bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Omics Analysis on Neurodevelopment in Preterm Neonates
Authors: Casavant Sharon G. , Chen Jie , Xu Wanli , Lainwala Shabnam , Matson Adam , Chen Ming-Hui , Starkweather Angela , Maas Kendra , Cong Xiaomei S. 
Published: August 2021

Background
The gut microbiome is an important determinant of health and disease in preterm infants.

Objectives
The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants.

Methods
This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8–12, and 18–24 months corrected age were measured.

Discussion
As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes.
Electrical Brain Stimulation and Continuous Behavioral State Tracking in Ambulatory Humans
Authors: Mivalt Filip , Kremen Vaclav , Sladky Vladimir , Balzekas Irena , Nejedly Petr , Gregg Nick , Lundstrom Brian , Lepkova Kamila , Pridalova Tereza , Brinkmann Benjamin H. , Jurak Pavel , Van Gompel Jamie J. , Miller Kai , Denison Timothy , Louis Erik St , Worrell Gregory A. 
Published: August 2021

AbstractObjectiveElectrical deep brain stimulation (DBS) is an established treatment for patients with drug-resistant epilepsy. Sleep disorders are common in people with epilepsy, and DBS may actually further disturb normal sleep patterns and sleep quality. Novel devices capable of DBS and continuous intracranial EEG (iEEG) telemetry enable detailed assessments of therapy efficacy and tracking sleep related comorbidities. Here, we investigate the feasibility of automated sleep classification using continuous iEEG data recorded from Papez’s circuit in four patients with drug resistant mesial temporal lobe epilepsy using an investigational implantable sensing and stimulation device with electrodes implanted in bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT).ApproachThe iEEG recorded from HPC is used to classify sleep during concurent DBS targeting ANT. Simultaneous polysomnography and HPC sensing were used to train, validate and test an automated classifier for a range of ANT DBS frequencies: no stimulation, 2 Hz, 7 Hz, and high frequency (>100 Hz).Main resultsWe show that it is possible to build a patient specific automated sleep staging classifier using power in band features extracted from one HPC sensing channel. The patient specific classifiers performed well under all thalamic DBS frequencies with an average F1-score 0.894, and provided viable classification into awake and major sleep categories, rapid eye movement (REM) and non-REM. We retrospectively analyzed classification performance with gold-standard polysomnography annotations, and then prospectively deployed the classifier on chronic continuous iEEG data spanning multiple months to characterize sleep patterns in ambulatory patients living in their home environment.SignificanceThe ability to continuously track behavioral state and fully characterize sleep should prove useful for optimizing DBS for epilepsy and associated sleep, cognitive and mood comorbidities.
Specificity of SARS-CoV-2 antibody-detection assays against S and N protein among pre-COVID-19 sera from patients with protozoan and helminth parasitic infections
Authors: Yansouni Cedric P , Papenburg Jesse , Cheng Matthew P. , Corsini Rachel , Caya Chelsea , Camargo Fabio Vasquez , Harrison Luke B , Zaharatos Gerasimos , Büscher Philippe , Faye Babacar , Ndiaye Magatte , Matlashewski Greg , Ndao Momar 
Published: August 2021

ABSTRACTBackgroundWe aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections.MethodsWe tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera.ResultsThe specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥ 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay.ConclusionsThe specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.
Independently paced calcium oscillations in progenitor and differentiated cells in an ex vivo epithelial organ
Authors: Kim Anna A. , Nguyen Amanda , Marchetti Marco , Montell Denise J. , Pruitt Beth. L. , O’Brien Lucy Erin 
Published: August 2021

ABSTRACTCytosolic calcium is a highly dynamic, tightly regulated, and broadly conserved cellular signal. Calcium dynamics have been studied widely in cellular monocultures, yet in vivo most organs comprise heterogeneous populations of stem and differentiated cells. We examined calcium dynamics in each cell type of the adult Drosophila intestine, a self-renewing epithelial organ where multipotent stem cells give rise to mature absorptive enterocytes and secretory enteroendocrine cells. Here we perform live imaging of whole organs ex vivo, and we employ orthogonal expression of red and green calcium sensors to determine whether calcium oscillations between different cell types are coupled. We show that stem cell daughters adopt strikingly distinct patterns of calcium oscillations when they acquire their terminal fates: Enteroendocrine cells exhibit single-cell calcium oscillations, while enterocytes exhibit rhythmic, long-range calcium waves. These multicellular waves do not propagate through progenitor cells (stem cells and enteroblasts), whose oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates calcium oscillations in all three cell types, even, intriguingly, in progenitor and enteroendocrine cells that are surrounded only by enterocytes. Our findings establish that cells adopt fate-specific modes of calcium dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.
The rate of ecosystem acclimation is the dominant uncertainty in long-term projections of an ecosystem service
Authors: Felton Andrew J. , Shriver Robert K. , Stemkovski Michael , Bradford John B. , Suding Katharine N. , Adler Peter B. 
Published: August 2021

AbstractRapid climate change may exceed ecosystems’ capacity to respond through processes including phenotypic plasticity, compositional turnover and evolutionary adaption. However, research predicting impacts of climate change on ecosystem services rarely consider this rate of “ecosystem acclimation.” Combining statistical models fit to historical climate data and remotely-sensed estimates of herbaceous productivity with an ensemble of climate models, we demonstrate that assumptions concerning acclimation rates are a dominant source of uncertainty: models assuming minimal acclimation project widespread decreases in forage production in the western US by 2100, while models assuming that acclimation keeps pace with climate change project widespread forage increases. Uncertainty related to ecosystem acclimation is larger than uncertainties from variation among climate models or emissions pathways. A better understanding of ecosystem acclimation is essential to improve long-term forecasts of ecosystem services, and shows that management to facilitate ecosystem acclimation may be necessary to maintain ecosystem services at historical baselines.
Identification of Subpallial Neuronal Populations Across Zebrafish Larval Stages that Express Molecular Markers for the Striatum
Authors: Aguda Vernie , Chasiotis Helen , Riadi Indira , Thiele Tod 
Published: August 2021

AbstractStriatal neurons play a central role in vertebrate action selection; however, their location in larval zebrafish is not well defined. We assayed for conserved striatal markers in the zebrafish subpallium using fluorescentin situhybridization (FISH) and immunohistochemistry. Whole mount FISH revealed an inhibitory neuronal cluster rostral to the anterior commissure that expressestac1, a gene encoding substance P. This molecular profile is shared by mammalian striatal direct pathway neurons. A second partially overlapping population of inhibitory neurons was identified that expressespenka, a gene encoding enkephalin. This molecular profile is shared by striatal indirect pathway neurons. Immunostaining for substance P and enkephalin confirmed the presence of these peptides in the subpallium. Thetac1andpenkapopulations were both found to increase linearly across larval stages. Together, these findings support the existence of a striatal homologue in larval zebrafish that grows to match the development and increasing behavioural complexity of the organism.
The transmission of African Animal Trypanosomiasis (Nagana) in two districts in the forest zone of Ghana
Authors: Tweneboah Austine , Rosenau Jana , Agyapong Addo Kofi , Addison Thomas Kwame , Moussa Ibrahim Mahamat Alhadj , Weber Judith Sophie , Kelm Soerge , Badu Kingsley 
Published: August 2021

AbstractThe African Animal Trypanosomiasis (nagana) is caused by several species of trypanosome species which results in significant clinical diseases. This consequently leads to huge economic losses. We carried out a cross-sectional survey to investigate the composition of vectors, parasite diversity and intensities in two districts in the Eastern region of Ghana. Cytochrome c oxidase subunit 1 (COI) and internal transcribed spacer (ITS1) dependent PCR assays identified tsetse fly species and trypanosome parasites circulating in the area. A total of 229 tsetse flies, 65 pigs and 20 were sampled. Female and male flies 155 (51.8%), 74 (32.3%) respectively were collected with biconical traps. The overall vector density of 4.3 flies/trap/day was observed. Typanosome prevalence of 58.9% (95% CI: 52.5–65.1), 46.2% (95% CI: 34.6–58.1) and 0.0% (95% CI: 0.0–16.1) in tsetse flies, pigs and cattle respectively were detected.Trypanosoma congolensewas the predominant species with a prevalence of 80.7% (95% CI: 73.3–86.5) in flies and 60.0% (95% CI: 42.3–75.4). There was evidence of multiple trypanosome infection withT. congolense/T. simiaeoccurring highest with prevalence of 38.0% (95% CI: 30.7–46.9). The parasite prevalence in pigs across the communities was high with significant differences associated between locations (Chi2= 28.06, 95% CI: 0.05–0.81, P=0.0009). Blood meal with flies revealed feeding on both domesticSus scrofa domesticus(pig) andPhacochoerus africanus(warthog). Tsetse flies in this area remain highly infected with trypanosomes and continue to transmit the parasites to livestock and human populations in the communities.
Infinite storage capacity of memory-like mechanisms in the hippocampus: a cryptographic perspective on animal’s caching and retrieval behaviors
Authors: Mordechay Sharon , Forkosh Oren 
Published: August 2021

AbstractThe brain’s extraordinary abilities are often associated with its ability to learn and adapt. But memory and plasticity have their limitations, especially when faced with tasks such as retrieving thousands of food items such as in the case of scatter-hoarding animals. Here, we suggest a brain mechanism that works by utilizing cryptographic principles in lieu of plasticity. Rather than memorizing the locations of their caches, as previously suggested, we propose that cache-hoarding animals use a single cryptographic-like mechanism for both caching and retrieval. The mathematical model we developed functions similarly to hippocampal spatial cells, which respond to an animal’s positional attention. We know that the region that activates each spatial cell remains consistent across subsequent visits to the same area but not between areas. This remapping, combined with the uniqueness of cognitive maps, produces a persistent crypto-hash function for both food caching and retrieval. We show that our model is consistent with previous observations, such as animals’ ability to prioritize food items that are perishable or by their nutritional value. The model makes several measurable predictions regarding scattered hoarding and what factors can limit an animal’s retrieval success. Finally, while focusing here on scatter-hoarding, the mechanism we present might be utilized by the brain in other ways providing essentially infinite retention capacity for structured data.
The spatio-temporal program of liver zonal regeneration
Authors: Ben-Moshe Shani , Veg Tamar , Manco Rita , Dan Stav , Kolodziejczyk Aleksandra A. , Halpern Keren Bahar , Elinav Eran , Itzkovitz Shalev 
Published: August 2021

SummaryThe liver carries a remarkable ability to regenerate rapidly after acute zonal damage. Single-cell approaches are necessary to study this process, given the spatial heterogeneity of multiple liver cell types. Here, we use spatially-resolved single cell RNA sequencing (scRNAseq) to study the dynamics of mouse liver regeneration after acute acetaminophen (APAP) intoxication. We find that hepatocytes proliferate throughout the liver lobule, creating the mitotic pressure required to repopulate the necrotic pericentral zone rapidly. A subset of hepatocytes located at the regenerating front transiently up-regulate fetal-specific genes, including Afp and Cdh17, as they reprogram to a pericentral state. Zonated endothelial, hepatic-stellate cell (HSC) and macrophage populations are differentially involved in immune recruitment, proliferation and matrix remodeling. We observe massive transient infiltration of myeloid cells, yet stability of lymphoid cell abundance, in accordance with global decline in antigen presentation. Our study provides a resource for understanding the coordinated programs of zonal liver regeneration.
Evaluation of the speed, accuracy and precision of the QuickMIC rapid antibiotic susceptibility testing assay in a clinical setting
Authors: Malmberg Christer , Torpner Jessie , Fernberg Jenny , Öhrn Håkan , Johansson Cecilia , Tängdén Thomas , Kreuger Johan 
Published: August 2021

AbstractThe rapidly changing landscape of antimicrobial resistance poses a challenge for empirical antibiotic therapy in severely ill patients and highlights the need for fast antibiotic susceptibility diagnostics to guide treatment. Traditional methods for antibiotic susceptibility testing (AST) of bacteria such as broth microdilution (BMD) or the disc diffusion method (DDM) are comparatively slow and show high variability. Rapid AST methods under development often trade speed for resolution, sometimes only measuring responses at a single antibiotic concentration. QuickMIC is a recently developed lab-on-a-chip system for rapid AST. Here we evaluate the performance of the QuickMIC method with regard to speed, precision and accuracy in comparison to traditional diagnostic methods. 151 blood cultures of clinical Gram-negative isolates with a high frequency of drug resistance were tested with the QuickMIC system and compared with BMD for 12 antibiotics. To investigate sample turnaround time and functionality in a clinical setting, another 41 clinical blood culture samples were acquired from the Uppsala University Hospital and analyzed on site in the clinical laboratory with the QuickMIC system, and compared with DDM for 8 antibiotics routinely used in the clinical laboratory. The overall essential agreement between MIC values obtained by QuickMIC and BMD was 83.2%, with an average time to result of 3 h 2 min (SD: 24.8 min) for the QuickMIC method. For the clinical dataset, the categorical agreement was 94.9%, and the total turnaround time as compared to routine diagnostics reduced by 40% (33 h vs. 55 h). Interexperiment variability was low (average SD: 44.6% from target MIC) compared to the acceptable standard of ±1 log2unit (i.e. -50% to +100% deviation from target MIC) in BMD. We conclude that the QuickMIC method can provide rapid and accurate AST, and may be especially valuable in settings with high resistance rates and for antibiotics where wildtype and resistant MIC distributions are close or overlapping.
MODEL BASED OPTIMIZACION OF THE TERPENOIDS BIOSYNTHESIS INE. coli
Authors: Álvarez-Vasquez Fernando , González-Alcón Carlos , Gallego-Jara Julia , de Diego Teresa , Cánovas Manuel , Torres Néstor V. 
Published: August 2021

ABSTRACTTerpenoids are a family of compounds with high industrial interest and the development of biotechnological production methods is essential to achieve more sustainable alternatives to traditional extraction and synthesis methods. The modification and engineering of the catalytic activity (kcat) have been shown to be a feasible strategy in the biotechnological realm. Accordingly, we introduce a novel optimization strategy based in the modification of the kcat of the enzymes and applied it to the maximization of the terpenoids synthesis inE. coli. This approach is fairly general and can be applied alone or in conjunction with classic optimization strategies such as the modification of enzymatic specific activities.For this purpose we first build up a reliable dynamic mathematical model of the alternative mevalonate pathway synthesis leading terpenoids biosynthesis inE. colithrough the methyl-D-erythritol 4-phosphate (MEP) pathway. This model includes the 2-C-methyl-D-erythritol 2, 4-diphosphate (MEC) pumps that mediate MEC extracellular extrusion. Although the physiological significance of the MEC extrusion is still discussed and their biological function is not clear, we find that this process is a must to guarantee bacteria homeostasis and cell viability.We have identified the enzyme IspA as a bottleneck of the terpenoids biosynthesis, which is dual substrate for the two bisubstrate final reactions. Here are presented different ways to overcome this enzymatic flux restriction by modification of the IspA kcat or by introduction of new enzymes with parallel function.Our results show that the MEP pathway optimized solutions for kcat can yield a maximum of 17.68 fold increment in the terpenoids biosynthetic flux when the kcat are modified. This maximal solution involves the modification of 8 kcat and the corresponding Km’s and Kd’s. Remarkably, this increase doesn’t imply a change in the total enzyme concentration of the cell. This is favorable output since enzyme overproduction can compromise cell functionality.We also apply the overexpression of the enzyme activity approach and then we have compared and combined both strategies including scenarios as the deletion or import of the genes expressing enzymes not naturally present inE. coli.A combined strategy of enzymes concentrations and kcat modifications with changes up ti six enzyme levels allows a flux increment of 21.22 fold the basal value. It involves the incorporation of two IspA with similar GPP and IPP bisubstrate functions than the native one but low affinity for the DMAPP as substrate.
DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling
Authors: Kim Stephanie S. , Kycia Ina , Karski Michael , Ma Rosanna K. , Bordt Evan A. , Kwan Julian , Karki Anju , Winter Elle , Aktas Ranan G. , Wu Yuxuan , Emili Andrew , Bauer Daniel E. , Sethupathy Praveen , Vakili Khashayar 
Published: August 2021

ABSTRACTFibrolamellar carcinoma (FLC) is a primary liver cancer that most commonly arises in adolescents and young adults in a background of normal liver tissue and has an poor prognosis due to lack of effective chemotherapeutic agents. The DNAJB1-PRKACA gene fusion (DP) has been reported in the majority of FLC tumors, however its oncogenic mechanisms remain unclear. Given the paucity of cellular models, in particular FLC tumor cell lines, we hypothesized that engineering the DP fusion gene in HEK293T cells would provide insight into the cellular effects of the fusion gene. We used CRISPR/Cas9 to engineer HEK293T clones expressing DP fusion gene (HEK-DP) and performed transcriptomic, proteomic, and mitochondrial studies to characterize this cellular model. Proteomic analysis of DP interacting partners identified mitochondrial proteins as well as proteins in other subcellular compartments. HEK-DP cells demonstrated significantly elevated mitochondrial fission, which suggests a role for DP in altering mitochondrial dynamics. Transcriptomic analysis of HEK-DP cells revealed a significant increase in LINC00473 expression, similar to what has been observed in primary FLC samples. LINC00473 overexpression was reversible with siRNA targeting of PRKACA as well as pharmacologic targeting of PKA and Hsp40 in HEK-DP cells. Therefore, our model suggests that LINC00473 is a candidate marker for DP activity.
RESTORING GLUTAMATE RECEPTOR SIGNALING IN PANCREATIC ALPHA CELLS RESCUES GLUCAGON RESPONSES IN TYPE 1 DIABETES
Authors: Panzer Julia K. , Tamayo Alejandro , Caicedo Alejandro 
Published: August 2021

ABSTRACTGlucagon secretion from pancreatic alpha cells is crucial to prevent hypoglycemia. For reasons still unknown, people with type 1 diabetes lose this glucoregulatory mechanism and are susceptible to dangerous hypoglycemia. Here we show that alpha cells in living pancreas slices from donors with type 1 diabetes failed to secrete glucagon in response to decreases in glucose concentration, thus mirroring the in vivo unresponsiveness to hypoglycemia. Glucagon content and responses to KCl depolarization were not affected, suggesting that alpha cells retained their secretory potential. By contrast, alpha cells had severely impaired signaling via glutamate receptors of the AMPA/kainate type. Under healthy conditions, activating these receptors was required to elicit full glucagon responses to decreases in glucose levels. In type 1 diabetes, reactivating residual glutamate receptor function with the positive allosteric modulators cyclothiazide and aniracetam restored glucagon secretion in response to hypoglycemia. These positive allosteric modulators are already approved to treat other conditions and could be repurposed to prevent hypoglycemia and improve management of diabetes.