes in the carbohydrates, proteins, and DNA profiles were observed over time in the ATR-FTIR spectra. These results were translated into the physiological effects such as the reduction of both the biomass and the EPS contents, the inhibition of the biofilm growth, and the promotion of the detachment. In E. coli sessile cells, the comparative proteome analysis revealed that, while the stress responses were upregulated, the pathways belonging to the DNA replication and repair were downregulated in the ZA-treated biofilms.

Conclusions

The ZA reduced the binding capability of E. coli cells onto the ZnSe crystal, hindering the firm adhesion and the subsequent biofilm development on a mineral surface. The variation of the protein patterns indicated that the ZA acted as a stress factor on the sessile cells that seemed to discourage biomass proliferation, consequently decreasing the surface colonization.
Myocardial repair of bioengineered cardiac patches with decellularized placental scaffold and human-induced pluripotent stem cells in a rat model of myocardial infarction
Authors: Jiang Yu , Sun Si-Jia , Zhen Zhe , Wei Rui , Zhang Nannan , Liao Song-Yan , Tse Hung-Fat
Published: January 2021

Background

The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown.

Objective

We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair.

Methods and results

A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor-1, basic fibroblast growth factor, angiogenin, and angiopoietin-2. In vitro optical mapping showed that the BCP exhibited organized mechanical contraction and synchronized electrical propagation. RNA sequencing showed that DP enhanced the maturation of hiPSC-CMs compared with the monolayer of cultured hiPSC-CMs. At 4 weeks follow-up, the BCP significantly improved left ventricular (LV) function, as determined by LV ejection fraction, fractional shortening, + dP/dtmax, and end-systolic pressure-volume relationship, compared with the MI, MI + DP, and MI + CM groups. Moreover, histological examination revealed that engraftment of the BCP at the infarct zone decreased infarct size and increased cell retention and neovascularization compared with the MI, MI + DP, and MI + CM groups.

Conclusions

Our results demonstrate that a DP scaffold contains multiple growth and angiogenic factors that enhance the maturation and survival of seeded hiPSC-CMs. Transplantation of a BCP is superior to DP or hiPSC-CMs alone in reducing infarct size and improving cell retention and neovascularization, thus providing a novel therapy for myocardial repair following MI.
The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C) priming through promoting the expression of indoleamine 2,3-dioxygenase
Authors: Lim Ji-Young , Kim Byung-Su , Ryu Da-Bin , Kim Tae Woo , Park Gyeongsin , Min Chang-Ki
Published: January 2021

Background

Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner.

Methods

To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9.

Results

Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC.

Conclusions

The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.
Efficacy of stem cells therapy for Crohn’s fistula: a meta-analysis and systematic review
Authors: Cao Yantian , Su Qi , Zhang Bangjie , Shen Fangfang , Li Shaoshan
Published: January 2021

Background

Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn’s fistula.

Methods

Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn’s fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0.

Results

Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn’s fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 107 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14).

Conclusions

Our study has highlighted that stem cells was a promising method in the treatment of Crohn’s fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.
GDF-5 promotes epidermal stem cells proliferation via Foxg1-cyclin D1 signaling
Authors: Zhao Xiaohong , Bian Ruyu , Wang Fan , Wang Ying , Li Xue , Guo Yicheng , Zhang Xiaorong , Luo Gaoxing , Zhan Rixing
Published: January 2021

Objective

Epidermal stem cells (EpSCs) can self-renew, which are responsible for the long-term maintenance of the skin, and it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. GDF-5, also known as BMP-14, is a member of the BMP family and can be used as a self-renewal supporter. Here, we studied the effects of GDF-5 on mouse EpSCs proliferation mechanism in wound healing.

Methods

Firstly, the effects of GDF-5 on EpSCs proliferation was tested by using CCK8 reagent and PCNA expression was analyzed by Western blotting. Secondly, we screened genes that promote EpSCs proliferation in the FOX and cyclin family by qPCR, and then the protein expression level of the selected genes was further analyzed by Western blotting. Thirdly, siRNA plasmids and pAdEasy adenovirus were transfected or infected, respectively, into mouse EpSCs to detect the effect of target genes on GDF-5-induced cell proliferation. Furthermore, we injected GDF-5 to a deep partial thickness burn mouse model for finding out whether EpSCs proliferation can be detected by immunohistochemical. Finally, the relevant target genes were analyzed by qPCR, immunoblotting, and dual-luciferase reporter gene detection.

Results

We discovered that 100 ng/ml recombinant mouse GDF-5 was the optimal concentration for promoting mouse EpSCs proliferation. Through preliminary screened by qPCR, we found that Foxg1 and cyclin D1 could be the downstream molecules of GDF-5, and the results were confirmed by Western blotting. And the effect of GDF-5 on mouse EpSCs proliferation was adjusted by Foxg1/cyclin D1 in vitro and in vivo. Besides, GDF-5-induced transcription of cyclin D1 was regulated by Foxg1-mediated cyclin D1 promoter activity.

Conclusion

This paper showed that GDF-5 promotes mouse EpSCs proliferation via Foxg1-cyclin D1 signal pathway. It is suggested that GDF-5 may be a new approach to make EpSCs proliferation which can be used in wound healing.
Sex-dependent differences in the secretome of human endothelial cells
Authors: Cattaneo Maria Grazia , Banfi Cristina , Brioschi Maura , Lattuada Donatella , Vicentini Lucia M.
Published: January 2021

Background

Cellular sex has rarely been considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and “omics” approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.

Methods

We performed proteomic and Gene Ontology (GO) analyses of the secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and Western blot techniques and efferocytosis through the ability of the macrophage cell line RAW 264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR.

Results

Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison with female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggested that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seemed to be independent on PTX3 expression.

Conclusions

Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.
Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke
Authors: Manwani Bharti , Fall Pamela , Zhu Liang , O’Reilly Meaghan Roy , Conway Sarah , Staff Ilene , McCullough Louise D.
Published: January 2021

Background

Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.

Methods

Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17β-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression.

Results

We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04).

Conclusions

Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.
New insights into the taxonomy and evolution of Jurassic planktonic foraminifera
Authors: Gradstein Felix , Waskowska Anna
Published: January 2021

Globuligerina glinskikhae nov. sp. Gradstein & Waskowska and Globuligerina waskowskae nov. sp. Gradstein are new species of Jurassic planktonic foraminifera from the Middle Jurassic of Dagestan and Poland. G. glinskikhae nov. sp. with its remarkable ‘protoglobigerine’ test may be an early evolutionary offshoot of Globuligerina oxfordiana (Grigelis). It may be an index taxon for upper Bajocian through Bathonian strata in Eastern Europe and Southwest Asia, and might be recognizable also in thin sections. We consider G. waskowskae nov. sp. to be a possible forerunner of Conoglobigerina helvetojurassica (Haeusler), the first planktonic foraminiferal species with a reticulate wall texture. Currently, is only known from Poland. In some localities, specimens of G. oxfordiana and of G. glinskikhae nov. sp. posses an additional apertural opening, often lacking a rim; its function is enigmatic. The postulated lineage from Jurassic Globuligerina balakhmatovae (Morozova) to Cretaceous Clavihedbergella eocretacea Neagu is refined with the description of Petaloglobigerina simmonsi nov. gen., nov. sp. Gradstein from the Kimmeridgian of Portugal. The evolutionary transition from G. balakhmatovae to P. simmonsi occurs by means of the ontogenic development of a petaloid test, with a pronounced flattening of the whorl with ovate chambers, the last ones often offset and twisted. Jurassic planktonic foraminifera, now known to consist of three genera and 12+ species underwent long periods of stasis, interrupted by late Bajocian, mid-Oxfordian and early Kimmeridgian evolution. The three ‘stasis and root’ taxa G. oxfordiana, G. bathoniana and G. balakhmatovae are geographically widespread in lower to mid palaeo-latitudes, and stratigraphically long ranging within the Middle and Late Jurassic. Modern digital microscopes, with co-axial and side LED lighting and excellent image stacking software are important tools in the study of Jurassic planktonic foraminifera, and fast and cost-effective communication tools in modern micropalaeontology.

ZooBank LSID: urn:lsid:zoobank.org:pub:A2927FFD-8C2B-4712-A06F-EE9D45ACA481.
Biological properties and roles of a Trichinella spiralis inorganic pyrophosphatase in molting and developmental process of intestinal larval stages
Authors: Hu Chen Xi , Zeng Jie , Hao Hui Nan , Xu Yang Xiu Yue , Liu Fang , Liu Ruo Dan , Long Shao Rong , Wang Zhong Quan , Cui Jing
Published: January 2021

Inorganic pyrophosphatase (PPase) participates in energy cycle and plays a vital role in hydrolysis of inorganic pyrophosphate (PPi) into inorganic phosphate (Pi). The aim of this study was to investigate the biological properties of a Trichinella spiralis PPase (TsPPase) and its role in larval molting and developmental process. The predicted TsPPase consisted of 367 amino acids with a molecular mass of 41.48 kDa and a pI of 5.76. Amino acid sequence alignment and phylogenetic analysis showed that the TsPPase gene encodes a functional family I soluble PPase with the same characteristics as prokaryotic, plant and animal/fungal soluble PPase. The rTsPPase was expressed and purified, it has the activity to catalyze the hydrolysis of PPi to Pi, and the activity was dependent on Mg2+, pH and temperature. The enzymatic activity of rTsPPase was significantly inhibited after its metal binding sites mutation. TsPPase was transcribed and expressed in all T. spiralis phases, especially in muscle larvae (ML) and intestinal infective larvae (IIL). Immunofluorescence assay (IFA) revealed that TsPPase was mainly located in cuticle and stichosome. When the ML and IIL were treated with TsPPase-specific siRNA-279, TsPPase expression and enzymatic activity were obviously reduced, the larval molting and development were also impeded. Intestinal IIL as well as AW burden, IIL molting rates from mice infected with siRNA-treated ML were obviously suppressed. The results indicated that rTsPPase possesses the enzymatic activity of native inorganic pyrophosphatase, and TsPPase plays an important role in development and molting process of intestinal T. spiralis larval stages.
Microbial keratinase and the bio-economy: a three-decade meta-analysis of research exploit
Authors: Nnolim Nonso E. , Nwodo Uchechukwu U.
Published: January 2021

Microbial keratinase research has been on an upward trajectory due to the robustness and efficiency of the enzyme toward various green technological processes that promote economic development and environmental sustainability. A compendium of research progression and advancement within the domain was achieved through a bibliometric study to understand the trend of research productivity, scientific impacts, authors' involvement, collaboration networks, and the advancement of knowledge gaps for future research endeavours. A three-decade (1990 to 2019) scholarly published articles were retrieved from the web of science database using a combination of terms "keratinas* or keratinolytic proteas* or keratinolytic enzym*", and subsequently analyzed for bibliometric indicators. A collection of 330 peer-reviewed, research, articles were retrieved for the survey period and authored by 1063 researchers with collaboration index of 3.27. Research productivity was most in 2013 with total research output of 28 articles. The top three authors' keywords were keratinase, keratin and protease with a respective frequency of 188, 26 and 22. India, China and Brazil ranked top in terms of keratinase research outputs and total citation with respective article productivity (total citations) of 85 (1533), 57 (826), and 36 (764). This study evaluated the trend of keratinase research outputs, scientific impact, collaboration networks and biotechnology innovations. It has the potentials to influence positively decision making on future research direction, collaborations and development of products for the bio-economy.
Acceleration of emergence of E. coli antibiotic resistance in a simulated sublethal concentration of copper and tetracycline co-contaminated environment
Authors: Li Jinmei , Phulpoto Irfan Ali , Zhang Guilong , Yu Zhisheng
Published: January 2021

An environment co-contaminated with metals and antibiotics ultimately exposes bacteria to these metals and antibiotics simultaneously. This study aims to explore the efficacy of sublethal concentrations of copper ions contaminated with tetracycline regarding antibiotic resistance in a sensitive strain of E. coli K12. The study proved that a copper ions and tetracycline co-contaminated environment could considerably enhance the mutation frequencies of chloramphenicol and polymyxin B resistance in antibiotic susceptible E. coli; however, the equivalent copper ions and tetracycline alone showed weaker effects. Results also demonstrated that an environment co-contaminated with relatively high sublethal concentrations of copper ion and tetracycline co-contaminated environment could induce much higher antibiotic resistance than the low sublethal and control groups. Whole-genome characterization results indicated that variability existed within the genotype and phenotype involved in antibiotic resistance. Additionally, the evolved resistant strains displayed hereditary resistance after 5 round culture cycles in LB broth over 5 days. Results implied that co-contamination with metals and antibiotics environment could strengthen resistance and contribute to the induction and dissemination of antibiotic resistance in metal and antibiotic co-contaminated environment.
Selonsertib, a potential drug for liver failure therapy by rescuing the mitochondrial dysfunction of macrophage via ASK1–JNK–DRP1 pathway
Authors: Lou Guohua , Li Aichun , Cen Yelei , Yang Qin , Zhang Tianbo , Qi Jinjin , Chen Zhi , Liu Yanning
Published: January 2021

Background

Acute liver failure (ALF) is associated with a high mortality rate, and there are still no effective treatments except liver transplantation and artificial liver therapies. This study aimed to determine the effects, therapeutic window and mechanisms of selonsertib, a selective inhibitor of ASK1, for ALF therapy.

Results

Lipopolysaccharide and d-galactosamine (LPS/GalN) were used to simulate ALF. We found that selonsertib pretreatment significantly ameliorated ALF, as determined by reduced hepatic necrosis and serum alanine aminotransferase, aspartate aminotransferase and inflammatory cytokine levels. However, selonsertib is only effective early after LPS/GalN administration, and the limited therapeutic window is related to the activation and mitochondrial translocation of JNK and DRP1. Further experiments revealed that selonsertib could alleviate LPS-induced mitochondrial damage in macrophages by evaluating the mitochondrial membrane potential and mitochondrial permeability transition pore opening in macrophages. Selonsertib also suppressed the release of inflammatory cytokines from macrophages by reducing DRP1-mediated mitochondrial dysfunction, which was confirmed by using mdivi, a specific DRP1 inhibitor.

Conclusions

Selonsertib protected against LPS/GalN-induced ALF by attenuating JNK-mediated DRP1 mitochondrial translocation and then rescuing mitochondrial damage in macrophages and may have therapeutic potential for early ALF patients.
Preoperative endothelial dysfunction in cutaneous microcirculation is associated with postoperative organ injury after cardiac surgery using extracorporeal circulation: a prospective cohort study
Authors: Abrard Stanislas , Fouquet Olivier , Riou Jérémie , Rineau Emmanuel , Abraham Pierre , Sargentini Cyril , Bigou Yannick , Baufreton Christophe , Lasocki Sigismond , Henni Samir
Published: January 2021

Background

Cardiac surgery is known to induce acute endothelial dysfunction, which may be central to the pathophysiology of postoperative complications. Preoperative endothelial dysfunction could also be implicated in the pathophysiology of postoperative complications after cardiac surgery. However, the relationship between preoperative endothelial function and postoperative outcomes remains unknown. The primary objective was to describe the relationship between a preoperative microcirculatory dysfunction identified by iontophoresis of acetylcholine (ACh), and postoperative organ injury in patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB).

Methods

Sixty patients undergoing elective cardiac surgery using CPB were included in the analysis of a prospective, observational, single-center cohort study conducted from January to April 2019. Preoperative microcirculation was assessed with reactivity tests on the forearm (iontophoresis of ACh and nitroprusside). Skin blood flow was measured by laser speckle contrast imaging. Postoperative organ injury, the primary outcome, was defined as a Sequential Organ Failure Assessment score (SOFA) 48 h after surgery greater than 3.

Results

Organ injury at 48 h occurred in 29 cases (48.3%). Patients with postoperative organ injury (SOFA score > 3 at 48 h) had a longer time to reach the peak of preoperative iontophoresis of acetylcholine (133 s [104–156] vs 98 s [76–139] than patients without, P = 0.016), whereas endothelium-independent vasodilation to nitroprusside was similar in both groups. Beyond the proposed threshold of 105 s for time to reach the peak of preoperative endothelium-dependent vasodilation, three times more patients presented organ dysfunction at 48 h (76% vs 24% below or equal 105 s). In multivariable model, the time to reach the peak during iontophoresis of acetylcholine was an independent predictor of postoperative organ injury (odds ratio = 4.81, 95% confidence interval [1.16–19.94]; P = 0.030).

Conclusions

Patients who postoperatively developed organ injury (SOFA score > 3 at 48 h) had preoperatively a longer time to reach the peak of endothelium-dependent vasodilation.

Trial registration Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797
Progressive loss functions for speech enhancement with deep neural networks
Authors: Llombart Jorge , Ribas Dayana , Miguel Antonio , Vicente Luis , Ortega Alfonso , Lleida Eduardo
Published: January 2021

The progressive paradigm is a promising strategy to optimize network performance for speech enhancement purposes. Recent works have shown different strategies to improve the accuracy of speech enhancement solutions based on this mechanism. This paper studies the progressive speech enhancement using convolutional and residual neural network architectures and explores two criteria for loss function optimization: weighted and uniform progressive. This work carries out the evaluation on simulated and real speech samples with reverberation and added noise using REVERB and VoiceHome datasets. Experimental results show a variety of achievements among the loss function optimization criteria and the network architectures. Results show that the progressive design strengthens the model and increases the robustness to distortions due to reverberation and noise.
Stress and pore fluid pressure control of seismicity rate changes following the 2016 Kumamoto earthquake, Japan
Authors: Nakagomi Kodai , Terakawa Toshiko , Matsumoto Satoshi , Horikawa Shinichiro
Published: January 2021

We quantitatively examined the influence of pore fluid pressure and coseismic stress changes on the seismicity rate changes that followed the 2016 Kumamoto earthquake, on the basis of two approaches. One is a numerical calculation of the classic stress metric of ∆CFS, and the other is an inversion analysis of pore fluid pressure fields with earthquake focal mechanism data. The former calculation demonstrated that seismicity rate changes were consistent with the expectation from ∆CFS in 65% of the target region, whereas they were not in the remaining 35% of the region. The latter analysis indicates that seismicity rates increased in the regions where pore fluid pressure before the Kumamoto earthquake sequence was remarkably enhanced above hydrostatic, regardless of values of ΔCFS. This suggests that the increase in pore fluid pressure is one of the important physical mechanisms triggering aftershock generation. We obtained evidence that pore fluid pressure increased around the southern part of the main rupture zone after the mainshock, examining temporal changes in types of focal mechanism data. The average increases in pore fluid pressure were estimated to be 17, 20, and 17 MPa at depths of 5, 10, and 15 km, respectively. These large increases in pore fluid pressure cannot be explained under the undrained condition. The spatial derivative of the pore fluid pressure field in the depth direction implies that fluid supply from greater depths may have controlled increases in seismicity rates that followed the large earthquake.
Effect of cycling exercise on motor excitability and gait abnormalities in stroke patients
Authors: El-Tamawy Mohamed S. , Darwish Moshera H. , Basheer Mye A. , Reda Abdelazim M. , Elzanaty Mahmoud , Khalifa Heba A.
Published: January 2021

Background

The concepts of brain excitability are still re-wiring in response to changes in environment. Ambulation is often limited in stroke patients.

Objective

To determine the effect of cycling exercise on motor excitability and consequences on spatiotemporal gait parameters in stroke patients.

Methods

Forty male ischemic stroke patients were included; their age ranged from 45 to 60 years. The patients were assigned into two equal groups: control group (GI) and study group (GII). The GI is treated by a design physical therapy program in the form of task-oriented progressive resistance exercise for lower limb muscles, and the GII is treated by the same program in addition to cycling exercise for 30 min. Treatment was conducted three times per week for 10 weeks. The excitability over motor area (Cz) was assessed by the quantitative electroencephalogram (QEEG). The spatiotemporal gait parameters were assessed by the Biodex Gait Trainer 2TM.

Results

There was a significant increase of speed, step cycle, and step length of the affected side (P < 0.05) and a non-significant difference of step length of the non-affected side in the study group compared with that of the control group (P > 0.05). There was a significant increase of excitability over motor area (Cz) in the study group compared with that of the control group (P < 0.05).

Conclusion

Cycling exercise has a positive effect on excitability over motor area of lower limbs and can improve gait parameters in stroke patients.
PUMPNET: a deep learning approach to pump operation detection
Authors: Ma Luyao , Meng Qingyu , Pan Shirui , Liebman Ariel
Published: January 2021

Non-urgent high energy-consuming residential appliances, such as pool pumps, may significantly affect the peak to average ratio (PAR) of energy demand in smart grids. Effective load monitoring is an important step to provide efficient demand response (DR) to PAR. In this paper, we focus on pool pump analytics and present a deep learning framework, PUMPNET, to identify the pool pump operation patterns from power consumption data. Different from conventional time-series based Non-intrusive Load Monitoring (NILM) methods, our approach transfers the time-series data into image-like (date-time matrix) data. Then a U-shaped fully convolutional neural network is developed to detect and segment the image-like data in pixel level for operation detection. Our approach identify whether pool pumps operate given thirty-minute interval aggregated active power consumption data in kilowatt-hours only. Furthermore, the PUMPNET algorithm could identify pool pump operation status with high accuracy in the low-frequency sampling scenario for thousands of household, compared to traditional NILM algorithms which process high sampling rate data and can only apply to limited number of households. Experiments on real-world data validate the promising results of the proposed PUMPNET model.
Quantitative estimation of cilnidipine and valsartan in rat plasma by RP-HPLC: its pharmacokinetic application
Authors: Kachave Ramanlal N. , Yelmame Shanker S. , Mundhe Akshay G.
Published: January 2021

Background

Cilnidipine (CLD) and valsartan (VAL) are antihypertensive agents used in the treatment of hypertension. So, pharmacokinetic study of CLD and VAL in rat plasma was carried out using chromatographic method. The chromatographic separation was performed on the Inertsil ODS column, using mobile phase methanol: water 85:15 v/v (pH 3.0) at the flow rate of 1.1 mL/min., detected at 254 nm.

Result

Cilnidipine (CLD) (1 mg/kg) and valsartan (VAL) (1 mg/kg) was administered orally in rats, and blood samples were collected at time intervals of 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 h after dosing. The retention time of plasma, CLD, and VAL was found to be 2.7, 6.6, and 4.3 min, respectively. The result was validated statistically and by recovery studies. Linearity was acceptable in the range of 1–5 and 8–40 μg/mL for CLD and VAL, respectively. Maximal concentration (Cmax) of CLD and VAL was observed to be 338 ± 13.85 and 1282.21 ± 39.23 (ng/mL). The half-life of CLD and VAL was found to be 1.08 ± 0.21 and 1.43 ± 0.12 h, respectively.

Conclusion

The present method was successfully applied to the pharmacokinetic study of cilnidipine (CLD) and valsartan (VAL) in rat plasma after oral administration.
Respiratory and voice outcomes of office-based injection laryngoplasty in patients with unilateral vocal fold paralysis
Authors: Elsaeed Asser , Afsah Omayma , Moneir Waleed , Elhadidy Tamer , Abou-Elsaad Tamer
Published: January 2021

Background

Injection laryngoplasty is a surgical procedure used in management of glottal insufficiency. The objective of this study was to assess respiratory and voice outcomes of office-based injection laryngoplasty in patients with unilateral vocal fold paralysis (UVFP). Ten patients underwent office-based injection via transcutaneous approach using Radiesse or hyaluronic acid. Auditory perceptual assessment (APA), voice handicap index (VHI), size of the glottic gap, acoustic parameters (jitter, shimmer, and harmonic to noise ratio), maximum phonation time (MPT), stroboscopic evaluation, pulmonary function tests (PFTs), and videofluoroscopic evaluation of swallowing were done pre-injection, 1 week and 3 months post-injection.

Results

Subjective and objective voice outcomes, in addition to laryngostroboscopic parameters improved after injection. Non-significant difference was found between pre- and post-injection results of the PFTs.

Conclusions

Office-based injection laryngoplasty is a safe and effective method for treating UVFP. Patients with glottic gap (< 1–3 mm) are perfect candidates for such procedure. Injection laryngoplasty improves patients’ voice quality and does not impair respiration.