bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connexinplexity: the spatial and temporal expression of connexin genes during vertebrate organogenesis
Authors: Lukowicz-Bedford Rachel M , Farnsworth Dylan R , Miller Adam C 
Published: March 2022

Abstract
Animal development requires coordinated communication between cells. The Connexin family of proteins is a major contributor to intercellular communication in vertebrates by forming gap junction channels that facilitate the movement of ions, small molecules, and metabolites between cells. Additionally, individual hemichannels can provide a conduit to the extracellular space for paracrine and autocrine signaling. Connexin-mediated communication is widely used in epithelial, neural, and vascular development and homeostasis, and most tissues likely use this form of communication. In fact, Connexin disruptions are of major clinical significance contributing to disorders developing from all major germ layers. Despite the fact that Connexins serve as an essential mode of cellular communication, the temporal and cell-type-specific expression patterns of connexin genes remain unknown in vertebrates. A major challenge is the large and complex connexin gene family. To overcome this barrier, we determined the expression of all connexins in zebrafish using single-cell RNA-sequencing of entire animals across several stages of organogenesis. Our analysis of expression patterns has revealed that few connexins are broadly expressed, but rather, most are expressed in tissue- or cell-type-specific patterns. Additionally, most tissues possess a unique combinatorial signature of connexin expression with dynamic temporal changes across the organism, tissue, and cell. Our analysis has identified new patterns for well-known connexins and assigned spatial and temporal expression to genes with no-existing information. We provide a field guide relating zebrafish and human connexin genes as a critical step toward understanding how Connexins contribute to cellular communication and development throughout vertebrate organogenesis.
Phage-mediated horizontal gene transfer and its implications for the human gut microbiome
Authors: Borodovich Tatiana , Shkoporov Andrey N , Ross R Paul , Hill Colin 
Published: March 2022

Abstract
Horizontal gene transfer (HGT) in the microbiome has profound consequences for human health and disease. The spread of antibiotic resistance genes, virulence, and pathogenicity determinants predominantly occurs by way of HGT. Evidence exists of extensive horizontal transfer in the human gut microbiome. Phage transduction is a type of HGT event in which a bacteriophage transfers non-viral DNA from one bacterial host cell to another. The abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut microbiome. Here we review in detail the known mechanisms of phage-mediated HGT, namely specialized and generalized transduction, lateral transduction, gene-transfer agents, and molecular piracy, as well as methods used to detect phage-mediated HGT, and discuss its potential implications for the human gut microbiome.
Nontransgenic Guinea Pig Strains Exhibit Hallmarks of Human Brain Aging and Alzheimer’s Disease
Authors: Wahl Devin , Moreno Julie A , Santangelo Kelly S , Zhang Qian , Afzali Maryam F , Walsh Maureen A , Musci Robert V , Cavalier Alyssa N , Hamilton Karyn L , LaRocca Thomas J 
Published: March 2022

Abstract
Older age is the primary risk factor for most chronic diseases, including Alzheimer’s disease (AD). Current preclinical models to study brain aging and AD are mainly transgenic and harbor mutations intended to mirror brain pathologies associated with human brain aging/AD (eg, by increasing production of the amyloid precursor protein, amyloid beta [Aβ], and/or phosphorylated tau, all of which are key pathological mediators of AD). Although these models may provide insight on pathophysiological processes in AD, none completely recapitulate the disease and its strong age-dependence, and there has been limited success in translating preclinical results and treatments to humans. Here, we describe 2 nontransgenic guinea pig (GP) models, a standard PigmEnTed (PET) strain, and lesser-studied Dunkin-Hartley (DH) strain, that may naturally mimic key features of brain aging and AD in humans. We show that brain aging in PET GP is transcriptomically similar to human brain aging, whereas older DH brains are transcriptomically more similar to human AD. Both strains/models also exhibit increased neurofilament light chain (NFL, a marker of neuronal damage) with aging, and DH animals display greater S100 calcium-binding protein B (S100β), ionized calcium-binding adapter molecule 1 (Iba1), and Aβ and phosphorylated tau—which are all important markers of neuroinflammation-associated AD. Collectively, our results suggest that both the PET and DH GP may be useful, nontransgenic models to study brain aging and AD, respectively.
Association Between Homocysteine, Frailty and Biomechanical Response of the CNS in NPH-Suspected Patients
Authors: Guillotin Sophie , Vallet Alexandra , Lorthois Sylvie , Cestac Philippe , Schmidt Eric , Delcourt Nicolas 
Published: March 2022

Abstract
Frailty is a geriatric syndrome that combines physiological decline, disruptions of homeostatic mechanisms across multiple physiologic systems and thus, strong vulnerability to further pathological stress. Previously, we provided the first evidence that increased risk of poor health outcomes, as quantified by a frailty index (FI), is associated with an alteration of the central nervous system (CNS) biomechanical response to blood pulsatility. In this study, we explored correlation between 14 biological parameters, the CNS elastance coefficient and FI. We included 60 adults (52–92 years) suspected of normal pressure hydrocephalus and presenting with markers of multiple coexisting brain pathologies, including Parkinson disease, Alzheimer disease, and vascular dementia. We showed that the homocysteine (Hcy) level was independently and positively associated with both the FI and the CNS elastance coefficient (adjusted R² of 10% and 6%). We also demonstrated that creatinine clearance and folate level were independently associated with Hcy level. Based on previous literature results describing the involvement of Hcy in endothelial dysfunction, glial activation, and neurodegeneration, we discuss how Hcy could contribute to the altered biomechanical response of the CNS and frailty.
The haplotype-resolved chromosome pairs of a heterozygous diploid African cassava cultivar reveal novel pan-genome and allele-specific transcriptome features
Authors: Qi Weihong , Lim Yi-Wen , Patrignani Andrea , Schläpfer Pascal , Bratus-Neuenschwander Anna , Grüter Simon , Chanez Christelle , Rodde Nathalie , Prat Elisa , Vautrin Sonia , Fustier Margaux-Alison , Pratas Diogo , Schlapbach Ralph , Gruissem Wilhelm 
Published: March 2022

Abstract

Background
Cassava (Manihot esculenta) is an important clonally propagated food crop in tropical and subtropical regions worldwide. Genetic gain by molecular breeding has been limited, partially because cassava is a highly heterozygous crop with a repetitive and difficult-to-assemble genome.

Findings
Here we demonstrate that Pacific Biosciences high-fidelity (HiFi) sequencing reads, in combination with the assembler hifiasm, produced genome assemblies at near complete haplotype resolution with higher continuity and accuracy compared to conventional long sequencing reads. We present 2 chromosome-scale haploid genomes phased with Hi-C technology for the diploid African cassava variety TME204. With consensus accuracy &gt;QV46, contig N50 &gt;18 Mb, BUSCO completeness of 99%, and 35k phased gene loci, it is the most accurate, continuous, complete, and haplotype-resolved cassava genome assembly so far. Ab initio gene prediction with RNA-seq data and Iso-Seq transcripts identified abundant novel gene loci, with enriched functionality related to chromatin organization, meristem development, and cell responses. During tissue development, differentially expressed transcripts of different haplotype origins were enriched for different functionality. In each tissue, 20–30% of transcripts showed allele-specific expression (ASE) differences. ASE bias was often tissue specific and inconsistent across different tissues. Direction-shifting was observed in &lt;2% of the ASE transcripts. Despite high gene synteny, the HiFi genome assembly revealed extensive chromosome rearrangements and abundant intra-genomic and inter-genomic divergent sequences, with large structural variations mostly related to LTR retrotransposons. We use the reference-quality assemblies to build a cassava pan-genome and demonstrate its importance in representing the genetic diversity of cassava for downstream reference-guided omics analysis and breeding.

Conclusions
The phased and annotated chromosome pairs allow a systematic view of the heterozygous diploid genome organization in cassava with improved accuracy, completeness, and haplotype resolution. They will be a valuable resource for cassava breeding and research. Our study may also provide insights into developing cost-effective and efficient strategies for resolving complex genomes with high resolution, accuracy, and continuity.
Environmental effects and seismogenic source characterization of the December 2020 earthquake sequence near Petrinja, Croatia
Authors: Baize S , Amoroso S , Belić N , Benedetti L , Boncio P , Budić M , Cinti F R , Henriquet M , Jamšek Rupnik P , Kordić B , Markušić S , Minarelli L , Pantosti D , Pucci S , Špelić M , Testa A , Valkaniotis S , Vukovski M , Atanackov J , Barbača J , Bavec M , Brajkovič R , Brčić V , Caciagli M , Celarc B , Civico R , De Martini P M , Filjak R , Iezzi F , Moulin A , Kurečić T , Métois M , Nappi R , Novak A , Novak M , Pace B , Palenik D , Ricci T 
Published: March 2022

SUMMARYOn 29 December 2020, a shallow earthquake of magnitude Mw 6.4 struck northern Croatia, near the town of Petrinja, more than 24 hr after a strong foreshock (ML 5). We formed a reconnaissance team of European geologists and engineers, from Croatia, Slovenia, France, Italy and Greece, rapidly deployed in the field to map the evidence of coseismic environmental effects. In the epicentral area, we recognized surface deformation, such as tectonic breaks along the earthquake source at the surface, liquefaction features (scattered in the fluvial plains of Kupa, Glina and Sava rivers), and slope failures, both caused by strong motion. Thanks to this concerted, collective and meticulous work, we were able to document and map a clear and unambiguous coseismic surface rupture associated with the main shock. The surface rupture appears discontinuous, consisting of multi-kilometre en échelon right stepping sections, along a NW–SE striking fault that we call the Petrinja-Pokupsko Fault. The observed deformation features, in terms of kinematics and trace alignments, are consistent with slip on a right lateral fault, in agreement with the focal solution of the main shock. We found mole tracks, displacement on faults affecting natural features (e.g. drainage channels), scarplets and more frequently breaks of anthropogenic markers (roads, fences). The surface rupture is observed over a length of ∼13 km from end-to-end, with a maximum displacement of 38 cm, and an average displacement of ∼10 cm. Moreover, the liquefaction extends over an area of nearly 600 km2 around the epicentre. Typology of liquefaction features include sand blows, lateral spreading phenomenon along the road and river embankments, as well as sand ejecta of different grain size and matrix. Development of large and long fissures along the fluvial landforms, current or ancient, with massive ejections of sediments is pervasive. These features are sometimes accompanied by small horizontal displacements. Finally, the environmental effects of the earthquake appear to be reasonably consistent with the usual scaling relationships, in particular the surface faulting. This rupture of the ground occurred on or near traces of a fault that shows clear evidence of Quaternary activity. Further and detailed studies will be carried out to characterize this source and related faults in terms of future large earthquakes potential, for their integration into seismic hazard models.
Functional analysis of the ScAG and ScAGL11 MADS-box transcription factors for anthocyanin biosynthesis and bicolour pattern formation inSenecio cruentusray florets
Authors: Qi Fangting , Liu Yuting , Luo Yiliu , Cui Yumeng , Lu Chenfei , Li Hao , Huang He , Dai Silan 
Published: March 2022

AbstractCineraria (Senecio cruentus) is an ornamental plant with pure colour and bicolour cultivars, widely used for landscaping. Anthocyanin biosynthesis influences coloration patterns in cineraria. However, how anthocyanins accumulate and distribute in cineraria is poorly understood. This study investigated the molecular mechanisms underlying anthocyanin biosynthesis and bicolour formation in cineraria using pure colour and bicolour cultivars. Transcriptome and gene expression analysis showed that five genes, ScCHS2, ScF3H1, ScDFR3, ScANS, and ScbHLH17, were inhibited in the white cultivar and colourless regions of bicolour cultivars. In contrast, two MADS-box genes, ScAG and ScAGL11, showed significantly higher expression in the colourless regions of bicolour cultivars. ScAG and ScAGL11 were localized in the nucleus and co-expressed with the bicolour trait. Further functional analysis verified that ScAG inhibits anthocyanin accumulation in tobacco (Nicotiana tabacum). However, virus-induced gene silencing (VIGS) experiments showed that silencing of ScAG and ScAGL11 increases anthocyanin content in cineraria leaves. Similar results were observed when ScAG and ScAGL11 were silenced in the cineraria capitulum, accompanied by the smaller size of the colourless region, specifically in the ScAG/ScAGL11-silenced plants. The expression of ScCHS2, ScDFR3, and ScF3H1 increased in silenced cineraria leaves and capitulum. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation experiments demonstrated that ScAG interacts with ScAGL11. Moreover, ScAG directly inhibited the transcription of ScF3H1 while ScAGL11 inhibited ScDFR3 expression by binding to their promoters separately. The findings reported herein indicate that ScAG and ScAGL11 negatively regulate anthocyanin biosynthesis in cineraria ray florets, and their differential expression in ray florets influences the bicolour pattern appearance.
Engineering high levels of saffron apocarotenoids in tomato
Authors: Ahrazem Oussama , Diretto Gianfranco , Rambla José Luis , Rubio-Moraga Ángela , Lobato-Gómez María , Frusciante Sarah , Argandoña Javier , Presa Silvia , Granell Antonio , Gómez-Gómez Lourdes 
Published: March 2022

Abstract
Crocins and picrocrocin are high-value hydrophilic pigments produced in saffron and used commercially in the food and pharmaceutical industries. These apocarotenoids are derived from the oxidative cleavage of zeaxanthin by specific carotenoid cleavage dioxygenases. The pathway for crocins and picrocrocin biosynthesis was introduced into tomato using fruit specific and constitutive promoters and resulted in 14.48 mg/g of crocins and 2.92 mg/g of picrocrocin in the tomato DW, without compromising plant growth. The strategy involved expression of CsCCD2L to produce crocetin dialdehyde and 2,6,6-trimethyl-4-hydroxy-1-carboxaldehyde-1-cyclohexene, and of glycosyltransferases UGT709G1 and CsUGT2 for picrocrocin and crocins production, respectively. Metabolic analyses of the engineered fruits revealed picrocrocin and crocetin-(β-D-gentiobiosyl)-(β-D-glucosyl)-ester, as the predominant crocin molecule, as well as safranal, at the expense of the usual tomato carotenoids. The results showed the highest crocins content ever obtained by metabolic engineering in heterologous systems. In addition, the engineered tomatoes showed higher antioxidant capacity and were able to protect against neurological disorders in a Caenorhabditis elegans model of Alzheimer’s disease. Therefore, these new developed tomatoes could be exploited as a new platform to produce economically competitive saffron apocarotenoids with health-promoting properties.
Positivity-preserving and energy-dissipative finite difference schemes for the Fokker–Planck and Keller–Segel equations
Authors: Hu Jingwei , Zhang Xiangxiong 
Published: March 2022

Abstract
In this work we introduce semi-implicit or implicit finite difference schemes for the continuity equation with a gradient flow structure. Examples of such equations include the linear Fokker–Planck equation and the Keller–Segel equations. The two proposed schemes are first-order accurate in time, explicitly solvable, and second-order and fourth-order accurate in space, which are obtained via finite difference implementation of the classical continuous finite element method. The fully discrete schemes are proved to be positivity preserving and energy dissipative: the second-order scheme can achieve so unconditionally while the fourth-order scheme only requires a mild time step and mesh size constraint. In particular, the fourth-order scheme is the first high order spatial discretization that can achieve both positivity and energy decay properties, which is suitable for long time simulation and to obtain accurate steady state solutions.
Actions of Nilpotent Groups on Complex Algebraic Varieties
Authors: Abboud Marc 
Published: March 2022

AbstractWe study nilpotent groups that act faithfully on complex algebraic varieties. In the finite case, we show that when $\textbf {k}$ is a number field, a finite $p$-subgroup of the group of polynomial automorphisms of $\textbf {k}^d$ is isomorphic to a subgroup of $\textrm {GL}_d(\textbf {k})$. In the case of infinite nilpotent group actions, we show that a finitely generated nilpotent group $H$ acting on a complex quasiprojective variety $X$ of dimension $d$ can be embedded in a $p$-adic Lie group that acts faithfully and analytically on $\textbf {Z}_p^d$. As a consequence, we show that the virtual derived length of $H$ is at most the dimension of $X$.
Bounds on Entries in Bianchi Group Generators
Authors: Martin Daniel E 
Published: March 2022

Abstract
Upper and lower bounds are given for the maximum Euclidean curvature among faces in the Ford domain for $\text {PSL}_2({\mathcal{O}})$ in the upper-half space model of hyperbolic space, where ${\mathcal{O}}$ is an imaginary quadratic ring of integers with discriminant $\Delta $. We prove these bounds are asymptotically within $(\log |\Delta |)^{8.54}$ of one another. This improves on the previous best upper bound, which is roughly off by a factor between $\Delta ^2$ and $|\Delta |^{5/2}$ depending on the smallest prime dividing $\Delta $. The gap between our upper and lower bounds is determined by an analog of Jacobsthal’s function, introduced here for imaginary quadratic fields.
515 Deficiencies of Rule-based Technology generated Antibiograms and Application in Patients with Prolonged Lengths of Stay
Authors: Hill David M , Arif Faisal , Sultan-Ali Ibrahim , Velamuri Sai R 
Published: March 2022

Abstract

Introduction
Antibiograms are unit specific annual reports of cumulative pathogen incidence and antibiotic susceptibilities, used to guide selection of empiric antibiotic therapies. Rule-based technology (RBT) expedites data compilation, but follows “first pathogen, per patient” and limits applicability, especially for prescribing antibiotics in units with higher lengths of stay. The objective was to compare the pathogens and susceptibilities of the current automated RBT antibiogram with one manually collected through chart review with additional rules applied.

Methods
This is a single-center, retrospective cohort study utilizing chart review to assess patients admitted to the Burn Center between January 2018 and December 2019 from whom significant bacterial cultures were obtained. Demographics and burn injury characteristics were collected. Treatment data related to the infection and antibiotic usage was also collected. Specific to the culture, timing, site, pathogen, and sensitivity were collected. All cultures within the first 30 days of admission were included. The current RBT antibiogram served as the control. And new antibiogram versions were created using additional rules and compared to the RBT antibiogram.

Results
During the 2 years, 657 patients were admitted. Two-hundred four patients remained after applicable exclusions. Sixty-one percent were excluded due to lack of cultures. Mean age was 50.6 ± 16.5 years and 66% were male. Forty-nine percent were Caucasian. Seventy-two percent were admitted for an acute burn injury with flame as the primary mechanism and a median percent total body surface area of 10 (3, 21). Fifty-nine percent had at least one hospital acquired risk factor with over one-third having recent illicit drug use and one-third having a recent hospitalization. Of the 410 cultures included, 57% were Gram-negative and half were from wound infections. Sensitivities were significantly different when comparing the RBT to those created from significant cultures within 7 days of admission, cultures within 7 days of admission and without hospital-acquired infection risk factors (Figure 1), and those being treated with an initial or subsequent course of antibiotics. Recommended empiric antibiotic changed from double coverage to a single β-lactam with &gt; 90% susceptibility. The susceptibilities between first and subsequent courses were dramatically different (Figure 2)

Conclusions
The antibiogram was significantly different from the RBT version after including factors, such as days since admission, presence of hospital acquired risk factors, or previous antibiotic courses. Before developing an antibiogram or interpreting the output, it is important to consider which automated criteria are utilized, especially for units with extended lengths of stay.