bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeobox A5 and C10 genes modulate adaptation of brown adipose tissue during exercise training in juvenile rats
Authors: Kato Hisashi , Ario Takuto , Kishida Toshiaki , Tadano Manami , Osawa Seita , Maeda Yuki , Takakura Hisashi , Izawa Tetsuya 
Published: December 2020

New Findings
What is the central question of this study?
Exercise can stimulate brown adipose tissue (BAT) with subsequent increase in uncoupling protein 1 expression and mitochondrial biogenesis. In that case, do BAT‐specific Hox genes modify BAT functioning and cause uncoupling protein expression changes due to exercise?
What is the main finding and its importance?
Exercise enhanced brown adipocyte markers, with significant upregulation of HoxA5 and downregulation of HoxC10 mRNA expression in rat BAT. HoxA5 and HoxC10 are thus likely to play distinct roles in exercise‐induced changes in BAT markers during the early postnatal period. These findings provide new insight into the mechanisms underlying exercise‐induced changes in BAT function.
AbstractBrown adipose tissue (BAT) recruitment is involved in increased energy expenditure associated with cold exposure and exercise training. We explored whether exercise training induced changes in expression levels of brown adipocyte‐selective factors and Homeobox (Hox) genes during the post‐weaning growth period of male Wistar rats. Relative to total body weight, BAT weights alone were lower in exercise‐trained (EX) rats compared to sedentary control (SED) rats. mRNA expression of HoxA5 was higher and that of HoxC10 was lower in EX rats than in SED rats, accompanied by both higher citrate synthase activity and protein expression levels for uncoupling protein 1 (UCP1), peroxisome proliferator‐activated receptor (PPAR) α, and PPARγ‐coactivator (PGC)‐1α. HoxA5 knockdown with siRNA reduced the expression of PR‐domain containing 16 (Prdm16), cell death‐inducing DNA fragmentation factor‐α‐like effector A (Cidea) gene, type 2 deiodinase mRNA, and PRDM16 protein. Comparatively, HoxC10 knockdown with siRNA enhanced mRNA expression of Prdm16, Pparα and Pgc1α and protein expression of UCP1, PPARα and PGC1α in brown adipocytes. The stimulation of brown adipocytes with isoproterenol, a β‐adrenoceptor agonist, caused a phenomenon similar to the effect of exercise training on the genes tested: upregulation of HoxA5 mRNA, downregulation of HoxC10 mRNA, and increased protein expression for UCP1 and PGC1α. Collectively, HoxA5 and HoxC10 may have unique functions that contribute to modulating the expression of BAT‐selective markers in BAT of juvenile rats during exercise training. The study findings regarding activation and recruitment of BAT during exercise training have implications for anti‐obesity management.
Dynamic Advanced Exergetic, Exergoeconomic, and Environmental Analyses of a Hybrid Solar City Gate Station
Authors: Khoshgoftar Manesh M. H. , Abdolmaleki M. , Vazini Modabber H. , Rosen M. A. 
Published: December 2020

Abstract
The use of solar energy to preheat natural gas before a city gate station (CGS) for reducing fuel consumption and environmental emissions is investigated in a real CGS. All analyses are conducted with a 1-h time-step throughout the entire year so that seasonal climate changes are accounted for precisely. A thermodynamic analysis of the hybrid system is performed with TRNSYS and verified with THERMOFLEX so as to ensure reliability. In addition, dynamic exergetic, exergoeconomic, and exergoenvironmental analyses for the proposed system are carried out. A life cycle assessment (LCA) based on Eco-indicator 99 is performed using SIMA PRO to compute the environmental impacts for each component of the system. The exergetic, exergoeconomic, and environmental analyses are performed in Engineering Equation Solver (EES) software. To perform the transient exergetic, exergoeconomic, and environmental analyses, the results of the thermodynamic analysis from TRNSYS are automatically imported into the EES code. The advanced exergetic, exergoeconomic, and exergoenvironmental analyses are performed to better determine components that have high potentials for improving the system; potentials are considered based on the exergy destruction, exergetic cost of destruction, and environmental impacts associated with exergy destruction.
Investigation of Liquid Droplet Flow Behavior in a Vertical Nozzle Chamber
Authors: Abousabae Mohamed , Amano Ryoichi S. , Casper Cody 
Published: December 2020

Abstract
This study aims to better understand the aluminum oxide agglomerates breakup mechanism, consequently determining the best solution for the solid rocket motor (SRM) nozzle erosion problem. Two-phase air-water flow experimental investigation was conducted as a substitute for liquid aluminum agglomerates and exhaust combustion gases. The results show that increasing the exhaust air velocity enhances the droplet's breakup tendency to reduce the average diameter and increase droplet numbers per the testing channel volume. Numerical models were constructed and validated using the experimental results. The percentage error in the droplets’ average diameter and the number is between 6 and 15% and 8 and 18%, respectively. Furthermore, the effect of reducing the liquid surface tension was studied. The results showed that it facilitates water bodies’ separation from the interface surface, because of the reduced bounding forces between surface’s molecules, which enhances the breakup process (0.5–17% increase in the droplets’ average diameter and 4–100% increase in its number) and reduces the droplets impact on the nozzle walls, hence reducing the SRM nozzle erosion problem.
Various Types of Defects Detection in Flat and Curved Laminated Composite Plates Using Nonintrusive Lamb Wave System
Authors: Yu Lingyu , Ma Zhaoyun 
Published: December 2020

Abstract
Composite materials are widely used in aerospace industries due to their light weight, strength, and various other desired properties. However, they are susceptible to various defects occurring during the manufacturing process or in service. Typical defects include porosity, wrinkles, and delamination. Nondestructive means of detection of the defects at any stage are of great importance to ensure quality and safety of composite structures. A nonintrusive removable Lamb wave system and accompanied methodology that is not material dependent are presented in this paper to detect various types of typical defects in laminated composite plates, flat or curved. Through multidimensional data acquisition and processing, abnormality in waves caused by defects is captured and presented in inspection images. The methodologies are demonstrated in two cases: delamination in a curved plate and wrinkles in a flat plate. Overall, the results show that Lamb waves using the piezoelectric transducer and laser vibrometer system can be used for various types of defects inspection in flat or curved composite plates.
At the Crossroads of Bioenergetics and Antibiotic Discovery
Authors: Lewis K. 
Published: December 2020

Abstract
Dr. Vladimir Skulachev was my mentor, and his pioneering work in the field of bioenergetics inspired the discoveries described in this review, written in the form of a personal account of events. Examining basic mechanisms of chemiosmotic coupling unexpectedly led us to transenvelope multidrug resistance pumps (MDR pumps) that severely limit development of novel antibiotics. One of the major advances of Skulachev and his group was the discovery of the mitochondrial membrane potential with the use of permeant cations such as TPP+, which served as electric probes. We describe our finding of their natural counterparts in plants, where they act as antimicrobials. The most challenging problems in antimicrobial drug discovery are antibiotic tolerance of chronic infections caused by dormant persister cells; antibiotic resistance, responsible for the current antimicrobial resistance crisis (AMR); and finding novel compounds acting against Gram-negative bacteria, protected by their powerful multidrug resistance pumps. Our study of persisters shows that these are rare cells formed by stochastic fluctuation in expression of Krebs cycle enzymes, leading to a drop in ATP, target shutdown, and antibiotic tolerance. Searching for compounds that can corrupt targets in the absence of ATP, we identified acyldepsipeptide (ADEP) that activates the ClpP protease, forcing cells to self-digest. Growing previously uncultured bacteria led us to teixobactin, a novel cell wall acting antibiotic. Teixobactin avoids efflux by targeting lipid II and lipid III, precursors of peptidoglycan and wall teichoic acid, located on the surface. The targets are immutable, and teixobactin is the first antibiotic with no detectable resistance. Our search for compounds acting against Gram-negative bacteria led to the discovery of darobactins, which also hit a surface target, the essential chaperone BamA.
Clinically latent and autopsy-verified inflammatory disorders and malignant tumours in transplant patients
Authors: Mund Elias , Salem Johannes , Kreipe Hans H , Hussein Kais 
Published: December 2020

AimsThe number of clinical autopsies decreases while the rate of missed relevant diagnoses is known to be 2%–20%. In this study, we focused on postmortem examinations of patients after transplantation of solid organs.MethodsA total of 122 cases were assessed for this study. Transplant organs included liver (LiTx; n=42/122, 34%), heart (n=8/122, 7%), lungs (n=32/122, 26%), kidney (KTx; n=38/122, 31%) and KTx+LiTx (n=2/122, 2%).ResultsThe most frequent autopsy-verified causes of death were cardiac or respiratory failure (together n=85/122, 70%). The frequency of malignant tumours that were identified at autopsy was 5% (n=6/122). In 3% (n=4/122) of cases, Goldman class I discrepancies between clinical diagnosis and autopsy findings were identified.ConclusionsThe rate of missed relevant diagnoses might be relatively low, but these cases nevertheless refute the contention that modern diagnostic techniques negate the need for autopsies in patients who died after transplantation.
Clinical governance programme in patients with acute coronary syndrome: design and methodology of a quality improvement initiative
Authors: Leonardi Sergio , Montalto Claudio , Casella Gianni , Grosseto Daniele , Repetto Alessandra , Portolan Monica , Fortuni Federico , Ottani Filippo , Galvani Marcello , Cardelli Laura Sofia , De Servi Stefano , Rubboli Andrea , De Ferrari Gaetano Maria , Oltrona Visconti Luigi , Campo Gianluca 
Published: December 2020

IntroductionDespite the availability of diverse evidence-based diagnostic and treatment options, many patients with acute coronary syndrome (ACS) still fail to receive effective, safe and timely diagnoses and therapies. The Association of Acute CardioVascular Care of the European Society of Cardiology has proposed and retrospectively validated a set of ACS-specific quality indicators. Combining these indicators with the principles of clinical governance—a holistic, patient-centred approach intended to promote continuous quality improvement—we designed the clinical governance programme in patients with ACS.Methods and analysisThis is a multicentre quality improvement initiative exploring multiple dimensions of care, including diagnosis, therapy, patient satisfaction, centre organisation and efficiency in all comers patients with ACS.The study will enrol ≈ 5000 patients prospectively (ie, at the time of the first objective qualifying ACS criterion) with a 1-year follow-up. Consecutive inclusion will be promoted by a simplified informed consent process and quantified by the concordance with corresponding hospital administrative records using diagnosis-related group codes of ACS.Coprimary outcome measures are (1) timely reperfusion in patients with ST-elevation ACS and (2) optimal medical therapy at discharge in patients with confirmed acute myocardial infarction. Secondary outcomes broadly include multiple indicators of the process of care. Clinical endpoints (ie, death, myocardial infarction, stroke and bleeding) will be adjudicated by a clinical event committee according to predefined criteria.Ethics and disseminationThe study has been approved by local ethics committee of all study sites. As a quality improvement initiative and to promote consecutive inclusion of the population of interest, a written informed consent will be requested only to patients who are discharged alive. Dissemination will be actively promoted by (1) the registration site (ClinicalTrials.Gov IDNCT04255537), (2) collaborations with investigators through open data access and sharing.
Schwarzschild-like solutions in Finsler–Randers gravity
Authors: Triantafyllopoulos A. , Basilakos S. , Kapsabelis E. , Stavrinos P. C. 
Published: December 2020

AbstractIn this work, we extend for the first time the spherically symmetric Schwarzschild and Schwarzschild–De Sitter solutions with a Finsler–Randers-type perturbation which is generated by a covector $$A_\gamma $$

A
γ

. This gives a locally anisotropic character to the metric and induces a deviation from the Riemannian models of gravity. A natural framework for this study is the Lorentz tangent bundle of a spacetime manifold. We apply the generalized field equations to the perturbed metric and derive the dynamics for the covector $$A_\gamma $$

A
γ

. Finally, we find the timelike, spacelike and null paths on the Schwarzschild–Randers spacetime, we solve the timelike ones numerically and we compare them with the classic geodesics of general relativity. The obtained solutions are new and they enrich the corresponding literature.
Interacting ghost dark energy in complex quintessence theory
Authors: Liu Yang 
Published: December 2020

AbstractWe employ a ghost model of interacting dark energy to obtain the equation of state $$\omega $$
ω
for ghost energy density in an FRW universe in complex quintessence theory. We reconstruct the potential and study the dynamics of the scalar field that describes complex quintessence cosmology. We perform $$\omega -\omega '$$

ω
-

ω
′

analysis and stability analysis for both non-interacting and interacting cases and find that the same basic conclusion as for the real model, where $$\omega ' = d\omega / d ln a$$

ω
′

=
d
ω
/
d
l
n
a

. Taking account of the effect of the complex part and assuming the real part of the quintessence field to be a slow-rolling field, we conclude that the non-interacting model cannot describe the real universe since this will lead to fractional energy density $$\Omega _D > 1$$

Ω
D

>
1

, where $$\Omega _D$$

Ω
D

can be defined as the ratio of $$\rho _D$$

ρ
D

to $$\rho _{cr}$$

ρ

cr

. However, for the interacting case, if we take present $$\Omega _D =0.73$$

Ω
D

=
0.73

, then we can determine that $$b^2 = 0.0849$$

b
2

=
0.0849

, where $$b^2$$

b
2

is the interaction coupling parameter between matter and dark energy. In the real quintessence model, $$\Omega _D$$

Ω
D

and $$b^2$$

b
2

are independent parameters, whereas in the complex quintessence model, we conclude that there is a relationship between these two parameters.
Association of Side-Branch Treatment and Patient Factors in Left Anterior Descending Artery True Bifurcation Lesions: Analysis from the GRAND-DES Pooled Registry
Authors: Oh Gyu Chul , Park Kyung Woo , Kang Jeehoon , Han Jung-Kyu , Yang Han-Mo , Kang Hyun-Jae , Koo Bon Kwon , Kim Hyo-Soo 
Published: December 2020

Background and Objectives. In most bifurcation lesions, keeping the procedure simple by not treating the side-branch (SB) lesion when possible is considered the best method. However, because of improvements with 2nd generation drug-eluting stents (DESs), it remains unknown whether treatment of the SB may improve outcomes in certain subgroups, especially when exclusively using 2nd generation DESs. We report the outcome of SB treatment in a group of patients exclusively receiving newer generation DES for bifurcation PCI. Methods. Patients undergoing PCI to left anterior descending (LAD) bifurcation lesions with contemporary DES were analyzed from a nationwide registry. Baseline risk was assessed using the Age, Creatinine, and Ejection Fraction (ACEF) score. Target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization, was assessed at 3 years. Results. Among 1,089 patients with LAD bifurcation lesions, 548 (50.3%) patients underwent SB treatment. The SB treatment group showed a nonsignificant, but numerically lower rate of 3-year TLF (6.6% vs. 9.2%, HR 0.75, 95%CI 0.44–1.28,

p

= 0.29). In patients with low pretreatment risk (ACEF<1.22), SB treatment was associated with a lower rate of 3-year TLF (HR 0.43, 95%CI 0.19–0.96,

p

= 0.04), while no significant difference was observed in patients with high risk (ACEF≥1.22). The difference in the low risk group was mostly driven by target lesion revascularization (HR 0.24, 95%CI 0.08–0.75,

p

= 0.01). Conclusions. SB treatment for LAD bifurcation lesions showed favorable long-term outcomes compared with main-branch-only intervention, especially in patients with low pretreatment risk.
Subcellular Distribution of p53 by the p53-Responsive lncRNA NBAT1 Determines Chemotherapeutic Response in Neuroblastoma
Authors: Mitra Sanhita , Muralidharan Somsundar Veppil , Di Marco Mirco , Juvvuna Prasanna Kumar , Kosalai Subazini Thankaswamy , Reischl Silke , Jachimowicz Daniel , Subhash Santhilal , Raimondi Ivan , Kurian Leo , Huarte Maite , Kogner Per , Fischer Matthias , Johnsen John Inge , Mondal Tanmoy , Kanduri Chandrasekhar 
Published: December 2020

Abstract

Neuroblastoma has a low mutation rate for the p53 gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation of wild-type p53. However, mechanisms leading to p53 inactivation via cytoplasmic accumulation are not well investigated. Here we show that the neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor NBAT1 is a p53-responsive lncRNA that regulates p53 subcellular levels. Low expression of NBAT1 provided resistance to genotoxic drugs by promoting p53 accumulation in cytoplasm and loss from mitochondrial and nuclear compartments. Depletion of NBAT1 altered CRM1 function and contributed to the loss of p53-dependent nuclear gene expression during genotoxic drug treatment. CRM1 inhibition rescued p53-dependent nuclear functions and sensitized NBAT1-depleted cells to genotoxic drugs. Combined inhibition of CRM1 and MDM2 was even more effective in sensitizing aggressive neuroblastoma cells with p53 cytoplasmic accumulation. Thus, our mechanistic studies uncover an NBAT1-dependent CRM1/MDM2-based potential combination therapy for patients with high-risk neuroblastoma.

Significance:
This study shows how a p53-responsive lncRNA mediates chemotherapeutic response by modulating nuclear p53 pathways and identifies a potential treatment strategy for patients with high-risk neuroblastoma.
Differential Regulation of Cancer Progression by CDK4/6 Plays a Central Role in DNA Replication and Repair Pathways
Authors: Dai Meiou , Boudreault Julien , Wang Ni , Poulet Sophie , Daliah Girija , Yan Gang , Moamer Alaa , Burgos Sergio A. , Sabri Siham , Ali Suhad , Lebrun Jean-Jacques 
Published: December 2020

Abstract

Although the cyclin-dependent kinases CDK4 and CDK6 play fundamental roles in cancer, the specific pathways and downstream targets by which they exert their tumorigenic effects remain elusive. In this study, we uncover distinct and novel functions for these kinases in regulating tumor formation and metastatic colonization in various solid tumors, including those of the breast, prostate, and pancreas. Combining in vivo CRISPR-based CDK4 and CDK6 gene editing with pharmacologic inhibition approaches in orthotopic transplantation and patient-derived xenograft preclinical models, we defined clear functions for CDK4 and CDK6 in facilitating tumor growth and progression in metastatic cancers. Transcriptomic profiling of CDK4/6 CRISPR knockouts in breast cancer revealed these two kinases to regulate cancer progression through distinct mechanisms. CDK4 regulated prometastatic inflammatory cytokine signaling, whereas CDK6 mainly controlled DNA replication and repair processes. Inhibition of CDK6 but not CDK4 resulted in defective DNA repair and increased DNA damage. Multiple CDK6 DNA replication/repair genes were not only associated with cancer subtype, grades, and poor clinical outcomes, but also facilitated primary tumor growth and metastasis in vivo. CRISPR-based genomic deletion of CDK6 efficiently blocked tumor formation and progression in preestablished cell- and patient-derived xenograft preclinical models of breast cancer, providing a potential novel targeted therapy for these deadly tumors.

Significance:
In-depth transcriptomic analysis identifies cyclin-dependent kinases CDK4 and CDK6 as regulators of metastasis through distinct signaling pathways and reveals the DNA replication/repair pathway as central in promoting these effects.
Strobilanthes affinis (Acanthaceae): a new addition to the flora of Manipur, India
Authors: Kumar Sanjeet , Devi Rajkumari Supriya 
Published: December 2020

Strobilanthes affinis (Griff.) Terao ex J.R.I. Wood J.R. Benn, a lesser known species of Acanthaceae family, is reported here as new to the flora of Manipur State, India. A brief description of the species is provided along with phenological data, microscopic structure of pollen, distribution, and notes on associated flora and habitat. Photographs are also provided for easy identification in the field.
Diversity, distribution and conservation status of the Adder’s-tongue ferns in Goa, India
Authors: Patil Sachin M. , Rajput Kishore 
Published: December 2020

The cosmopolitan fern genus Ophioglossum (Ophioglossaceae) is distributed from low to high altitude plateaux, coastal plains and forest floors of India. This genus has received special attention from pteridologists worldwide since the discovery that Ophioglossum reticulatum possesses the largest number of chromosomes. There are, however, no reported studies of Ophioglossum in Goa, hence the present investigation was undertaken to study the diversity, distribution and conservation status of Ophioglossum in that state. A total of six species were collected from different localities, of which four (O. nudicaule, O. lusitanicum, O. parvifolium, and O. reticulatum) are reported as new distributional records for Goa State. A detailed morpho-taxonomy, illustration and photographs of all collected species are given, along with a key to the species.