bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of co-infections and secondary infections in patients with COVID-19
Authors: Feldman Charles , Anderson Ronald 
Published: April 2021

AbstractBackgroundIt has been recognised for a considerable time-period, that viral respiratory infections predispose patients to bacterial infections, and that these co-infections have a worse outcome than either infection on its own. However, it is still unclear what exact roles co-infections and/or superinfections play in patients with COVID-19 infection.Main bodyThis was an extensive review of the current literature regarding co-infections and superinfections in patients with SARS-CoV-2 infection. The definitions used were those of the Centers for Disease Control and Prevention (US), which defines coinfection as one occurring concurrently with the initial infection, while superinfections are those infections that follow on a previous infection, especially when caused by microorganisms that are resistant, or have become resistant, to the antibiotics used earlier. Some researchers have envisioned three potential scenarios of bacterial/SARS-CoV-2 co-infection; namely, secondary SARS-CoV-2 infection following bacterial infection or colonisation, combined viral/bacterial pneumonia, or secondary bacterial superinfection following SARS-CoV-2. There are a myriad of published articles ranging from letters to the editor to systematic reviews and meta-analyses describing varying ranges of co-infection and/or superinfection in patients with COVID-19. The concomitant infections described included other respiratory viruses, bacteria, including mycobacteria, fungi, as well as other, more unusual, pathogens. However, as will be seen in this review, there is often not a clear distinction made in the literature as to what the authors are referring to, whether true concomitant/co-infections or superinfections. In addition, possible mechanisms of the interactions between viral infections, including SARS-CoV-2, and other infections, particularly bacterial infections are discussed further. Lastly, the impact of these co-infections and superinfections in the severity of COVID-19 infections and their outcome is also described.ConclusionThe current review describes varying rates of co-infections and/or superinfections in patients with COVID-19 infections, although often a clear distinction between the two is not clear in the literature. When they occur, these infections appear to be associated with both severity of COVID-19 as well as poorer outcomes.
Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment
Authors: Guebel Daniel V. , Torres Néstor V. , Acebes Ángel 
Published: April 2021

ABSTRACT
Compromise of the vascular system has important consequences on cognitive abilities and neurodegeneration. The identification of the main molecular signatures present in the blood vessels of human hippocampus could provide the basis to understand and tackle these pathologies. As direct vascular experimentation in hippocampus is problematic, we achieved this information by computationally disaggregating publicly available whole microarrays data of human hippocampal homogenates. Three conditions were analyzed: ‘Young Adults’, ‘Aged’, and ‘aged with Mild Cognitive Impairment’ (MCI). The genes identified were contrasted against two independent data-sets. Here we show that the endothelial cells from the Younger Group appeared in an ‘activated stage’. In turn, in the Aged Group, the endothelial cells showed a significant loss of response to shear stress, changes in cell adhesion molecules, increased inflammation, brain-insulin resistance, lipidic alterations, and changes in the extracellular matrix. Some specific changes in the MCI group were also detected. Noticeably, in this study the features arisen from the Aged Group (high tortuosity, increased bifurcations, and smooth muscle proliferation), pose the need for further experimental verification to discern between the occurrence of arteriogenesis and/or vascular remodeling by capillary arterialization.
This article has an associated First Person interview with the first author of the paper.
A widely distributed antigen developmentally regulated in the nervous system
Authors: Pourquié Olivier , Coltey Monique , Thomas Jean-Léon , Le Douarin Nicole M. 
Published: April 2021

Abstract
We have identified a glycoprotein (BEN) of 95 –100 ×103Mr using a monoclonal antibody. This protein is transiently expressed at the cell surface of the peripherally projecting neurons, i.e. motoneurons of the spinal cord and cranial nuclei, sensory neurons of the dorsal root and cranial sensory ganglia and sympathetic, parasympathetic and enteric neurons. In vitro cultures of dorsal root and sympathetic ganglia have shown that BEN is expressed on neurons but not on glial cells. On motor and sensory neurons, BEN first appears at the level of the cell body just after withdrawal from the cell cycle. Soon afterwards, expression of the antigen extends to the elongating axon. After a few days, BEN is no longer expressed by the motor and sensory neurons, disappearing first from the cell body and then progressively from the fibres. The loss of expression is concomitant with the onset of intense proliferation of satellite and Schwann cells. This modulated expression within the nervous sytem is unlike that of any surface glycoprotein so far described in vertebrates. Preliminary biochemical analysis indicates that, although it bears the adhesion-associated epitope HNK-1, BEN does not share characteristics with any previously described axonal glycoprotein. Consequently, we speculate that this glycoprotein might be a novel molecule implicated in selective adhesion phenomena, such as axonal fasciculation.
Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system
Authors: Dressler Gregory R. , Deutsch Urban , Chowdhury Kamal , Nornes Howard O. , Gruss Peter 
Published: April 2021

Abstract
The murine genome contains multiple genes with protein domains homologous to the Drosophila paired box, present in certain segmentation genes. At least one of these murine paired box (Pax) genes is associated with a developmental mutation. This report, in conjunction with the accompanying paper, describes a second member of this gene family, Pax2, that is also expressed during embryogenesis. Two overlapping cDNA clones were isolated and sequenced. At least two forms of the Pax2 protein can be deduced from the cDNA sequence. In addition to the highly conserved paired domain, an octapeptide sequence is located downstream. Expression of Pax2 is primarily restricted to the developing embryo in the excretory and central nervous systems. The transient nature of Pax2 expression during kidney organogenesis correlates with polarization and induction of epithelial structures and may indicate an important morphogenetic role for this gene.
Spatially and temporally restricted expression of Pax2 during murine neurogenesis
Authors: Nornes Howard O. , Dresslert Gregory R. , Knapik Elzbieta W. , Deutsch Urban , Gruss Peter 
Published: April 2021

Abstract
The expression of the murine paired-box-containing gene, Pax2, is examined in the developing central nervous system by in situ hybridization. Pax2 expression is detected along the boundaries of primary divisions of the neural tube. Initially, Pax2 is expressed in the ventricular zone in two compartments of cells on either side of the sulcus limitans and along the entire rhombencephalon and spinal cord. At later times, Pax2 is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, Pax2 expression is restricted to the ventral half of the optic cup and stalk and later to the optic disc and nerve. In the ear, expression is restricted to regions of the otic vesicle that form neuronal components. The transient and restricted nature of Pax2 expression suggests that this murine segmentation gene homologue may also establish compartmental boundaries and contribute to the specification of neuronal identity, as do certain Drosophila segmentation genes.
Autonomous determination of anterior structures in the early Drosophila embryo by the bicoid morphogen
Authors: Driever Wolfgang , Siegel Vivian , Nüsslein-Volhard Christiane 
Published: April 2021

Abstract
A small number of maternal effect genes determine anterior-posterior pattern in the Drosophila embryo. Embryos from females mutant for the maternal gene bicoid lack head and thorax, bcd mRNA becomes localized to the anterior tip of the egg during oogenesis and is the source for the morphogen gradient of bcd protein.
Here we show that in vitro transcribed bicoid mRNA that has its own leader sequences substituted by the Xenopus β-globin 5′ untranslated sequences is translated more efficiently than bicoid mRNA with the natural 5′ mRNA leader when tested in vitro and in Drosophila Schneider cells. When injected into bicoid mutant embryos, only the bcd mRNA with the ′-globin leader sequence, substituted for the natural leader, is able to induce anterior development. We used P-transformation to show that sequences in the 5′ leader are neither necessary for localization of the transcript nor for the translational block of the bcd mRNA during oogenesis.
For our injection experiments, we used only one of the identified splicing forms of bcd mRNA. The bcd protein species derived from this mRNA is able to induce anterior development at any position along the anterior-posterior axis. Thus bicoid protein can induce development of head and thorax independent of any other specifically localized morphogenetic factor. Our findings further support the notion that the concentration gradient of bcd protein, and not the existence of different forms of bcd protein, is responsible for specifying subregions of the embryo.
Tentacle morphogenesis in hydra: II. Formation of a complex between a sensory nerve cell and a battery cell
Authors: Hobmayer Engelbert , Holstein Thomas W. , David Charles N. 
Published: April 2021

Abstract
Differentiation of sensory nerve cells in tentacles of Hydra magnipapillata was Investigated using the monoclonal antibody NV1. NV1+ sensory nerve cells form specific complexes with battery cells in tentacles. NV1+ cells can only be formed by differentiation from interstitial cell precursors. These precursors complete a terminal cell cycle in the distal gastric region at the base of tentacles; differentiation from the S/G&gt;2 boundary to expression of the NV1 antigen requires 30 h. During this time, precursors move from the distal gastric region into the tentacles, differentiate to morphologically fully formed nerve cells and then begin expressing NV1 antigen. The neuropeptide head activator stimulates NV1+ differentiation in S-phase of the precursor’s cell cycle.
Developmental expression of c-kit, a proto-oncogene encoded by the W locus
Authors: Orr-Urtreger Avi , Avivi Aaron , Zimmer Yitzhak , Givol David , Yarden Yosef , Lonai Peter 
Published: April 2021

Abstract
Developmental expression of the c-kit proto-oncogene, a receptor tyrosine kinase encoded by the W locus, was investigated by in situ hybridization in normal mouse embryos. Early after implantation transcripts were detectable only in the maternal placenta ( days p.c.). Subsequently ( days p.c.) numerous ectodermal (neural tube, sensory placodes) and endodermal (embryonic gut) derivatives expressed c-kit. Later transcripts were detected also in the blood islands of the yolk sac and in the embryonic liver, the main sites of embryonic hemopoiesis. Around midgestation, transcripts accumulated in the branchial pouches and also in primordial germ cells of the genital ridges. This complex pattern of expression remained characteristic also later in gestation, when c-kit was expressed in highly differentiated structures of the craniofacial area, in presumptive melanoblasts and in the CNS. In the adult ovary, maternal c-kit transcripts were detected. They were present in the oocytes of both immature and mature ovarian follicles, but not in the male germ line, where c-kit expression may be down regulated. Thus, c-kit activity is complex and appears in multiple tissues including those that also display defects in mutations at the W locus where c-kit is encoded. Correlation between W phenotypes and c-kit expression, as well as the regulation of the complex and multiple expression of polypeptide growth factors and receptors, is discussed.
The formation of basal body domains in the membrane skeleton of Tetrahymena
Authors: Williams Norman E. , Honts Jerry E. , Kaczanowska Janina 
Published: April 2021

Abstract
Differentiated regions within the membrane skeleton are described around basal bodies in the ciliary rows of Tetrahymena. These domains, approximately 1μm in diameter, are characterized by a relatively dense ultra-structure, the presence of a family of proteins called K antigens (Mr 39– 44 × 103) that are recognized by mAb 424A8, and the apparent exclusion of major membrane skeleton proteins that are present in most other regions of the cell (MT 135, 125 ×103). Mature basal body domains are asymmetric, reflecting the polarity of the cell as a whole. A similar differentiation of the membrane skeleton occurs in the oral apparatus, except here the K antigens surround four clusters of basal bodies (from which this cell takes its name) rather than the individual basal bodies. The development of new basal body domains in the cell cycle is described, with similarities and differences noted between somatic and oral regions of the cell. It is concluded that the capacity of this cell for precise topographic regulation of molecular events in the membrane skeleton makes it a useful model for the study of cortical differentiation in cells generally.
Proper timing of a quiescence period in precursor prospermatogonia is required for stem cell pool establishment in the male germline
Authors: Du Guihua , Oatley Melissa J. , Law Nathan C. , Robbins Colton , Wu Xin , Oatley Jon M. 
Published: April 2021

ABSTRACTThe stem cell-containing undifferentiated spermatogonial population in mammals, which ensures continual sperm production, arises during development from prospermatogonial precursors. Although a period of quiescence is known to occur in prospermatogonia prior to postnatal spermatogonial transition, the importance of this has not been defined. Here, using mouse models with conditional knockout of the master cell cycle regulator Rb1 to disrupt normal timing of the quiescence period, we found that failure to initiate mitotic arrest during fetal development leads to prospermatogonial apoptosis and germline ablation. Outcomes of single-cell RNA-sequencing analysis indicate that oxidative phosphorylation activity and inhibition of meiotic initiation are disrupted in prospermatogonia that fail to enter quiescence on a normal timeline. Taken together, these findings suggest that key layers of programming are laid down during the quiescent period in prospermatogonia to ensure proper fate specification and fitness in postnatal life.
FGF signaling acts on different levels of mesoderm development within Spiralia
Authors: Andrikou Carmen , Hejnol Andreas 
Published: April 2021

ABSTRACT
FGF signaling is involved in mesoderm induction in members of deuterostomes (e.g. tunicates, hemichordates), but not in flies and nematodes, in which it has a role in mesoderm patterning and migration. However, we need comparable studies in other protostome taxa in order to decipher whether this mesoderm-inducing function of FGF extends beyond the lineage of deuterostomes. Here, we investigated the role of FGF signaling in mesoderm development in three species of lophophorates, a clade within the protostome group Spiralia. Our gene expression analyses show that the mesodermal molecular patterning is conserved between brachiopods and phoronids, but the spatial and temporal recruitment of transcription factors differs significantly. Moreover, the use of the inhibitor SU5402 demonstrates that FGF signaling is involved in different steps of mesoderm development, as well as in morphogenetic movements of gastrulation and axial elongation. Our findings suggest that the mesoderm-inducing role of FGF extends beyond the group of deuterostomes.
Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration
Authors: Esteban-Collado José , Corominas Montserrat , Serras Florenci 
Published: April 2021

ABSTRACT
Regeneration after damage requires early signals to trigger the tissue repair machinery. Reactive oxygen species (ROS) act as early signals that are sensed by the MAP3 kinase Ask1, which in turn activates by phosphorylation the MAP kinases p38 and JNK. The sustained or high activation of these kinases can result in apoptosis, whereas short or low activation can promote regeneration. Using the Ask1-dependent regeneration program, we demonstrate in Drosophila wing that PI3K/Akt signaling is necessary for Ask1 to activate p38, but not JNK. In addition, nutrient restriction or mutations that target Ser83 of the Drosophila Ask1 protein, a PI3K/Akt-sensitive residue, block regeneration. However, these effects can be reversed by the ectopic activation of p38, but not of JNK. Our results demonstrate that Ask1 controls the activation of p38 through Ser83, and that the phosphorylation of p38 during regeneration is nutrient sensitive. This mechanism is important for discriminating between p38 and JNK in the cells involved in tissue repair and regenerative growth.
PRSS50 is a testis protease responsible for proper sperm tail formation and function
Authors: Scovell Jason M. , Bournat Juan C. , Szafran Adam T. , Solis Minerva , Moore Joshua , Rivera Armando , Chen Ching H. , Zhang Jason , Wilken Nathan , Seth Abhishek , Jorgez Carolina J. 
Published: April 2021

ABSTRACT
Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane). Our data support that, in the testis, as in tumorigenesis, PRSS50 activates NFκB target genes, such as the centromere protein leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1), which is required for heterochromatin maintenance. Prss50-null testes have increased IκκB, and reduced LRWD1 and histone expression. Low levels of de-repressed histone markers, such as H3K9me3, in the Prss50-null mouse testis may cause increases in post-meiosis proteins, such as AKAP4, affecting sperm formation. We provide important insights into the complex mechanisms of sperm development, the importance of testis proteases in fertility and a novel mechanism for MMAF.
Eukaryotic initiation factor 4A3 inhibits Wnt/β-catenin signaling and regulates axis formation in zebrafish embryos
Authors: Wang Bo , Rong Xiaozhi , Zhou Yumei , Liu Yunzhang , Sun Jiqin , Zhao Beibei , Deng Bei , Lu Lei , Lu Ling , Li Yun , Zhou Jianfeng 
Published: April 2021

ABSTRACT
A key step in the activation of canonical Wnt signaling is the interaction between β-catenin and Tcf/Lefs that forms the transcription activation complex and facilitates the expression of target genes. Eukaryotic initiation factor 4A3 (EIF4A3) is an ATP-dependent DEAD box-family RNA helicase and acts as a core subunit of the exon junction complex (EJC) to control a series of RNA post-transcriptional processes. In this study, we uncover that EIF4A3 functions as a Wnt inhibitor by interfering with the formation of β-catenin/Tcf transcription activation complex. As Wnt stimulation increases, accumulated β-catenin displaces EIF4A3 from a transcriptional complex with Tcf/Lef, allowing the active complex to facilitate the expression of target genes. In zebrafish embryos, eif4a3 depletion inhibited the development of the dorsal organizer and pattern formation of the anterior neuroectoderm by increasing Wnt/β-catenin signaling. Conversely, overexpression of eif4a3 decreased Wnt/β-catenin signaling and inhibited the formation of the dorsal organizer before gastrulation. Our results reveal previously unreported roles of EIF4A3 in the inhibition of Wnt signaling and the regulation of embryonic development in zebrafish.
Germ cell determination and the developmental origin of germ cell tumors
Authors: Nicholls Peter K. , Page David C. 
Published: April 2021

ABSTRACT
In each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal development, when do cells of the germline irreversibly commit to producing gametes? Integrating findings from diverse species, we conclude that the final commitment of the germline to gametogenesis – the process of germ cell determination – occurs after primordial germ cells (PGCs) colonize the gonads. Combining this understanding with medical findings, we present a model whereby germ cell tumors arise from cells that failed to undertake germ cell determination, regardless of their having colonized the gonads. We propose that the diversity of cell types present in these tumors reflects the broad developmental potential of migratory PGCs.
Sur le déterminisme de la qualitérégionale des régénérais d’appendices chezla Blatte, Blabera craniifer
Authors: Bullière Désiré 
Published: April 2021

ABSTRACT
Dans tous les phénomènes de régénération, il est bien évident que la qualité et l’organisation des tissus néoformés sont sous la dépendance des tissus anciens. Dans le cas de la régénération d’un appendice amputé, le moignon détermine la qualité régionale du régénérât. Mais la question se pose de savoir si le moignon agit par l’ensemble de ses organes laissés en place ou si seuls les tissus situés immédiatement en arrière de la section ont une action déterminante. En modifiant expérimentalement la qualité des tissus proches de la section on peut espérer obtenir une réponse à cette question. Les expériences de greffes hétéro-spécifiques, faites sur les Némertes par exemple (Bierne, 1967 a, b), montrent bien que le régénérât est sous la dépendance des tissus voisins de la section. Chez les Insectes, où les processus de régénération se déroulentà l’intérieur du segment de membre resté en place, les résultats obtenus jusqu’ici sont moins nets. Les expériences d’implantation de patte à la place de l’antenne faites par Urvoy (1963 a) et par Bohn (1965 b) conduisent à admettre un contrôle du régénérât par les tissus du greffon. Ce contrôle serait complet d’après Bohn et incomplet d’après Urvoy, qui pense à une influence du moignon antennaire sur le régénérât par l’intermédiaire du système nerveux de l’antenne. Les nerfs de l’antenne, en envahissant le régénérât du type patte conforme au greffon, le transformerait quelque peu dans le sens antenne. Les expériences d’implantation d’une partie de la patte prothoracique (P 1) sur un moignon de la patte métathoracique (P 3) ont été interprétées très différemment par leurs auteurs. Urvoy (1963 b), après avoir remplacé l’extrémité d’une hanche de patte métathoracique par l’extrémité d’une hanche prothoracique, conclut à la prédominance des tissus de l’hôte sur la qualité du régénérât. Bohn (1965 a), en greffant la partie distale de P x (tibia + tarse) sur l’extrémité du tibia de P 3, puis en sectionnant, après la première mue post-opératoire, le tarse de P 1 à sa base, conclut à l’influence prédominante du greffon sur la qualité du tarse régénéré. Ainsi, en ne considérant que le cas des Insectes, les résultats sont presque concordants lorsqu’il s’agit de régénération après greffe d’une partie d’appendice très différente du moignon porte-greffe (par exemple, patte sur antenne), mais divergent lorsqu’il s’agit de combinaisons entre parties d’appendices semblables (patte prothoracique sur patte méta-thoracique).