bluuebunny/crossref_metadata_2025 huggingface dataset:
The Nature of Septuagint Greek
Authors: Evans Trevor V.
Published: February 2021

Language provides core evidence for addressing most of the central questions of LXX studies. The achievement of an accurate understanding of the special nature of the Greek in which the LXX is composed is thus a key scholarly desideratum. Although the corpus does not lightly yield its linguistic secrets, significant progress has been made in recent scholarship. This chapter considers the linguistic and stylistic heterogeneity of the LXX corpus. It outlines the development of the main lines of interpretation, from emphasis on the ‘Semitic’ features of translation Greek to focus on natural Greek characteristics. It also traces the history of LXX lexicography from Rosenbach to Muraoka, taking into account the oblique impact of recent large-scale translation projects. Lastly it addresses the dynamic current state of research, and points to results that may flow from systematic analyses of the material that locate it within its broader linguistic context as a set of key specimens of early Koine Greek.
The Books of Kings
Authors: Kauhanen Tuukka , Piquer Otero Andrés , Tekoniemi Timo , Torijano Pablo A.
Published: February 2021

The books of Kings have some of the most challenging text-historical problems in all of the Hebrew Bible. The Septuagint edition (known as 3–4 Kingdoms) differs widely from MT Kings in both individual readings and the ordering of the textual units. These differences can be traced to its Hebrew Vorlage. The translation from the Hebrew was made in a highly literal, albeit not slavish, style. The study of the Septuagint of Kings is further complicated by the fact that most of its text was later subjected to the Kaige revision and that this revised text form is now found in most Greek witnesses. Thus the Old Greek translation is best preserved in different Greek manuscript traditions in different sections of Kings. Often the daughter versions, especially the Old Latin, are of great significance for the text-critical study of both the Old Greek and also its probable Vorlage.
Philo and the Septuagint
Authors: Pearce Sarah J. K.
Published: February 2021

This chapter deals with the fundamental place of the LXX in the writings of Philo of Alexandria, with particular attention to the treatment of the LXX text in the following: (1) the Questions and Answers on Genesis and Exodus; (2) the Allegorical Commentary; (3) the Exposition of the Law; (4) the Life of Moses Books 1–2. It also discusses questions of Philo’s citation practice; terminology applied to Jewish sacred books; the transmission history of Philo’s scriptural citations; his presentation of the translation of the books of Moses on the island of Pharos (Mos. 2.25–44); his use of etymologies; and his knowledge of Hebrew.
The Social and Historical Setting of the Septuagint
Authors: Aitken James K.
Published: February 2021

The history of both Palestine and the regions forming the Diaspora is one of changing political power and rivalry between empires. For many Jews living in these areas the change in ruler had little effect on daily life. The one noticeable difference would have been the rise in the use of Greek, which would especially have been stimulated in Judea by the Hasmonean and Herodian courts. In such a context translation into Greek could have been possible, and the later a translation is placed in the Second Temple period the greater chance it could have been translated outside of Egypt. However, for the Diaspora communities our evidence is scant and nothing more than speculation is feasible, although social circumstances render translation there a possibility.
The Social and Historical Setting of the Septuagint
Authors: Capponi Livia
Published: February 2021

This chapter examines the civic status, political role, and social standing of the Jewish community in Egypt from its establishment under Ptolemy I until its destruction at the time of the Diaspora Revolt under Trajan, and beyond. It revises some debated issues, such as the relationship between Macedonian and Jewish status in Ptolemaic Egypt, the role of Jews as ‘guardians of the river’, the Augustan reforms and their consequences under Gaius and Claudius, the migration of Jewish rebels after 70 ce, and the traces of some Egyptian solidarity with the Jewish rebels under Trajan. Its aim is to show the complexities of a region where Egyptian and Jewish cultures were in close contact since the very ancient past, and which cannot be explained through a simplistic categorization ‘Judaism versus Hellenism’.
New Testament
Authors: Wagner J. Ross
Published: February 2021

Septuagint research has vital contributions to make to contemporary conversations in New Testament studies. Nowhere is this more evident than in current debates about the interpretation of Israel’s Scriptures in the New Testament writings and the nature of New Testament Greek. Key areas of investigation include the influence of the LXX on the vocabulary of the NT; the pluriformity of Greek scriptural texts in the first century ce; the difficulty of distinguishing between citation, allusion, citations from memory, and echoes of Scripture in Greek.
Manuscripts, Papyri, and Epigraphy
Authors: Bossina Luciano
Published: February 2021

Owing to their number, chronological distribution, and geographical diffusion, the manuscript witnesses of the Septuagint amount to one of the major corpora of Greek literature, comparable only to the New Testament and Homer. The LXX corpus was in constant evolution, covering all the major turning points in the history of Greek manuscripts: the transition from roll to codex, from majuscule to minuscule writing, from papyrus to parchment, and from parchment to paper. The variety of uses is also comprehensive. There are both luxury manuscripts written by professional calligraphers, and manuscripts for daily use created from recycled materials and using cursory handwriting. It is a corpus of relevance not solely for the biblical scholar, but also for the philologist, the palaeographer and codicologist, the historian, the art historian, the Byzantinist, the theologian, and more. This chapter will focus on the parchment and paper manuscripts between the fourth and the sixteenth centuries.
Xylem network connectivity and embolism spread in grapevine(Vitis viniferaL.)
Authors: Wason Jay , Bouda Martin , Lee Eric F , McElrone Andrew J , Phillips Ronald J , Shackel Kenneth A , Matthews Mark A , Brodersen Craig
Published: February 2021

Xylem networks are vulnerable to the formation and spread of gas embolisms that reduce water transport. Embolisms spread through interconduit pits, but the three-dimensional (3D) complexity and scale of xylem networks means that the functional implications of intervessel connections are not well understood. Here, xylem networks of grapevine (Vitis vinifera L.) were reconstructed from 3D high-resolution X-ray micro-computed tomography (microCT) images. Xylem network performance was then modeled to simulate loss of hydraulic conductivity under increasingly negative xylem sap pressure simulating drought stress conditions. We also considered the sensitivity of xylem network performance to changes in key network parameters. We found that the mean pit area per intervessel connection was constant across 10 networks from three, 1.5-m stem segments, but short (0.5 cm) segments fail to capture complete network connectivity. Simulations showed that network organization imparted additional resistance to embolism spread beyond the air-seeding threshold of pit membranes. Xylem network vulnerability to embolism spread was most sensitive to variation in the number and location of vessels that were initially embolized and pit membrane vulnerability. Our results show that xylem network organization can increase stem resistance to embolism spread by 40% (0.66 MPa) and challenge the notion that a single embolism can spread rapidly throughout an entire xylem network.
A semi-dominant NLR allele causes whole-seedling necrosis in wheat
Authors: Jia Haiyan , Xue Shulin , Lei Lei , Fan Min , Peng Shuxia , Li Tian , Nagarajan Ragupathi , Carver Brett , Ma Zhengqiang , Deng Junpeng , Yan Liuling
Published: February 2021

Programmed cell death (PCD) and apoptosis have key functions in development and disease resistance in diverse organisms; however, the induction of necrosis remains poorly understood. Here, we identified a semi-dominant mutant allele that causes the necrotic death of the entire seedling (DES) of wheat (Triticum aestivum L.) in the absence of any pathogen or external stimulus. Positional cloning of the lethal allele mDES1 revealed that this premature death via necrosis was caused by a point mutation from Asp to Asn at amino acid 441 in a nucleotide-binding leucine-rich repeat protein containing nucleotide-binding domain and leucine-rich repeats. The overexpression of mDES1 triggered necrosis and PCD in transgenic plants. However, transgenic wheat harboring truncated wild-type DES1 proteins produced through gene editing that exhibited no significant developmental defects. The point mutation in mDES1 did not cause changes in this protein in the oligomeric state, but mDES1 failed to interact with replication protein A leading to abnormal mitotic cell division. DES1 is an ortholog of Sr35, which recognizes a Puccinia graminis f. sp. tritici stem rust disease effector in wheat, but mDES1 gained function as a direct inducer of plant death. These findings shed light on the intersection of necrosis, apoptosis, and autoimmunity in plants.
Impact of Current Pain Status on Low-Barrier Buprenorphine Treatment Response Among Patients with Opioid Use Disorder
Authors: Peck Kelly R , Ochalek Taylor A , Streck Joanna M , Badger Gary J , Sigmon Stacey C
Published: February 2021

Objective

Chronic non-cancer pain (CNCP) is prevalent among individuals with opioid use disorder (OUD). However, the impact of CNCP on buprenorphine treatment outcomes is largely unknown. In this secondary analysis, we examined treatment outcomes among individuals with and without CNCP who received a low-barrier buprenorphine maintenance regimen during waitlist delays to more comprehensive opioid treatment.

Methods

Participants were 28 adults with OUD who received 12 weeks of buprenorphine treatment involving bimonthly clinic visits, computerized medication dispensing, and phone-based monitoring. At intake and monthly follow-up assessments, participants completed the Brief Pain Inventory, Beck Anxiety Inventory, Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI), Addiction Severity Index, and staff-observed urinalysis.

Results

Participants with CNCP (n = 10) achieved comparable rates of illicit opioid abstinence as those without CNCP (n = 18) at weeks 4 (90% vs 94%), 8 (80% vs 83%), and 12 (70% vs 67%) (P = 0.99). Study retention was also similar, with 90% and 83% of participants with and without CNCP completing the 12-week study, respectively (P = 0.99). Furthermore, individuals with CNCP demonstrated significant improvements on the BDI-II and Global Severity Index subscale of the BSI (P < 0.05). However, those with CNCP reported more severe medical problems and smaller reductions in legal problems relative to those without CNCP (P = 0.03).

Conclusions

Despite research suggesting that chronic pain may influence OUD treatment outcomes, participants with and without CNCP achieved similar rates of treatment retention and significant reductions in illicit opioid use and psychiatric symptomatology during low-barrier buprenorphine treatment.
Identifying unmet needs in SSc-ILD by semi-qualitative in-depth interviews
Authors: Hoffmann-Vold Anna-Maria , Bendstrup Elisabeth , Dimitroulas Theodoros , Hesselstrand Roger , Morais Antonio , Peltomaa Ritva , Smith Vanessa , Welling Joep , Vonk Madelon C , Wuyts Wim A
Published: February 2021

Objectives

Interstitial lung disease is frequent in SSc (SSc-ILD) and associates with significantly reduced quality of life. Here we aimed to analyse patient pathways, and experiences of patients and healthcare providers (HCPs) in order to identify unmet needs in the management of SSc-ILD patients.

Methods

Semi-structured qualitative interviews conducted in eight European countries looked at HCP (n = 95) and patient perspectives (n = 47) using two sets of 70 research questions. Pre-diagnostic, diagnostic and post-diagnostic phases of the patient pathway were systematically explored.

Results

(i) In the pre-diagnostic phase several gaps were identified by HCPs and patients in all participating countries: limited disease knowledge among primary care physicians and specialists, lack of accurate patient information, and delayed and/or inappropriate referral. (ii) The diagnostic phase is in most countries coordinated by rheumatologists, who are also the main point of care. Depending on the local health system, organization of multidisciplinary collaboration varies. HCPs issued lack of national guidelines, while patients stated difficulties obtaining disease-related information. (iii) In the post-diagnostic phase, HCPs and patients indicated lack of curative treatment, specialized nurses, and paramedical  and psychological support. Patients and caregivers additionally expressed the need for clear information on SSc-ILD.

Conclusion

Lack of disease specific knowledge, gaps in national healthcare systems and insufficient information and support for patients and caregivers were identified as unmet needs to ensure timely diagnosis, provide better patient management and to improve quality of life in SSc-ILD patients.
Genome Sequence of the Fungus Trichoderma asperellum SM-12F1 Revealing Candidate Functions of Growth Promotion, Biocontrol, and Bioremediation
Authors: Li Lijuan , Zeng Xibai , Chen Jieyin , Tian Jian , Huang Jinqun , Su Shiming
Published: February 2021

Trichoderma spp. are versatile probiotic fungi that are known to promote plant growth and disease resistance under biotic stress, abiotic stress, or both. They are often used to prevent plant diseases caused by pathogens, act as biofertilizers, and are used in mycoremediation. In our previous study, Trichoderma asperellum strain SM-12F1 was isolated from soils contaminated with arsenic (As), adjacent to a realgar mine. SM-12F1 promoted plant growth and was useful for biocontrol and bioremediation. However, the genomic sequence of this strain was not characterized. This study aimed to generate high-quality genome resources for T. asperellum SM-12F1, and to determine the genomic basis of mechanisms behind plant growth promotion, biocontrol, and bioremediation of As in soil. Genome data of this fungus will provide perspectives on the molecular basis underlying biocontrol activity and mycoremediation.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Key Enzymes for the Mevalonate Pathway in the Cardiovascular System
Authors: Zhang Chi , Jin Dan-Dan , Wang Xi-Ying , Lou Lian , Yang Jian
Published: February 2021

Isoprenylation is an important post-transcriptional modification of small GTPases required for their activation and function. Isoprenoids, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate, are indispensable for isoprenylation by serving as donors of a prenyl moiety to small G proteins. In the human body, isoprenoids are mainly generated by the mevalonate pathway (also known as the cholesterol-synthesis pathway). The hydroxymethylglutaryl coenzyme A reductase catalyzes the first rate-limiting steps of the mevalonate pathway, and its inhibitor (statins) are widely used as lipid-lowering agents. In addition, the FPP synthase is also of critical importance for the regulation of the isoprenoids production, for which the inhibitor is mainly used in the treatment of osteoporosis. Synthetic FPP can be further used to generate geranylgeranyl pyrophosphate and cholesterol. Recent studies suggest a role for isoprenoids in the genesis and development of cardiovascular disorders, such as pathological cardiac hypertrophy, fibrosis, endothelial dysfunction, and fibrotic responses of smooth-muscle cells. Furthermore, statins and FPP synthase inhibitors have also been applied for the management of heart failure and other cardiovascular diseases rather than their clinical use for hyperlipidemia or bone diseases. In this review, we focus on the function of several critical enzymes, including hydroxymethylglutaryl coenzyme A reductase, FPP synthase, farnesyltransferase, and geranylgeranyltransferase in the mevalonate pathway which are involved in regulating the generation of isoprenoids and isoprenylation of small GTPases, and their pathophysiological role in the cardiovascular system. Moreover, we summarize recent research into applications of statins and the FPP synthase inhibitors to treat cardiovascular diseases, rather than for their traditional indications respectively.
How We Assess Spatial Neglect Matters
Authors: Gillen Robert W. , Fusco-Gessick Benjamin , Harmon Erin Y.
Published: February 2021

Objective

The aim of this study was to determine the prevalence and functional impact of unilateral spatial neglect on right hemisphere stroke patients in an inpatient rehabilitation facility using a multidimensional, functionally based behavioral measure (Catherine Bergego Scale [CBS]).

Design

This was a retrospective cohort study of 742 consecutive admissions of patients with right hemispheric stroke to an inpatient rehabilitation facility. Spatial neglect was assessed using the CBS. Functional impact of neglect was measured by hospital length of stay, Functional Independence Measure change per day, discharge destination, and number of falls.

Results

As measured by the CBS, 86% of the right hemisphere stroke patients had symptoms of spatial neglect. Moderate and severe neglect was associated with less Functional Independence Measure change per day and lower rates of community discharge. The presence of neglect was not significantly associated with fall rate or length of hospital stay after controlling for admission Functional Independence Measure scores and age. The “difficulty looking left” CBS item had the strongest relationship with total CBS scores and effectively predicted Functional Independence Measure change per day and discharge destination.

Conclusions

Using a sensitive measure, the CBS, rates of spatial neglect are extremely high in right hemisphere stroke patients entering inpatient rehabilitation. Both identification and determination of neglect severity are extremely important given their significant relationship to rehabilitation outcomes and discharge destinations.

To Claim CME Credits

Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives

Upon completion of this article, the reader should be able to (1) describe why carefully assessing spatial neglect in right hemisphere stroke patients is important; (2) identify multiple dimensions of spatial neglect assessed by the Catherine Bergego Scale and how this approach differs from traditional paper and pencil assessment methods; and (3) describe the relationship between spatial neglect as measured by the Catherine Bergego Scale and functional outcomes of right hemisphere stroke patients in inpatient rehabilitation settings.

Level

Advanced

Accreditation

The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Association of Academic Physiatrists designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Pulmonary aspergillosis in two COVID-19 patients from Kuwait
Authors: Alobaid Khaled , Yousuf Beena , Al-Qattan Eman , Muqeem Zainab , Al-Subaie Nawaf
Published: February 2021

Critically ill patients with coronavirus disease 2019 (COVID-19) are at risk of invasive pulmonary aspergillosis. The clinical manifestations of a superimposed fungal infection in those patients are difficult to underpin. This is compounded by the non-specific radiological findings associated with this infection and the challenges associated with performing bronchoscopy in COVID-19 patients. We would like to present two COVID-19 cases who developed secondary Aspergillus pulmonary infection in the intensive care unit as shown by respiratory cultures, serum galactomannan and radiological images. Despite advanced intensive care and use of antifungal agents, both patients died eventually. This report illustrates the negative impact of secondary Aspergillosis and calls for the need of increased awareness of COVID19-associated pulmonary aspergillosis.
Syntrophotalea acetylenivorans sp. nov., a diazotrophic, acetylenotrophic anaerobe isolated from intertidal sediments
Authors: Baesman Shaun M. , Sutton John M. , Fierst Janna L. , Akob Denise M. , Oremland Ronald S.
Published: February 2021

A Gram-stain-negative, strictly anaerobic, non-motile, rod-shaped bacterium, designated SFB93T, was isolated from the intertidal sediments of South San Francisco Bay, located near Palo Alto, CA, USA. SFB93Twas capable of acetylenotrophic and diazotrophic growth, grew at 22–37 °C, pH 6.3–8.5 and in the presence of 10–45 g l−1NaCl. Phylogenetic analyses based on 16S rRNA gene sequencing showed that SFB93Trepresented a member of the genusSyntrophotaleawith highest 16S rRNA gene sequence similarities toSyntrophotalea acetylenicaDSM 3246T(96.6 %),Syntrophotalea carbinolicaDSM 2380T(96.5 %), andSyntrophotalea venetianaDSM 2394T(96.7 %). Genome sequencing revealed a genome size of 3.22 Mbp and a DNA G+C content of 53.4 %. SFB93Thad low genome-wide average nucleotide identity (81–87.5 %) and <70 % digital DNA–DNA hybridization value with other members of the genusSyntrophotalea. The phylogenetic position of SFB93Twithin the familySyntrophotaleaceaeand as a novel member of the genusSyntrophotaleawas confirmed via phylogenetic reconstruction based on concatenated alignments of 92 bacterial core genes. On the basis of the results of phenotypic, genotypic and phylogenetic analyses, a novel species,Syntrophotalea acetylenivoranssp. nov., is proposed, with SFB93T(=DSM 106009T=JCM 33327T=ATCC TSD-118T) as the type strain.
The UCR Minicore: a valuable resource for cowpea research and breeding
Authors: Muñoz-Amatriaín María , Lo Sassoum , Herniter Ira A. , Boukar Ousmane , Fatokun Christian , Carvalho Márcia , Castro Isaura , Guo Yi-Ning , Huynh Bao-Lam , Roberts Philip A. , Carnide Valdemar , Close Timothy J.
Published: February 2021

Incorporation of new sources of genetic diversity into plant breeding programs is crucial for continuing to improve yield and quality, as well as tolerance to abiotic and biotic stresses. A minicore (the “UCR Minicore”) composed of 368 worldwide accessions of cultivated cowpea has been assembled, having been derived from the University of California, Riverside cowpea collection. High-density genotyping with 51,128 SNPs followed by principal component and genetic assignment analyses identified six subpopulations in the UCR Minicore, mainly differentiated by cultivar group and geographic origin. All six subpopulations were present to some extent in West African material, suggesting that West Africa is a center of diversity for cultivated cowpea. Additionally, population structure analyses supported two routes of introduction of cowpea into the U.S.: (1) from Spain to the southwest U.S. through Northern Mexico, and (2) from Africa to the southeast U.S. via the Caribbean. Genome-wide association studies (GWAS) of important agronomic traits including flowering time, resulted in the identification of significant SNPs for all traits and environments. The mapping resolution achieved by high-density genotyping of this diverse minicore collection allowed the identification of strong candidate genes, including orthologs of the ArabidopsisFLOWERING LOCUS T.In summary, this diverse, yet compact cowpea collection constitutes a suitable resource to identify loci controlling complex traits, consequently providing markers to assist with breeding to improve this crop of high relevance to global food and nutritional security.
Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach
Authors: Gu Jialiang , Fuller Chris , Zheng Jiashun , Li Hao
Published: February 2021

Phenotypic correlations between complex human traits have long been observed based on epidemiological studies. However, the genetic basis and underlying mechanisms are largely unknown. The recent accumulation of GWAS data has made it possible to analyze the genetic similarity between human traits through comparative analysis. Here we developed a gene-based approach to measure genetic similarity between a pair of traits and to delineate the shared genes/pathways, through three steps: 1) translating SNP-phenotype association profile to genephenotype association profile by integrating GWAS with eQTL data; 2) measuring the similarity between a pair of traits by a normalized distance between the two gene-phenotype association profiles; 3) delineating genes/pathways supporting the similarity. Application of this approach to a set of GWAS data covering 59 human traits detected significant similarity between many known and unexpected pairs of traits; a significant fraction of them are not detectable by SNP based similarity measures. Examples include Height and Schizophrenia, Cancer and Alzheimer’s Disease, and Rheumatoid Arthritis and Crohn’s disease. Functional analysis revealed specific genes/pathways shared by these pairs. For example, Height and Schizophrenia are co-associated with genes involved in neural development, skeletal muscle regeneration, protein synthesis, magnesium homeostasis, and immune response, suggesting growth and development as a common theme underlying both traits. Our approach can detect yet unknown relationships between complex traits and generate mechanistic hypotheses, and has the potential to improve diagnosis and treatment by transferring knowledge from one disease to another.
Neuroprotective and Mitoprotective Effects of Lemon IntegroPectin on SH-SY5Y Cells
Authors: Nuzzo Domenico , Picone Pasquale , Giardina Costanza , Scordino Miriana , Mudò Giuseppa , Pagliaro Mario , Scurria Antonino , Meneguzzo Francesco , Ilharco Laura M. , Fidalgo Alexandra , Presentato Alessandro , Alduina Rosa , Ciriminna Rosaria , Di Liberto Valentina
Published: February 2021

Lemon IntegroPectin obtained via hydrodynamic cavitation of organic lemon processing waste in water shows significant neuroprotective activityin vitro, as first reported in this study investigating the effects of both lemon IntegroPectin and commercial citrus pectin on cell viability, cell morphology, reactive oxygen species (ROS) production and mitochondria perturbation induced by treatment of neuronal SH-SY5Y human cells with H2O2. Mediated by ROS including H2O2and its derivatives, oxidative stress alters numerous cellular processes, including mitochondrial regulation and cell signaling, propagating cellular injury that leads to incurable neurodegenerative diseases. These results, and the absence of toxicity of this new pectic substance rich in adsorbed flavonoids and terpenes, support further investigations to verify its activity in preventing, retarding, or even curing neurological diseases.
Modeling changes in vascular and extracellular matrix integrity that can occur in decellularized kidneys after implantation
Authors: Corridon Peter R.
Published: February 2021

A method was established to identify alterations in vascular patency and extracellular matrix integrity of decellularized porcine kidney scaffolds. These scaffolds were perfused with blood at physiologically normal (500 and 650 ml/min) and abnormal (200 ml/min) rates. Variations in venous outflow were then assessed over 24 hours. Angiographic data confirmed that standard arterial branching patterns and the integrity of the extracellular matrix were considerably disrupted. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow across the 24 hours. These reductions rose from roughly 40% after 12 hours to 60% after 24 hours. At the end of the test period, regardless of the underlying damage that occurred, the kidneys appeared intact on the surface, and there were no apparent signs of clotting. In comparison, venous flow rates decreased by 80 to 100% across the 24 hours in acellular scaffolds subjected to a far lower perfusion rate of 200 ml/min. These kidneys also appeared intact after 24 hours of perfusion, but presented several arterial, venous, and ureteral clots. The results of this study provide insight into circumstances that limit scaffold viability and provide a simplified model to analyze other conditions that can better prepare scaffolds for long-term transplantation.
Effects of Perinatal Fluoxetine Exposure on Novelty-induced Social and Non-Social Investigation Behaviors in a Seminatural Environment
Authors: Sylte Ole Christian , Johansen Jesper Solheim , Heinla Indrek , Houwing Danielle J , Olivier Jocelien DA , Heijkoop Roy , Snoeren Eelke MS
Published: February 2021

Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed as medication for various affective disorders during pregnancy. SSRIs cross the placenta and affect serotonergic neurotransmission in the fetus, but the neurobehavioral consequences for the offspring remain largely unclear. Recent rodent research has linked perinatal SSRI exposure to alterations in both social and non-social aspects of behavior. However, this research has mainly focused on behavior within simplified environments. The current study investigates the effects of perinatal SSRI exposure on social and non-social investigation behaviors of adult rat offspring upon introduction to a novel seminatural environment with unknown conspecifics. During the perinatal period (gestational day 1 until postnatal day 21), rat dams received daily treatment with either an SSRI (fluoxetine, 10 mg/kg) or vehicle. Adult male and female offspring were observed within the first hour after introduction to a seminatural environment. The results showed that perinatal fluoxetine exposure altered aspects of non-social investigation behaviors, while not altering social investigation behaviors. More specifically both fluoxetine exposed males and females spent more total time on locomotor activity than controls. Furthermore, fluoxetine exposed females spent less time exploring objects and specific elements in the environment. The data suggest that perinatal exposure to SSRIs leads to a quicker, less detailed investigation strategy in novel environments, and that the alteration is mostly pronounced in females.
Medicago SPX1 and SPX3 regulate phosphate homeostasis, mycorrhizal colonization and arbuscule degradation
Authors: Wang Peng , Snijders Roxane , Kohlen Wouter , Liu Jieyu , Bisseling Ton , Limpens Erik
Published: February 2021

To acquire sufficient mineral nutrients such as phosphate (Pi) from the soil, most plants engage in a symbiosis with arbuscular mycorrhizal (AM) fungi. Attracted by plant-secreted strigolactones, the fungi colonize the roots and form highly-branched hyphal structures called arbuscules inside inner cortex cells. It is essential that the host plant controls the different steps of this interaction to maintain its symbiotic nature. However, how plants sense the amount of Pi obtained from the fungus and how this determines the arbuscule lifetime is far from understood. Here, we show thatMedicago truncatulaSPX-domain containing proteins SPX1 and SPX3 regulate root phosphate starvation responses as well as fungal colonization and arbuscule degradation.SPX1andSPX3are induced upon phosphate starvation but become restricted to arbuscule-containing cells upon establishment of the symbiosis. Under Pi-limiting conditions they facilitate the expression of the strigolactone biosynthesis geneDWARF27, which correlates with increased fungal branching by root exudates and increased root colonization. Later, in the arbuscule-containing cells SPX1 and SPX3 redundantly control the timely degradation of arbuscules. This regulation does not seem to involve direct interactions with known transcriptional regulators of arbuscule degradation. We propose a model where SPX1 and SPX3 control arbuscule degeneration in a Pi-dependent manner via a yet-to-identify negative regulator.
Abscisic-acid-dependent regulation ofArabidopsis thalianaammonium transport relies on ABI1 control of CIPK23 and AMT1
Authors: Ganz Pascal , Porras-Murillo Romano , Ijato Toyosi , Menz Jochen , Straub Tatsiana , Stührwohldt Nils , Moradtalab Narges , Ludewig Uwe , Neuhäuser Benjamin
Published: February 2021

Ammonium uptake at plant roots is regulated at the transcriptional, post-transcriptional and post-translational levels. Phosphorylation by the protein kinase CIPK23 transiently inactivates the ammonium transporters (AMT1s) but the phosphatases activating AMT1s remain unknown. Here, we have identified the PP2C phosphatase ABI1 as an activator of AMTs inArabidopsis thaliana. We show that high external ammonium concentrations elevate the stress phytohormone abscisic acid (ABA) by de-glycosylation. Active ABA is sensed by ABI1-PYL complexes followed by the inactivation of ABI1 activating CIPK23. Under favourable growth conditions, ABI1 reduces AMT1 phosphorylation, both by binding and inactivating CIPK23, and by the direct dephosphorylation of AMT1s. Thus, ABI1 is a positive regulator of ammonium uptake, coupling nutrient acquisition to abiotic stress signalling. Elevated ABA reduces ammonium uptake during stress situations, such as ammonium toxicity, whereas ABI1 reactivates AMT1s under favourable growth conditions.
A molecular framework for control of oriented cell division in the Arabidopsis embryo
Authors: Vaddepalli Prasad , de Zeeuw Thijs , Strauss Sören , Bürstenbinder Katharina , Liao Che-Yang , Smith Richard , Weijers Dolf
Published: February 2021

Premitotic control of cell division orientation is critical for plant development, as cell walls prevent extensive cell remodelling or migration. Whilst many divisions are proliferative and add cells to existing tissues, some divisions are formative, and generate new tissue layers or growth axes. Such formative divisions are often asymmetric in nature, producing daughters with different fates. We have previously shown that in theArabidopsis thalianaembryo, developmental asymmetry is correlated with geometric asymmetry, creating daughter cells of unequal volume. Such divisions are generated by division planes that deviate from a default “minimal surface area” rule. Inhibition of auxin response leads to reversal to this default, yet the mechanisms underlying division plane choice in the embryo have been unclear. Here we show that auxin-dependent division plane control involves alterations in cell geometry, but not in cell polarity or nuclear position. Through transcriptome profiling, we find that auxin regulates genes controlling cell wall and cytoskeleton properties. We confirm the involvement of microtubule (MT)-binding proteins in embryo division control. Topology of both MT and Actin cytoskeleton depend on auxin response, and genetically controlled MT or Actin depolymerization in embryos leads to disruption of asymmetric divisions, including reversion to the default. Our work shows how auxin-dependent control of MT- and Actin cytoskeleton properties interacts with cell geometry to generate asymmetric divisions during the earliest steps in plant development.
Ectomycorrhizas accelerate decomposition to a greater extent than arbuscular mycorrhizas in a northern deciduous forest
Authors: Carteron Alexis , Cichonski Fabien , Laliberté Etienne
Published: February 2021

It has been proposed that ectomycorrhizal (EcM) fungi slow down decomposition by competing with free-living saprotrophs for organic nutrients and other soil resources (known as the “Gadgil effect”), thereby increasing soil carbon sequestration. As such, this Gadgil effect should depend on soil organic matter age and quality, but this remains unstudied. In addition, the Gadgil effect is not expected to occur in arbuscular mycorrhizal (AM) forests since AM fungi cannot access directly nutrients from soil organic matter, yet few direct comparisons between EcM and AM forests have been made. We performed a two-year reciprocal decomposition experiment of soil organic horizons (litter - L, fragmented - F, humic - H) in adjacent temperate deciduous forests dominated by EcM or AM trees. Litterbags were made of different mesh sizes allowing or excluding ingrowth of external fungal hyphae, which are primarily mycorrhizal in these forests other than for the most-recent superficial litter horizon. As expected, organic matter originating from deeper horizons and from EcM forests was of lower quality (e.g. higher lignin to nitrogen ratios) and decomposed more slowly. However, contrary to the Gadgil effect, organic matter exposed to external fungal hyphae (i.e. primarily mycorrhizal) actually decomposed faster in both forest types, and this effect was strongest in EcM forests, particularly in the F horizon. Unexpectedly, organic matter decomposition was faster in EcM than in AM forests, regardless of organic matter origin. Overall, our study reinforces the view that temperate EcM forests store greater amounts of soil organic carbon than AM forests, but suggests that this is due to factors other than the Gadgil effect.
Generating controlled gusts using vortex rings
Authors: Gupta Dipendra , Sane Sanjay P. , Arakeri Jaywant H.
Published: February 2021

The control and stability of flying and swimming animals is typically determined by measuring their responses to discrete gust perturbations. For the rigorous measurement and analysis of such responses, it is necessary to generate gusts that are precise, controllable and repeatable. Here, we present a method to generate discrete gusts under laboratory conditions using a vortex ring. Unlike other methods of gust generation, the vortex ring can be well characterized and is highly controllable. We first outline the theoretical basis for the design of a gust generator, and then describe an apparatus that we developed to generate discrete gusts. As a case study, we tested the efficacy of this method on freely-flying soldier fliesHermetia illucens. The method described here can be used to study diverse phenomena ranging from natural flight and swimming in insects, birds, bats and fishes, to the artificial flight of drones and micro-aerial vehicles.
A masculinizing supergene underlies an exaggerated male reproductive morph in a spider
Authors: Hendrickx Frederik , De Corte Zoë , Sonet Gontran , Belleghem Steven M. Van , Köstlbacher Stephan , Vangestel Carl
Published: February 2021

In many species, individuals can develop into strikingly different morphs, which are determined by a simple Mendelian locus. How selection shapes loci that control complex phenotypic differences remains poorly understood. In the spiderOedothorax gibbosus, males either develop into a ‘hunched’ morph with conspicuous head structures or as a fast developing ‘flat’ morph with a female-like appearance. We show that the hunched-differs from the flat-determining allele by a hunch-specific genomic fragment of approximately 3 megabases. This fragment comprises dozens of genes that duplicated from genes found at different chromosomes. All functional duplicates, includingdoublesex- a key sexual differentiation regulatory gene, show male-specific expression, which illustrates their combined role as a masculinizing supergene. Our findings demonstrate how extensive indel polymorphisms and duplications of regulatory genes may contribute to the evolution of co-adapted gene clusters, sex-limited reproductive morphs, and the enigmatic evolution of exaggerated sexual traits in general.
Signaling amplitude molds theRasmutation tropism of urethane
Authors: Li Siqi , Counter Christopher M.
Published: February 2021

RAS genes are commonly mutated in cancers yet despite many possible mutations, cancers have a ‘tropism’ towards a specific subset. As driver mutations, these patterns ostensibly originate from normal cells. High oncogenic RAS activity causes oncogenic stress and different oncogenic mutations can impart different levels of activity. Here we show that changing rare codons to common in the murineKrasgene to increase translation shifts tumors induced by the carcinogen urethane from arising from canonical Q61to biochemically less active G12Krasdriver mutations, despite the carcinogen still being biased towards generating Q61mutations. Loss of p53 to blunt oncogenic stress partially reversed this effect, restoring Q61mutations. Finally, transcriptional analysis revealed similar signaling amongst tumors driven by different mutations andKrasalleles. These finding suggest that the RAS mutation tropism of urethane is largely product of selection in normal cells for mutations promoting proliferation without causing oncogenic stress.

Impact statement

The bias towards specificKrasdriver mutations during urethane carcinogenesis appears to arise predominantly from the selection of a narrow window of oncogenic signaling in normal cells.
Development of a Triazolobenzodiazepine-Based PET Probe for Subtype-Selective Vasopressin 1A Receptor Imaging
Authors: Haider Ahmed , Xiao Zhiwei , Xia Xiaotian , Chen Jiahui , Van Richard S. , Kuang Shi , Zhao Chunyu , Rong Jian , Shao Tuo , Ramesh Perla , Aravind Appu , Shao Yihan , Ran Chongzhao , Young Larry J. , Liang Steven H.
Published: February 2021

Objectives

To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imagingin vitroandin vivo.

Methods

We synthesized a high-affinity and -selectivity ligand, designated compound17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments.

Results

Compound17(PF-184563) and the respective precursor for radiolabeling were synthesized in an overall yield of 49% (over 7 steps) and 40% (over 8 steps), respectively. An inhibitory constant of 0.9 nM towards the V1A receptor was measured, while excellent selectivity over the related V1B, V2 and OT receptor (IC50>10,000 nM) were obtained. Cell uptake studies revealed considerable V1A binding, which was significantly reduced in the presence of V1A antagonists. Conversely, there was no significant blockade in the presence of V1B and V2 antagonists.In vitroautoradiography and PET imaging studies in rodents indicated specific tracer binding mainly in the liver. Further, the pancreas, spleen and the heart exhibited specific binding of [11C]17([11C]PF-184563) byex vivobiodistribution experiments.

Conclusion

We have developed the first V1A-targeted PET ligand that is suitable for subtype-selective receptor imaging in peripheral organs including the liver, heart, pancreas and spleen. Our findings suggest that [11C]PF-184563 can be a valuable tool to study the role of V1A receptors in liver diseases, as well as in cardiovascular pathologies.
N-glycosylation onOryza SativaRoot Germin-like Protein 1 is conserved but not required for stability or activity
Authors: Rubbab Tehseen , Pegg Cassandra L. , Phung Toan K. , Nouwens Amanda S. , Yeo K. Y. Benjamin , Zacchi Lucia F. , Muhammad Amna , Naqvi S. M. S Saqlan , Schulz Benjamin L.
Published: February 2021

Germin and germin-like proteins (GLPs) are a broad family of extracellular glycoproteins ubiquitously distributed in plants. Overexpression ofOryza sativaroot germin like protein 1 (OsRGLP1) enhances superoxide dismutase (SOD) activity in transgenic plants. Here, we report bioinformatic analysis and heterologous expression ofOsRGLP1 to study the role of glycosylation onOsRGLP1 protein stability and activity. Sequence analysis ofOsRGLP1 homologs identified diverseN-glycosylation sequons, one of which was highly conserved. We therefore expressedOsRGLP1 in glycosylation-competentSaccharomyces cerevisiaeas a Maltose Binding Protein (MBP) fusion. Mass spectrometry analysis of purifiedOsRGLP1 showed it was expressed byS. cerevisiaein bothN-glycosylated and unmodified forms. Glycoprotein thermal profiling showed little difference in the thermal stability of the glycosylated and unmodified protein forms. Circular Dichroism spectroscopy of MBP-OsRGLP1 and a N-Q glycosylation-deficient variant showed that both glycosylated and unmodified MBP-OsRGLP1 had similar secondary structure, and both forms had equivalent SOD activity. Together, we concluded that glycosylation was not critical forOsRGLP1 protein stability or activity, and it could therefore likely be produced inEscherichia coliwithout glycosylation. Indeed, we found thatOsRGLP1 could be efficiently expressed and purified from K12 shuffleE. coliwith a specific activity of 1251±70 Units/mg. In conclusion, we find that some highly conservedN-glycosylation sites are not necessarily required for protein stability or activity, and describe a suitable method for production ofOsRGLP1 which paves the way for further characterization and use of this protein.
Prediction of occult tumor progression via platelet RNAs in a mouse melanoma model: a potential new platform of cancer screening for early detection of cancer
Authors: Yin Yue , Jiang Ruilan , Shen Mingwang , Li Zhaofang , Yan Ni , Feng Junqiao , Jiang Hong , Lv Jiaxin , Shi Lijuan , Wang Lina , Liu Xi , Zhang Kaiyun , Chen Di
Published: February 2021

Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects1,2. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required. Here, our proof-of-concept study shows blood platelets could be a platform for liquid biopsy-based early cancer detection. By using a simple suboptimal inoculation melanoma mouse model, we identified differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of cancer cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. These RNAs were strongly enriched in pathways related to immune response and regulation. Moreover, 36 genes selected from the eDEGs via bioinformatics analyses were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was employed to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice. The prediction models showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e). Our study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer. Furthermore, the eDEGs are mostly immune-related, not tumor-specific. Hence it is possible platelets-based liquid biopsy could enable simultaneous early detection of cancers from multiple organs of origin3. It is also feasible to determine the origin of cancer since platelet profiles are influenced by tumor type3.