bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Sublayer Analysis Of Human Retinal Inner Plexiform Layer Obtained By Visible-Light Optical Coherence Tomography
Authors: Ghassabi Zeinab , Kuranov Roman V. , Wu Mengfei , Tayebi Behnam , Wang Yuanbo , Rubinoff Ian , Liu Xiaorong , Wollstein Gadi , Schuman Joel S. , Zhang Hao F. , Ishikawa Hiroshi 
Published: January 2021

PurposeGrowing evidence suggests, in glaucoma, the dendritic degeneration of subpopulation of the retinal ganglion cells (RGCs) may precede RGCs soma death. Since different RGCs synapse in different IPL sublayers, visualization of the lamellar structure of the IPL could enable both clinical and fundamental advances in glaucoma understanding and management. In this pilot study, we investigated whether visible-light optical coherence tomography (vis-OCT) could detect the difference in the inner plexiform layer (IPL) sublayers thicknesses between small cohorts of healthy and glaucomatous subjects.MethodWe investigated vis-OCT retinal images from nine healthy and five glaucomatous subjects. Four of the healthy subjects were scanned three times each in two separate visits, and five healthy and five glaucoma subjects were scanned three times during a single visit. Raster speckle-reduction scans (3 by 3 by 1.2 mm^3: horizontal; vertical; axial directions with 8192×8×1024 samplings, respectively) of the superior macular were acquired. IPL sublayers were then manually segmented using averaged A-line profiles.ResultsThe mean ages of glaucoma and healthy subjects are 59.6 +/- 13.4 and 45.4 +/- 14.4 years (p =0.02, Wilcoxon rank-sum test), respectively. The visual field mean deviation (MD) are −26.4 to −7.7 dB in glaucoma patient and −1.6 to 1.1 dB in healthy subjects (p =0.002). The mean circumpapillary retinal nerve fiber layer (RNFL) thicknesses are 59.6 +/- 9.1 μm in glaucoma and 99.2 +/- 16.2 μm in healthy subjects (p=0.004). Median coefficients of variation (CVs) of intra-session repeatability for the entire IPL and three sublayers are 3.1%, 5.6%, 6.9%, and 5.6% in healthy subjects and 1.8%, 6.0%, 7.7%, and 6.2% in glaucoma patients, respectively. The mean entire IPL thicknesses are 36.2 +/- 1.5 μm in glaucomatous and 40.1 +/- 1.7 micrometer in healthy eyes (p=0.003, Mixed-effects model). We found that the middle sublayer thickness was responsible for the majority of the difference (14.2 +/- 1.8 μm in glaucomatous and 17.5 +/- 1.4 in healthy eyes, p<0.01).ConclusionsIPL sublayer analysis revealed that the middle sublayer could be responsible for the majority of IPL thinning in glaucoma. Vis-OCT quantified IPL sublayers with good repeatability in both glaucoma and healthy subjects. Visualization of the IPL sublayers may enable the investigation of lamella-specific changes in the IPL in glaucoma and may help elucidate the response of different types of RGCs to the disease.
An “individualist” model of an active genome in a developing embryo
Authors: Huang Shao-Kuei , Dutta Sayantan , Whitney Peter H. , Shvartsman Stanislav Y. , Rushlow Christine A. 
Published: January 2021

SummaryThe earlyDrosophilaembryo provides unique experimental advantages for addressing fundamental questions of gene regulation at multiple levels of organization, from individual gene loci to the whole genome. UsingDrosophilaembryos undergoing the first wave of genome activation, we detected discrete “speckles” of RNA Polymerase II (Pol II), and showed that they overlap with transcribing loci. We characterized the spatial distribution of Pol II speckles and quantified how this distribution changes in the absence of the primary driver ofDrosophilagenome activation, the pioneer factor Zelda. Although the number and size of Pol II speckles were reduced, indicating that Zelda promotes Pol II speckle formation, we observed a uniform distribution of distances between active genes in the nuclei of both wildtype andzeldamutant embryos. This suggests that the topologically associated domains identified by Hi-C studies do little to spatially constrain groups of transcribed genes at this time. We provide evidence that linear genomic distance between transcribed genes is the primary determinant of measured physical distance between the active loci. Furthermore, we show active genes can have distinct Pol II pools even if the active loci are in close proximity. In contrast to the emerging model whereby active genes are clustered to facilitate co-regulation and sharing of transcriptional resources, our data support an “individualist” model of gene control at early genome activation inDrosophila. This model is in contrast to a “collectivist” model where active genes are spatially clustered and share transcriptional resources, motivating rigorous tests of both models in other experimental systems.
Controlled spatial organization of bacterial clusters reveals cell filamentation is vital forXylella fastidiosabiofilm formation
Authors: Anbumani Silambarasan , da Silva Aldeliane M. , Fischer Eduarda Regina , de Souza e Silva Mariana , von Zuben Antônio A.G. , Carvalho Hernandes F. , de Souza Alessandra A. , Janissen Richard , Cotta Monica A. 
Published: January 2021

ABSTRACTThe morphological plasticity of bacteria to form filamentous cells commonly represents an adaptive strategy induced by stresses. In contrast, for diverse pathogens filamentous cells have been observed during biofilm formation, with function yet to be elucidated. To identify prior hypothesized quorum sensing as trigger of such cell morphogenesis, spatially controlled cell adhesion is pivotal. Here, we demonstrate highly-selective cell adhesion of the biofilm-forming phytopathogenXylella fastidiosato gold-patterned SiO2substrates with well-defined geometries and dimensions. The consequent control of both cell density and distances between cell clusters using these patterns provided evidence of quorum sensing governing filamentous cell formation. While cell morphogenesis is induced by cell cluster density, filamentous cell growth is oriented towards neighboring cell clusters and distance-dependent; large interconnected cell clusters create the early biofilm structural framework. Together, our findings and investigative platform could facilitate therapeutic developments targeting biofilm formation mechanisms ofX. fastidiosaand other pathogens.
A Novel Approach to Study Gamma-Band Coherence inEx VivoHippocampal Slices from a Mouse Model of Bipolar Disorder
Authors: Rodríguez Díaz Jean C. , Jenkins Paul M. , Pritchett Dominique L. , Jones Kevin S. 
Published: January 2021

AbstractOscillations play crucial roles in many cognitive processes such as memory formation and attention. GABAergic interneurons can synchronize neuronal activity leading to gamma oscillations (30-60 Hz). Abnormalities in oscillatory activity in the hippocampus have been implicated in the pathology of some mental health disorders including schizophrenia and bipolar disorder, however the neurobiological mechanism underlying these abnormal oscillations are not yet fully understood. We set out to develop a reliable approach to study gamma oscillations inex vivohippocampal preparations using perforated microelectrode arrays. Perforated microelectrode arrays allow for the simultaneous measurement of electrical activity at multiple sites while allowing solutions to pass through the brain section. We obtained extracellular electrophysiological recordings from acute sections of mouse hippocampus situated on a 60-channel, perforated microelectrode arrays (pMEAs). Bath application of kainate rapidly induced and maintained oscillatory activity in the CA1 and CA3 regions of the hippocampus. Kainate-induced oscillations were quickly abolished by the GABAA receptor antagonist, bicuculline. Furthermore, we employed this approach on a mouse model of bipolar disorder. Sections prepared from mutant mice exhibited an increase in the coherence of gamma power within CA1 despite a reduction in gamma band power.
Beyond coral-algal regimes: high taxonomic resolution surveys and trait-based analyses reveal multiple benthic regimes
Authors: Reverter Miriam , Jackson Matthew , Rohde Sven , Moeller Mareen , Bara Robert , Lasut Markus T. , Reinach Marco Segre , Schupp Peter J. 
Published: January 2021

AbstractAs coral reef communities change and reorganise in response to anthropogenic and climate disturbances, there is a growing need of detecting and understanding the different emerging species regimes and their contribution to key ecosystem processes. Using a case study on coral reefs at the epicentre of tropical marine biodiversity (North Sulawesi), we explored how application of different biodiversity approaches (i.e. use of major taxonomic categories, high taxonomic resolution categories and trait-based approaches) affects the detection of distinct fish and benthic community assemblages. Our results show that using major categories (family level or above) to study coral reef communities fails to identify distinct regimes. We also show that for detection of different benthic regimes, especially communities dominated by non-coral organisms, monitoring of only scleractinian coral communities is insufficient, and that all types of benthic organisms (e.g. sponges, ascidians, soft corals, algae etc.) need to be considered. We have implemented for the first time, the use of a trait-based approach to study the functional diversity of whole coral reef benthic assemblages, which allowed us to detect five different community regimes, only one of which was dominated by scleractinian corals. We circumvented the challenge that for some benthic groups (e.g. sponges, ascidians or some soft corals) visual identification up to the species level is not possible, by identifying and categorising traits that can be applied to groups of similar organisms instead of specific species. Furthermore, by the parallel study of benthic and fish communities we provide new insights into key processes and functions that might dominate or be compromised in the different community regimes.
Eye tracking impairments in children with protein-energy malnutrition
Authors: Almeida Natalia L. , Silva Jessica B. S. , Silva Nayara P. , Fernandes Thiago P. , Santos Natanael A. 
Published: January 2021

AbstractBackground: Malnutrition is characterized by impaired nutrient ingestion and absorption, and it is still one of the most substantial causes of morbidity and mortality in children worldwide. To the best of our knowledge, this is the first study investigating eye tracking in children with protein-energy malnutrition (PEM). We sought to investigate how PEM may affect eye movement. Methods: Twenty children without PEM (mean age = 10.8; SD = 1.0 years) and 18 children with PEM (mean age = 10.9; SD = 1.2 years). Here we used three types of tests or stimuli: one formed by a maze and two by seven errors games (boats and elephants). Results: Our results indicated that children with PEM had impaired performance on all of the tests used here. These data suggest that the nutritional impairments during the first year of life, the critical period in visual system development, can have direct impact on eye movement patterns. Conclusions: Our findings must be replicated so that neurophysiological patterns of PEM can be precisely understood. However, this study has repercussions in several areas of knowledge.
Bottom-up inputs are required for the establishment of top-down connectivity onto cortical layer 1 neurogliaform cells
Authors: Ibrahim Leena A , Huang Shuhan , Fernandez-Otero Marian , Sherer Mia , Vemuri Spurti , Xu Qing , Machold Robert , Rudy Bernardo , Fishell Gord 
Published: January 2021

AbstractHigher order feedback projections to sensory cortical areas converge on layer 1 (L1), the primary site for integration of top-down information via the apical dendrites of pyramidal neurons and L1 GABAergic interneurons. Here, we investigated the contribution of early thalamic inputs onto L1 interneurons for the establishment of top-down inputs in the primary visual cortex. We find that bottom-up thalamic inputs predominate during early L1 development and preferentially target neurogliaform cells. We find that these projections are critical for the subsequent strengthening of feedback inputs from the anterior cingulate cortex. Enucleation or selective removal of thalamic afferents blocked this phenomenon. Notably, while early activation of anterior cingulate afferents resulted in a premature strengthening of these top-down inputs to neurogliaform cells, this was also dependent on thalamic inputs. Our results demonstrate that the proper establishment of top-down feedback inputs critically depends on bottom-up inputs from the thalamus during early postnatal development.
Dicer promotes genome stability via the bromodomain transcriptional co-activator Brd4
Authors: Gutbrod MJ , Roche B , Steinberg JI , Lakhani AA , Chang K , Schorn AJ , Martienssen RA 
Published: January 2021

AbstractRNA interference is essential for transcriptional silencing and genome stability, but conservation of this role in mammals has been difficult to demonstrate.Dicer1-/-mouse embryonic stem cells have microRNA-independent proliferation defects, and we conducted a CRISPR-Cas9 screen to restore viability. We identified suppressor mutations in transcriptional activators, H3K9 methyltransferases, and chromosome segregation factors, strongly resembling Dicer suppressors in fission yeast. Suppressors rescued chromosomal defects, and reversed strand-specific transcription of major satellite repeats inDicer1-/-. The strongest suppressors were inBrd4, and in the transcriptional elongator/histone acetyltransferaseElp3. Using viable mutants and pharmaceutical inhibitors, we demonstrate that deletion of specific residues inBrd4rescue genome instability defects ofDicer1-/-in both mammalian cells and fission yeast, implicating Dicer in coordinating transcription and replication of satellite repeats.SummaryReplication and segregation defects inDicer1-/-stem cells depend on centromeric transcription byBrd4, and are deeply conserved in fission yeast.
Unveiling unexpected complexity and multipotentiality of early heart fields
Authors: Zhang Qingquan , Carlin Daniel , Zhu Fugui , Cattaneo Paola , Ideker Trey , Evans Sylvia M. , Bloomekatz Joshua , Chi Neil C. 
Published: January 2021

AbstractComplex organs are composed of a multitude of specialized cell types which assemble to form functional biological structures. How these cell types are created and organized remains to be elucidated for many organs including the heart, the first organ to form during embryogenesis. Here, we show the ontogeny of mammalian mesoderm at high-resolution single cell and genetic lineage/clonal analyses, which revealed an unexpected complexity of the contribution and multi-potentiality of mesodermal progenitors to cardiac lineages creating distinct cell types forming specific regions of the heart. Single-cell transcriptomics ofMesp1lineage-traced cells during embryogenesis and corresponding trajectory analyses uncovered unanticipated developmental relationships between these progenitors and lineages including two mesodermal progenitor sources contributing to the first heart field (FHF), an intraembryonic and a previously uncharacterized extraembryonic-related source, that produce distinct cardiac lineages creating the left ventricle. Lineage-tracing studies revealed that these extraembryonic-related FHF progenitors reside at the extraembryonic-intraembryonic interface in gastrulating embryos and generate cardiac cell types that form the epicardium and the dorsolateral regions of the left ventricle and atrioventricular canal myocardium. Clonal analyses further showed that these progenitors are multi-potent, creating not only cardiomyocytes and epicardial cell types but also extraembryonic mesoderm. Overall, these results reveal unsuspected multiregional origins of the heart fields, and provide new insights into the relationship between intraembryonic cardiac lineages and extraembryonic tissues and the associations between congenital heart disease and placental insufficiency anomalies.
Does land use matter? Carbon consequences of alternative land use futures in New England
Authors: MacLean Meghan Graham , Duveneck Matthew , Plisinski Joshua , Morreale Luca , Laflower Danelle , Thompson Jonathan 
Published: January 2021

ABSTRACTGlobally, forests play an important role in climate change mitigation. However, land-use impacts the ability of forests to sequester and store carbon. Here we quantify the impacts of five divergent future land-use scenarios on aboveground forest carbon stocks and fluxes throughout New England. These scenarios, four co-designed with stakeholders from throughout the region and the fifth a continuation of recent trends in land use, were simulated by coupling a land cover change model with a mechanistic forest growth model to produce estimates of aboveground carbon over 50 years. Future carbon removed through harvesting and development was tracked using a standard carbon accounting methodology, modified to fit our modeling framework. Of the simulated changes in land use, changes in harvesting had the most profound and immediate impacts on carbon stocks and fluxes. In one of the future land-use scenarios including a rapid expansion of harvesting for biomass energy, this changed New England’s forests from a net carbon sink to a net carbon source in 2060. Also in these simulations, relatively small reductions in harvest intensities (e.g., 10% reduction), coupled with an increased percent of wood going into longer-term storage, led to substantial reductions in net carbon emissions (909 MMtCO2eq) as compared to a continuation of recent trends in land use. However, these projected gains in carbon storage and reduction in emissions from less intense harvesting regimes can only be realized if it is paired with a reduction in the consumption of the timber products, and their replacements, that otherwise would result in additional emissions from leakage and substitution.
Host-pathogen Immune Feedbacks Can Explain Widely Divergent Outcomes from Similar Infections
Authors: Ellner Stephen P. , Buchon Nicolas , Dörr Tobias , Lazzaro Brian P. 
Published: January 2021

AbstractA longstanding question in infection biology is why two very similar individuals, with very similar pathogen exposures, may have very different outcomes. Recent experiments have found that even isogenicDrosophila melanogasterhosts, given identical inoculations of some bacterial pathogens at suitable doses, can experience very similar initial bacteria proliferation but then diverge to either a lethal infection or a sustained chronic infection with much lower pathogen load. We hypothesized that divergent infection outcomes are a natural result of mutual negative feedbacks between pathogens and the host immune response. Here we test this hypothesisin silicoby constructing process-based dynamic models for bacterial population growth, host immune induction, and the feedbacks between them, based on common mechanisms of immune system response. Mathematical analysis of a minimal conceptual model confirms our qualitative hypothesis that mutual negative feedbacks can magnify small differences among hosts into life-or-death differences in outcome. However, explaining observed features of chronic infections requires an extension of the model to include induced pathogen modifications that shield themselves from host immune responses at the cost of reduced proliferation rate. Our analysis thus generates new, testable predictions about the mechanisms underlying bimodal infection outcomes.
The kidney protects against sepsis by producing systemic uromodulin
Authors: LaFavers Kaice A. , Hage Chadi , Gaur Varun , Micanovic Radmila , Hato Takashi , Khan Shehnaz , Winfree Seth , Doshi Simit , Moorthi Ranjani N. , Twigg Homer , Wu Xue-Ru , Dagher Pierre C. , Srour Edward , El-Achkar Tarek M. 
Published: January 2021

AbstractSepsis is a significant cause of mortality in hospitalized patients. Concomitant development of acute kidney injury (AKI) increases sepsis mortality through unclear mechanisms. While electrolyte disturbances and toxic metabolite buildup during AKI could be important, it is possible that the kidney produces a protective molecule lost during sepsis with AKI. We previously demonstrated that systemic Tamm-Horsfall Protein (THP, uromodulin), a kidney-derived protein with immunomodulatory properties, falls in AKI. Using a mouse sepsis model without severe kidney injury, we show that the kidney increases circulating THP by enhancing basolateral release of THP from medullary thick ascending limb cells. In sepsis patients, changes in circulating THP are positively associated with critical illness. THP is also foundde novoin injured lungs. Genetic ablation of THP in mice leads to increased mortality and bacterial burden during sepsis. Consistent with the increased bacterial burden, the presence of THPin vitroandin vivoleads macrophages and monocytes to upregulate a transcriptional program promoting cell migration, phagocytosis and chemotaxis and treatment of macrophages with purified THP increases phagocytosis. Rescue of septic THP-/-mice with exogenous systemic THP improves survival. Together, these findings suggest that through releasing THP, the kidney modulates the immune response in sepsis by enhancing mononuclear phagocyte function and systemic THP has therapeutic potential in sepsis.Significance StatementSepsis is a significant contributor to kidney injury as well as morbidity and mortality worldwide. Specific therapies to improve outcomes in sepsis with kidney injury have largely been limited to symptom management and infectious agent control, in part because it is unclear how kidney injury increases sepsis mortality. This paper describes the identification of Tamm-Horsfall protein, previously known to protect in ischemic models of AKI, as protective in preclinical models of sepsis. It demonstrates how the loss of THP leads to decreased mononuclear phagocyte function and diversity, increased pathogen burden and decreased survival. THP also increases in sepsis without severe kidney injury and concentrates in injured organs. Further study of THP in sepsis could lead to novel sepsis therapeutics.
Partition Quantitative Assessment (PQA): A quantitative methodology to assess the embedded noise in clustered omics and systems biology data
Authors: Camacho-Hernández Diego A. , Nieto-Caballero Victor E. , León-Burguete José E. , Freyre-González Julio A. 
Published: January 2021

AbstractIdentifying groups that share common features among datasets through clustering analysis is a typical problem in many fields of science, particularly in post-omics and systems biology research. In respect of this, quantifying how a measure can cluster or organize intrinsic groups is important since currently there is no statistical evaluation of how ordered is, or how much noise is embedded in the resulting clustered vector. Many of the literature focuses on how well the clustering algorithm orders the data, with several measures regarding external and internal statistical measures; but none measure has been developed to statistically quantify the noise in an arranged vector posterior a clustering algorithm, i.e., how much of the clustering is due to randomness. Here, we present a quantitative methodology, based on autocorrelation, to assess this problem.