bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Biotechnology Projects of Different Inquiry Level to Promote Career Success of Non‐Science Majors
Authors: Valverde Paloma
Published: June 2021

Wentworth Institute of Technology is an undergraduate teaching institution that emphasizes experiential learning and career success by implementing Externally‐collaborative, Project‐based, Interdisciplinary Curricula for Learning (EPIC‐L) pedagogy and through inclusion of two required coops in all programs. In this work, an EPIC‐L course named Directed Study in Biological Research is described. This 4‐credit course has been offered since Fall 2012 as part of the biology and bioinformatics minors and is taught entirely at one of the biology labs for a minimum of 6 hours per week. Students were enrolled in first, second or third year of biomedical engineering, civil engineering and computer science programs. Extensive reading assignments prior to class combined with just‐in time informal discussions and assignments were used instead of traditional lectures. Biotechnology laboratory projects involving living organisms (planarian, daphnia, bacteria or eukaryotic cells in culture) or advanced biotechnology instrumentation were proposed by either the professor, the students or external collaborators invited to the lab. The different projects varied in their degree of inquiry and creativity with those of lower inquiry level being used to teach lab skills and provide practice in scientific writing and proper lab documentation whereas those of inquiry level 3 or pure research gave students the opportunity to implement their own ideas and present their work to the rest of the class and at conferences. Students' Learning reflections, written and oral students' work examples and laboratory practicums demonstrate that this pedagogy helps students gain soft and technical skills important for their academic and career success in undergraduate STEM programs.
Respiratory Control in Female Adult Rats
Authors: da Silva Glauber , Marques Danuzia , de Carvalho Débora , Bícego Kênia , Gargaglioni Luciane
Published: June 2021

Sex hormones may influence many physiological processes. It is still unclear whether sex hormones and hormonal fluctuations that occur during the estrous cycle can affect respiratory control. Our study aimed to evaluate the ventilatory responses to hypoxia in female adult rats. To do so, we measured ventilation (VE), tidal volume (VT), respiratory frequency (fR), oxygen consumption (VO2) and body temperature (Tc) of female rats at different stages of estrous cycle (proestrus, estrus, metaestrus and diestrous) and ovariectomized (OVX) female rats during normoxia (21%O2) and hypoxia (7% O2). VE, VT, fR, VO2 and VE/VO2 were not different among animals in different stages of the estrous cycle in normoxia and hypoxia. However, Tc was higher in female rats in estrus. Hormone replacement in females did not change the ventilatory and metabolic parameters. However, females OVX, OVX + E2 and OVX + EP showed a lower ventilatory response to hypoxia compared with intact females in estrus. Thus, our data suggest that the different phases of the estrous cycle did not alter ventilation in normoxia and hypoxia. OVX animals presented an attenuated response to hypoxia. Hormone replacement with E2 or P4 did not cause significant difference in hypoxic ventilatory response. Our data suggest that other gonadal factors might be involved in the process. Financial Support: FAPESP
Online Homework with Targeted Instructional Feedback Leads to Improved Student Learning Outcomes
Authors: Robus Hannah
Published: June 2021

A significant disadvantage of out‐of‐classroom assignments is the lack of feedback available to students as they work through activities. Consequently, instructors have become increasingly interested in online homework systems that provide this advantage. While many homework systems offer similar features, such as immediate feedback, online grading, and student statistics, few offer targeted instructional feedback that is proven to help students succeed in the classroom. Several peer reviewed efficacy studies have investigated the benefits of using Sapling Learning, an online homework system that offers unique “surrogate tutoring” feedback. When students were asked “Would you like to use online homework again?”, over 90% of those who had used Sapling Learning responded favorably. In addition to being a tool students desire using, the ratio of successful to unsuccessful grades increased significantly when Sapling Learning was utilized. Engagement in Sapling Learning activities was also positively correlated with students' overall grade. This poster will further explore studies that investigate the benefits of using an online homework system with a surrogate tutoring style of feedback.
Genetic Modification of Porcine Endogenous Retrovirus (PERV) Sequences in Cultured Pig Cells as a Model for Decreasing Infectious Risk in Xenotransplantation
Authors: Dunn David , DaCosta Mary , Harris Mikaela , Idriss Ridaa , O'Brien Ashley
Published: June 2021

Xenotransplantation of porcine (pig) organs into human patients has been proposed as a solution to the shortage of transplantable organs in human medicine. A potential safety barrier to clinical implementation of xenotransplantation is the infectious risk associated with expression of endogenous retroviral sequences in the porcine genome. Notably, Porcine Endogenous Retroviruses (PERVs) have been shown capable of infecting human cells in culture. The ability to specifically modify genomic loci in a wide range of in vitro and in vivo models has recently become widely accessible due to development of synthetic engineered nuclease technologies. Among them, Tal Effector Nucleases (TALENs) can be designed to recognize and catalyze double stranded DNA breaks (DSBs) in investigator‐specified genomic loci. These DSBs, when resolved by endogenous DNA repair mechanisms, commonly leave mutagenic insertions or deletions (indels) in target loci. This pilot study addresses the possibility of genetically modifying the porcine genome to specifically ablate PERV sequences via Tal Effector Nuclease (TALEN) genome editing techniques. TALEN sequences were designed and constructed against PERV pol and gag genes and were transfected into porcine PK(15) cells. Targeted pol and gag loci in PK(15) cells displayed TALEN‐induced genetic modification. These results suggest the potential utility of genome engineering strategies in ablating PERV gene expression in porcine xenotransplantation.
Phylogenetic Analysis of Wolbachia from Folsomia Candida (Collembola: Isotomidae) via Sequences from WspB and Ribosomal Protein Genes
Authors: Li Yang , Fallon Ann
Published: June 2021

Folsomia candida (Collembola: Isotomidae), a springtail that occurs commonly in soils throughout the world, is widely used in soil pollution and ecotoxicological studies. F. candida typically reproduces by parthenogenesis, which is widely believed to result from Wolbachia infection. Wolbachia is a cytoplasmically transmitted alpha‐proteobacterium that induces diverse reproductive alterations in its invertebrate hosts. Wolbachia is currently divided into six supergroups (A to F). Wolbachia from F. candida (wCan) is defined as a member of supergroup E based on sequences of 16S rDNA and ftsZ genes. Unexpectedly, however, no additional gene sequences have been described since wCan was first discovered in 1999. We have observed that recovery of undegraded DNA from springtails can be difficult. The objective of this study is to obtain additional gene sequences for wCan phylogenetic studies. We optimized recovery of DNA by lysing springtail eggs in the presence of 20mM EDTA, followed by extraction of undegraded DNA from agarose gels after electrophesis. Characterization of a nuclease that co‐purifies with springtail DNA is in progress. We used purified genomic DNA as template to amplify Wolbachia surface protein B (wspB) gene and five ribosomal protein genes by polymerase chain reaction (PCR). A concatenated phylogenetic tree based on these six gene sequences from wCan, together with corresponding sequences from nine additional Wolbachia strains, shows a closer relationship with supergroup B relative to supergroup A. Our study expands the DNA sequencing information of wCan and sheds light on its phylogeny.
Medical Device-Related Pressure Injury to the Ear from a Mask
Authors: Levine Jeffrey M. , Ayello Elizabeth A. , Persaud Balwant , Spinner Ruth
Published: June 2021

Mask wearing is now ubiquitous because of the COVID-19 pandemic and has given rise to medical device-related pressure injuries in persons at risk of skin breakdown. The ear has unique anatomy that is particularly susceptible to injury from pressure. In this time of mandatory personal protective equipment requirements in healthcare facilities, protection and assessment of skin in the vulnerable postauricular area are needed. This article presents a case report of a pressure injury on the ear, reviews the anatomy of the ear, and provides strategies for assessment and treatment of pressure injuries in this often overlooked anatomic region.
Hemodynamic Patterns Before Inhospital Cardiac Arrest in Critically Ill Children: An Exploratory Study
Authors: Erez Ely , Mazwi Mjaye L. , Marquez Alexandra M. , Moga Michael-Alice , Eytan Danny
Published: June 2021

OBJECTIVES:

To characterize prearrest hemodynamic trajectories of children suffering inhospital cardiac arrest.

DESIGN:

Exploratory retrospective analysis of arterial blood pressure and electrocardiogram waveforms.

SETTING:

PICU and cardiac critical care unit in a tertiary-care children’s hospital.

PATIENTS:

Twenty-seven children with invasive blood pressure monitoring who suffered a total of 31 inhospital cardiac arrest events between June 2017 and June 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We assessed changes in cardiac output, systemic vascular resistance, stroke volume, and heart rate derived from arterial blood pressure waveforms using three previously described estimation methods. We observed substantial prearrest drops in cardiac output (population median declines of 65–84% depending on estimation method) in all patients in the 10 minutes preceding inhospital cardiac arrest. Most patients’ mean arterial blood pressure also decreased, but this was not universal. We identified three hemodynamic patterns preceding inhospital cardiac arrest: subacute pulseless arrest (n = 18), acute pulseless arrest (n = 7), and bradycardic arrest (n = 6). Acute pulseless arrest events decompensated within seconds, whereas bradycardic and subacute pulseless arrest events deteriorated over several minutes. In the subacute and acute pulseless arrest groups, decreases in cardiac output were primarily due to declines in stroke volume, whereas in the bradycardic group, the decreases were primarily due to declines in heart rate.

CONCLUSIONS:

Critically ill children exhibit distinct physiologic behaviors prior to inhospital cardiac arrest. All events showed substantial declines in cardiac output shortly before inhospital cardiac arrest. We describe three distinct prearrest patterns with varying rates of decline and varying contributions of heart rate and stroke volume changes to the fall in cardiac output. Our findings suggest that monitoring changes in arterial blood pressure waveform-derived heart rate, pulse pressure, cardiac output, and systemic vascular resistance estimates could improve early detection of inhospital cardiac arrest by up to several minutes. Further study is necessary to verify the patterns witnessed in our cohort as a step toward patient rather than provider-centered definitions of inhospital cardiac arrest.
Lactobacillus Endocarditis Complicated by Presumed Vertebral Osteomyelitis and Embolic Stroke
Authors: Argotsinger Jill , Beganovic Maya , Taha Rami , Anderson Morgan
Published: June 2021

Lactobacillus species is a facultative anaerobic gram-positive bacillus that is part of the normal flora and is rarely considered pathogenic. In fact, frequently it is used therapeutically as a probiotic. Although normally considered benign, Lactobacillus has been reported to cause bacteremia with and without endocarditis, vertebral osteomyelitis, abscesses, meningitis, peritonitis, and pneumonia. Recommended treatment of choice based on expert opinion for severe infections due to Lactobacillus species endocarditis is high-dose penicillin in combination with an aminoglycoside. In this report, we describe a case in which a 47-year old man with no past medical history develops native aortic valve endocarditis complicated by embolic stroke and presumed lumbar vertebral osteomyelitis.
Salmonella Aortitis Related to Rheumatoid Arthritis
Authors: Mansoor Armaghan-e-Rehman , Ladani Amit
Published: June 2021

A 65-year-old woman with a history of rheumatoid arthritis on immunosuppression with methotrexate and etanercept presented with abdominal pain, fever, and diarrhea. Symptoms initially improved with a short course of oral ciprofloxacin but soon recurred. Computed tomography imaging of the abdomen was concerning for intramural abscess, aortitis, and a 3.8-cm aneurysm. She was initiated on broad-spectrum antibiotics and underwent emergent endovascular repair and graft. Blood and intraoperative cultures remained negative. After completing 6 weeks of broad-spectrum antibiotics, she had recurrence of symptoms, with blood cultures showing Salmonella species, requiring explant of hardware and a surgical bypass. She had several subsequent morbidities, including iatrogenic chylous leak, and Clostridium difficile colitis, and ultimately died.

A high degree of suspicion is needed for a timely diagnosis of infectious aortitis in patients with compatible findings. Despite optimal therapy, infectious aortitis continues to have significant morbidity and mortality.
Comparison Between Short Text Messages and Phone Calls to Reduce No-Show Rates in Outpatient Medical Appointments
Authors: Lance Rogério Cortecioni , Pazin-Filho Antônio , Neves Fábio Fernandes
Published: June 2021

The objective of this study was to evaluate the impact of telephone calls and short text messages (SMS) on no-show rates regarding scheduled appointments with a general practitioner. In a prospective, intervention-controlled, and randomized study, we divided 306 patients into 3 groups: telephone call, SMS, and no intervention. We compared no-show rates, as well as variables that influenced it. The lowest percentage of no-show (9.5%) occurred in the telephone call group, while the SMS group presented at 21% and the no-intervention group at 22.8% (P = .025). Telephone calls proved to be a superior strategy to text messaging.
Matched Cohort Analysis of the Effect of the Facial Recess Approach on Cerebrospinal Fluid Leak After Translabyrinthine Surgery for Schwannoma
Authors: Christopher Laura , Slattery William , Lekovic Gregory P. , Mehta Gautam U. , Miller Mia
Published: June 2021

Objective:

The facial recess approach during translabyrinthine surgery has been used to expose the eustachian tube (ET) for packing. We sought to determine the effect of this technique on the development of postoperative nasopharyngeal cerebrospinal fluid (CSF) leaks.

Patients:

Cohorts of patients with cerebellopontine angle schwannomas who underwent a facial recess approach or no facial recess approach were matched based on tumor size.

Interventions:

Translabyrinthine surgery for tumor resection.

Main Outcome Measures:

Postoperative CSF leaks were recorded and nasopharyngeal CSF leaks were utilized as the primary outcome measure.

Results:

Using an exact matching protocol based on tumor size, 102 patients were included in each group (204 total, 111 female, 93 male). Overall, 9 patients (4.4%) demonstrated a postoperative nasopharyngeal CSF leak. Postoperative CSF rhinorrhea was noted in 3.9% of the group who underwent a facial recess approach for packing of the ET and 4.9% of the group who did not undergo a facial recess approach. This rate was not significantly different between groups (p = 0.99, Odds ratio: 0.79, 95% CI: 0.15–3.8). Secondary variables including age, tumor size, a diagnosis of NF2, and the packing material used were not significant predictors of nasopharyngeal CSF leaks.

Conclusions:

CSF rhinorrhea is infrequent after translabyrinthine surgery. The incidence of this complication is not affected by whether or not a facial recess approach is performed during surgery to pack the ET. Based on these data, use of this technique should be based on surgeon comfort and preference.
Intensive Bimanual Intervention for Children Who Have Undergone Hemispherectomy: A Pilot Study
Authors: Robert Maxime T. , Ferre Claudio L. , Chin Karen Y. , Brandao Marina B. , Carmel Jason , Araneda Rodrigo , Bleyenheuft Yannick , Friel Kathleen , Gordon Andrew M.
Published: June 2021

Purpose:

To conduct a pilot study to assess the feasibility and effectiveness of an intensive bimanual intervention on upper limb function in children who have undergone hemispherectomy.

Methods:

Thirteen children received 90 hours of intensive bimanual training (Hand-Arm Bimanual Intensive Therapy, HABIT). The Jebsen-Taylor Test of Hand Function (JTTHF), Box and Block Test (BBT), Assisting Hand Assessment (AHA), ABILHAND-Kids, and Canadian Occupational Performance Measure (COPM) were assessed by a masked clinician twice before, immediately, and 6 months after treatment.

Results:

Significant improvements over time were found in the JTTHF, AHA, ABILHAND-Kids, and COPM.

Conclusion:

Completion of HABIT was feasible for children with hemispherectomy. Improvement of bimanual function and functional goals can be related to the nature of the activities prioritized in HABIT training.
Bicycling and Tricycling Road Race Performance in International Para-Cycling Events Between 2011 and 2019
Authors: Borg David N. , Osborne John O. , Tweedy Sean M. , Liljedahl Johanna B. , Nooijen Carla F. J.
Published: June 2021

This study described bicycling (C classes) and tricycling (T classes) performance in the International Cycling Federation road race events between 2011 and 2019. A total of 3243 race results from 33 events were analyzed. Race velocity was calculated for each result. Bicycling and tricycling data were separately modeled using a linear mixed-effects model. Bicycling velocity was statistically different between all adjacent men’s classes (Cohen d = 0.14–0.73) and between the women’s C1 and C2 (d = 1.15) and C3 and C4 (d = 0.48) classes. The absence of statistical differences between some women’s bicycling classes may be due to a limited number of observations in these classifications. As expected, velocity was statistically different between men’s (d = 1.64) and women’s (d = 1.38) T1 and T2 classes. Road race performance was hierarchical within the disciplines of bicycling and tricycling, although not all adjacent women’s bicycling classes were statistically different. The existence of a performance hierarchy does not necessarily validate the classification system. The integration of information regarding athlete impairment type and severity, with performance data, would provide greater insight into the validity of the classification system and should be prioritized as an area of future research.
Improving the Delivery of High-Quality Cancer Care in Medically Underserved Communities: A Formative Evaluation Method
Authors: Quinn Doris , Jacobson Joseph O. , Wong Sandra L. , Wollins Dana , Gilmore Terry , Cunningham Gene
Published: June 2021

Background and Objectives:

In 2015, the American Society of Clinical Oncology launched a new program: Improving Quality of Care in Underserved Communities with the overarching aim of serving patients with cancer who have traditionally had difficulty accessing the care they need. Cancer care requires intense coordination of complex services to provide safe, effective, timely, and equitable care. If chemotherapy and/or radiation is needed, patients must navigate a complex system of care many times, a formidable challenge for many disadvantaged patients. Many practices believe that these patients face such significant issues that it is almost impossible to provide high-quality care. A grant from the Stavros Niarchos Foundation allowed us to select 4 oncology practices serving high proportions of racial minorities and persons of low socioeconomic status to participate in the new American Society of Clinical Oncology program. The program had 2 objectives: (1) to improve the capacity and capability of the participating practices to provide evidence-based, high-quality care; and (2) to identify and disseminate lessons learned for improving quality of care among oncology practices serving underserved patients.

Methods:

The program leveraged existing programs including the Quality Oncology Practice Initiative, which is a national performance measurement and improvement program that collects data about processes of care provided in the outpatient medical oncology setting, and the American Society of Clinical Oncology Quality Training Program, which provides training in how to apply the tools and methods of quality improvement in routine care settings. Training was provided in face-to-face and virtual meetings and participants were provided mentors throughout the program. At the conclusion, a formative evaluation method was used to assess whether the goals had been achieved. Objectives, activities, and desired outcomes were identified for each of the goals and thus became the framework for the evaluation.

Results:

The program met the stated goals and objectives. The evaluation revealed many successes, some surprises, and a list of improvements that were incorporated in the next iteration of this program. Based on data from the evaluation, the Niarchos Foundation provided funds for an additional 10 practices to participate in a similar program in 2020.

Conclusion:

This article outlines the evaluation of a new program demonstrating that medical oncology practices can make improvements in the care of their underserved populations if provided with the proper tools, methods, and coaching. The use of formative evaluation methodology also identified opportunities for improvement and ultimately resulted in additional funding for more practices to participate in the program.
Shining new light on sensory brain activation and physiological measurement in seals using wearable optical technology
Authors: McKnight J. Chris , Ruesch Alexander , Bennett Kimberley , Bronkhorst Mathijs , Balfour Steve , Moss Simon E. W. , Milne Ryan , Tyack Peter L. , Kainerstorfer Jana M. , Hastie Gordon D.
Published: June 2021

Sensory ecology and physiology of free-ranging animals is challenging to study but underpins our understanding of decision-making in the wild. Existing non-invasive human biomedical technology offers tools that could be harnessed to address these challenges. Functional near-infrared spectroscopy (fNIRS), a wearable, non-invasive biomedical imaging technique measures oxy- and deoxyhaemoglobin concentration changes that can be used to detect localized neural activation in the brain. We tested the efficacy of fNIRS to detect cortical activation in grey seals (Halichoerus grypus) and identify regions of the cortex associated with different senses (vision, hearing and touch). The activation of specific cerebral areas in seals was detected by fNIRS in responses to light (vision), sound (hearing) and whisker stimulation (touch). Physiological parameters, including heart and breathing rate, were also extracted from the fNIRS signal, which allowed neural and physiological responses to be monitored simultaneously. This is, to our knowledge, the first time fNIRS has been used to detect cortical activation in a non-domesticated or laboratory animal. Because fNIRS is non-invasive and wearable, this study demonstrates its potential as a tool to quantitatively investigate sensory perception and brain function while simultaneously recording heart rate, tissue and arterial oxygen saturation of haemoglobin, perfusion changes and breathing rate in free-ranging animals.

This article is part of the theme issue ‘Measuring physiology in free-living animals (Part I)’.
Deaths involving COVID-19 by disability status: a retrospective analysis of 29 million adults during the first two waves of the Coronavirus pandemic in England
Authors: Bosworth Matthew L. , Ayoubkhani Daniel , Nafilyan Vahé , Foubert Josephine , Glickman Myer , Davey Calum , Kuper Hannah
Published: June 2021

Objectives

To assess the association between self-reported disability and deaths involving COVID-19 among adults in England.

Design

Cohort study of >29 million adults using data from the Office for National Statistics Public Health Data Asset.

Setting

People living in private households or communal establishments (including care homes) in England.

Participants

29,293,845 adults (47% male) aged 30-100 years (mean age = 56) present at the 2011 Census who were alive on 24 January 2020. The main exposure was self-reported disability from the 2011 Census.

Main outcome measures

Death involving COVID-19, occurring between 24 January 2020 and 28 February 2021. We estimated the age-standardised mortality rate per 100,000 person-years at-risk, stratified by sex, disability status, and wave of the pandemic. We calculated hazard ratios (HRs) for disabled people compared with non-disabled people, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions.

Results

Disabled people made up 17% of the study population, including 7% who were ‘more-disabled’ and 10% ‘less-disabled’. From 24 January 2020 to 28 February 2021, 105,213 people died from causes involving COVID-19 in England, 58% of whom were disabled. Age-adjusted analyses showed that, compared to non-disabled people, mortality involving COVID-19 was higher among both more-disabled people (HR=3.05, 95% CI: 2.98 to 3.11 in males; 3.48, 3.41 to 3.56 in females) and less-disabled people (HR=1.88, 95% CI: 1.84 to 1.92 in males; 2.03, 1.98 to 2.08 in females). Among people aged 30-69, HRs reached 8.47 (8.01 to 8.95) among more-disabled females and 5.42 (5.18 to 5.68) for more-disabled males. Sequential adjustment for residence type, geography, socio-demographics, and health conditions partly explained the associations, indicating that a combination of these factors contributed towards the increased risk.

Conclusion

Disabled people in England had markedly increased risk of mortality involving COVID-19 compared to non-disabled people and should be prioritised within the pandemic response.
FiberSim: a flexible open-source model of myofilament-level contraction
Authors: Kosta S. , Colli D. , Ye Q. , Campbell K. S.
Published: June 2021

FiberSim is a flexible open-source model of myofilament-level contraction. The code uses a spatially explicit technique, meaning that it tracks the position and status of each contractile molecule within the lattice framework. This allows the model to simulate some of the mechanical effects modulated by myosin binding protein-C, as well as dose-dependence of myotropes and the effects of varying isoform expression levels. This paper provides a short introduction to FiberSim and presents simulations of tension-pCa curves with and without regulation of thick filament transitions by myosin-binding protein C. The software was designed to be flexible (the user can define their own model and/or protocol) and computationally efficient (simulations can be performed on a regular laptop). We hope that other investigators will use FiberSim to explore myofilament level mechanisms and to accelerate research focusing on the contractile properties of sarcomeres.

Statement of significance

Myotropes, such as omecamtiv mecarbil and mavacamten, are new therapeutics that bind directly to sarcomeric proteins. Their clinical development has reenergized interest in mechanistic understanding of sarcomere level function. FiberSim is an open-source spatially-explicit computer model that simulates myofilament level mechanics and can predict how modulating the function of a sarcomeric protein will impact contractility. The software was specifically designed to be flexible and user-friendly and may help to further accelerate myofilament-research.
Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies
Authors: Haider Madiha , Anand Vivek , Dholakia Dhwani , Enayathullah M. Ghalib , Parekh Yash , Ram Sushma , Kumari Surekha , Anmol  , Bokara Kiran Kumar , Sharma Upendra , Prasher Bhavana , Mukerji Mitali
Published: June 2021

Background

Viral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present.

Purpose

Herbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach.

Methods

We analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed.

Results

Several predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa.
Plant biomechanics and resilience to environmental changes are controlled by specific lignin chemistries in each vascular cell type and morphotype
Authors: Ménard Delphine , Blaschek Leonard , Kriechbaum Konstantin , Lee Cheng Choo , Serk Henrik , Zhu Chuantao , Lyubartsev Alexander , Nuoendagula  , Bacsik Zoltán , Bergström Lennart , Mathew Aji , Kajita Shinya , Pesquet Edouard
Published: June 2021

The biopolymer lignin, deposited in the cell walls of vascular cells, is essential for long-distance water conduction and structural support of plants. Independently of the species, each different vascular cell type contains a conserved lignin chemistry with specific aromatic and aliphatic substitutions. Yet, the biological role of this conserved and specific lignin chemistry for each cell type remained unclear. Herein, we investigate the role of specific lignin chemistries for cellular function by producing single cell analyses on vascular cell morphotypes, all enabling sap conduction but differing in morphology. We found that specific lignin chemistries accumulate in each morphotype. Moreover, lignin accumulates dynamically, increasing in quantity and changing composition, to alter the cell wall biomechanics of each morphotype during their maturation. For similar aromatic substitution, residues with alcohol aliphatic functions increased stiffness whereas aldehydes increased flexibility. Modifying this specific lignin chemistry impairs the cell wall biomechanics of each morphotype and consequently reduces their capacity to optimally conduct water in normal conditions, and to recover from drought. Altogether, lignin chemistry is differently controlled for each sap conducting cell types during their maturation to dynamically adjust their biomechanics and hydraulic properties to adapt to developmental and environmental constraints.
The extra-embryonic space is a geometric constraint regulating cell arrangement in nematodes
Authors: Seirin-Lee Sungrim , Kimura Akatsuki
Published: June 2021

In multicellular systems, cells communicate with adjacent cells to decide their positions and fates. Cellular arrangement in space is thus important for development. Orientation of cell division, cell-cell interaction (i.e., attraction and repulsion), and geometrical constraints are the three major factors that define cell arrangement. Here we found that the amount and location of extra-embryonic space (ES), the empty space within the eggshell not occupied by embryonic cells, are critical to define cell arrangement in the 4-cell stage embryo of nematodes. This discovery was motivated by observations of a T-reversed-type arrangement, which was not explained by a model assuming simplified shapes of the eggshell, in our previous experiments. In this study, we incorporated the precise shape of the C. elegans eggshell in our newly developed multicellular morphology model based on the phase-field method. The new model succeeded in reproducing the T-reverse arrangement, demonstrating the importance of the precise shape of the eggshell. Further analyses revealed that the amount and location of ES is critical to develop various cell arrangements. Overall, our analyses characterized the roles of new geometrical contributors to cell arrangements, which should be considered for any multicellular system.
Pharmacologic and genetic inhibition of cholesterol esterification reduces tumour burden: a pan-cancer systematic review and meta-analysis of preclinical models
Authors: Websdale Alex , Kiew Yi , Chalmers Philip , Chen Xinyu , Cioccoloni Giorgia , Hughes Thomas A , Luo Xinyu , Mwarzi Rufaro , Poirot Marc , Røberg-Larsen Hanne , Wu Ruoying , Xu Mengfan , Zulyniak Michael A. , Thorne James L
Published: June 2021

Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, and Web of Science for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p<0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p≤0.002). SOAT inhibition increased tumour apoptosis (p=0.007), CD8+ lymphocyte infiltration and cytotoxicity (p≤0.05), and reduced proliferation (p=0.0003) and metastasis (p<0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size was overestimated. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.
Multimodal Single-Cell Characterization of the Human Granulocyte Lineage
Authors: Qi Jingjing , D’Souza Darwin , Dawson Travis , Geanon Daniel , Stefanos Hiyab , Marvin Robert , Walker Laura , Rahman Adeeb H.
Published: June 2021

High throughput single cell transcriptomics (scRNA-seq) has been successfully applied to characterize immune cell heterogeneity across a diverse range of settings; however, analysis of human granulocytes remains a significant challenge due to their low gene expression transcript detection. Consequently, granulocytes are typically either absent or highly under-represented and inaccurately enumerated in most human scRNA-seq datasets. Here, we apply multi-modal CITE-seq profiling to characterize granulocytes in human whole blood and bone marrow, and we show that these populations can be accurately detected and analyzed using the antibody-based modality, and that their frequencies and phenotype align well with antibody-based characterization of the same samples using CyTOF. These analyses also clearly highlight extremely low gene transcript detection across the entire granulocyte lineage including the earliest neutrophil progenitor populations when using the 10X Genomics platform. By contrast, when performing parallel analyses of the same samples using the BD Rhapsody platform, we recovered a much higher proportion of granulocyte gene transcripts, enabling true multi-modal characterization of human granulocyte heterogeneity.
Single-nucleus transcriptomes reveal functional and evolutionary properties of cell types in the Drosophila accessory gland
Authors: Majane Alex C. , Cridland Julie M. , Begun David J.
Published: June 2021

Many traits responsible for male reproduction evolve quickly, including gene expression phenotypes in germline and somatic male reproductive tissues. Rapid male evolution in polyandrous species is thought to be driven by competition among males for fertilizations and conflicts between male and female fitness interests that manifest in post-copulatory phenotypes. In Drosophila, seminal fluid proteins secreted by three major cell types of the male accessory gland and ejaculatory duct are required for female sperm storage and use, and influence female post-copulatory traits. Recent work has shown that these cell types have overlapping but distinct effects on female post-copulatory biology, yet relatively little is known about their evolutionary properties. Here we use single-nucleus RNA-Seq of the accessory gland and ejaculatory duct from Drosophila melanogaster and two closely related species to comprehensively describe the cell diversity of these tissues and their transcriptome evolution for the first time. We find that seminal fluid transcripts are strongly partitioned across the major cell types, and expression of many other genes additionally define each cell type. We also report previously undocumented diversity in main cells. Transcriptome divergence was found to be heterogeneous across cell types and lineages, revealing a complex evolutionary process. Furthermore, protein adaptation varied across cell types, with potential consequences for our understanding of selection on male post-copulatory traits.

SIGNIFICANCE STATEMENT

Rapid evolution of male traits may result from competition among males or antagonistic interactions between the sexes over control of reproduction. In animals with internal fertilization, interactions may occur in the female reproductive tract. Drosophila seminal fluid proteins, which are secreted by three major cell types of the male accessory gland and ejaculatory duct, are required for female sperm storage and use, and influence female behavior and physiology. These cell types have distinct effects on females, yet relatively little is known about their evolutionary properties. Here we characterize diversity and transcriptome evolution of seminal fluid-producing tissues at the cell level. These data reveal new functional properties of these cells and complex evolutionary patterns that vary across cell types and lineages.
A PMMA bone cement composite that functions as a drug-refillable depot for localized, multi-window chemotherapeutic treatment of bone cancer
Authors: Cyphert Erika L. , Kanagasegar Nithya , Zhang Ningjing , Learn Greg D. , von Recum Horst A.
Published: June 2021

Standard chemotherapy for primary and secondary bone tumors typically involves systemic administration of chemotherapeutic drugs, such as doxorubicin (DOX). However, non-targeted delivery increases dose requirements, and results in off-target toxicity and suboptimal chemotherapeutic efficacy. When chemotherapy is ineffective, substantial resection of tissue and/or total amputation become necessary – a debilitating outcome for any patient. In this work, we developed a proof-of-concept, non-biodegradable, mechanically robust, and refillable composite system for chemotherapeutic (i.e. DOX) delivery comprised of poly(methyl methacrylate) (PMMA) bone cement and insoluble polymeric γ-cyclodextrin (γ-CD) microparticles. The porosity and compressive strength of DOX-filled PMMA composites were characterized. DOX filling capacity, elution kinetics, cytotoxicity against primary osteosarcoma and lung cancer cells, and refilling capacity of composites were evaluated. PMMA composites containing up to 15wt% γ-CD microparticles provided consistent, therapeutically-relevant release of DOX with ~100% of the initial DOX released after 100 days. Over the same period, only ~6% of DOX was liberated from PMMA with free DOX. Following prolonged curing, PMMA composites with up to 15wt% γ-CD surpassed compressive strength requirements outlined by international standards for acrylic bone cements. Compared to DOX-filled PMMA, DOX-filled PMMA/γ-CD composites provided long-term release with decreased burst effect, correlating to long-term cytotoxicity against cancer cells. Refillable properties demonstrated by the PMMA composite system may find utility for treating local recurrences, limiting chemoresistance, and altering drug combinations to provide customized treatment regimens. Overall, findings suggest that PMMA composites have the potential to serve as a platform for the delivery of combinatorial chemotherapeutics to treat bone tumors.
Horizontal transfer and subsequent explosive expansion of a DNA transposon in sea kraits (Laticauda)
Authors: Galbraith James D. , Ludington Alastair J. , Sanders Kate L. , Suh Alexander , Adelson David L.
Published: June 2021

Transposable elements (TEs) are self replicating genetic sequences and are often described as important “drivers of evolution”. This driving force is because TEs promote genomic novelty by enabling rearrangement, and through exaptation as coding and regulatory elements. However, most TE insertions will be neutral or harmful, therefore host genomes have evolved machinery to supress TE expansion. Through horizontal transposon transfer (HTT) TEs can colonise new genomes, and since new hosts may not be able to shut them down, these TEs may proliferate rapidly. Here we describe HTT of the Harbinger-Snek DNA transposon into sea kraits (Laticauda), and its subsequent explosive expansion within Laticauda genomes. This HTT occurred following the divergence of Laticauda from terrestrial Australian elapids ~15-25 Mya. This has resulted in numerous insertions into introns and regulatory regions, with some insertions into exons which appear to have altered UTRs or added sequence to coding exons. Harbinger-Snek has rapidly expanded to make up 8-12% of Laticauda spp. genomes; this is the fastest known expansion of TEs in amniotes following HTT. Genomic changes caused by this rapid expansion may have contributed to adaptation to the amphibious-marine habitat.
Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53
Authors: Segeren Hendrika A. , van Liere Elsbeth A. , Riemers Frank M. , de Bruin Alain , Westendorp Bart
Published: June 2021

Cancer cells often experience high basal levels of DNA replication stress (RS), for example due to hyperactivation of oncoproteins like MYC or RAS. Therefore, cancer cells are considered to be sensitive to drugs that exacerbate the level of RS or block the intra S-phase checkpoint. Consequently, RS-inducing drugs including ATR and CHK1 inhibitors are used or evaluated as anti-cancer therapies. However, drug resistance and lack of biomarkers predicting therapeutic efficacy limit efficient use. This raises the question what determines sensitivity of individual cancer cells to RS. Here, we report that oncogenic RAS does not only enhance the sensitivity to ATR/CHK1 inhibitors by directly causing RS. Instead, we observed that HRASG12V dampens the activation of the P53-dependent transcriptional response to drug-induced RS, which in turn confers sensitivity to RS. We demonstrate that inducible expression of HRASG12V sensitized retina pigment epithelial (RPE-hTERT) as well as osteosarcoma (U2OS) cells to ATR and CHK1 inhibitors. Using RNA-sequencing of FACS-sorted cells we discovered that P53 signaling is the sole transcriptional response to RS. However, oncogenic RAS attenuates the transcription of P53 and its target genes. Accordingly, live cell imaging showed that HRASG12V exacerbates RS in S/G2-phase, which could be rescued by stabilization of P53. Thus, our results demonstrate that transcriptional control of P53 is a prime determinant in the response to ATR/CHK1 inhibitors and show that hyperactivation of the MAPK pathway impedes this response. Our findings suggest that the level of oncogenic MAPK signaling could predict sensitivity to intra-S-phase inhibition in cancers with intact P53.
Bottom-up but not Top-down Attention Dominates the Value Representation in the Orbitofrontal Cortex
Authors: Zhang Wenyi , Xie Yang , Yang Tianming
Published: June 2021

The orbitofrontal cortex (OFC) is essential for value-based learning and decision making. Understanding the attentional modulation of the representation of value in the OFC provides us key information on its functional roles and links the OFC to other cognitive processes. We examined how top-down and bottom-up attention modulates the value encoding in the OFC. Two macaque monkeys were trained to detect a luminance change at a cued location between a pair of visual stimuli, which were over-trained pictures associated with different amount of juice rewards and, thus, different salience. While the monkeys’ behavior and the DLPFC neuronal activities indicated that the monkeys actively directed their attention toward the cued location during the task, the OFC neurons’ value encoding, however, was dominated by the bottom-up attention based on stimulus salience and only reflected the top-down attention weakly. The disassociation between the top-down and bottom-up attention signals in the OFC indicates that the OFC occupies an early stage of value information processing in the brain.