bluuebunny/crossref_metadata_2025 huggingface dataset:
A QI Partnership to Decrease CT Use for Pediatric Appendicitis in the Community Hospital Setting
Authors: Goldman Michael P. , Lynders William , Crain Michael , Nocera Kelley Mariann , Solomon Daniel M. , Bokhari Syed A.J. , Tiyyagura Gunjan , Auerbach Marc A. , Emerson Beth L.
Published: September 2021

Introduction:

The primary aim of this quality improvement initiative was to decrease the use of computerized tomography (CT) in the evaluation of pediatric appendicitis in a community general emergency department (GED) system by 50% (from 32% to 16%) in 1 year.

Methods:

Colleagues within a State Emergency Medical Service for Children (EMSC) community of practice formed the quality improvement team, representing multiple stakeholders across 3 independent institutions. The team generated project aims by reviewing baseline practice trends and implemented changes using the Model for Improvement. Ultrasound (US) use and nondiagnostic US rates served as process measures. Transfer and “over-transfer” rates served as balancing measures. Interventions included a GED pediatric appendicitis clinical pathway, US report templates, and case audit and feedback. Statistical process control tracked the main outcomes. Additionally, frontline GED providers shared perceptions of knowledge gains, practice changes, and teamwork.

Results:

The 12-month baseline revealed a GED CT scan rate of 32%, a US rate of 63%, a nondiagnostic US rate of 77%, a transfer to a children’s hospital rate of 23.5%, and an “over-transfer” rate of 0%. Project interventions achieved and sustained the primary aim by decreasing the CT scan rate to 4.5%. Frontline GED providers reported positive perceptions of knowledge gains and standardization of practice.

Conclusions:

Engaging regional colleagues in a pediatric-specific quality improvement initiative significantly decreased CT scan use in children cared for in a community GED system. The emphasis on the community of practice facilitated by Emergency Medical Service for Children may guide future improvement work in the state and beyond.
Pain experience and mood disorders during the lockdown of the COVID-19 pandemic in the United States: an opportunistic study
Authors: Colloca Luana , Thomas Sharon , Yin Margaret , Haycock Nathaniel R. , Wang Yang
Published: September 2021

Introduction:

The unknown and uncontrollable situation of the coronavirus disease 2019 (COVID-19) pandemic may have triggered changes in pain, anxiety, and depression along with a perception of nonspecific COVID-19 symptoms.

Objectives:

We determined how anxiety, depression, and pain outcomes varied during the “Stay-at-Home” order compared with the prepandemic period and whether nonspecific COVID-19 symptoms would occur.

Methods:

We conducted an online survey to opportunistically reassess clinical anxiety, depression, pain intensity, and pain interference while controlling for somatic symptom severity during the prepandemic and Stay-at-Home order period. During the Stay-at-Home period, anxiety, depression, pain intensity, and pain interference were reassessed. Coping strategies were assessed as a critical factor influencing pain behaviors. In addition, we explored the occurrence of nonspecific COVID-19 symptoms with an ad hoc survey referencing the Centers for Disease Control and Prevention publicly available COVID-19 symptoms.

Results:

We observed a significant increase in depression and anxiety levels during the Stay-at-Home period. Coping strategy changes (eg, increased exercise) were linked to lower pain severity and interference which improved overall. Participants who self-reported nonspecific COVID-19 symptoms had higher prepandemic depression. Among the 72 participants not diagnosed with COVID-19, 70.8% of the participants experienced symptoms resembling those associated with COVID-19.

Conclusion:

We suggest the parallel between pain outcome improvement and worsening anxiety and depression during the Stay-at-Home order might reflect a shift in symptoms, indicating that those patients with underlying mood disorders may require more help than they did before the pandemic.
Psychophysiologic symptom relief therapy for chronic back pain: a pilot randomized controlled trial
Authors: Donnino Michael W. , Thompson Garrett S. , Mehta Shivani , Paschali Myrella , Howard Patricia , Antonsen Sofie B. , Balaji Lakshman , Bertisch Suzanne M. , Edwards Robert , Ngo Long H. , Grossestreuer Anne V.
Published: September 2021

Introduction:

Chronic back pain is the leading cause of disability in the United States. Based on the hypothesis that nonspecific back pain may be rooted in a psychophysiologic etiology, we propose a new approach to chronic back pain.

Objectives:

A pilot study was conducted to assess whether psychophysiologic symptom relief therapy (PSRT) can reduce disability and back pain bothersomeness for patients with chronic back pain.

Methods:

This was a three-armed, randomized trial for adults with nonspecific chronic back pain that compared PSRT with usual care and an active comparator (mindfulness-based stress reduction [MBSR]). Psychophysiologic symptom relief therapy–randomized participants received a 12-week (36 hours) course based on the psychophysiological model of pain. All groups were administered validated questionnaires at baseline and at 4, 8, 13, and 26 weeks. The primary outcome was the reduction in pain disability measured by the Roland–Morris Disability Questionnaire.

Results:

The mean Roland–Morris Disability Questionnaire score for the PSRT group (n = 11) decreased from 9.5 (±4.3 SDs) to 3.3 (±5.1) after 26 weeks which was statistically significant compared with both MBSR (n = 12) (P = 0.04) and usual care (n = 12) (P = 0.03). Pain bothersomeness scores and pain-related anxiety decreased significantly over 26 weeks in PSRT compared with MBSR and usual care (data in manuscript). At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively. Psychophysiologic symptom relief therapy attendance was 76%, and there was 100% follow-up of all groups.

Conclusion:

Psychophysiologic symptom relief therapy is a feasible and potentially highly beneficial treatment for patients with nonspecific back pain.
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.
Pengzhenrongella sicca gen. nov., sp. nov., a new member of suborder Micrococcineae isolated from High Arctic tundra soil
Authors: Kim Myong Chol , Ju Yun Hui , Hwang Un A , Liu Ping , Pak Sung Ho , Peng Fang
Published: September 2021

A yellow bacterial strain, designated LRZ-2T, was isolated from High Arctic tundra near the settlement Ny-Ålesund in the Svalbard Archipelago, Norway. The cells were Gram-stain-positive, aerobic and non-sporulating. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain LRZ-2T represented a novel member of the suborder

Micrococcineae

. Its nearest phylogenetic neighbours were the members of the genus

Luteimicrobium

, with 16S rRNA gene sequence similarity of 95.3–96.9 %. The average nucleotide identity and digital DNA–DNA hybridization values between the genomes of strain LRZ-2T and its closely related strains were 77.4–74.3 % and 21.4–19.6 %, respectively. The DNA G+C content was 72.4 mol%. The peptidoglycan type of the isolate was A4β with an interpeptide bridge comprising l-ornithine and d-glutamic acid. The predominant menaquinone was MK-9 (H4) and the major fatty acids were anteiso-C15 : 0, C16 : 0, anteiso-C15 : 1 A, anteiso-C17 : 0 and iso-C15 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, phosphatidylinositol dimannoside, unidentified phosphoglycolipid, four unidentified phospholipids and two unidentified polar lipids. Strain LRZ-2T showed a 16S rRNA gene signature pattern consisting of nucleotides at positions 120 (A), 131–231 (C-G), 196 (C), 342–347 (C-G), 444–490 (A-U), 580–761 (C-G), 602–636 (C-G), 670–736 (A-U), 822–878 (G-C), 823–877 (G-C), 826–874 (C-G), 827 (U), 843 (C), 950–1231 (U-A), 1047–1210 (G-C), 1109 (C), 1145 (G), 1309–1328 (G-C), 1361 (G) and 1383 (C), which clearly distinguished it from all genera previously reported in the suborder

Micrococcineae

. On the basis of the phylogenetic, phenotypic and chemotaxonomic data, strain LRZ-2T is considered to represent a novel species of a new genus, for which the name Pengzhenrongella sicca gen. nov., sp. nov. is proposed. The type strain of Pengzhenrongella sicca is LRZ-2T (=CCTCC AB 2012163T=DSM 100332T).
Different evolutionary trends form the twilight zone of the bacterial pan-genome
Authors: Horesh Gal , Taylor-Brown Alyce , McGimpsey Stephanie , Lassalle Florent , Corander Jukka , Heinz Eva , Thomson Nicholas R.
Published: September 2021

The pan-genome is defined as the combined set of all genes in the gene pool of a species. Pan-genome analyses have been very useful in helping to understand different evolutionary dynamics of bacterial species: an open pan-genome often indicates a free-living lifestyle with metabolic versatility, while closed pan-genomes are linked to host-restricted, ecologically specialized bacteria. A detailed understanding of the species pan-genome has also been instrumental in tracking the phylodynamics of emerging drug resistance mechanisms and drug-resistant pathogens. However, current approaches to analyse a species’ pan-genome do not take the species population structure into account, nor do they account for the uneven sampling of different lineages, as is commonplace due to over-sampling of clinically relevant representatives. Here we present the application of a population structure-aware approach for classifying genes in a pan-genome based on within-species distribution. We demonstrate our approach on a collection of 7500

Escherichia coli

genomes, one of the most-studied bacterial species and used as a model for an open pan-genome. We reveal clearly distinct groups of genes, clustered by different underlying evolutionary dynamics, and provide a more biologically informed and accurate description of the species’ pan-genome.
Analysis of quality changes and generation of sulfur volatiles
according to the storage period of chicken
Authors: Kim Bu-Min , Jang Yu-Na , Kang Sun Moon , Kim Yunseok , Lee Eun-Seon , Kim Jong-Hui
Published: September 2021

This study aimed to evaluate quality changes and generation of sulfur volatiles
of different chicken parts (whole-chicken, breast, and leg), according to the
storage period (1, 3, 5, 7, and 9 days). All samples eventually exceeded 6 log
CFU/mL of total viable counts (TVC) after storage for 9 days (whole chicken), 7
days (breast), and 5 days (leg). pH of the whole chicken, breast, and leg
significantly increased with the storage period. The volatile basic nitrogen
(VBN) value of whole chicken was 16.70 mg% on day 9, whereas that of the breast
and leg exceeded 20 mg% on day 9. The thiobarbituric acid reactive substance
(TBARS) values of the whole chicken and leg exceeded 0.30 mg MDA/kg on the 9th
and 7th day, respectively, but the breast had not exceeded 0.30 mg MDA/kg even
after 9 days. The amounts of sulfur volatiles from spoiled chicken samples,
including hydrogen sulfide (HS), methyl mercaptan (MM), dimethyl disulfide
(DMDS) and dimethyl sulfide (DMS), increased during storage. In particular,
among these four compounds, DMS increased most markedly. When TVC exceeded 7 log
CFU/g, the amount of generated DMS increased rapidly. Thus, the presence of DMS
was characteristics of potential spoilage bacteria on chilled chicken;
therefore, it could be adopted as a potential indicator to monitor freshness
based on whether the number of microorganisms on chicken has reached the level
of spoilage.
Immunity enhancement efficacy of the extracts prepared from blanched and dried aerial part in Cirsium setdens Nakai
Authors: Heo Seong Il , Jung Sang Mi
Published: September 2021

Immune stimulation has emerged as a novel strategy for improving the immune system of the body. Research attention has been focused on identification of natural and dietary substances that can potentially improve immune activity, with fewer side effects than those of chemical substances. Cirsium setidens Nakai, also called ‘gondre,’ is a perennial plant belonging to the Asteraceae family and grows only in Korea. It has alternate leaves and leafy edges, and its tip is pointed. The leaf is somewhat broader, and the flower is purple from July to October. It is used in the treatment of inflammation, edema, and hypertension. Various physiological activities of raw C. setidens Nakai aerial part extracts have been reported recently. Here, we evaluated the antioxidant activity and immune enhancement efficacy of extracts prepared from blanched and dried C. setidens Nakai in addition to their potential use in not only regular but also functional health food. The total phenolic compound content was five times higher in the extract prepared by freeze drying than in that prepared by blanching. However, production of nitric oxide and secretion of immunostimulating cytokines such as IL-6 and TNF-α were relatively higher in the extract prepared by blanching than in that prepared by drying. Overall, an immunostimulating effect was observed for the C. setidens Nakai aerial part extract prepared by blanching, confirming its potential as a functional health food ingredient.
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

Antifreeze 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

Background

Neuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders.

Objective

The 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.

Methods

The 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.

Results

The 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.

Conclusion

TUS 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

In 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.
Efficient Flocking: Metric Versus Topological Interactions
Authors: Kumar Vijay , De Rumi
Published: September 2021

Flocking is a fascinating phenomenon observed across a wide range of living organisms. We investigate, based on a simple self-propelled particle model, how the emergence of ordered motion in a collectively moving group is influenced by the local rules of interactions among the individuals, namely, metric versus topological interactions as debated over in the current literature. In the case of the metric ruling, the individuals interact with the neighbours within a certain metric distance; in contrast, in the topological ruling, interaction is confined within a number of fixed nearest neighbours. Here, we explore how the range of interaction versus the number of fixed interacting neighbours affects the dynamics of flocking in an unbounded space, as observed in natural scenarios. Our study reveals the existence of a certain threshold value of the interaction radius in the case of metric ruling and a threshold number of interacting neighbours for the topological ruling to reach an ordered state. Interestingly, our analysis shows that topological interaction is more effective in bringing the order in the group, as observed in field studies. We further compare how the nature of the interactions affects the dynamics for various sizes and speeds of the flock.
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

The 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 Noteworthy

A 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

Glioblastoma (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

Objective 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

During 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

Peripheral 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

Members 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.

Significance

This 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

This 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

Despite 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

Helicases 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

A 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

Non-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).
SMC1A facilitates gastric cancer cells proliferation, migration and invasion via promoting SNAI2 activated EMT
Authors: Liu Yaling , Fang Xianrui , Wang Qianqian , Xiao Da , Peng Zhenyu , Zhou Ting , Ren Feng , Zhou Jingyu
Published: September 2021

Background

structural maintenance of chromosomes protein 1A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participate in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC).

Materials and methods

RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT)were analyzed. Furthermore,the mechanism of SMC1A action was investigated.

Results

SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS remarkably promoted cell proliferation, migration and invasion. While knockdown of SMC1A in HCG27 inhibited cell proliferation, migration and invasion of HGC27 cells. Moreover, it’s observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAI2

Conclusion

our study revealed SMC1A facilitates gastric cancer cell proliferation, migration and invasion via promoting SNAI2 activated EMT, which indicated SMC1A may be a potential target for gastric cancer therapy.
Influence of high energy diet and polygenic predisposition for obesity on postpartum health in rat dams
Authors: Leuthardt Andrea S. , Bayer Julia , Monné Rodriguez Josep M. , Boyle Christina N.
Published: September 2021

It is estimated that 30% of pregnant women worldwide are overweight or obese, which leads to adverse health effects for both the mother and child. Women with obesity during pregnancy are at higher risk for developing both metabolic and mental disorders, such as diabetes and depression. Numerous studies have used rodent models of maternal obesity to understand its consequences on the offspring, yet characterization of changes in the dams is rare, and most rodent models rely solely on a high fat diet to induce maternal obesity, without regarding genetic propensity for obesity. Here we present the influence of both peripartum high energy diet (HE) and obesity-proneness on maternal health using selectively-bred diet-resistant (DR) and diet-induced obese (DIO) rat dams. Outbred Sprague-Dawley rats were selected and bred according to their propensity to gain weight. From F1 onward, dams consuming a HE diet displayed higher body weight gain during pregnancy, and HE diet had a strong effect on meal patterns. Sensitivity to the hormone amylin was preserved during pregnancy, regardless of diet. After several rounds of selective breeding, dams from generation F3 were assessed for their postpartum physiology and behaviors. We observed strong diet and phenotype effects on gestational weight gain, with DIO-HE dams gaining 119% more weight than DR-chow. A high-resolution analysis of maternal behaviors on postpartum day 2 (P2) did not detect main effects of diet or phenotype, but a subset of DIO dams showed decreased pup-related behaviors. During a sucrose preference test (SPT) on P14, all DR dams consumed at least 70% sucrose, while a subset of DIO dams preferred water. In generation F6/F7 dams, effects on gestational weight gain persisted, and we observed a main effect of phenotype of SPT, with DIO-chow dams showing the lowest sucrose preference. Both DIO and DR dams consuming HE diet had severe postpartum liver lipidosis and exhibited reduced leptin sensitivity in the arcuate nucleus at the time of pup-weaning. These data demonstrate that both diet and genetic obesity-proneness have consequences on maternal health.
FirmicutesandBacteroidetesexplain mass gain variation in an obligate hibernator
Authors: Johnson Gina C. , Degregori Samuel , Barber Paul H. , Blumstein Daniel T.
Published: September 2021

Body condition is an important life history challenge that directly impacts individual fitness and is particularly important for hibernating animals, whose maintenance of adequate body fat and mass is essential for survival.

It is well documented that symbiotic microorganisms play a vital role in animal physiology and behaviour. Recent work demonstrates that gut microbes are associated with fat accumulation and obesity;Firmicutesis consistently associated with obesity whileBacteroidetesis associated with leanness both in humans and other animals.

The focus of most microbiome studies has been on human health or involved lab reared animals used as a model system. However, these microbes likely are important for individual fitness in wild populations and provide potential mechanistic insights into the adaptability and survival of wildlife.

Here we test whether symbiotic microorganisms within the phyla ofFirmicutesandBacteroidetesare associated with summer mass gain in an exceptionally well-studied wild population of yellow-bellied marmots (Marmota flaviventer) by quantifying microbial abundance over five years of fecal samples (2015 – 2019) collected during their summer active season.

Results show that marmots with higher mass gain rates have a greater abundance ofFirmicutes. In contrast, higher abundance ofBacteroideteswas associated with lower mass gain rates, but only for marmots living in harsher environments. Similar patterns were found at the family level whereRuminococcaceae, a member ofFirmicutes, was associated with higher mass gain rates, andMuribaculaceae, a member ofBacteroidetes, was associated with lower mass gain rates, and similarly in harsher environments.

Although correlative, these results highlight the importance of symbiotic gut microbiota to mass gain in the wild, a trait associated with survival and fitness in many taxonomic groups.
A phenotypic screen using splitCas9 identifies essential genes required for actin regulation during host cell egress and invasion by Toxoplasma gondii
Authors: Li Wei , Grech Janessa , Stortz Johannes Felix , Gow Matthew , Periz Javier , Meissner Markus , Jimenez-Ruiz Elena
Published: September 2021

Apicomplexan parasites, such as Toxoplasma gondii, possess unique organelles, cytoskeletal structures, signalling cascades, replicate by internal budding within a specialised compartment and actively invade and exit the host cell, to name a few aspects of the unique biology that characterise this phylum. Due to their huge phylogenetic distance from well established model organisms, such as opisthokonts, comparative genomics has a limited capacity to infer gene functions and conserved proteins can fulfil different roles in apicomplexans. Indeed, approximately 30% of all genes are annotated as hypothetical and many had a crucial role during the asexual life cycle in genome-wide screens. While the current CRISPR/Cas9-based screens allow the identification of fitness conferring genes, only little information about the respective functions can be obtained. To overcome this limitation, and to group genes of interest into functional groups, we established a conditional Cas9-system in T. gondii that allows phenotypic screens. Using an indicator strain for F-actin dynamics and apicoplast segregation, we identified critical genes required for defined steps during the asexual life cycle. The detailed characterisation of two of these candidates revealed them to be critical for host cell egress and invasion and to act at different time points in the disassembly of the intravacuolar F-actin network. While the signalling linking factor (SLF) is an integral part of a signalling complex required for early induction of egress, a novel conoid protein (conoid gliding protein, CGP) acts late during egress and is required for the activation of gliding motility.
Alpha oscillations link action to cognition: An oculomotor account of the brain’s dominant rhythm
Authors: Popov Tzvetan , Miller Gregory A. , Rockstroh Brigitte , Jensen Ole , Langer Nicolas
Published: September 2021

Power modulations in alpha oscillations (8-14Hz) have been associated with most human cognitive functions and psychopathological conditions studied. These reports are often inconsistent with the prevailing view of a specific relationship of alpha oscillations to attention and working memory (WM). We propose that conceptualizing the role of alpha oscillations in oculomotor control resolves this inconsistency. This proposition is based on a review of results across species (human Npooled=295, one non-human primate, honey bee N=5), experimental conditions (rest, attention, and working memory), and recording techniques (EEG, ECOG, eye-tracking, and MEG) that encourage the following relationships between alpha oscillations and eye-movement control: (i) saccade initiation prompts power decrease in brain circuits associated with saccadic control; (ii) the direction of a saccade is consistent with alpha lateralization, both during task and resting conditions; (iii) the phase of alpha activity informs saccade occurrence and biases miniature eye movements during fixation (e.g. fixational tremor); and (iv) oculomotor action differentiates WM load. A new theory on how alpha oscillations link oculomotor action to cognition is proposed. Generalizing across tasks and species: low oculomotor activity is associated with high alpha power and vice versa. Alpha oscillations regulate how long to look at a given target and how fast to saccade to a next. By ensuring steady gaze position, any potential input outside foveal vision is “suppressed”.