bluuebunny/crossref_metadata_2025_split huggingface dataset:
The methanol sensor Wsc1 and MAPK Mpk1 suppress degradation of methanol-induced peroxisomes in methylotrophic yeast
Authors: Ohsawa Shin , Inoue Koichi , Isoda Takahiro , Oku Masahide , Yurimoto Hiroya , Sakai Yasuyoshi 
Published: March 2021

ABSTRACT
In nature, methanol is produced during the hydrolysis of pectin in plant cell walls. Methanol on plant leaves shows circadian dynamics, to which methanol-utilizing phyllosphere microorganisms adapt. In the methylotrophic yeast Komagataella phaffii (Kp; also known as Pichia pastoris), the plasma membrane protein KpWsc1 senses environmental methanol concentrations and transmits this information to induce the expression of genes for methanol metabolism and the formation of huge peroxisomes. In this study, we show that KpWsc1 and its downstream MAPK, KpMpk1, negatively regulate pexophagy in the presence of methanol concentrations greater than 0.15%. Although KpMpk1 was not necessary for expression of methanol-inducible genes and peroxisome biogenesis, KpMpk1, the transcription factor KpRlm1 and phosphatases were found to suppress pexophagy by controlling phosphorylation of KpAtg30, the key factor in regulation of pexophagy. We reveal at the molecular level how the single methanol sensor KpWsc1 commits the cell to peroxisome synthesis and degradation according to the methanol concentration, and we discuss the physiological significance of regulating pexophagy for survival in the phyllosphere.
This article has an associated First Person interview with Shin Ohsawa, joint first author of the paper.
Evolution and insights into the structure and function of the DedA superfamily containing TMEM41B and VMP1
Authors: Okawa Fumiya , Hama Yutaro , Zhang Sidi , Morishita Hideaki , Yamamoto Hayashi , Levine Tim P. , Mizushima Noboru 
Published: March 2021

ABSTRACT
TMEM41B and VMP1 are endoplasmic reticulum (ER)-localizing multi-spanning membrane proteins required for ER-related cellular processes such as autophagosome formation, lipid droplet homeostasis and lipoprotein secretion in eukaryotes. Both proteins have a VTT domain, which is similar to the DedA domain found in bacterial DedA family proteins. However, the molecular function and structure of the DedA and VTT domains (collectively referred to as DedA domains) and the evolutionary relationships among the DedA domain-containing proteins are largely unknown. Here, we conduct a remote homology search and identify a new clade consisting mainly of bacterial proteins of unknown function that are members of the Pfam family PF06695. Phylogenetic analysis reveals that the TMEM41, VMP1, DedA and PF06695 families form a superfamily with a common origin, which we term the DedA superfamily. Coevolution-based structural prediction suggests that the DedA domain contains two reentrant loops facing each other in the membrane. This topology is biochemically verified by the substituted cysteine accessibility method. The predicted structure is topologically similar to that of the substrate-binding region of Na+-coupled glutamate transporter solute carrier 1 (SLC1) proteins. A potential ion-coupled transport function of the DedA superfamily proteins is discussed.
This article has an associated First Person interview with the joint first authors of the paper.
Metal(II) Ion Dependence of the Structures and Properties of Square-Grid Coordination Polymers of Tetrabromobenzenedicarboxylate and Pyrazine as Bridging Ligands
Authors: Kumagai Hitoshi , Setoyama Norihiko , Kawata Satoshi , Sakamoto Yoshiyuki 
Published: March 2021

Abstract
In this study, we report the synthesis and crystal structures of coordination polymers employing tetrabromobenzenedicarboxylate (Br4bdc2−) and pyrazine (pyz). Uncoordinated pyz molecules are stabilized between the layers by both hydrogen H-bonding and π–π stacking interactions in [M(Br4bdc)(pyz)(H2O)2](pyz), where M = Co(II) and Zn(II). In addition, water molecules are incorporated between the layers in [Cu(Br4bdc)(pyz)(H2O)2](H2O) owing to Jahn–Teller distortion of the Cu(II) ions, which prevents π–π stacking interactions between the pyz and Br4bdc2−. Depending on the metal(II) centers, structural changes that occur during the heating and hydration processes exhibit different behavior. Co(II) compound slowly changes structure by heating and rapidly recovers the crystalline state in air. Conversely, Zn(II) compound assumes the amorphous phase by heating and slowly yields the crystalline phase in ambient conditions. Although the Cu(II) compound also shows structural changes by heating, the dehydrated phase exhibits hydrophobic characteristics. Ion conductivity measurements of the as-synthesized forms show conductivities of 1.9 × 10−6 Scm−1, 4.6 × 10−7 Scm−1, and 1.3 × 10−6 Scm−1, for the Co(II), Zn(II), and Cu(II) complexes at 90 °C and 95% relative humidity (RH), respectively. The relatively low values of the as-synthesized Co(II) and Zn(II) compounds are attributed to the H-bonding interaction and π–π stacking of pyz molecules, which prevent the dynamics of the pyz molecules needed for proton conduction.
Self-Assembly of Peptide-Containing Mesogens: Thermotropic Liquid-Crystalline Properties and Macroscopic Alignment of Amphiphilic Bioconjugates
Authors: Eimura Hiroki , Niwa Anna , Uchida Junya , Kato Takashi 
Published: March 2021

Abstract
Thermotropic liquid crystals having tripeptide moieties are reported. A series of peptide chains including arginine-glycine-aspartic acid (RGD), glycine-glycine-aspartic acid (GGD), and triglycine (GGG) moieties is connected to a rigid-rod core through a flexible tetraoxyethylene spacer. These bioconjugated mesogens form intermolecular hydrogen bonds through amide groups in the tripeptide moieties. It is found that side chains in the tripeptide-conjugated mesogens constrain intermolecular hydrogen bonding in the bulk states, which affects the formation of the liquid-crystalline phases. The rigid-rod mesogens bearing RGD and GGD peptide sequence exhibit smectic phases with high thermal stability of the mesophases. The liquid-crystalline assemblies of the mesogen-containing peptides are macroscopically oriented by mechanical shearing. The present design of bioconjugated liquid crystals could lead to the development of new self-assembled materials for biological applications.
Recognition of Target Site in Various Forms of DNA and RNA by Peptide Nucleic Acid (PNA): From Fundamentals to Practical Applications
Authors: Liang Xingguo , Liu Mengqin , Komiyama Makoto 
Published: March 2021

Abstract
Peptide nucleic acid (PNA) is a DNA analog, in which the sugar-phosphate backbone in DNA is replaced by poly[N-(2-aminoethyl)glycine]. Since its discovery in the early 1990s, PNA has been widely employed in chemistry, biochemistry, medicine, nanotechnology, and many other fields. This account surveys recent developments on the design of PNA derivatives and their applications. In the first part, PNAs for sequence-specific recognition of DNA and RNA (single-strands, double-strands, G-quadruplexes, i-motifs, and others) are comprehensively covered. Modifications of nucleobases and of the main chain effectively promote both the strength of binding and the selectivity of recognition. In the second half of this account, practical applications of PNA are presented. Structural restraints, induced by complex formation of PNA with DNA and RNA substrates, lead to selective transformation of target sites to desired structures. Applications to regulation of gene expression, gene editing, construction of sophisticated nanostructures, and others are also described. Advantages and disadvantages of PNAs, compared with other sequence-recognizing molecules hitherto reported, are discussed in terms of various physicochemical and biological features.
Global equity in protection of pregnant frontline workers
Authors: Jaffe Elana F. , Karron Ruth A. , Krubiner Carleigh B. , Wonodi Chizoba B. , Beigi Richard H. , Sheffield Jeanne S. , Faden Ruth R. 
Published: March 2021

Vaccination of frontline workers against COVID-19 is underway in some countries. With women comprising a majority of health, education, and other essential workforces, many on the front lines of the pandemic response will be pregnant at the time that they are offered COVID-19 vaccines. However, pregnant people were not included in any of the COVID-19 vaccine trials that regulatory agencies evaluated when considering authorization. Without pregnancy-specific data, pregnant frontline workers in some settings are being denied COVID-19 vaccines. In other settings, pregnant frontline workers are able to access these same vaccines, but are faced with the burden of decision-making in the absence of an explicit recommendation for use and without pregnancy-specific data. While permissive recommendations for use in pregnancy are ethically preferable to unjustly denying vaccine access, objectives to protect the frontline workforce will fall short until there is evidence to support explicit recommendations for COVID-19 vaccination in pregnancy. In this article, we provide three actionable recommendations to ensure equitable protection of pregnant frontline workers as vaccines against COVID-19 continue to be developed and rolled out globally. First, efforts must be taken now to leverage critical opportunities for narrowing the evidence gaps around currently authorized COVID-19 vaccines in pregnancy. Next, action in the near term is needed to preempt evidence gaps for COVID-19 vaccines still in development. Finally, in the absence of an explicit recommendation for use in pregnancy, and while pregnancy-specific data lags behind, pregnant people should be prioritized for alternate preventive and treatment measures. Achieving equitable protection for those who are pregnant and serving on the frontlines of the pandemic will require no less.
O Código Florestal de 2012 sob a ótica do Supremo Tribunal Federal: a consolidação do retrocesso socioambiental
Authors: Moreira Danielle De Andrade , Marques de Carvalho de Oliveira Daniela , Rêgo Teixeira Lima Letícia Maria 
Published: March 2021

Este artigo objetiva demonstrar que, além da dificuldade de implementação das normas ambientais já existentes, o Direito Ambiental enfrenta novo desafio: a edição de diplomas normativos tendentes a reduzir direitos socioambientais já positivados. O Código Florestal de 2012 se insere neste contexto e é, até o momento, o principal exemplo concretizado de diminuição da proteção ao meio ambiente, em desrespeito ao princípio da vedação ao retrocesso socioambiental, cuja função é garantir que o nível de proteção alcançado pelos direitos socioambientais não seja reduzido, impedindo agressões ao núcleo essencial do direito fundamental ao meio ambiente ecologicamente equilibrado. Para o estudo dos retrocessos promovidos pela nova legislação florestal, foi realizado levantamento bibliográfico e documental, acompanhado de catalogação e análise crítica do material selecionado. A metodologia adotada incluiu levantamento, sistematização e análise qualitativa dos acórdãos do Supremo Tribunal Federal relativos às ações judiciais que questionavam a constitucionalidade de diversos dispositivos do novo Código Florestal. Ao declarar a constitucionalidade da grande maioria das alterações da Lei 12.651/2012, o Supremo Tribunal Federal confirmou e consolidou um conjunto de retrocessos normativos em matéria de meio ambiente, esvaziando de modo substancial a orientação do princípio da vedação ao retrocesso socioambiental.
Como as cidades brasileiras estão lidando com o Airbnb? Colocando a regulação em perspectiva
Authors: Souza Rafael Braga de , Leonelli Gisela Cunha Viana 
Published: March 2021

Nos últimos anos, empresas tem florescido no ambiente digital a partir de premissas do compartilhamento de produtos e serviços. O Airbnb é uma empresa que opera dentro dessa lógica conhecida como Economia do Compartilhamento e tem gerado impactos no ambiente urbano. Nesse sentido, cidades, principalmente na Europa e nos EUA, tem estabelecido marcos regulatórios com estratégias variadas visando ampliar os benefícios e mitigar os impactos negativos dessa plataforma. No entanto, é desconhecida a legislação voltada para o Airbnb no Brasil e sua abordagem. O objetivo desse trabalho é contrastar as legislações brasileiras concernentes ao Airbnb com os marcos regulatórios internacionais. A partir de revisão bibliográfica e da análise das legislações brasileiras, constatou-se que as estas tem abordagens que não exercem efetivo controle e monitoramento sobre o Airbnb. Além disso distanciam-se das legislações internacionais em termos de problemática enfrentada, estas buscam garantir habitação à preços acessíveis, enquanto as brasileiras privilegiam a concorrência mais equilibrada com o mercado de hospedagem. Palavras-chave: Airbnb; Regulação Urbana; Economia do Compartilhamento; dinâmica imobiliária; Mercado de hospedagem
Influence of calcination temperature on the fluorescence and magnetic properties of Gd2O3:Tb3+, K+ nanoparticles
Authors: Zhou Hao , Fu Rong , Yang Chunlin , Ou Meigui , Xue Chengjie 
Published: March 2021

G
d

2

O

3

:

T
b

3
+

nanoparticles were synthesized by using diethylene glycol as a solvent and doped with 3 mol%

K

+

ions.

G
d

2

O

3

:

T
b

3
+

,

K

+

nanoparticles were calcinated at 600°C, 700°C, 800°C, and 900°C and subjected to the analysis of x-ray diffractometer, transmission electron microscope, Fourier transform infrared spectrometer, fluorescence spectroscopy, and magnetization. The experimental results showed that as the calcination temperature increased from 600°C to 800°C, the morphology and particle size of the

G
d

2

O

3

:

T
b

3
+

,

K

+

nanoparticles did not change significantly; whereas when the calcination temperature rose from 800°C to 900°C, the structure of

G
d

2

O

3

particles changed from cubic to monoclinic. As the temperature increased (below 800°C), the crystallinity of the cubic particles increased and the surface defects of the particles decreased, resulting in an increase in fluorescence intensity. For the monoclinic particles, the fluorescence intensity was significantly decreased and the magnetization was increased. The measured magnetic results confirmed the good paramagnetism of the synthesized nanoparticles.
Knowledge, perceptions and attitude of Egyptian physicians towards biobanking issues
Authors: Abdelhafiz Ahmed Samir , Sultan Eman A. , Ziady Hany H. , Sayed Douaa M. , Khairy Walaa A. 
Published: March 2021

Objectives
Collection and storage of biospecimens and data for biobanking raise many ethical concerns. Stakeholders’ opinions about these ethical issues are important since they can help in the development of ethical guidelines to govern biobanking activities. Physicians are among the important stakeholders since they contact potential participants and could be biobank users. The goal of this study is to evaluate the perceptions and attitude of Egyptian physicians towards ethical issues in biobanking.

Methods
A cross-sectional online survey was designed and distributed with the target group between November 2019 and January 2020.

Results
The questionnaire was completed by 223 physicians. While 65.5% reported hearing the term "Biobanking" before, 45.7% knew that there are biobanks in Egypt. Participants had a general positive attitude towards the value of biobanks in research. About 73% agreed that biobanks can share biospecimens with international research organizations, but only 42.6% supported collaboration with pharmaceutical companies, and 44% agreed to the use of user fees by biobanks. About 48% supported the use of broad consent in biobanks, and 73.1% believed that donors of biospecimens should be informed about results of research performed on their biospecimens.

Conclusion
Although many Egyptian physicians heard about biobanking, they had limited knowledge about the existence of biobanks in Egypt. They had concerns about commercialization, use of broad consent and user fees. A knowledge gap exists among these stakeholders, which should be covered by different educational activities. Community discussions should start to reach consensus about the issues of commercialization and return of research results.
Analysis of treatment cost and persistence among migraineurs: A two-year retrospective cohort study in Pakistan
Authors: Khan Kamran , Arain Mudassar Iqbal , Asghar Muhammad Arif , Rehman Ahad Abdul , Ghoto Muhammad Ali , Dayo Abdullah , Imtiaz Muhammad Suleman , Rana Mohsin Hamied , Asghar Muhammad Asif 
Published: March 2021

Objectives
The persistence pattern of anti-migraine drugs’ use among migraineurs is very low in the United States and different European countries. However, the cost and persistence of antimigraine drugs in Asian countries have not been well-studied. Hence, the present study aimed to evaluate the treatment cost and persistence among migraineurs in Pakistan.

Methods
Data from prescriptions collected from migraineurs who visited the Outpatient Department (OPD) of different public and private sector tertiary-care hospitals of Karachi, Pakistan were used to conduct this retrospective cohort study from 2017 to 2019. The minimum follow up period for each migraineur was about 12 months for persistence analysis while dropped-out patients data were also included in survival analysis as right censored data. Pairwise comparisons from Cox regression/hazards ratio were used to assess the predictors of persistence with the reference category of non-binary variables i.e. hazard ratio = 1 for low frequency migraineurs and NSAIDs users. Persistence with anti-migraine drugs was estimated using the Kaplan-Meier curve along with the Log Rank test.

Results
A total of 1597 patients were included in this study, 729 (45.6%) were male and 868 (54.3%) were female. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most prescribed class of drug initially for all classes of migraineurs (26.1%). Of them, 57.3% of migraineurs discontinued their treatment, 28.5% continued while 14.8% were switched to other treatment approaches. Persistence with initial treatment was more profound in female (58.8%) patients compared to males while the median age of continuers was 31 years. The total cost of migraine treatment in the entire study cohort was 297532.5 Pakistani Rupees ($1901.1). By estimating the hazard ratios (HR) using the Cox regression analysis, it can be observed that patients with high frequency (HR, 1.628; 95%CI, 1.221–2.179; p<0.0001) migraine, depression (HR, 1.268; 95%CI, 1.084–1.458; p<0.0001), increasing age (HR, 1.293; 95%CI, 1.092–1.458; p<0.0001), combination analgesics (HR, 1.817; 95%CI, 0.841–2.725; p = 0.0004) and prophylaxis drugs (HR, 1.314; 95%CI, 0.958–1.424; p<0.0001) users were at a higher risk of treatment discontinuation. However, patients with chronic migraine (HR, 0.881; 95%CI, 0.762–0.912; p = 0.0002), epileptic seizure (HR, 0.922; 95%CI, 0.654–1.206; p = 0.0002), other comorbidities (HR, 0.671; 95%CI, 0.352–1.011; p = 0.0003) and users of triptan(s) (HR, 0.701; 95%CI, 0.182–1.414; p = 0.0005) and triptan(s) with NSAIDs (HR, 0.758; 95%CI, 0.501–1.289; p<0.0001) had more chances to continue their initial therapy.

Conclusion
Similar to western countries, the majority of migraineurs exhibited poor persistence to migraine treatments. Various factors of improved persistence were identified in this study.
The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: A systematic review and meta-analysis
Authors: Ye Peng , Cai Peiling , Xie Jing , Wei Yuanyuan 
Published: March 2021

IntroductionBefore anti-EGFR therapy is given to patients with colorectal cancer, it is required to determineKRASmutation status in tumor. When tumor tissue is not available, cell-free DNA (liquid biopsy) is commonly used as an alternative. Due to the low abundance of tumor-derived DNA in cell-free DNA samples, methods with high sensitivity were preferred, including digital polymerase chain reaction, amplification refractory mutation system and next-generation sequencing. The aim of this systemic review and meta-analysis was to investigate the accuracy of those methods in detectingKRASmutation in cell-free DNA sample from patients with colorectal cancer.MethodsLiterature search was performed in Pubmed, Embase, and Cochrane Library. After removing duplicates from the 170 publications found by literature search, eligible studies were identified using pre-defined criteria. Quality of the publications and relevant data were assessed and extracted thereafter. Meta-DiSc and STATA softwares were used to pool the accuracy parameters from the extracted data.ResultsA total of 33 eligible studies were identified for this systemic review and meta-analysis. After pooling, the overall sensitivity, specificity, and diagnostic odds ratio were 0.77 (95%CI: 0.74–0.79), 0.87 (95%CI: 0.85–0.89), and 23.96 (95%CI: 13.72–41.84), respectively. The overall positive and negative likelihood ratios were 5.55 (95%CI: 3.76–8.19) and 0.29 (95%CI: 0.21–0.38), respectively. Area under curve of the summarized ROC curve was 0.8992.ConclusionDigital polymerase chain reaction, amplification refractory mutation system, and next-generation sequencing had overall high accuracy in detectingKRASmutation in cell-free DNA sample. Large prospective randomized clinical trials are needed to further convince the accuracy and usefulness ofKRASmutation detection using cfDNA/liquid biopsy samples in clinical practice.Trial registrationPROSPERO CRD42020176682;https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176682.