bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus Donor Seropositivity Negatively Affects Survival After Heart Transplantation
Authors: Heim Christian , Müller Philipp P. , Tandler René , Cherikh Wida S. , Toll Alice E. , Stehlik Josef , Weyand Michael , Khush Kiran K. , Ensminger Stephan M. 
Published: September 2021

Background.
Prior studies have shown that cytomegalovirus (CMV) infection is a risk factor for the development of cardiac allograft vasculopathy (CAV) and is associated with reduced long-term survival after heart transplantation (HTx). The aim of this International Society for Heart and Lung Transplantation Transplant Registry study was to compare posttransplant survival in different CMV donor:recipient serologic combinations.

Methods.
We performed a retrospective cohort study, using the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, on 15 885 adult primary heart transplant recipients with known CMV serologic status between July 2004 and June 2014. Posttransplant survival and risk of developing CAV were compared across 4 groups: CMV-seronegative recipients (R–) receiving CMV-positive grafts (D+), intermediate-risk patients (D+R+ and D–R+), and low-risk patients (D–R–).

Results.
Baseline characteristics (donor/recipient age, body mass index, recipient serum creatinine, blood group, donor cause of death, recipient diagnosis, and ischemic time) were mostly balanced between the groups. Kaplan-Meier survival analyses over a follow-up of 10 y revealed significantly worse survival for both D+ groups as compared to the CMV low-risk group (D+R+: 56.61% [95% confidence interval, 53.94-59.41] versus D–R–: 63.09% [59.74-66.64] P < 0.01 and D+R–: 57.69% [56.03-59.39] versus D–R–; P < 0.001), whereas recipient seropositivity alone was not associated with reduced survival (D–R+ versus D–R–
P = 0.178). The risk of developing CAV after HTx was not significantly increased in D+ as compared to D– groups.

Conclusions.
In a large contemporary cohort, CMV status at the time of HTx was not associated with CAV development. However, there was a significant association between donor CMV seropositivity and reduced short- and long-term survival after HTx. Approaches to mitigate the impact of CMV on posttransplant survival are needed.
Origin of the type I antifreeze gene in flounders in response to Cenozoic climate change
Authors: Graham Laurie A. , Gauthier Sherry Y. , Davies Peter L. 
Published: September 2021

AbstractAntifreeze proteins (AFPs) inhibit ice growth within fish and protect them from freezing in icy seawater. Alanine-rich, alpha-helical AFPs (type I) have independently (convergently) evolved in four branches of fishes, one of which is a subsection of the righteye flounders. The origin of this gene family has been elucidated by sequencing two loci from a starry flounder, Platichthys stellatus, collected off Vancouver Island, British Columbia. The first locus had two alleles that demonstrated the plasticity of the AFP gene family, one encoding 33 AFPs and the other allele only four. In the closely related Pacific halibut, this locus encodes multiple Gig2 (antiviral) proteins, but in the starry flounder, the Gig2 genes were found at a second locus due to a lineage-specific duplication event. An ancestral Gig2 gave rise to a 3-kDa “skin” AFP isoform, encoding three Ala-rich 11-a.a. repeats, that is expressed in skin and other peripheral tissues. Subsequent gene duplications, followed by internal duplications of the 11 a.a. repeat and the gain of a signal sequence, gave rise to circulating AFP isoforms. One of these, the “hyperactive” 32-kDa Maxi likely underwent a contraction to a shorter 3.3-kDa “liver” isoform. Present day starry flounders found in Pacific Rim coastal waters from California to Alaska show a positive correlation between latitude and AFP gene dosage, with the shorter allele being more prevalent at lower latitudes. This study conclusively demonstrates that the flounder AFP arose from the Gig2 gene, so it is evolutionarily unrelated to the three other classes of type I AFPs from non-flounders. Additionally, this gene arose and underwent amplification coincident with the onset of ocean cooling during the Cenozoic ice ages.
Transcranial Focused Ultrasound Neuromodulation of the Thalamic Visual Pathway in a Large Animal Model
Authors: Mohammadjavadi Morteza , Ash Ryan T. , Gaur Pooja , Kubanek Jan , Saenz Yamil , Glover Gary H. , Popelka Gerald R. , Norcia Anthony Matthew , Pauly Kim Butts 
Published: September 2021

AbstractBackgroundNeuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders.ObjectiveThe purpose of this study was to determine whether MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) and cortical brain oscillations in a large animal model.MethodsThe lateral geniculate nucleus (LGN) on one side was identified with T2-weighted MRI in sheep (all male, n=9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm a tight sonication focus. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time-frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics.ResultsThe VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input, but not when TUS is applied by itself.ConclusionTUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.
A report on a characteristic vocalization in Corvus macrorhynchos osai with an indication of vocal learning
Authors: Kondo Noriko 
Published: September 2021

AbstractIn the process of vocal learning, animals give immature vocalization, such as babbling and subsong. Here I report a characteristic vocalization given by a subspecies of large-billed crow, Corvus macrorhynchos osai, that live in Kuroshima Island, Okinawa, Japan. This vocalization (type-K) is characterized by very rapid bill movements (ca. 13 times/sec). The type-K was heard throughout the island, indicating that the population of the Kuroshima Island share this call type. In addition, a juvenile crow was observed giving immature type-K repeatedly. This observation suggests that this call type is not innate but acquired through vocal learning.
Objective method reveals minimum time required to quantify net cost of transport across slow to fast walking speeds
Authors: Adeyeri Bolatito , Thomas Shernice A. , Arellano Christopher J. 
Published: September 2021

AbstractThe U-shaped net cost of transport (COT) curve of walking has helped scientists understand the biomechanical basis that underlies energy minimization during walking. However, to produce an individual’s net COT curve, data must be analyzed during periods of steady-rate metabolism. Traditionally, studies analyze the last few minutes of a 6-10 min trial, assuming that steady-rate metabolism has been achieved. Yet, it is possible that an individual achieves steady rates of metabolism much earlier. However, there is no consensus on how to objectively quantify steady-rate metabolism across a range of walking speeds. Therefore, we developed an objective method to determine the minimum time needed for humans to achieve steady rates of metabolism across slow to fast walking speeds. We hypothesized that a shorter time window could be used to produce a net COT curve that is comparable to the net COT curve created using traditional methods. We analyzed metabolic data from twenty-one subjects who completed several 7-min walking trials ranging from 0.50-2.00 m/s. We partitioned the metabolic data for each trial into moving 1-min, 2-min, and 3 min intervals and calculated their slopes. We statistically compared these slope values to values derived from the last 3-min of the 7-min trial, our ‘gold’ standard comparison. We found that a minimum of 2 min is required to achieve steady-rate metabolism and that data from 2-4 min yields a net COT curve that is not statistically different from the one derived from experimental protocols that are generally accepted in the field.New and NoteworthyA simple slope method reveals that 4-min of walking at speeds between 0.50-1.75 m/s is the minimum time required to produce an accurate net cost of transport curve.
Algorithmic Reconstruction of GBM Network Complexity
Authors: Uthamacumaran Abicumaran , Craig Morgan 
Published: September 2021

SUMMARYGlioblastoma (GBM) is a complex disease that is difficult to treat. Establishing the complex genetic interactions regulating cell fate decisions in GBM can help to shed light on disease aggressivity and improved treatments. Networks and data science offer alternative approaches to classical bioinformatics pipelines to study gene expression patterns from single-cell datasets, helping to distinguish genes associated with control of differentiation and thus aggressivity. Here, we applied a host of data theoretic techniques, including clustering algorithms, Waddington landscape reconstruction, trajectory inference algorithms, and network approaches, to compare gene expression patterns between pediatric and adult GBM, and those of adult glioma-derived stem cells (GSCs) to identify the key molecular regulators of the complex networks driving GBM/GSC and predict their cell fate dynamics. Using these tools, we identified critical genes and transcription factors coordinating cell state transitions from stem-like to mature GBM phenotypes, including eight transcription factors (OLIG1/2, TAZ, GATA2, FOXG1, SOX6, SATB2, YY1) and four signaling genes (ATL3, MTSS1, EMP1, and TPT1) as clinically targetable novel putative function interactions differentiating pediatric and adult GBMs from adult GSCs. Our study provides strong evidence of the applicability of complex systems approaches for reverse-engineering gene networks from patient-derived single-cell datasets and inferring their complex dynamics, bolstering the search for new clinically relevant targets in GBM.
A serum protein network predicts the need for systemic immunomodulatory therapy in autoimmune uveitis
Authors: Kuiper Jonas J.W. , Verhagen Fleurieke H. , Hiddingh Sanne. , Wennink Roos A.W. , Hansen Anna M. , Casey Kerry A. , Hoefer Imo E. , Haitjema Saskia , Drylewicz Julia , Yakin Mehmet , Sen H. Nida , Radstake Timothy R.D.J. , de Boer Joke H. 
Published: September 2021

AbstractObjective biomarkers that can predict a severe disease course of autoimmune uveitis are lacking, and warranted for early identification of high-risk patients to improve visual outcome. The need for non-steroid immunomodulatory therapy (IMT) to control autoimmune uveitis is indicative of a more severe disease course. We used aptamer-based proteomics and a bioinformatic pipeline to uncover the serum protein network of 52 treatment-free patients and 26 healthy controls, and validation cohorts of 114 and 67 patients. Network-based analyses identified a highly co-expressed serum signature (n=85 proteins) whose concentration was consistently low in controls, but varied between cases. Patients that were positive for the signature at baseline showed a significantly increased risk for IMT during follow-up, independent of anatomical location of disease. In an independent cohort (n=114), we established robust risk categories that confirmed that patients with high levels of the signature at diagnosis had a significantly increased risk to start IMT during follow-up. Finally, we further validated the predictive power of the signature in a third cohort of 67 treatment-naive North-American patients. A serum protein signature was highly predictive for IMT in human autoimmune uveitis and may serve as an objective blood biomarker to aid in clinical-decision making.Abstract Figure
Consequences of COVID-19 vaccine allocation inequity in Chicago
Authors: Zeng Sharon , Pelzer Kenley M. , Gibbons Robert D. , Peek Monica E. , Parker William F. 
Published: September 2021

ABSTRACTDuring Chicago’s initial COVID-19 vaccine rollout, the city disproportionately allocated vaccines to zip codes with high incomes and predominantly White populations. However, the impact of this inequitable distribution on COVID-19 outcomes is unknown. This observational study determined the association between zip-code level vaccination rate and COVID-19 mortality in residents of 52 Chicago zip codes. After controlling for age distribution and recovery from infection, a 10% higher vaccination rate by March 28, 2021, was associated with a 39% lower relative risk of death during the peak of the spring wave of COVID-19. Using a difference-in-difference analysis, Chicago could have prevented an estimated 72% of deaths in the least vaccinated quartile of the city (vaccination rates of 17.8 – 26.9%) if it had had the same vaccination rate as the most vaccinated quartile (39.9 – 49.3%). Inequitable vaccine allocation in Chicago likely exacerbated existing racial disparities in COVID-19 mortality.
LXR agonist Prevents Peripheral Neuropathy and modifies PNS immune cells in Aged Mice
Authors: Gavini Chaitanya K. , Elshareif Nadia , Germanwala Anand V. , Aubert Gregory , Calcutt Nigel A. , Mansuy-Aubert Virginie 
Published: September 2021

AbstractPeripheral neuropathy is a common and progressive disorder in the elderly that interferes with daily activities and increases the risk of injury. It is of importance to find efficient treatments to treat or delay this age-related neurodegeneration. We previously demonstrated that activation of the cholesterol sensor Liver X receptor (LXR) with the potent agonist GW3965, alleviates pain in a diet-induced obesity model. Because cholesterol had also been linked to neuropathy during aging, we sought to test whether LXR activation may improve neuropathy and pain in aged mice by treating 21-month-old mice for 3 months with GW3965. Treatment resulted in a significant increase in nerve fibers of the sub-basal plexus, accompanied by a change in polarization, metabolism, and cholesterol content of macrophages in the sciatic nerve. These results suggest that activation of the LXR may block the progression of neuropathy associated with aging by modifying nerve-immune cell cholesterol, thereby providing new pathways to target in efforts to delay neuropathy during aging.
Brain fatty acid binding protein exhibits non-preferential and mutation-resistant binding towards fatty acids
Authors: Bodnariuc I. , Lenz S. , Renaud-Young M. , Shandro T. M. , Ishida H. , Vogel H. J. , MacCallum J. L. 
Published: September 2021

AbstractMembers of the fatty acid binding protein (FABP) family function as intracellular transporters of long chain fatty acids and other hydrophobic molecules to different cellular compartments. Brain fatty acid binding protein (FABP7) exhibits ligand-directed differences in cellular transport behavior. For example, when FABP7 binds to docosahexaenoic acid (DHA), the complex relocates to the nucleus and influences transcriptional activity, whereas FABP7 bound with monosaturated fatty acids remain in the cytosol. We used a variety of biophysical techniques to enhance understanding of ligand-directed transport. Specifically, we examine how FABP7 binds to fatty acids, including saturated stearic acid (SA), monounsaturated oleic acid (OA), and polyunsaturated DHA. We find that at 37°C FABP7 has near equivalent binding affinities for the fatty acids, while at lower temperatures, FABP7 exhibits a preference for the unsaturated fatty acids. Therefore, nuclear localization of the FABP7-DHA complex cannot be explained by binding preferences. Using NMR spectroscopy and molecular dynamics simulations, we observe that DHA uniquely affects the portal region of FABP7, which could enhance the complex’s nuclear localization. Mutations to purported critical binding residues (R126L and Y128F) have little effect on fatty acid binding, with molecular dynamics simulations revealing that the bound fatty acid can adopt binding poses that can accommodate the mutations.SignificanceThis work studies FABP7 at physiological temperature and shows that nuclear localization of FABP7 cannot be initiated by tighter ligand interactions. Through biophysical experiments and simulations, we show ligand-dependent conformational changes, instead of binding affinities, are associated with certain biological outcomes. Extensive simulations reveal redundancy in available ligand binding conformations, which permits mutant-resistant binding. This suggests that these mutations do not affect ligand binding affinities, but changes in protein conformation and dynamics may result in disease associated cellular outcomes.
Virucidal activity of Nasaleze® Cold & Flu Blocker and Nasaleze® Travel in cell cultures infected with human pathogenic coronavirus 229-E
Authors: Hunt N , Suleman L , Josling PD , Popov TA 
Published: September 2021

AbstractThis in vitro study determined the anti-viral efficacy of a unique blend of powder cellulose supplemented with powdered garlic extract (PGE) and a signalling agent. The composition, presented as Nasaleze® Cold & Flu Blocker/Nasaleze® Travel, was assessed against Human Coronavirus 229E, CoV 229E {ATCC VR-740} in an in vitro experiment. The test substance was used at sub-optimal dosing levels to explore its prevention and treatment capabilities. The virucidal activity of this novel formulation was measured at 48, 72 and 112 hour periods after incubation. Results showed strong reductions in viral titre of Coronavirus 229E compared to a control, while no toxicity to human cells from the test formulation was noted. The extract Nasaleze® Cold/Travel showed potential to be used as a therapeutic and preventive agent.The data reconfirms the established anti-viral activity of this formulation acting as a barrier preventing the virus from accessing the nasal mucosa and disrupting its replication.1,2,3
On the edge of criticality: strength-dependent perturbation unveils delicate balance between fluctuation and oscillation in brain dynamics
Authors: Perl Yonatan Sanz , Escrichs Anira , Tagliazucchi Enzo , Kringelbach Morten L. , Deco Gustavo 
Published: September 2021

SummaryDespite decades of research, there is still a lack of understanding of the role and generating mechanisms of the ubiquitous fluctuations and oscillations found in recordings of brain dynamics. Here, we used a strength-dependent perturbative framework to provide a causal mechanistic description of how human brain function is perched at the delicate balance between fluctuation and oscillation. Applying local strength-dependent perturbations and subsequently measuring the perturbative complexity index clearly demonstrates that the overall balance of brain dynamics is shifted towards fluctuations for providing much needed flexibility. Importantly, stimulation in the fluctuation regime modulates specific resting state network, thus providing a mechanistic explanation of experimentally reported brain dynamics. Furthermore, this framework generates specific, testable empirical predictions for human stimulation studies using strength-dependent rather than constant perturbation. Overall, the strength-dependent perturbative framework demonstrates how the human brain is poised on the edge of criticality, between fluctuations to oscillations, allowing for maximal flexibility.
Nanopore tweezers measurements of RecQ conformational changes reveal the energy landscape of helicase motion
Authors: Craig Jonathan M. , Mills Maria , Laszlo Andrew H. , Kim Hwanhee C. , Huang Jesse R. , Abell Sarah J. , Mount Jonathan W , Neuman Keir C. , Gundlach Jens H. 
Published: September 2021

AbstractHelicases are essential for nearly all nucleic acid processes across the tree of life. Using Nanopore Tweezers we observed the small, fast steps taken by single RecQ helicases as they step along and unwind DNA at ultrahigh spatiotemporal resolution. By directly measuring conformational substates of RecQ we determine the coupling between helicase domain motions and chemical reactions that together produce forward motion along the DNA. Application of assisting and opposing forces shows that RecQ has a highly asymmetric energy landscape that reduces its sensitivity to opposing mechanical forces that could be encountered in vivo by molecular roadblocks such as DNA bound proteins. This energy landscape enables RecQ to maintain speed against an opposing load.
The Synechocystis sp. PCC 6803 open reading frame slr0201 that is homologous to sdhC from Archaea codes for a [2Fe-2S] protein
Authors: Xiong Fusheng , LoBrutto Russell , Vermaas Wim F. J. 
Published: September 2021

AbstractA hypothetical protein encoded by Synechocystis sp. PCC 6803 open reading frame slr0201shows high sequence similarity to the C subunit of a group of unusual succinate dehydrogenases found in some archaeal species. Slr0201 was originally annotated as HdrB, the B subunit of heterodisulfide reductase, but appears to be SdhC instead. This protein was overexpressed in E. coli by cloning the PCR-derived slr0201 open reading frame into a pET16b-based expression vector. The overproduced Slr0201 accumulated predominantly in inclusion bodies with an apparent molecular mass of 33 kDa. The protein contained at least one [2Fe-2S] cluster based on UV-visible absorbance and CD spectra and EPR spectroscopy, in conjunction with stoichiometric analysis of protein-bound iron and sulfur content. Redox titration showed a midpoint potential (Em) of + 17 mV at pH 7.0, which is consistent with Slr0201 serving a role in transferring electrons between succinate and plastoquinone. Slr0201 was also overproduced in Synechocystis sp. PCC 6803 by introducing an additional, His-tagged slr0201 into the Synechocystis genome replacing psbA3, creating the slr0201+-His overexpression strain. Immunoblot analysis shows that Slr0201 is membrane-associated in the wild type. However, in the Slr0201+-His strain, immunoreaction occurred in both the membrane and soluble fractions, possibly as a consequence of processing near the N-terminus. The results obtained with Slr0201 are discussed in the light of one of the cyanobacterial SdhB subunits, which shares redox commonalities with archaeal SdhB.
Alkaliphilus flagellata sp. nov., Butyricicoccus intestinisimiae sp. nov., Clostridium mobile sp. nov., Clostridium simiarum sp. nov., Dysosmobacter acutus sp. nov., Paenibacillus brevis sp. nov., Peptoniphilus ovalis sp. nov., and Tissierella simiarum sp. nov., isolated from monkey feces
Authors: Li Dan-Hua , Abuduaini Rexiding , Du Meng-Xuan , Wang Yu-Jing , Chen Hong-He , Zhou Nan , Zhu Hai-Zhen , Lu Yong , Yu Pei-Jun , Yang Shu-Peng , Jiang Cheng-Ying , Sun Qiang , Liu Chang , Liu Shuang-Jiang 
Published: September 2021

AbstractNon-human primates harbor diverse microbiomes in their guts. As a part of China Microbiome Initiatives, we cultivated and characterized the gut microbiome of cynomolgus monkeys (Macaca fascicularis). In this report, we communicate the characterization and taxonomy of 8 bacterial strains that were obtained from fecal samples of captive cynomolgus monkeys. The results revealed that they represented 8 novel bacterial species. The proposed names of the 8 novel species are Alkaliphilus flagellate (type strain MSJ-5T =CGMCC 1.45007T=KCTC 15974T), Butyricicoccus intestinisimiae MSJd-7T (type strain MSJd-7T =CGMCC 1.45013T =KCTC 25112T), Clostridium mobile (type strain MSJ-11T =CGMCC 1.45009T=KCTC 25065T), Clostridium simiarum (type strain MSJ-4T =CGMCC 1.45006T =KCTC 15975T), Dysosmobacter acutus (type strain MSJ-2T =CGMCC 1.32896T=KCTC 15976T), Paenibacillus brevis MSJ-6T (type strain MSJ-6T =CGMCC 1.45008T=KCTC 15973T), Peptoniphilus ovalis (type strain MSJ-1T =CGMCC 1.31770T=KCTC 15977T), and Tissierella simiarum (type strain MSJ-40T =CGMCC 1.45012T=KCTC 25071T).