bluuebunny/crossref_metadata_2025 huggingface dataset:
What Makes Content Engaging? How Emotional Dynamics Shape Success
Authors: Berger Jonah , Kim Yoon Duk , Meyer Robert
Published: February 2021

Some cultural products (e.g., books and movies) catch on and become popular, while others fail. Why? While some have argued that success is unpredictable, we suggest that period-to-period shifts in sentiment—what we term sentiment volatility—enhance engagement. Automated sentiment analysis of over 4,000 movies demonstrates that more volatile movies are evaluated more positively. Consistent with the notion that sentiment volatility makes experiences more stimulating, the effect is stronger in genres where evaluations are more likely to be driven stimulation (i.e., thrillers rather than romance). Further, analysis of over 30,000 online articles demonstrate that people are more likely to continue reading more volatile articles. By manipulating sentiment volatility in follow-up experiments, we underscore its causal impact on evaluations, and provide evidence for the role of stimulation in these effects. Taken together, the results shed light on what drives engagement, the time dynamics of sentiment, and cultural analytics or why some cultural items are more successful.
How and Why Our Eating Decisions Neglect Infrequently Consumed Foods
Authors: Sussman Abigail B , Paley Anna , Alter Adam L
Published: February 2021

This article introduces a novel distinction between foods as a function of the frequency with which consumers eat them, and investigates how this distinction influences dietary beliefs and decisions. It compares food types perceived to be consumed relatively infrequently (i.e., infrequent foods) to those perceived to be consumed relatively frequently (i.e., frequent foods). Across an analysis of archival data from a popular calorie tracking app and five experiments examining hypothetical consumption decisions, findings support the conclusion that infrequent foods provide unique challenges for consumers. All else equal, consumers select larger portions of infrequent (vs. frequent) foods. Further, consumers are less likely to compensate (i.e., eat less) after consuming equal amounts of infrequent versus frequent foods. This pattern of results arises because consumers erroneously believe that infrequent foods have a smaller impact on their weight than frequent foods do, even in the presence of caloric information. Optimistically, participants can be taught to overcome this bias through a brief informational intervention.
Tattoo Trouble: A Case of Drug-induced Thrombocytopenic Purpura
Authors: Jahncke Alexander , Kay Victoria , Fiore Benjamin
Published: February 2021

Trimethoprim–sulfamethoxazole, otherwise known as Bactrim or Septra, is a commonly prescribed antibiotic for soft tissue infections. Drug-induced thrombocytopenia is a rare but serious adverse reaction to sulfonamide antibiotics like Bactrim/Septra. A 34-year-old active duty marine male with no significant past medical history presented with a chief complaint of a rash on his lower extremities. The patient stated that 2 weeks earlier, he was prescribed Bactrim for cellulitis at the site of a new tattoo. The intern noted a petechial rash that was pathognomonic for thrombocytopenia. Laboratory testing confirmed the patient’s thrombocytopenia with platelets of 2,000/μL on initial complete blood count, without pancytopenia or other coagulopathies. The blood smear indicated a profound lack of platelets but otherwise normal cell counts and morphology. In the emergency department, the patient was typed and crossed, platelets were ordered, and hematology–oncology was consulted. Once admitted to the internal medicine ward, he was administered glucocorticoids as well as platelet transfusions. He was monitored for 3 days and discharged with a diagnosis of resolved drug-induced thrombocytopenia. This case illustrates the importance of conducting a thorough review of systems and physical examination in stable and otherwise healthy patients. In this case, the seemingly benign rash was one of the only clinical signs of severe thrombocytopenia, with a high risk of spontaneous bleeding in clinically significant organ systems. It is important to recognize immune thrombocytopenic purpura as a potential complication of Bactrim/Septra, as this antibiotic is widely used by military providers in operational settings.
Anthems and Politics in the Restoration Chapel Royal
Authors: White Bryan
Published: February 2021

This article investigates occasional anthems written for the Chapel Royal by Henry Purcell, John Blow, and William Turner in an attempt to understand the political work enacted through their texts and settings. The anthem’s place in the liturgy and its relationship to the sermon is considered, along with the ways in which anthem texts were selected, compiled, and adapted from source texts. Though occasional anthems usually served to interpret current events favourably for the regime, during the crisis caused by James II’s prosecution of the Seven Bishops Blow set texts that can be interpreted as challenging the king’s pro-Catholic policies. The article concludes by considering the extent to which the characteristics of an anthem text can be used to speculate on the occasion for which it was selected when that occasion is unknown, using the example of Purcell’s My song shall be alway.
Microsurgical Resection of a Pontine Cavernoma Using an Expanded Retrosigmoid Corridor: 2-Dimensional Operative Video
Authors: Khan Nickalus R , Silva Michael A , Elarjani Turki , Morcos Jacques J
Published: February 2021

Cavernous malformations that have not previously bled have been reported to have an annual bleeding rate of 0.6% per year.
1
Those with prior hemorrhage have been reported to have rebleeding rates of up to 4.5%.
1
Additionally, infratentorial location, young age, and female gender have been associated with increased risk.
1
We present the case of a 26-yr-old female who initially presented to an outside institution with left-sided weakness. She improved following her initial bleeding event and presented to us for further management. A large, cavernous malformation in the right pons was identified on imaging. The patient underwent a right expanded retrosigmoid craniotomy with splitting of the horizontal cerebellar fissure to completely remove the lesion. The expanded retrosigmoid craniotomy allows for an enhanced view of the medial pontine region and can be utilized for appropriately selected brainstem cavernous malformations. The case presentation, surgical anatomy, operative nuances, and postoperative course and outcome are reviewed. The patient gave verbal consent for participating in the procedure and surgical video. The patient also consented to the publication of her image.
PerspectivesRe-legalizing cannabis for medical use in the USA
Authors: Victor Brenda , Hager Kathy , Stacy Shannon
Published: February 2021

Background

The purpose of this paper is to discuss the history of cannabis, its benefits, risks and the federal re-legalization of cannabis for medical use in the USA.

Methods

Thirty-six states have legalized cannabis as a medicinal substance. Cannabis is a Schedule I drug, an illegal and controlled substance, making research on the substance challenging. Both the American Medical Association and the American Nurses Association have called for the re-scheduling of marijuana, so that research can be conducted, its benefits and risks discovered.

Results

Data are demonstrating that medical marijuana may be beneficial as a step-down drug, decreasing the use of opioids and benzodiazepines, as well as deaths related to their overdose. Studies have indicated that cannabis is a low-risk substance, when compared to alcohol and opioids. There appear to be specific conditions in which cannabis provides relief of symptoms which no other medications can provide. There is also evidence of cannabis’s negative effects on the developing brain.

Conclusion

Cannabis should be rescheduled and researched, so that its risks and benefits can be identified. Its medicinal use should be monitored, and its availability protected in children, pregnant women and pets.
The influence of changes in work stressors and coping resources on sleep disturbances: evidence from the OHSPIW cohort study
Authors: Jiang Yu , Li Peixin , Zhong Ling , Liu Baoying , Gao Xiaoyan , Ning Li , Lian Yulong , Liu Jiwen
Published: February 2021

Study Objectives

We investigated whether changes in psychosocial work conditions affect the risk of sleep disturbances.

Methods

Data pertaining to 2738 males and 1431 females were obtained from the Occupational Health Study of Petroleum Industry Workers (OHSPIW), a prospective cohort study of Chinese petroleum industry workers. The subjects were assessed with regard to work-related stressors, coping resources, and sleep disturbances at baseline (2012) and follow-up (2018). The variations in work stressors and coping resources, which were assessed using the Occupation Stress Inventory-Reviewed (OSI-R), were calculated. Sleep disturbances were evaluated with the self-reported Pittsburgh Sleep Quality Index (PSQI).

Results

Increased work stressors (OR = 1.57, 95% CI = 1.24–1.99) and decreased coping resources (OR = 2.03, 95% CI = 1.48–2.78) were correlated with the likelihood of sleep disturbances in male and female workers. The primary risk factors included high role overload, increased responsibility, enhanced physical environment stressors, reduced self-care, and reduced rational coping. A reduction in work stressors was a protective factor against sleep disturbances in females only (OR = 0.63, 95% CI = 0.45–0.88). Coping resources had a modifying effect on the relationship between increased work stressors and sleep disturbances, with increased coping resources being associated with a lower odds of increased works stressors on sleep disturbances (OR = 1.29, 95% CI = 1.01–1.66) than decreased coping resources (OR = 3.60, 95% CI = 1.10–11.81).

Conclusions

Changes in work stressors and coping resources have a significant influence on the risk of sleep disturbances. Our findings highlight important precautionary strategies to abate adverse psychosocial working environments and to strengthen coping resources to prevent work-related sleep disturbances.
What happens when the party moves home? The effect of the COVID-19 pandemic on U.S. college student alcohol consumption as a function of legal drinking status using longitudinal data
Authors: Ryerson Nicole C , Wilson Oliver W A , Pena Alejandra , Duffy Michele , Bopp Melissa
Published: February 2021

Many young adults in the United States (U.S.) moved from college accommodations to live with their parents/family during the Spring 2020 semester due to the COVID-19 pandemic. While alcohol consumption fluctuates during a typical semester among students, the impact of the sudden changes stemming from the pandemic on students’ alcohol consumption patterns is unclear. To examine the impact of the COVID-19 pandemic on college student alcohol consumption while accounting for legal drinking age and living situation. Data were collected from students (n = 302) at a large, northeastern U.S. university at the beginning and end of the of the 2019 and 2020 Spring semesters via an online survey that assessed socio-demographic characteristics (age, gender, race/ethnicity, living situation) and alcohol consumption using the daily drinking questionnaire. Data were analyzed using a 2 (cohort group: COVID-19 vs. normal) × 2 (age group: above 21 vs. under 21) × 2 (time: beginning vs. end of the semester) mixed model ANOVA. There was a significant three-way interaction. Students over the legal drinking age impacted by the pandemic demonstrated a drastic decrease in alcohol consumption by the end of the semester compared to those under normal circumstances. Change in living situation as a result of the pandemic drastically impacted the alcohol consumption patterns of students over the legal drinking age. Suggestions for future research on the continuing effects of the pandemic on students are discussed.
Transitioning Newly Licensed Nurses Into Practice Through an Academic-Practice Partnership
Authors: Fletcher Janet , Moore Farren , Riley Elizabeth
Published: February 2021

Research illustrates a clear gap between academic and practice facilities concerning new graduate nurses. Nursing programs are charged with training nursing graduates who can provide safe, quality patient care. One way to enhance the quality of patient care and aid with retention of new graduate nurses in health care facilities is through academic-practice partnerships. This article describes the planning, implementation, and evaluation of a partnership between a health care facility and an associate of applied science nursing degree program to aid with registered nurse retention and quality patient care.
Directly Cooling Gut Prevents Mortality in the Rat Model of Reboa Management of Lethal Hemorrhage
Authors: Liu Chunli , Yuan Dong , Crawford Robert , Sarkar Rajabrata , Hu Bingren
Published: February 2021

Background:

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving technique for the management of lethal torso hemorrhage. Its benefit, however, must be weighed against the lethal distal organ ischemia-reperfusion injury (IRI). This study uses a novel direct gut cooling technique to manage the distal organ IRI.

Methods:

A rat lethal hemorrhage model was established by bleeding of 50% of the estimated total blood volume via inferior vena cava. A novel TransRectal Intra-Colon (TRIC) temperature management device was positioned in the descending colon either to maintain intra-colon temperature at 37°C or 12°C. The upper body temperature was maintained at as close to 37°C as possible in both groups. A 2F Fogarty balloon catheter was inserted via the femoral artery into the descending thoracic aorta for the implementation of REBOA. After REBOA, the balloon was deflated, and the shed blood was returned. The temperature managements were continued for additional 180 to 270 min during the post-REBOA period.

Results:

All rats subjected to REBOA management of lethal hemorrhage at 37°C had severe histopathological gut and abdominal organ IRI, severe functional deficits, and died within 24 h with 100% mortality. By contrast, directly cooling the colon to 10°C to 12°C with the novel TRIC device abolished mortality, and dramatically improved ABG parameters, prevented the abdominal organ injury, and reduced the functional deficits during the 7-day post-REBOA period.

Conclusions:

Direct trans-rectal colon cooling during REBOA management of lethal hemorrhage offers extraordinary functional improvement and amazing tissue protection, and abolishes mortality.
Comparison of Vasopressin versus Norepinephrine in a Pig Model of Refractory Cardiogenic Shock Complicated by Cardiac Arrest and Resuscitated with Veno-arterial ECMO
Authors: Klein Thomas , Grandmougin Daniel , Liu Yihua , Orlowski Sophie , Albuisson Eliane , Tran N’Guyen , Levy Bruno
Published: February 2021

Background:

The choice of the best vasopressor after ExtraCorporeal Membrane Oxygenation (ECMO) implantation after cardiac arrest is not well defined. Circulatory flow recovery with ECMO is associated with vasoplegia and vasopressor need. The present study aimed to compare the effects of norepinephrine and vasopressin in the first 6 h after ECMO initiation.

Methods:

Cardiac arrest was induced in 20 pigs by coronary surgical ligature and veno-arterial-ECMO was started after a 30-min period of cardio-pulmonary resuscitation. Pigs were randomized into two groups, arginine vasopressin (AVP) or norepinephrine (NE), with the drugs titrated to maintain a mean arterial pressure (MAP) at 65 mm Hg. Macrocirculatory and metabolic parameters were assessed by lactate clearance. Microcirculatory parameters were assessed by sublingual microcirculation with Sidestream Dark Field imaging and peripheral Near InfraRed Spectroscopy. Pulmonary edema was evaluated by measuring lung wet/dry weight ratio.

Results:

No difference was found between groups regarding ECMO flow and MAP. Fluid resuscitation volume was higher in the NE group (14,000 [11,250–15,250] mL vs. 3,500 [1,750–4,000] mL in the AVP group, P < 0.05). Lung wet/dry weight ratio was higher in the Norepinephrine group. Lactate clearance between H0 and H6 was higher in the AVP group (47.84 [13.42–82.73]% vs. the NE group 25.66 [−7.31 to 35.34)% vs. P < 0.05). No significant difference was observed for sublingual microcirculation values. Baseline tissue oxygen saturation was comparable and higher at both H3 and H6 in the Vasopressin group comparatively to the Norepinephrine group (P < 0.05). Renal and liver function evolution also remained similar in the two groups throughout the study.

Conclusions:

AVP administration in refractory cardiac arrest resuscitated by veno-arterial-ECMO is associated with a faster lactate clearance, less fluid resuscitation, and less pulmonary edema when compared with NE for similar global and regional hemodynamic effects.
Predicting mortality, duration of treatment, pulmonary embolism and required ceiling of ventilatory support for COVID-19 inpatients: A Machine-Learning Approach
Authors: Vepa Abhinav , Saleem Amer , Rakhshan Kambiz , Omar Amr , Dharmaraj Diana , Sami Junaid , Parekh Shital , Ibrahim Mohamed , Raza Mohammed , Kapila Poonam , Chakrabarti Prithwiraj , Sedighi Tabassom , Chatrabgoun Omid , Daneshkhah Alireza
Published: February 2021

Introduction

Within the UK, COVID-19 has contributed towards over 103,000 deaths. Multiple risk factors for COVID-19 have been identified including various demographics, co-morbidities, biochemical parameters, and physical assessment findings. However, using this vast data to improve clinical care has proven challenging.

Aims

to develop a reliable, multivariable predictive model for COVID-19 in-patient outcomes, to aid risk-stratification and earlier clinical decision-making.

Methods

Anonymized data regarding 44 independent predictor variables of 355 adults diagnosed with COVID-19, at a UK hospital, was manually extracted from electronic patient records for retrospective, case-controlled analysis. Primary outcomes included inpatient mortality, level of ventilatory support and oxygen therapy required, and duration of inpatient treatment. Secondary pulmonary embolism was the only secondary outcome. After balancing data, key variables were feature selected for each outcome using random forests. Predictive models were created using Bayesian Networks, and cross-validated.

Results

Our multivariable models were able to predict, using feature selected risk factors, the probability of inpatient mortality (F1 score 83.7%, PPV 82%, NPV 67.9%); level of ventilatory support required (F1 score varies from 55.8% “High-flow Oxygen level” to 71.5% “ITU-Admission level”); duration of inpatient treatment (varies from 46.7% for “≥ 2 days but < 3 days” to 69.8% “≤ 1 day”); and risk of pulmonary embolism sequelae (F1 score 85.8%, PPV of 83.7%, and NPV of 80.9%).

Conclusion

Overall, our findings demonstrate reliable, multivariable predictive models for 4 outcomes, that utilize readily available clinical information for COVID-19 adult inpatients. Further research is required to externally validate our models and demonstrate their utility as clinical decision-making tools.

Highlights

Using COVID-19 risk-factor data to assist clinical decision making is a challenge

Anonymous data from 355 COVID-19 inpatients was collected & balanced

Key independent variables were feature selected for 4 different outcomes

Accurate, multi-variable predictive models were computed, using Bayesian Networks

Future research should externally validate our models & demonstrate clinical utility
Behavioral control by depolarized and hyperpolarized states of an integrating neuron by
Authors: Sordillo Aylesse , Bargmann Cornelia I.
Published: February 2021

Coordinated transitions between mutually exclusive motor states are central to behavioral decisions. During locomotion, the nematodeCaenorhabditis elegansspontaneously cycles between forward runs, reversals, and turns with complex but predictable dynamics. Here we provide insight into these dynamics by demonstrating how RIM interneurons, which are active during reversals, act in two modes to stabilize both forward runs and reversals. By systematically quantifying the roles of RIM outputs during spontaneous behavior, we show that RIM lengthens reversals when depolarized through glutamate and tyramine neurotransmitters and lengthens forward runs when hyperpolarized through its gap junctions. RIM is not merely silent upon hyperpolarization: RIM gap junctions actively reinforce a hyperpolarized state of the reversal circuit. Additionally, the combined outputs of chemical synapses and gap junctions from RIM regulate forward-to-reversal transitions. Our results indicate that multiple classes of RIM synapses create behavioral inertia during spontaneous locomotion.
Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes
Authors: Shulgach Jonathan A. , Beam Dylan W. , Nanivadekar Ameya C. , Miller Derek M. , Fulton Stephanie , Sciullo Michael , Ogren John , Wong Liane , McLaughlin Bryan , Yates Bill J. , Horn Charles C. , Fisher Lee E.
Published: February 2021

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N=3) or ventral (N=3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that is was possible to selectively activate subpopulations of vagal afferents using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e. Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.
An mRNA expression-based signature for oncogene-induced replication-stress
Authors: Llobet Sergi Guerrero , Bhattacharya Arkajyoti , Everts Marieke , van der Vegt Bert , Fehrmann Rudolf S.N. , van Vugt Marcel A.T.M.
Published: February 2021

Background

Oncogene-induced replication stress characterizes many aggressive cancers, including triple-negative breast cancer (TNBC). Several drugs are being developed that target replication stress, although it is unclear how tumors with high levels of replication stress can be identified. We aimed to develop a gene expression signature of oncogene-induced replication stress.

Methods

TNBC and non-transformed RPE1-TP53wtand RPE1-TP53mutcell lines were engineered to overexpress the oncogenesCDC25A,CCNE1orMYC. DNA fiber analysis was used to measure replication kinetics. Analysis of RNA sequencing data of cell lines and patient-derived tumor samples (TCGA n=10,592) was used to identify differential gene expression. Immunohistochemical validation was conducted on breast cancer samples (n=330).

Results

RNA sequencing revealed 52 commonly upregulated genes after induction ofCDC25A,CCNE1orMYCin our cell line panel. Integration with gene expression data of TGCA samples with amplification of replication stress-inducing oncogenes (CDC25A,CCNE1,MYC,CCND1,MYB,MOS,KRAS,ERBB2, andE2F1), yielded a six-gene signature of oncogene-induced replication stress (NAT10,DDX27,ZNF48,C8ORF33,MOCS3,andMPP6). Expression of NAT10 in breast cancer samples was correlated with phospho-RPA (R=0.451, p=1.82×10−20) and γH2AX (R=0.304, p=2.95×10−9). Applying the oncogene-induced replication stress signature to patient samples (TCGA n=8,862 and GEO n=13,912) defined the replication stress landscape across 27 tumor subtypes, and identified diffuse large B cell lymphoma, ovarian cancer, TNBC and colorectal carcinoma as cancer subtypes with high levels of oncogene-induced replication stress.

Conclusion

We developed a gene expression signature of oncogene-induced replication stress, which may facilitate patient selection for agents that target replication stress.
Establishment of a human three-dimensional chip-based chondro-synovial co-culture joint model for reciprocal cross-talk studies in arthritis research
Authors: Rothbauer Mario , Byrne Ruth A. , Schobesberger Silvia , Calvo Isabel Olmos , Fischer Anita , Reihs Eva I. , Spitz Sarah , Bachmann Barbara , Sevelda Florian , Holinka Johannes , Holnthoner Wolfgang , Redl Heinz , Tögel Stefan , Windhager Reinhard , Kiener Hans P. , Ertl Peter
Published: February 2021

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane, which is the joint capsule’s inner layer, is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA’s synovial-chondral axis has yet not been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue co-culture model that simulates the reciprocal cross-talk between individual synovial and chondral organoids. We now demonstrate that chondral organoids, when co-cultivated with synovial organoids, induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross-talk in the modelling of arthritic diseases.
Relative and quantitative rhizosphere microbiome profiling result in distinct abundance patterns
Authors: Azarbad Hamed , Tremblay Julien , Bainard Luke D. , Yergeau Etienne
Published: February 2021

Next-generation sequencing is recognized as one of the most popular and cost-effective way of characterizing microbiome in multiple samples. However, most of the currently available amplicon sequencing approaches are inherently limited, as they are often presented based on the relative abundance of microbial taxa, which may not fully represent actual microbiome profiles. Here, we combined amplicon sequencing (16S rRNA gene for bacteria and ITS region for fungi) with real-time quantitative PCR (qPCR) to characterize the rhizosphere microbiome of wheat. We show that the increase in relative abundance of major microbial phyla does not necessarily result in an increase in abundance. One striking observation when comparing relative and quantitative abundances was a substantial increase in the abundance of almost all phyla associated with the rhizosphere of plants grown in soil with no history of water stress as compared with the rhizosphere of plants growing in soil with a history of water stress, which was in contradiction with the trends observed in the relative abundance data. Our results suggest that the estimated absolute abundance approach gives a different perspective than the relative abundance approach, providing complementary information that helps to better understand the rhizosphere microbiome.
Aedes albopictusbionomics in Procida Island, a promising Mediterranean site for the assessment of innovative and community-based integrated pest management methods
Authors: Caputo B. , Langella G. , Petrella V. , Virgillito C. , Manica M. , Filipponi F. , Varone M. , Primo P. , Puggioli A. , Bellini R. , D’Antonio C. , Iesu L. , Tullo L. , Rizzo C. , Longobardi A. , Sollazzo G. , Perrotta M. M. , Fabozzi M. , Palmieri F. , Saccone G , Rosà R. , della Torre A. , Salvemini M.
Published: February 2021

The colonization of Mediterranean Europe and of other temperate regions byAedes albopictuscreated in the last decades an unprecedented nuisance problem in highly infested areas, as well as a new public health threat due to the species competence to transmit exotic arboviruses, such as dengue, chikungunya and zika. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods relying on mass release of irradiated/manipulated males which are believed to have a potential in complementing existing and only partially effective control tools. Testing and implementing these approaches are challenging and selection of study sites is an instrumental and crucial step. We carried out a 4-year study in Procida Island (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate: i) the temporal dynamics, spatial distribution, and population size ofAe. albopictus; and ii) the dispersal and survival of irradiated males. Overall, results provide insights on the bionomics of the mosquito in Southern Europe and draw attention to Procida Island as an ideal site to test innovative control programs againstAe. albopictuswhich may be used in other Mediterranean and temperate areas.”
Complex polyploid and hybrid species in an apomictic and sexual tropical forage grass group: genomic composition and evolution inUrochloa(Brachiaria) species
Authors: Tomaszewska Paulina , Vorontsova Maria S. , Renvoize Stephen A. , Ficinski Sarah Z. , Tohme Joseph , Schwarzacher Trude , Castiblanco Valheria , de Vega José J. , Mitchell Rowan A. C. , Heslop-Harrison J. S. (Pat)
Published: February 2021

Background and Aims

Diploid and polyploidUrochloa(includingBrachiaria,PanicumandMegathyrsusspecies) C4tropical forage grasses originating from Africa and now planted worldwide are important for food security and the environment, often being planted in marginal lands. We aimed to characterize the nature of their genomes, the repetitive DNA, and the genome composition of polyploids, leading to a model of the evolutionary pathways within the group including many apomictic species.

Methods

Some 362 forage grass accessions from international germplasm collections were studied, and ploidy determined using an optimized flow cytometry method. Whole-genome survey sequencing and molecular cytogenetic analysis within situhybridization to chromosomes were used to identify chromosomes and genomes inUrochloaaccessions belonging to the different agamic complexes.

Key Results

Genome structures are complex and variable, with multiple ploidies and genome compositions within the species, and no clear geographical patterns. Sequence analysis of nine diploid and polyploid accessions enabled identification of abundant genome-specific repetitive DNA motifs.In situhybridization with a combination of repetitive DNA and genomic DNA probes, identified evolutionary divergence and allowed us to discriminate the different genomes present in polyploids.

Conclusions

We suggest a new coherent nomenclature for the genomes present. We develop a model of evolution at the whole-genome level in diploid and polyploid accessions showing processes of grass evolution. We support the retention of narrow species concepts forU. brizantha, U. decumbens, andU. ruziziensis. The results and model will be valuable in making rational choices of parents for new hybrids, assist in use of the germplasm for breeding and selection ofUrochloawith improved sustainability and agronomic potential, and will assist in measuring and conserving biodiversity in grasslands.
Efficiency Improvements and Discovery of New Substrates for a SARS-CoV-2 Main Protease FRET Assay
Authors: Dražić Tonko , Kühl Nikos , Leuthold Mila M. , Behnam Mira A. M. , Klein Christian D.
Published: February 2021

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has a huge impact on the world. Although several vaccines have recently reached the market, the development of specific antiviral drugs against SARS-CoV-2 is an important additional strategy in fighting the pandemic. One of the most promising pharmacological targets is the viral main protease (Mpro). Here, we present an optimized biochemical assay procedure for SARS-CoV-2 Mpro. We have comprehensively investigated the influence of different buffer components and conditions on the assay performance, and characterized six FRET substrates with a 2-Abz/Tyr(3-NO2) FRET pair. The substrates 2-AbzSAVLQSGTyr(3-NO2)R-OH, a truncated version of the established DABCYL/EDANS FRET substrate, and a new substrate 2-AbzVVTLQSGTyr(3-NO2)R-OH are promising candidates for screening and inhibitor characterization. In the latter substrate, the incorporation of Val at the position P5 improved the catalytic efficacy. Based on the obtained results, we present here a reproducible, reliable assay protocol using highly affordable buffer components.
SMAD4 governs a feedforward regulation of the TGF-β-effects in CD8 T cells that contributes to preventing chronic intestinal inflammation
Authors: Igalouzene Ramdane , Hernandez-Vargas Hector , Benech Nicolas , Bauché David , Barrachina Célia , Dubois Emeric , Marie Julien C. , Soudja Saïdi M’Homa
Published: February 2021

SMAD4, a key mediator of TGF-β signaling, plays a crucial role in T cells to prevent chronic gut inflammation. However, the molecular mechanisms underlying this control remain elusive. Using different genetic and epigenetic approaches, we unexpectedly reveal that SMAD4 in CD8 T cells prevents chronic intestinal inflammation by a feedforward mechanism that is TGF-β-independent. Prior to any TGF-β-receptor engagement, SMAD4 acts as an active and basal repressor of epigenetic, transcriptional and functional TGF-β imprinting in CD8 T cells. Thus, in sharp opposition to total TGF-β signaling deletion, SMAD4 deletion impairs naïve CD8 T cell effector predisposition but promotes CD8 T cell accumulation and epithelial retention by promoting their response to IL-7 and their expression of integrins such asItgae. Besides, SMAD4 deletion unleashes the induction of a wide range of TGF-β-signaling-repressors such asSmad7, Ski, Skil, andSmurf2and hampers TGF-β-mediated CD8 T cell immunosuppression. Mechanistically, prior to any TGF-β signal, SMAD4 binds to the loci of several TGF-β-target genes, and by regulating histone acetylation, represses their expression. The massive gut epithelial colonization, associated with their escape from the immunoregulatory TGF-β effects overtakes their poor effector preconditioning and elicits microbiota-driven chronic epithelial CD8 T cell activation. Hence, in an anticipatory manner, independently of TGF-β, SMAD4 governs a feedforward regulation of TGF-β effects in CD8 T cells, preventing chronic intestinal inflammation.
Viperin inhibits cholesterol biosynthesis and interacts with enzymes in the cholesterol biosynthetic pathway
Authors: Grunkemeyer Timothy J. , Ghosh Soumi , Patel Ayesha M. , Sajja Keerthi , Windak James , Basrur Venkatesha , Kim Youngsoo , Nesvizhskii Alexey I. , Kennedy Robert T. , Marsh E. Neil G.
Published: February 2021

Many enveloped viruses bud from cholesterol-rich lipid rafts on the cell membrane. Depleting cellular cholesterol impedes this process and results in viral particles with reduced viability. Viperin (virus inhibitory protein endoplasmic reticulum-associated, interferon-induced) is an ER membrane-associated enzyme that when expressed in response to viral infections exerts broad-ranging antiviral effects, including inhibiting the budding of some enveloped viruses. Here we have investigated the effect of viperin expression on cholesterol biosynthesis. We found that viperin expression reduces cholesterol levels by 20 – 30 % in HEK293T cells. A proteomic screen of the viperin interactome identified several cholesterol biosynthetic enzymes among the top hits. The two most highly enriched proteins were lanosterol synthase and squalene monooxygenase, enzymes that catalyze key steps establishing the sterol carbon skeleton. Co-immunoprecipitation experiments established that viperin, lanosterol synthase and squalene monooxygenase form a complex at the ER membrane. Co-expression of viperin was found to significantly inhibit the specific activity of lanosterol synthase in HEK293T cell lysates. Co-expression of viperin had no effect on the specific activity of squalene monooxygenase, but reduced its expression levels in the cells by approximately 30 %. Despite these inhibitory effects, co-expression of either LS or SM failed to reverse the viperin-induced depletion of cellular cholesterol levels in HEK293T cells. Our results establish a clear link between the down-regulation of cholesterol biosynthesis and viperin, although at this point the effect cannot be unambiguously attributed interactions between viperin and a specific biosynthetic enzyme.
Squidpy: a scalable framework for spatial single cell analysis
Authors: Palla Giovanni , Spitzer Hannah , Klein Michal , Fischer David , Schaar Anna Christina , Kuemmerle Louis Benedikt , Rybakov Sergei , Ibarra Ignacio L. , Holmberg Olle , Virshup Isaac , Lotfollahi Mohammad , Richter Sabrina , Theis Fabian J.
Published: February 2021

Spatial omics data are advancing the study of tissue organization and cellular communication at an unprecedented scale. Here, we present Squidpy, a Python framework that brings together tools from omics and image analysis to enable scalable description of spatial molecular data, such as transcriptome or multivariate proteins. Squidpy provides both infrastructure and numerous analysis methods that allow to efficiently store, manipulate and interactively visualize spatial omics data.
mRNA codon optimization on quantum computers
Authors: Fox Dillion M. , Branson Kim M. , Walker Ross C.
Published: February 2021

Reverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. An adiabatic quantum computer (AQC) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The AQC is found to be competitive in identifying optimal solutions and future generations of AQCs may be able to outperform classical GAs. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.
Genome-wide association study suggests an independent genetic basis of zinc and cadmium concentrations in fresh sweet corn kernels
Authors: Baseggio Matheus , Murray Matthew , Wu Di , Ziegler Gregory , Kaczmar Nicholas , Chamness James , Hamilton John P. , Buell C. Robin , Vatamaniuk Olena K. , Buckler Edward S. , Smith Margaret E. , Baxter Ivan , Tracy William F. , Gore Michael A.
Published: February 2021

Despite being one of the most consumed vegetables in the United States, the elemental profile of sweet corn (Zea maysL.) is limited in its dietary contributions. To address this through genetic improvement, a genome-wide association study was conducted for the concentrations of 15 elements in fresh kernels of a sweet corn association panel. In concordance with mapping results from mature maize kernels, we detected a probable pleiotropic association of zinc and iron concentrations withnicotianamine synthase5(nas5), which purportedly encodes an enzyme involved in synthesis of the metal chelator nicotianamine. Additionally, a pervasive association signal was identified for cadmium concentration within a recombination suppressed region on chromosome 2. The likely causal gene underlying this signal washeavy metal ATPase3(hma3), whose counterpart in rice,OsHMA3, mediates vacuolar sequestration of cadmium and zinc in roots, whereby regulating zinc homeostasis and cadmium accumulation in grains. In our association panel,hma3associated with cadmium but not zinc accumulation in fresh kernels. This finding implies that selection for low cadmium will not affect zinc levels in fresh kernels. Although less resolved association signals were detected for boron, nickel, and calcium, all 15 elements were shown to have moderate predictive abilities via whole-genome prediction. Collectively, these results help enhance our genomics-assisted breeding efforts centered on improving the elemental profile of fresh sweet corn kernels.
HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage independence
Authors: Kim Yeon Soo , Welles Jaclyn E , Tang Priscilla W , Javed Zaineb , Elhaw Amal T , Mythreye Karthikeyan , Kimball Scot R , Hempel Nadine
Published: February 2021

During metastasis, cancer cells must adapt to survive a loss of anchorage and evade anoikis. An important pro-survival adaptation is the ability of metastatic tumor cells to increase their antioxidant capacity and restore cellular redox balance. Although much is known about the transcriptional regulation of antioxidant enzymes in response to stress, how cells rapidly adapt to alter antioxidant enzyme levels is less well understood. Using ovarian cancer cells as a model, we demonstrate that an increase in protein expression of the mitochondrial superoxide dismutase SOD2 is a very early event initiated in response to cellular detachment. SOD2 protein synthesis is rapidly induced within 0.5-2 hours of matrix detachment, and polyribosome profiling demonstrates an increase in the number of ribosomes bound to SOD2 mRNA, indicating an increase in SOD2 translation in response to anchorage-independence. Mechanistically, we find that anchorage-independence specifically induces cytosolic accumulation of the RNA binding protein HuR/ELAVL1 and leads to increased HuR binding to SOD2 mRNA. Using HuR siRNA-mediated knock-down, we show that the presence of HuR is necessary for the increase in SOD2 mRNA association with the heavy polyribosome fraction and SOD2 protein synthesis observed in anchorage-independence. Cellular detachment activates the stress-response protein kinase p38 MAPK, which is necessary for HuR-SOD2 mRNA binding and optimal increases in SOD2 protein expression. These findings illustrate a novel post-transcriptional regulatory mechanisms of SOD2, enabling cells to rapidly increase their mitochondrial antioxidant capacity as an acute response to anchorage-independence.
Use of lignocellulosic residue from second-generation ethanol production to enhance methane production through co-digestion
Authors: Volpi Maria Paula. C. , Brenelli Lívia B. , Mockaitis Gustavo , Rabelo Sarita C. , Franco Telma T. , Moraes Bruna S.
Published: February 2021

This is a pioneer study evaluating the methane (CH4) production potential from residues of integrated 1st (vinasse and filter cake) and 2nd (deacetylation pretreatment liquor from straw) generation (1G2G) sugarcane biorefinery, providing a fully chemical characterization of them and their relation with the anaerobic digestion (AD) process. Small-scale assays provided fundamentals for basing the co-digestion optimization by assessing the optimal co-substrates synergistic conditions. Biochemical Methane Potential (BMP) tests showed co-digestion enhanced CH4 yield of isolated substrates, reaching up to 605 NmLCH4 gVS-1. The association of vinasse and deacetylation liquor as co-substrates increased the BMP by ~38% mostly by nutritionally benefiting the methanogenic activity. The kinetic analysis confirmed that the deacetylation liquor was the co-substrate responsible for improving the CH4 production in the co-digestion systems due to the highest CH4 conversion rate. The alkaline characteristic of the liquor (pH~12) also prevented alkalizing from being added to the co-digestion, an input that normally makes the process economically unfeasible to implement on an industrial scale due to the large quantities required for buffering the reactor. The filter cake had the lowest BMP (262 NmLCH4 gVS-1) and digestibility (≤ 40%), further limited by the required stirring to improve the mass transfer of biochemical reactions. The present study drives towards more sustainable use of vinasse, the most voluminous waste from the sugarcane industry, and lignin-rich residues derived from pre-treatment alkaline methods, aiming at an energy-efficient utilization, by at least 16% when compared to the traditional vinasse AD. The experimental and modeling elements from this work indicated the lignin-rich liquor is the main responsible for putting the co-digestion as a disruptive technological arrangement within the 1G2G sugarcane biorefineries, reinforcing the biogas production as the hub of the bioeconomy in the agroindustrial sector.
Evaluating how lethal management affects poaching of Mexican wolves
Authors: Louchouarn Naomi , Santiago-Ávila Francisco J. , Parsons David R. , Treves Adrian
Published: February 2021

Despite illegal killing (poaching) being the major cause of death among large carnivores globally, little is known about the effect of implementing lethal management policies on poaching. Two opposing hypotheses have been proposed in the literature: implementing lethal management may decrease poaching incidence (‘killing for tolerance’) or increase it (‘facilitated illegal killing’). Here, we report a test of the two opposed hypotheses that poaching (reported and unreported) of Mexican grey wolves (Canis lupus baileyi) in Arizona and New Mexico, USA, responded to changes in policy that reduced protections to allow more wolf-killing. We employ advanced biostatistical survival and competing-risk methods to data on individual resightings, mortality and disappearances of collared Mexican wolves, supplemented with Bayes Factors to assess strength of evidence. We find inconclusive evidence for any decreases in reported poaching. We also find strong evidence that Mexican wolves were 121% more likely to disappear during periods of reduced protections than during periods of stricter protections, with only slight changes in legal removals by the agency. Therefore, we find strong support for the ‘facilitated illegal killing’ hypothesis and none for the ‘killing for tolerance’ hypothesis. We provide recommendations for improving the effectiveness of US policy on environmental crimes, endangered species, and protections for wild animals. Our results have implications beyond the USA or wolves because the results suggest transformations of decades-old management interventions against human-caused mortality among wild animals subject to high rates of poaching.