bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the relationship between farmland prices and soil quality
Authors: Meissner Luise , Musshoff Oliver 
Published: June 2022

AbstractThis paper aims to examine the relationship between soil quality and farmland prices over time. Soil quality is often used as an explanatory variable for farmland prices in hedonic price models. However, the agricultural land market has shown an enormous price increase over the last decade. Therefore, revisiting the relationship between soil quality and farmland prices over time is of high relevance. This study aims to analyze farmland price time series in Germany. The series are aggregated within soil quality intervals and within parcel size intervals, treated as panel units. The fully modified ordinary least squares (FMOLS) panel group mean and the dynamic ordinary least squares (DOLS) panel group mean estimators are applied within a cointegration regression approach to estimate the relation of the time series. We found that soil quality causes a relative farmland price difference within an identified long-run relationship.
Molecular and clinical characteristics of carbapenem-resistant Enterobacteriaceae isolates collected at a tertiary hospital in northern China
Authors: Wang Hua , Yan Zhi , Mu Lan , Gao Xiang-Yu , Li Jia-Ying , Hu Zhi-De , Wang Jun-Rui , Zheng Wen-Qi 
Published: June 2022

Abstract

Background
Carbapenem-resistant Enterobacteriaceae (CRE) represent a severe public health problem.

Methods
In a tertiary hospital in northern China, 169 non-duplicated clinical CRE strains were analyzed by species identification, in vitro antibiotics sensitivity test, carbapenemase gene detection and genetic sequence typing.

Results
The CRE strains showed high resistance to most clinical antimicrobials. Enterobacter cloacae and Escherichia coli isolates mainly carried blaNDM, and Klebsiella pneumoniae isolates mainly carried blakpc. ST11 was the most common type in Klebsiella pneumoniae, and ST70 was the new emerging sequence type (ST) in Enterobacter cloacae.

Conclusions
The CRE strains isolated in northern China showed multidrug-resistant phenotypes, and the new emergence of ST70 Enterobacter cloacae should be closely supervised.
Clinical Pattern of Retinal Detachment at the University of Gondar Tertiary Eye Care and Training center, North-West Ethiopia
Authors: Kidanemariam Hagos , Tsegw Asamere 
Published: June 2022

AbstractObjectiveDue to increment in volume of cataract surgery and diabetic retinopathy, the incidence of retinal detachment (RD) is expected to rise in the future. However, little is known about the clinical patterns and risk factor of RD in Ethiopia. This study was aimed to determine the clinical pattern and risk factors of RD at University of Gondar Tertiary eye care and training center (UOG-TECTC).MethodsA hospital based prospective cross sectional study was done involving all consecutive patients with retinal detachment seen over six months period at the UOG-TECTC. Structured questionnaire was used to extract the required data which included demography, ophthalmic history and clinical examination results. Data were entered into SPSS version 20 and analyzed.ResultsA total of 73 eyes of 65 patients with RD were analyzed. Two-third of patients were males 42(64.6%) and the median age was 49 years. Rhegmatogenous RD (RRD) was the commonest type of RD found in 58(89.2%) patients. Three quarter of the patients, 49 (75 %), came after 1 month of the symptom occurrence; out of which 20 (41%) visited the center after 1year duration. The commonest identified risk factors were trauma 19(29%) followed by pseudophakia 11(17%). More than three-quarter of the patients 53(81.5%) had detached macula and 60 (92.3%) of the involved eyes were blind at presentation.Conclusion and recommendationsRRD was the commonest type of RD seen in our patients. Majority of the patients visited our center late after macular detachment and trauma was the commonest risk factor. People should be educated to seek health care immediately after the onset of symptoms. Ocular safety precautions should be advised to decrease the risk of ocular trauma. The center should be equipped to manage patients with RD.
Enhancing NeuroD1 Expression to Convert Lineage-Traced Astrocytes into Neurons
Authors: Xu Liang , Xiang Zong-Qin , Guo Yao-Wei , Xu Yu-Ge , Liu Min-Hui , Ji Wen-Yu , He Shu , Lei Wen-Liang , Li Wen , Wu Zheng , Chen Gong 
Published: June 2022

ABSTRACTRegenerating functional new neurons in adult mammalian brains has been proven a difficult task for decades. Recent advancement in direct glia-to-neuron conversion in vivo opens a new field for neural regeneration and repair. However, this emerging new field is facing serious challenges from misuse of viral vectors to misinterpretation of conversion data. Here, we employ a variety of AAV vectors with different promoters and enhancers to demonstrate that astrocytes can be converted into neurons in a NeuroD1 dose-dependent manner in both wildtype (WT) and transgenic mice. Notably, astrocytes in WT mice were relatively easy to convert with higher conversion efficiency, whereas lineage-traced astrocytes in Aldh1l1-CreERT2 mice showed high resistance to reprogramming but were still converted into neurons after enhancing NeuroD1 expression with CMV enhancer. Furthermore, under two-photon microscope, we observed direct astrocyte-to-neuron conversion within 3 weeks of serial live imaging in the mouse cortex. We also demonstrated that high titre AAV reaching 1013 GC/ml caused severe neuronal leakage using a variety of AAV GFAP::GFP vectors, highlighting the necessity to inject low titre AAV into healthy brains to avoid artifactual results. Together, our studies suggest that lineage-traced astrocytes can be converted into neurons but require stronger conversion force such as enhanced NeuroD1 expression. Failure to recognize the difference between WT astrocytes and lineage-traced astrocytes in terms of conversion barrier will lead to misinterpretation of data.
Enhancers of human and rodent oligodendrocyte formation predominantly induce cholesterol precursor accumulation
Authors: Sax Joel L , Hershman Samantha N , Hubler Zita , Allimuthu Dharmaraja , Elitt Matthew S , Bederman Ilya , Adams Drew J 
Published: June 2022

ABSTRACTRegeneration of myelin in the CNS is being pursued as a potential therapeutic approach for multiple sclerosis. Several labs have reported small molecules that promote oligodendrocyte formation and remyelination in vivo. Recently, we reported that many such molecules function by inhibiting a narrow window of enzymes in the cholesterol biosynthesis pathway. Here we describe a new high-throughput screen of 1,836 bioactive molecules and a thorough re-analysis of more than 60 molecules previously-identified as promoting oligodendrocyte formation from human, rat, or mouse oligodendrocyte progenitor cells (OPCs). These studies highlight that an overwhelming fraction of validated screening hits, including several molecules being evaluated clinically for remyelination, inhibit cholesterol pathway enzymes like EBP. To rationalize these findings, we suggest a model that relies on the high druggability of sterol-metabolizing enzymes and the ability of cationic amphiphiles to mimic the transition state of EBP. These studies further establish cholesterol pathway inhibition as a dominant mechanism among screening hits that enhance human, rat, or mouse oligodendrocyte formation.
Reprogramming brain immunosurveillance with engineered cytokines
Authors: Tabet Anthony , Agarwal Yash , Stinson Jordan , Apra Caroline , Will Veronica , Manthey Marie , Momin Noor , Sheen Allison , Murdock Mitchell , Santollani Luciano , Tsai Li-Huei , Chiu Isaac , Lawler Sean , Irvine Darrell J. , Wittrup K. Dane , Anikeeva Polina 
Published: June 2022

AbstractImmune surveillance of the brain is regulated by resident non-neuronal cells and the blood-brain barrier.1 Dys-regulation of immunosurveillance is a hallmark feature of several diseases2–5 including brain tumors6 that interact with and rely heavily on immune cells,7 suggesting that disrupting the neuroimmunology of tumors could slow their progression. Yet few tools are available to control brain immunology in vivo with local precision, and fewer yet are used for therapeutic intervention. 2 Here, we propose engineered cytokines as a neuroimmune-modulation platform. We demonstrate that the residence time of cytokines in the brain can be tuned by binding them to the extracellular matrix or synthetic scaffolds. We then show that the aluminum hydroxide adjuvant (alum) is retained in the brain >2 weeks. Tethering of inflammatory cytokines such as interleukins (IL) 2 and 12 to alum yields extended neuroinflammation and brain immunosurveillance after intracranial administration, while avoiding systemic toxicity. In mouse models of both immunologically hot and cold brain tumors, the intracranial deposition of alum-tethered cytokines causes significant delay in tumor progression. RNA profiling reveals that engineered cytokines engage both innate and adaptive immunity in the brain. These findings suggest that engineered cytokines can reprogram brain immunosurveillance, informing the development of future therapies for neuroimmune diseases.
COVID-19 vaccine breakthrough infections among fully vaccinated Health Care Workers in Lagos, Nigeria
Authors: Oladele David A. , Salako Abideen , Ayorinde James , Onwuamah Chika , Usman Olagoke , Abubakar Rufai , Liboro Gideon , Odubela Oluwatosin , Mogaji Sunday , Ige Fehintola , Ohihoin Gregory , Ezechi Oliver , Audu Rosemary , Adegbola Richard A. , Dada Adedamola , Salako Tunde 
Published: June 2022

AbstractBackgroundAccess to vaccines has contributed to the control of COVID-19. However, evaluation of the effectiveness of the vaccines in a setting where the vaccines were not originally tested is critically important. This study evaluates the clinical and laboratory characteristics of COVID-19 vaccine breakthrough infections among healthcare workers (HCWs).MethodsA multicentre prospective study among HCWs who had two doses of the Oxford/AstraZeneca ChAdOx1-S [recombinant] (AZD1222) vaccine were followed up 24 weeks. Nasopharyngeal and oropharyngeal specimens were tested using RT-PCR for SARS-CoV-2 and positive samples were subjected to whole genome sequencing for variant assignment.ResultA total of 369 HCWs were enrolled; of which 24 (6.5%) had breakthrough infections. There was equal sex distribution among the breakthrough cases. The majority were aged between 30 to 39years (37.5%), and had mild symptoms of cough, fever, headache, and nausea/vomiting (58%), with no hospitalization. Among the 24 breakthrough cases whose whole genomes were successfully sequenced, three were confirmed to be Delta B.1.617.2 variant during the 3rdwave and an additional three were confirmed as omicron B.1.1.529 variant during the 4thwave.ConclusionWe reported vaccine breakthrough cases among fully vaccinated HCWs with the majority presenting with mild illness. Both delta and omicron variants were identified during the different epidemiologic spectrums of SARS-CoV-2. Therefore, there is a need to scale up vaccination for all front-line health workers and high-risk populations in developing countries.
Regulation of heme utilization and homeostasis in Candida albicans
Authors: Andrawes Natalie , Weissman Ziva , Pinsky Mariel , Moshe Shilat , Berman Judith , Kornitzer Daniel 
Published: June 2022

ABSTRACTHeme (iron-protoporphyrin IX) is an essential but potentially toxic cellular cofactor. While most organisms are heme prototrophs, many microorganisms can utilize environmental heme as iron source. The pathogenic yeast Candida albicans can utilize host heme in the iron-poor host environment, using an extracellular cascade of soluble anchored hemophores, and plasma membrane ferric reductase-like proteins. To gain additional insight into the C. albicans heme uptake pathway, we performed an unbiased genetic selection for mutants resistant to the toxic heme analog Ga3+-protoporphyrin IX at neutral pH, and a secondary screen for inability to utilize heme as iron source. Among the mutants isolated were the genes of the pH-responsive RIM pathway, and a zinc finger transcription factor, HUF1. In the presence of hemin in the medium, HUF1 is induced, the Huf1 protein is stabilized and Huf1-GFP localizes to the nucleus. In the huf1 mutant, cytoplasmic heme levels are elevated, while influx of extracellular heme is lower. Gene expression analysis indicated that in the presence of extracellular hemin, Huf1 activates the heme oxygenase HMX1, which breaks down excess cytoplasmic heme, while at the same time it also activates all the known heme uptake genes. These results indicate that Huf1 is a heme-responsive transcription factor that plays a role both in cytoplasmic heme homeostasis and in utilization of extracellular heme. The induction of heme uptake genes by Huf1 under iron satiety indicates that preferential utilization of host heme can be a dietary strategy in a heme prototroph.
Nucleoid-Associated Proteins Undergo Liquid-Liquid Phase Separation with DNA into Multiphasic Condensates Resembling Bacterial Nucleoids
Authors: Gupta Archit , Joshi Ashish , Arora Kanika , Mukhopadhyay Samrat , Guptasarma Purnananda 
Published: June 2022

AbstractLiquid-liquid phase separation offers unique spatiotemporal control over myriad complex intracellular biochemical processes through compartmentalization of biomolecules into highly dynamic, liquid-like condensates known as membrane-less organelles. The bacterial nucleoid is thought to be one such phase-separated condensate; however, its formation, regulation, and biophysical characteristics are poorly understood. Our super-resolution imaging data suggests that nucleoids are dynamic assemblages of sub-micron-sized liquid-like droplets. We demonstrate that non-sequence-specific Nucleoid-Associated Proteins (NAPs) such as HU-A, HU-B and Dps, accrete nucleic acids and spontaneously condense with them into liquid-like, multicomponent, multiphasic, heterotypic phase-separated droplets. Upon mixing of HU-B, DNA and Dps, HU-B-enriched droplets are seen to contain demixed Dps-enriched droplets. Our findings indicate scope for the possible existence of multiphasic liquid-like compartments within nucleoids, providing insights into bacterial growth phase-dependent variations in the levels of different NAPs.
DNA-PKcs regulates myogenesis in an AKT-dependent manner independent of induced DNA damage
Authors: Sutcu Haser Hasan , Ricchetti Miria 
Published: June 2022

AbstractSkeletal muscle regeneration relies on muscle stem (satellite) cells. We previously demonstrated that satellite cells efficiently and accurately repair radiation-induced DNA double-strand breaks (DSBs)viathe DNA-dependent kinase DNA-PKcs. We show here that DNA-PKcs affects myogenesis independently of its role in DSB repair. Consequently, this process does not require the accumulation of DSBs and it is also independent of caspase-induced DNA damage. We report that in myogenic cells DNA-PKcs is essential for the expression of the differentiation factor Myogenin in an Akt2-dependent manner. DNA-PKcs interacts with the p300-containing complex that activatesMyogenintranscription. We show also that SCID mice that are deficient in DNA-PKcs, and are used for transplantation and muscle regeneration studies, display altered myofiber composition and delayed myogenesis upon injury. These defects are exacerbated after repeated injury/regeneration events resulting in reduced muscle size. We thus identify a novel regulator of myogenic differentiation, and define a differentiation phase that does not involve the DNA damage/repair process.
Genome-wide analysis of R2R3-MYB transcription factors in Japanese morning glory
Authors: Komatsuzaki Ayane , Hoshino Atsushi , Otagaki Shungo , Matsumoto Shogo , Shiratake Katsuhiro 
Published: June 2022

AbstractThe R2R3-MYB transcription factor is one of the largest transcription factor families in plants. R2R3-MYBs play a variety of functions in plants, such as cell fate determination, organ and tissue differentiations, primary and secondary metabolisms, stress and defense responses and other physiological processes. The Japanese morning glory (Ipomoea nil) has been widely used as a model plant for flowering and morphological studies. In the present study, 126 R2R3-MYB genes were identified in the Japanese morning glory genome. Information, including gene structure, protein motif, chromosomal location and gene expression, were assigned to the InR2R3-MYBs. Phylogenetic tree analysis revealed that the 126 InR2R3-MYBs were classified into 29 subfamilies (C1-C29). Herein, physiological functions of the InR2R3-MYBs are discussed based on the functions of their Arabidopsis orthologues. InR2R3-MYBs in C9, C15, C16 or C28 may regulate cell division, flavonol biosynthesis, anthocyanin biosynthesis or response to abiotic stress, respectively. C16 harbors the known anthocyanin biosynthesis regulator, InMYB1 (INIL00g10723), and putative anthocyanin biosynthesis regulators, InMYB2 (INIL05g09650) and InMYB3 (INIL05g09651). In addition, INIL05g09649, INIL11g40874 and INIL11g40875 in C16 were suggested as novel anthocyanin biosynthesis regulators. We organized the R2R3-MYB transcription factors in the morning glory genome and assigned information to gene and protein structures and presuming their functions. Our study is expected to facilitate future research on R2R3-MYB transcription factors in Japanese morning glory.
Predicting metabolomic profiles from microbial composition through neural ordinary differential equations
Authors: Wang Tong , Wang Xu-Wen , Lee-Sarwar Kathleen , Litonjua Augusto A. , Weiss Scott T. , Sun Yizhou , Maslov Sergei , Liu Yang-Yu 
Published: June 2022

AbstractCharacterizing the metabolic profile of a microbial community is crucial for understanding its biological function and its impact on the host or environment. Metabolomics experiments directly measuring these profiles are difficult and expensive, while sequencing methods quantifying the species composition of microbial communities are well-developed and relatively cost-effective. Computational methods that are capable of predicting metabolomic profiles from microbial compositions can save considerable efforts needed for metabolomic profiling experimentally. Yet, despite existing efforts, we still lack a computational method with high prediction power, general applicability, and great interpretability. Here we develop a new method — mNODE (Metabolomic profile predictor using Neural Ordinary Differential Equations), based on a state-of-the-art family of deep neural network models. We show compelling evidence that mNODE outperforms existing methods in predicting the metabolomic profiles of human microbiomes and several environmental microbiomes. Moreover, in the case of human gut microbiomes, mNODE can naturally incorporate dietary information to further enhance the prediction of metabolomic profiles. Besides, susceptibility analysis of mNODE enables us to reveal microbe-metabolite interactions, which can be validated using both synthetic and real data. The presented results demonstrate that mNODE is a powerful tool to investigate the microbiome-diet-metabolome relationship, facilitating future research on precision nutrition.
Pseudomonas aeruginosa mediates PqsA-dependent iron regulation of the RsmY and RsmZ sRNAs in static conditions
Authors: Chourashi Rhishita , Oglesby Amanda G. 
Published: June 2022

ABSTRACTPseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes acute and chronic lung infection in compromised hosts. During infection, the host innate immune system restricts iron to limit microbial growth. In response, P. aeruginosa induces expression of numerous virulence genes. Recently, our lab showed that some virulence factors are responsive to iron limitation in static but not shaking growth conditions, the former of which is likely to mimic growth in the chronically-infected lung. One of these novel iron-responsive factors is the HSI-2-type six secretion system (T6SS), which is also induced during chronic infection. Iron regulation of T6SS was partially impacted by deletion of the iron-responsive PrrF sRNA and completely dependent upon the Pseudomonas quinolone signal (PQS) biosynthetic gene pqsA. Here, we analyzed the impact of iron on the expression of two small regulatory RNAs (sRNAs), RsmY and RsmZ, that activate expression of T6SS by sequestering the RsmA translation inhibitor. Our results demonstrate that iron starvation induces expression of RsmY and RsmZ in static but not shaking cultures. We further show that this induction occurs through the rsmY and rsmZ promoters and is dependent upon PqsA. We identified interrupted palindromes in the rsmY and rsmZ promoters as putative PqsR binding sites, and disruption of these sites eliminated iron-dependent regulation of rsmY and rsmZ promoter activity. To determine if iron-dependent regulation of the Rsm sRNAs is likely responsible for iron regulation of HSI-2 T6SS, we constructed translational and transcriptional reporters of the hsiA2 T6SS gene. Analysis of these reporters revealed robust PqsA-mediated iron regulation of the transcriptional reporter, as well as modest PrrF-dependent iron regulation of the translational reporter. Taken together, our results show novel iron regulatory pathways that are promoted by static growth, highlighting the importance of studying regulatory mechanisms in static communities that are likely more representative of chronic P. aeruginosa infections.IMPORTANCEIron is a central component of various bacterial metabolic pathways making it an important host acquired nutrient for pathogens to establish infection. Previous iron regulatory studies primaried relied on shaking bacterial cultures; while these ensure cultural homogeneity they do not reflect growth conditions during infection. We recently showed that static growth of Pseudomonas aeruginosa promotes iron-dependent regulation of a type six secretion system (T6SS), a virulence factor that is induced during chronic infections. In the current study, we found that static growth also promotes iron-dependent regulation of the RsmY and RsmZ sRNAs, which are global regulators that affect T6SS during chronic P. aeruginosa lung infection. Hence, our work demonstrates the Rsm sRNAs as potential effectors of iron regulation during static growth that may also be relevant in chronic infection.
Half-calcified Calmodulin Promotes Basal Activity and Inactivation of the Calcium Channel CaV1.2
Authors: Bartels Peter , Salveson Ian , Coleman Andrea M. , Anderson David E. , Jeng Grace , Estrada-Tobar Zoila M. , Man Kwun Nok Mimi , Yu Qinhong , Kuzmenkina Elza , Nieves-Cintron Madeline , Navedo Manuel F. , Horne Mary C. , Hell Johannes W. , Ames James B. 
Published: June 2022

ABSTRACTThe L-type Ca2+channel CaV1.2 controls gene expression, cardiac contraction, and neuronal activity. Calmodulin (CaM) governs CaV1.2 open probability (Po) and Ca2+-dependent inactivation (CDI) but the mechanisms remain unclear. We identified a half Ca2+-saturated CaM species (Ca2/CaM) with Ca2+bound solely at the third and fourth EF-hands (EF3 and EF4) under resting Ca2+concentrations (50-100 nM) that constitutively pre-associates with CaV1.2 to promote Po and CDI. We present an NMR structure of a complex between the CaV1.2 IQ motif (residues 1644-1665) and Ca2/CaM12’, a calmodulin mutant in which Ca2+binding to EF1 and EF2 is completely disabled. The CaM12’N-lobe does not interact with the IQ motif. The CaM12’C-lobe bound two Ca2+ions and formed close contacts with IQ residues I1654 and Y1657. I1654A and Y1657D mutations impaired CaM binding, CDI, and Po, as did disabling Ca2+binding to EF3 and EF4 in the CaM34mutant when compared to wildtype CaM. Accordingly, a previously unappreciated Ca2/CaM species promotes CaV1.2 Po and CDI identifying Ca2/CaM as an important mediator of Ca signaling.