bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of heating, ventilation, and air conditioning design features on the transmission of viruses, including the 2019 novel coronavirus: a systematic review of filtration
Authors: Thornton Gail M. , Fleck Brian A. , Kroeker Emily , Dandnayak Dhyey , Fleck Natalie , Zhong Lexuan , Hartling Lisa 
Published: September 2021

AbstractHistorically, viruses have demonstrated airborne transmission. Emerging evidence suggests the novel coronavirus (SARS-CoV-2) that causes COVID-19 may also spread by airborne transmission. This is more likely in indoor environments, particularly with poor ventilation. In the context of potential airborne transmission, a vital mitigation strategy for the built environment is heating, ventilation, and air conditioning (HVAC) systems. HVAC features could modify virus transmission potential. A systematic review following international standards was conducted to comprehensively identify and synthesize research examining the effectiveness of filters within HVAC systems in reducing virus transmission. Twenty-three relevant studies showed that: filtration was associated with decreased transmission; filters removed viruses from the air; increasing filter efficiency (efficiency of particle removal) was associated with decreased transmission, decreased infection risk, and increased viral filtration efficiency (efficiency of virus removal); increasing filter efficiency above MERV 13 was associated with limited benefit in further reduction of virus concentration and infection risk; and filters with the same efficiency rating from different companies showed variable performance. Increasing filter efficiency may mitigate virus transmission; however, improvement may be limited above MERV 13. Adapting HVAC systems to mitigate virus transmission requires a multi-factorial approach and filtration is one factor offering demonstrated potential for decreased transmission.Practical ImplicationsIn order for filtration to be an effective means of virus removal and transmission control, proper installation is required. As well, professionals should be aware of the fact that similarly rated filters from different companies may offer different virus reduction results. While increasing filtration efficiency (i.e., increasing MERV rating or moving from MERV to HEPA) is associated with virus mitigation, there appears to be diminishing returns for filters rated MERV 13 or higher. Although costs increase with filtration efficiency, filtration costs are lower than the cost of ventilation options with the equivalent reduction in transmission.
White matter hyperintensities may be an early marker for age-related cognitive decline
Authors: Morrison Cassandra , Dadar Mahsa , Villeneuve Sylvia , Collins D. Louis ,   for Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

AbstractBackgroundResearch suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another, nor how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline in cognitively normal older adults without subjective cognitive decline.MethodsA total of 230 subjects with CSF Aß42, CSF pTau181, white matter hyperintensities (WMHs) used as a proxy of CSVD and cognitive scores from the Alzheimer’s Disease Neuroimaging Initiative were included. Associations between each pathology and cognitive score were investigated using regression models. Furthermore, relationships between the three pathologies were also examined using regression models.ResultsAt baseline, there was an inverse association between WMH load and Aß42 (t=-4.20, p<.001). There was no association between WMH load and pTau (t=0.32, p=0.75), nor with Aß42 and pTau (t=0.51, p=.61). Correcting for age, sex and education, baseline WMH load was associated with baseline ADAS-13 scores (t=2.59, p=.01) and lower follow-up executive functioning (t= -2.84, p=.005). Baseline Aß42 was associated with executive function at baseline (t=3.58, p<.004) but not at follow-up (t=1.05, p=0.30), nor with ADAS-13 at baseline (t=-0.24, p0.81) or follow-up (t=0.09, p=0.93). Finally, baseline pTau was not associated with any cognitive measure at baseline or follow-up.ConclusionBoth baseline Aß42 and WMH load are associated with some baseline cognition scores, but only baseline WMH load is associated with follow-up executive functioning, indicating that it may be one of the earliest pathologies that contributes to future cognitive decline, in cognitively healthy older adults. Given that healthy older adults with WMH pathology exhibit declines in cognitive functioning, they may be less resilient to future pathology increasing their risk for cognitive impairment due to dementia than those without WMHs.
Overcoming microenvironment-mediated chemoprotection through stromal galectin-3 inhibition in acute lymphoblastic leukemia
Authors: Tarighat Somayeh S. , Fei Fei , Joo Eun Ji , Abdel-Azim Hisham , Yang Lu , Geng Huimin , Bum-Erdene Khuchtumur , Grice I. Darren , Itzstein Mark von , Blanchard Helen , Heisterkamp Nora 
Published: September 2021

AbstractEnvironmentally-mediated drug resistance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) significantly contributes to relapse. Stromal cells in the bone marrow environment protect leukemia cells by secretion of chemokines as cues for BCP-ALL migration towards, and adhesion to, stroma. Stromal cells and BCP-ALL cells communicate through stromal galectin-3. Here, we investigated the significance of stromal galectin-3 to BCP-ALL cells. We used CRISPR/Cas9 genome editing to ablate galectin-3 in stromal cells and found that galectin-3 is dispensable for steady-state BCP-ALL proliferation and viability. However, efficient leukemia migration and adhesion to stromal cells are significantly dependent on stromal galectin-3. Importantly, loss of stromal galectin-3 production sensitized BCP-ALL cells to conventional chemotherapy. We therefore tested novel carbohydrate-based small molecule compounds (Cpd14 and Cpd17) with high specificity for galectin-3. Consistent with results obtained using galectin-3-knockout stromal cells, treatment of stromal-BCP-ALL co-cultures inhibited BCP-ALL migration and adhesion. Moreover, these compounds induced anti-leukemic responses in BCP-ALL cells including a dose-dependent reduction of viability and proliferation, induction of apoptosis and, importantly, inhibition of drug resistance. Collectively, these findings indicate galectin-3 regulates BCP-ALL cell responses to chemotherapy through the interactions between leukemia cells and the stroma, and show that a combination of galectin-3 inhibition with conventional drugs can sensitize the leukemia cells to chemotherapy.
Phostensin Enables Lymphocyte Integrin Activation and Population of Peripheral Lymphoid Organs
Authors: Lee Ho-Sup , Sun Hao , Lagarrigue Frédéric , Fox Jay W. , Sherman Nicholas E. , Gingras Alexandre R. , Ginsberg Mark H. 
Published: September 2021

ABSTRACTRap1 GTPase drives assembly of the Mig-10/RIAM/lamellipodin–Integrin–Talin (MIT) complex that enables integrin-dependent lymphocyte functions. Here we used tandem affinity tag-based proteomics to isolate and analyze the MIT complex and reveal that Phostensin (PTSN), a regulatory subunit of protein phosphatase 1, is a component of the complex. PTSN mediates de-phosphorylation of Rap1 thereby preserving the activity and membrane localization of Rap1 to stabilize the MIT complex. CRISPR/Cas9-induced deletion of PPP1R18, which encodes PTSN, markedly suppresses integrin activation in Jurkat human T cells. We generated apparently healthy Ppp1r18-/- mice that manifest lymphocytosis and reduced population of peripheral lymphoid tissues ascribable to defective activation of integrins αLβ2 and α4β7. Ppp1r18-/- T cells exhibit reduced capacity to induce colitis in a murine adoptive transfer model. Thus, PTSN enables lymphocyte integrin-mediated functions by dephosphorylating Rap1 to stabilize the MIT complex. As a consequence, loss of PTSN ameliorates T cell-mediated colitis.SUMMARYPhostensin, a protein phosphatase 1 regulatory subunit, supports lymphocyte integrin-dependent functions by mediating dephosphorylation of Rap1 to stabilize the MIT complex thereby enabling the population of peripheral lymphoid organs and T cell-mediated colitis.
Cell-adaptable dynamic hydrogel reinforced with stem cells improves the functional repair of spinal cord injury by alleviating neuroinflammation
Authors: Yuan Xin , Yuan Weihao , Ding Lu , Shi Ming , Luo Liang , Wan Yong , Oh Jiwon , Zhou Yanfang , Bian Liming , Deng David Y.B. 
Published: September 2021

ABSTRACTSpinal cord injury (SCI) is one of the most challenging clinical issues. It is characterized by the disruption of neural circuitry and connectivity, resulting in neurological disability. Adipose-derived stem cells (ADSCs) serve as a promising source of therapeutic cells for SCI treatment. However, the therapeutic outcomes of direct ADSCs transplantation are limited in the presence of an inflammatory microenvironment. Herein, a cell-adaptable neurogenic (CaNeu) hydrogel was developed as a delivery vehicle for ADSCs to promote neuronal regeneration after SCI. The dynamic network of CaNeu hydrogel loaded with ADSCs provides a cell-infiltratable matrix that enhances axonal growth and eventually leads to improved motor evoked potential, hindlimb strength, and coordination of complete spinal cord transection in rats. Furthermore, the CaNeu hydrogel also establishes an anti-inflammatory microenvironment by inducing a shift in the polarization of the recruited macrophages toward the pro-regeneration (M2) phenotype. Our study showed that the CaNeu-hydrogel‒mediated ADSCs delivery resulted in significantly suppressed neuroinflammation and apoptosis, and that this phenomenon involved the PI3K/Akt signaling pathway. Our findings indicate that the CaNeu hydrogel is a valuable delivery vehicle to assist stem cell therapy for SCI, providing a promising strategy for central nervous system diseases.
Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischemia
Authors: Freitas Felipe , Attwell David 
Published: September 2021

AbstractAcute kidney injury is common, with ∼13 million cases and 1.7 million deaths/year worldwide. A major cause is renal ischemia, typically following cardiac surgery, renal transplant or severe hemorrhage. We examined the cause of the sustained reduction in renal blood flow (“no-reflow”), which exacerbates kidney injury even after an initial cause of compromised blood supply is removed. After 60 min kidney ischemia and 30-60 min reperfusion, renal blood flow remained reduced, especially in the medulla, and kidney tubule damage was detected as Kim-1 expression. Constriction of the medullary descending vasa recta and cortical peritubular capillaries occurred near pericyte somata, and led to capillary blockages, yet glomerular arterioles and perfusion were unaffected, implying that the long-lasting decrease of renal blood flow contributing to kidney damage was generated by pericytes. Blocking Rho kinase to decrease pericyte contractility from the start of reperfusion increased the post-ischemic diameter of the descending vasa recta capillaries at pericytes, reduced the percentage of capillaries that remained blocked, increased medullary blood flow and reduced kidney injury. Thus, post-ischemic renal no-reflow, contributing to acute kidney injury, reflects pericytes constricting the descending vasa recta and peritubular capillaries. Pericytes are therefore an important therapeutic target for treating acute kidney injury.
Maturyoshka: a maturase inside a maturase, and other peculiarities of the novel chloroplast genomes of marine euglenophytes
Authors: Maciszewski Kacper , Dabbagh Nadja , Preisfeld Angelika , Karnkowska Anna 
Published: September 2021

AbstractOrganellar genomes often carry group II introns, which occasionally encode proteins called maturases that are important for splicing. The number of introns varies substantially among various organellar genomes, and bursts of introns have been observed in multiple eukaryotic lineages, including euglenophytes, with more than 100 introns in their plastid genomes. To examine the evolutionary diversity and history of maturases, an essential gene family among euglenophytes, we searched for their homologs in newly sequenced and published plastid genomes representing all major euglenophytes’ lineages. We found that maturase content in plastid genomes has a patchy distribution, with a maximum of eight of them present in Eutreptiella eupharyngea. The most basal lineages of euglenophytes, Eutreptiales, share the highest number of maturases, but the lowest number of introns. We also identified a peculiar convoluted structure of a gene located in an intron, in a gene within an intron, within yet another gene, present in some Eutreptiales. Further investigation of functional domains of identified maturases shown that most of them lost at least one of the functional domains, which implies that the patchy maturase distribution is due to frequent inactivation and eventual loss over time. Finally, we identified the diversified evolutionary origin of analysed maturases, which were acquired along with the green algal plastid or horizontally transferred. These findings indicate that euglenophytes’ plastid maturases have experienced a surprisingly dynamic history due to gains from diversified donors, their retention, and loss.
Fabrication and delivery of mechano-actived microcapsules containing osteogenic factors in a large animal model of osteochondral injury
Authors: Zlotnick Hannah M. , Locke Ryan C. , Hemdev Sanjana , Stoeckl Brendan D. , Gupta Sachin , Peredo Ana P. , Steinberg David R. , Carey James L. , Lee Daeyeon , Dodge George R. , Mauck Robert L. 
Published: September 2021

AbstractChondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated poly(D,L-lactide-co-glycolide) (PLGA) microcapsules containing the pro-osteogenic agents triiodothyronine and ß-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure. We demonstrate that developed microcapsules rupturedin vitrounder increasing mechanical loads, and readily sink within a liquid solution, allowing for gravity-based positioning onto the osteochondral surface. In a large animal, these mechano-active microcapsules (MAMCs) were assessed through two different delivery strategies. Intra-articular injection of control MAMCs enabled fluorescent quantification of MAMC rupture and cargo release in a synovial joint setting over time in vivo. This joint-wide injection also confirmed that the MAMCs do not elicit an inflammatory response. In the contralateral hindlimbs, chondral defects were created, MAMCs were locally administered, and nanofracture (Nfx), a clinically utilized method to promote cartilage repair, was performed. The NFx holes enabled marrow-derived stromal cells to enter the defect area and served as repeatable bone injury sites to monitor over time. Animals were evaluated 1 and 2 weeks after injection and surgery. Analysis of injected MAMCs showed that bioactive cargo was released in a controlled fashion over 2 weeks. A bone fluorochrome label injected at the time of surgery displayed maintenance of mineral labeling in the therapeutic group, but resorption in both control groups. Alkaline phosphatase (AP) staining at the osteochondral interface revealed higher AP activity in defects treated with therapeutic MAMCs. Overall, this study establishes a new micro-fluidically generated delivery platform that releases therapeutic factors in an articulating joint, and reduces this to practice in the delivery of therapeutics that preserve bone structure after osteochondral injury.
Mammals adjust diel activity across gradients of urbanization
Authors: Gallo Travis , Fidino Mason , Gerber Brian , Ahlers Adam A. , Angstmann Julia L. , Amaya Max , Concilio Amy L. , Drake David , Gray Danielle , Lehrer Elizabeth W. , Murray Maureen H. , Ryan Travis J. , St. Clair Colleen Cassady , Salsbury Carmen M. , Sander Heather A. , Stankowich Theodore , Williamson Jacque , Belaire J. Amy , Simon Kelly , Magle Seth B. 
Published: September 2021

AbstractTime is a fundamental component of ecological processes. How animal behavior changes over time has been explored through well-known ecological theories like niche partitioning and predator-prey dynamics. Yet, changes in animal behavior within the shorter 24-hour light-dark cycle have largely gone unstudied. Understanding if an animal can adjust their temporal activity to mitigate or adapt to environmental change has become a recent topic of discussion and is important for effective wildlife management and conservation. While spatial habitat is a fundamental consideration in wildlife management and conservation, temporal habitat is often ignored. We formulated a temporal resource selection model to quantify the diel behavior of eight mammal species across ten U.S. cities. We found high variability in diel activity patterns within and among species and species-specific correlations between diel activity and human population density, impervious land cover, available greenspace, vegetation cover, and mean daily temperature. We also found that some species may modulate temporal behaviors to manage both natural and anthropogenic risks. Our results highlight the complexity with which temporal activity patterns interact with local environmental characteristics, and suggest that urban mammals may use time along the 24-hour cycle to reduce risk, adapt, and therefore persist in human-dominated ecosystems.
Aging reduces calreticulin expression and alters spontaneous calcium signals in astrocytic endfeet of the mouse dorsolateral striatum
Authors: Zarate Sara M. , Huntington Taylor E. , Bagher Pooneh , Srinivasan Rahul 
Published: September 2021

AbstractAging-related impairment of the blood brain barrier (BBB) and neurovascular unit (NVU) increases risk for neurodegeneration. Among the various cells participating in BBB and NVU function, spontaneous Ca2+ signals in astrocytic endfeet are crucial for maintaining BBB and NVU integrity. To assess if aging is associated with changes in spontaneous Ca2+ signals within astrocytic endfeet of the dorsolateral striatum (DLS), we expressed a genetically encoded Ca2+ indicator, Lck-GCaMP6f in DLS astrocytes of young (3-4 month) and aging (20-24 month) mice. Compared to young mice, endfeet in the DLS of aging mice demonstrated a decrease in calreticulin (CALR) expression, and dramatic alterations in the dynamics of endfoot membrane-associated and mitochondrial Ca2+ signals. While young mice required both extracellular and endoplasmic reticulum (ER) Ca2+ sources for generating endfoot Ca2+ signals, aging mice showed exclusive dependence on ER Ca2+. These data suggest that aging is associated with significant changes in Ca2+ buffers and Ca2+ signals within astrocytic endfeet, which has important implications for understanding mechanisms involved in aging-related impairment of the BBB and NVU.Graphical abstractHighlightsAging mice show reduced calreticulin expression in astrocytic endfeetAging astrocytic endfeet show dramatic changes in spontaneous Ca2+ activityCa2+ signals in aging endfeet depend exclusively on endoplasmic reticulum Ca2+
Hemodynamic evaluation of chemical mediators of sepsis during systemic inflammatory response in an experimental animal model
Authors: Vieira Guilherme de Souza , Antunes Fernanda , Machado Josias Alves , Morales Isabella Cristina , de Jesus Priscilla Olivieri Benck , do Amaral Alexandra de Faria , de Abreu Oliveira André Lacerda 
Published: September 2021

AbstractThe early diagnosis of sepsis increases the chances of its successful treatment. Biomarkers are able to distinguish between systemic inflammatory response syndrome and sepsis and are used to monitor pro- and anti-inflammatory changes associated with the host response to pathogens. A total of 11 rats underwent sepsis induction and measured systolic, diastolic and mean arterial blood pressure. Leukocyte counts, procalcitonin, and nitric oxide also were measured 0, 2, and 4 hours after the induction of sepsis using the cecal ligation and puncture method. The animals were divided into two groups: control (SHAM) and induced. Procalcitonin levels remained within the normal range for an inflammatory response throughout the experiment. There was a statistically insignificant increase in nitric oxide levels. All animals showed increased diastolic arterial blood pressure; however, the increase in the induced animals was even more pronounced. Procalcitonin and nitric oxide levels can increase due to surgical manipulation, while arterial blood pressure was not a good predictor for the onset of sepsis during the time period studied here.
Topological insights into the neural basis of flexible behavior
Authors: Rouse Tevin C. , Ni Amy M. , Huang Chengcheng , Cohen Marlene R. 
Published: September 2021

It is widely accepted that there is an inextricable link between neural computations, biological mechanisms, and behavior, but it is challenging to simultaneously relate all three. Here, we show that topological data analysis (TDA) provides an important bridge between these approaches to studying how brains mediate behavior. We demonstrate that cognitive processes change the topological description of the shared activity of populations of visual neurons. These topological changes constrain and distinguish between competing mechanistic models, are connected to subjects’ performance on a visual change detection task, and, via a link with network control theory, reveal a tradeoff between improving sensitivity to subtle visual stimulus changes and increasing the chance that the subject will stray off task. These connections provide a blueprint for using TDA to uncover the biological and computational mechanisms by which cognition affects behavior in health and disease.Significance StatementAs the fields of systems, computational, and cognitive neuroscience strive to establish links between computations, biology, and behavior, there is an increasing need for an analysis framework to bridge levels of analysis. We demonstrate that topological data analysis (TDA) of the shared activity of populations of neurons provides that link. TDA allows us to distinguish between competing mechanistic models and to answer longstanding questions in cognitive neuroscience, such as why there is a tradeoff between visual sensitivity and staying on task. These results and analysis framework have applications to many systems within neuroscience and beyond.