bluuebunny/crossref_metadata_2025 huggingface dataset:
FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes
Authors: Kagawa Yoshiteru , Umaru Banlanjo Abdulaziz , Shima Hiroki , Ito Ryo , Zama Ryo , Islam Ariful , Kanno Shin-ichiro , Yasui Akira , Sato Shun , Jozaki Kosuke , Shil Subrata Kumar , Miyazaki Hirofumi , Kobayashi Shuhei , Yamamoto Yui , Kogo Hiroshi , Shimamoto-Mitsuyama Chie , Sugawara Akira , Sugino Norihiro , Kanamori Masayuki , Tominaga Teiji , Yoshikawa Takeo , Fukunaga Kohji , Igarashi Kazuhiko , Owada Yuji
Published: August 2020

Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.
The state of the art in scale inhibitor squeeze treatment
Authors: Kan Amy T. , Dai Zhaoyi , Tomson Mason B.
Published: August 2020

The mechanistic understanding of the reactions that govern the inhibitor retention and release, modeling, and the state-of-the-art innovation in squeeze treatment are reviewed. The retention and release are governed by (1) the amount of calcite that can dissolve prior to inhibitor-induced surface poisoning; (2) calcite surface poisoning after ~ 20 molecular layers of surface coverage by the adsorbed inhibitors to retard further calcite dissolution; (3) less base,$${\text{CO}}_{3}^{2 - }$$CO32-, is released into the aqueous solution; (4) formation of the more acidic inhibitor precipitates; (5) phase transformation and maturation of the more acidic inhibitor precipitates; and (6) dissolution of the less soluble crystalline inhibitor precipitates. The trend to advance squeeze technologies is through (1) enhancing scale inhibitor retention, (2) optimizing the delivery of scale inhibitors to the target zone, and (3) improving monitoring methods. Lastly, a prototype yardstick for measuring the squeeze performance is used to compare the squeeze life of 17 actual squeeze treatments. Even though the various squeeze treatments appear to be different, all published squeeze durations can be rated based on the normalized squeeze life per unit mass of inhibitors.
Plant iconography and its message: realism and symbolic message in the Bernini fountain of the four rivers in Rome
Authors: Caneva G. , Altieri A. , Kumbaric A. , Bartoli F.
Published: August 2020

The use of symbols in architecture of the past centuries is evident, even if sometimes cryptic. The reasons behind the representation of plants in artistic and architectural contexts are of great interest as they help in their understanding. We analysed the plants carved in the Fountain of Four Rivers (Rome), designed by G.L. Bernini (mid-seventeenth century), through iconographic and historical documents. The carved plants (about 34 species) creates a natural and symbolic association with the selected rivers and continents. Some species are chosen to characterise various geographic contexts or fluvial and rupestrian habitats or are referred to the papal coats of arms (Innocent X Pamphilj). A certain number has auspicious connotation and takes a strong symbolic salvific meaning and protective against the evil’s threat. The Kircherian influence emerges in several iconographic choices, as well as the river selection and orientation, in a philosophical-religious logic linked to the Papacy and Christianity role.
Multi-modal Approach for Benthic Impact Assessments in Moraine Habitats: a Case Study at the Block Island Wind Farm
Authors: Guarinello Marisa L. , Carey Drew A.
Published: August 2020

Benthic assessment techniques utilized in soft sediment areas are of limited utility in glacial moraine habitats that are structurally complex and largely composed of hard substrata. We present a multi-modal approach consisting of multibeam bathymetry, video, and still imagery that collectively provides the knowledge base necessary to perform impact assessments in these habitats. Baseline and post-construction surveys were conducted adjacent to the Block Island Wind Farm to develop and test these methodologies within the context of offshore wind development, specifically for detecting and documenting anchoring-related impacts to moraine habitats. Habitat data were evaluated using the substrate and biotic components of the national classification standard, the Coastal and Marine Ecological Classification Standard, recommended by federal regulators, with modifications to present results in terms of predicted vulnerability to disturbance. Habitats near the wind farm were diverse and patchy, ranging from rippled gravelly sand to continuous cobble/boulder fields with high biotic cover. Anchor furrows were detected in moderate value habitats in bathymetric and video data. The multi-modal survey approach tested at the Block Island Wind Farm and presented here is now specifically recommended by federal agencies and is being used to inform efforts currently underway to map and assess benthic habitats for a number of U.S. projects seeking federal permits.
Altered Cerebrospinal Fluid (CSF) in Children with Ataxia Telangiectasia
Authors: Woelke S. , Schrewe R. , Donath H. , Theis M. , Kieslich M. , Duecker R. , Auburger G. , Schubert R. , Zielen S.
Published: August 2020

Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with A-T from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, A-T score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood–brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the A-T patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in A-T patients, but low-grade inflammation is not detectable in serum and CSF.
Self-compassion and Perceived Criticism in Adults with Attention Deficit Hyperactivity Disorder (ADHD)
Authors: Beaton Danielle M. , Sirois Fuschia , Milne Elizabeth
Published: August 2020

Objectives

Attention deficit hyperactivity disorder (ADHD) is associated with increased criticism from others. To date, there is little research considering the consequences of how others respond to people with ADHD. Self-compassion is a positive way of relating to oneself during difficulty. Here, we investigate whether levels of self-compassion differ between people with and without ADHD, and whether perceived criticism mediates any differences in self-compassion between people with and without ADHD.

Methods

A cross-sectional design was used to conduct natural group comparisons. A sample of 1203 adults (46% with a self-reported ADHD diagnosis) recruited via social media, online forums and posters completed online self-report measures of diagnostic status, ADHD traits, self-compassion and perceived criticism. Between-group comparisons of self-compassion and perceived criticism were conducted on participants grouped by diagnosis, then grouped by ADHD trait severity. Perceived criticism was tested as a mediator variable between ADHD diagnosis and self-compassion.

Results

Adults with an ADHD diagnosis showed significantly lower self-compassion and higher perceived criticism than the participants without ADHD. Participants high in ADHD traits but without a diagnosis had significantly similar levels of self-compassion to the diagnosed group. Mediation analysis found that higher perceived criticism partially explained the relationship between ADHD diagnosis and self-compassion, even after accounting for co-occurring mood disorder diagnosis.

Conclusions

Adults with ADHD are less self-compassionate than adults without ADHD. This is partially explained by the higher level of criticism they perceive from others.
Formulation of cellulose using groundnut husk as an environment-friendly fluid loss retarder additive and rheological modifier comparable to PAC for WBM
Authors: Patidar Atul Kumar , Sharma Anjali , Joshi Dev
Published: August 2020

The hydrocarbon extraction and exploitation using state-of-the-art modern drilling technologies urge the use of biodegradable, environment-friendly drilling fluid and drilling fluid additives to protect the environment and humanity. As more environmental laws are enacted and new safety rules implemented to oust the usage of toxic chemicals as fluid additives, it becomes inevitable that we re-evaluate our choice of drilling fluid additives. Drilling fluids and its additives play a crucial role in drilling operations as well as project costing; hence, it is needed that we develop cost-effective environment-friendly drilling fluid additives that meet the requirements for smooth functioning in geologically complex scenarios as well as have a minimal ecological impact. The current research work demonstrates key outcomes of investigations carried out on the formulation of a sustainable drilling fluid system, where groundnut husk is used as a fluid loss additive and a rheological modifier having no toxicity and high biodegradability. Cellulose was generated from groundnut husk at two varying particle sizes using mesh analysis, which was then compared with the commercially available PAC at different concentrations to validate its properties as a comparable fluid loss retarder additive as well as a rheological modifier. In the present work, various controlling characteristics of proposed groundnut husk additive are discussed, where comparison at different concentrations with a commercially available additive, PAC, is also validated. The API filtration losses demonstrated by the (63–74) µm and the (250–297) µm proposed additive showed a decrease of 91.88% and 82.31%, respectively, from the base mud at 4% concentration. The proposed husk additives acted as a filtrate retarder additive without much deviation from base rheology and with considerably higher pH than the base mud. This investigation indicates that the proposed fluid loss additive and rheological modifier can minimize the environmental hazards and have proved to be a cost-effective eco-friendly alternative in this challenging phase of the hydrocarbon exploration industry.
Endobronchial Treatment of Bronchial Carcinoid in the Elderly
Authors: Daniels Johannes M. A. , Reuling Ellen M. B. P. , Dickhoff C.
Published: August 2020

Purpose of the Review

Although surgical resection is considered the gold standard of curative treatment for bronchial carcinoid, endobronchial treatment (EBT) can serve as a less invasive curative or palliative treatment in a selection of patients. It is unclear whether elderly patients with bronchial carcinoid should be treated in the same way as younger patients. In order to study the characteristics and treatment of elderly patients with bronchial carcinoid, we analyzed data from a cohort of patients that have been treated for bronchial carcinoid with EBT, surgical resection, or a combination of both. We used our existing database of patients referred for EBT and defined two groups of patients: ≥ 65 and < 65 years. We compared the characteristics, treatment, and causes of death between these groups. Successful EBT was defined as definitive treatment without signs of recurrence during follow-up with CT and bronchoscopy.

Recent Findings

Thirty-five patients (19%) were ≥ 65 years. The incidence of atypical carcinoid was the same in both age groups (31%). Thirty-six of 184 patients (20%) were directly referred for surgical resection and 148 (80%) underwent EBT. There was no significant difference in success of EBT between patients <65 years (58/122, 48%) and patients ≥ 65 years (15/26, 58%) (p = 0.347). Complication rates were similar in both groups. After unsuccessful EBT, only 70% (14/20) of the elderly patients was operated, whereas 93% (85/91) of the patients < 65 years was operated (p = 0.001). Disease specific mortality was 6% (2/35) in the group ≥ 65 years and 2% (3/149) in the group < 65 years.

The incidence of atypical carcinoid is similar between the elderly and younger patients. Success rate and complication rate of EBT do not differ significantly between the age groups. After unsuccessful EBT, elderly patients were less likely to undergo surgical resection, which does not seem associated with excess disease specific mortality, although the number of events in this study is low.
Conflicts Between Trade Mark Rights and Freedom of Expression Under EU Trade Mark Law: Reality or Illusion?
Authors: Bohaczewski Michal
Published: August 2020

The issue of reconciling trade mark rights and freedom of expression is a classic question discussed by European scholars which has recently been reopened because of the express reference to “fundamental rights and freedoms, and in particular the freedom of expression” in the preambles of Directive 2015/2436 and of Regulation 2017/1001. In this article, the author argues that, in the light of the EU legislation, conflicts between the freedom of expression and trade mark rights are often illusory. Indeed, in this debate we focus too quickly on the question of resolving a potential conflict, while EU trade mark law itself provides for limits that guarantee respect of the freedom of expression. It should also be borne in mind that commercial expressions enjoy a more restricted freedom since they serve private economic interests and not the interests of society as a whole. The freedom of commercial expression therefore needs to be limited by trade mark rights which are also fundamental rights, having equivalent value. Consequently, it seems unnecessary to envisage use related to the freedom of expression, of a sign reproducing or imitating a trade mark, as a specific limitation of trade mark rights, either in the speciality or in the field of enhanced protection of trade marks with a reputation.
Managing endpoints, the weakest link in the security chain
Authors: Waterson Dave
Published: August 2020

Endpoint security is a term open to interpretation. Traditionally, an endpoint would be any device or node connected to the LAN or WAN, such as a workstation or end-user PC, or a modem, a hub or a switch. But now endpoints incorporate a multitude of additional digital devices from laptops, tablets and mobile phones, which sit on the edge of the network, through to network printers, consumer and industrial IoT devices and point-of-sale systems.

Endpoints include a multitude of additional digital devices from laptops, tablets and mobile phones through to network printers, IoT devices and point-of-sale systems.

Securing this ever-expanding portfolio of endpoint technology has become an urgent necessity, not least because these devices represent a significant risk to the cloud ecosystem. By securing the input of sensitive data and by wrapping security around the applications that handle sensitive data, organisations can add another layer, boosting the protection of endpoint devices, explains Dave Waterson of SentryBay.
The Access Technology Program of the Indiana Clinical Translational Sciences Institute (CTSI): A model to facilitate access to cutting-edge technologies across a state
Authors: Orschell Christie M. , Skaar Todd C. , DeFord Melanie E. , Ybe Joel , Driscol Julie , Drury Christine , Reeves Lilith , Willis Monte S. , Reiter Jill L. , York Jenna , Orr Rob , McClintick Jeanette N. , Sors Thomas G. , Hunt Joe , Cornetta Kenneth , Shekhar Anantha
Published: August 2020

Introduction:

Access to cutting-edge technologies is essential for investigators to advance translational research. The Indiana Clinical and Translational Sciences Institute (CTSI) spans three major and preeminent universities, four large academic campuses across the state of Indiana, and is mandate to provide best practices to a whole state.

Methods:

To address the need to facilitate the availability of innovative technologies to its investigators, the Indiana CTSI implemented the Access Technology Program (ATP). The activities of the ATP, or any program of the Indiana CTSI, are challenged to connect technologies and investigators on the multiple Indiana CTSI campuses by the geographical distances between campuses (1–4 hr driving time).

Results:

Herein, we describe the initiatives developed by the ATP to increase the availability of state-of-the-art technologies to its investigators on all Indiana CTSI campuses, and the methods developed by the ATP to bridge the distance between campuses, technologies, and investigators for the advancement of clinical translational research.

Conclusions:

The methods and practices described in this publication may inform other approaches to enhance translational research, dissemination, and usage of innovative technologies by translational investigators, especially when distance or multi-campus cultural differences are factors to efficient application.
Evaluation of an exercise physiology service in a youth mental health service
Authors: Pearce M. , Foote L. , Brown E. , O’Donoghue B.
Published: August 2020

Background

Individuals who experience serious mental health disorders are at an increased risk of physical illness co-morbidity and early intervention is crucial. Recommendations to embed an exercise physiologist service into a mental health service have not been fully evaluated.

Objectives

This study aimed to determine (i) demographics and clinical characteristics of the young people referred to exercise physiology, (ii) adherence to metabolic monitoring, (iii) baseline physical health and (iv) level of engagement after referral.

Methods

This is a naturalistic cohort study and included all young people referred to the exercise physiology service between 2015 and 2019 at Orygen, a specialist youth mental health service in the north-western region of Melbourne.

Results

During the study period of 45 months, 312 young people were referred to exercise physiology, and of those, 51.3% were male. The mean age was 19.8 years. In regard to primary diagnoses, 47.4% had a psychotic disorder and 33.7% an affective disorder. Baseline weight measurements were completed for 71.8% of young people. The proportion of young people who were classified as overweight or obese increased from 55.1% to 70.4% (p< 0.001). For those referred, 61.5% attended either an individual session or a group session. A total of 29.5% did not attend their appointment following referral.

Conclusions

As over half of young people had poor physical health at presentation, integrating an exercise physiology service into a youth mental health service is a novel and needed intervention. However, there still needs to be an emphasis on metabolic monitoring and engagement.
Addressing punitive violence against children in Australia, Japan and the Philippines
Authors: Durrant Joan E. , Stewart-Tufescu Ashley , Ateah Christine , Holden George W. , Ahmed Rashid , Jones Alysha , Ly Gia , Plateau Dominique Pierre , Mori Ikuko
Published: August 2020

Physical and emotional punishment of children is highly prevalent in the Asia-Pacific region. These actions predict a range of physical and emotional harms, prompting a worldwide effort to eliminate them. A key strategy in this effort is to change parental beliefs regarding the acceptability of physical and emotional punishment. The Positive Discipline in Everyday Parenting (PDEP) program was designed to change those beliefs by teaching parents about child development and strengthening their problem-solving skills. A sample of 377 parents in the Asia-Pacific region completed the program: 329 mothers and 47 fathers of children ranging in age from infancy to adolescence. The parents lived in Australia ( n = 135), Japan ( n = 172) or the Philippines ( n = 70). In all three countries, parents’ approval of punishment in general, and physical punishment specifically, declined and they became less likely to attribute typical child behavior to intentional misbehavior. By the end of the program, at least 75% of parents in each country felt better prepared to respond nonviolently to conflict with their children.
ASSESSING THE STRATIGRAPHIC INTEGRITY OF PLANKTIC AND BENTHIC 14C RECORDS IN THE WESTERN PACIFIC FOR Δ14C RECONSTRUCTIONS AT THE LAST GLACIAL TERMINATION
Authors: Stott Lowell D
Published: August 2020

There is a growing database of radiocarbon (14C) reconstructions from biogenic carbonate taken from marine sediment cores being used to investigate changing ocean circulation and carbon cycling at the end of the last great ice age. Reported here are 14C results from a marine core taken in the Makassar Straits of the western equatorial Pacific that was intended to test whether there was evidence of geologic carbon release to the ocean during the glacial termination. A thorough investigation of planktic and benthic 14C ages with stable isotopes and CT-scans revealed extensive burrowing in the upper 2 m of the core that displaced younger sediments downward by more than half a meter into the glacial section of the core. The vertical displacement is evident in both planktic and benthic fossils. However, the extent of displacement and the stratigraphic disturbance became evident only after multiple measurements of different species and genera. A CT-scan prior to sampling would be an effective screening tool to avoid sampling problem cores such as this.
DATING OF REMAINS OF THE MEDIEVAL CHURCH SANTA MARIA DI CAMPOGROSSO IN SICILY IN THE LIGHT OF MULTIDISCIPLINARY STUDIES
Authors: Krąpiec Marek , Moździoch Sławomir , Moździoch Ewa
Published: August 2020

Excavations of the remains of the medieval church of Santa Maria di Campogrosso (Sicily) were conducted by the Institute of Archaeology and Ethnology of the Polish Academy of Sciences as part of scientific cooperation with Soprintendenza per i Beni Culturali ed Ambientali di Palermo. Based on the records of post-medieval historians, the construction of the church was placed in the second half of the 11th century, which contradicts the findings of architectural historians, who dated the building to the 13th-century and even later. As a result of archaeological excavations carried out in 2015–2018, it was possible to locate unknown fragments of the church’s structure and the remains of the cemetery adjacent to it. The 14C dating carried out for samples obtained from the walls of the existing building as well as from bone remains from the churchyard in combination with stratigraphic information from archaeological trenches and the chronology of coins indicates a high probability of the church construction in the second half of the 12th century and confirms the end of the monastery complex existence at the end of the 13th century.
Dietary changes in early-stage breast cancer patients from pre-surgery and over the 12 months post-surgery
Authors: Brunvoll Sonja H. , Thune Inger , Bertheussen Gro F. , Fjeldheim Frøydis , Flote Vidar G. , Frydenberg Hanne , Lundgren Steinar , Skjerven Helle , Lømo Jon , Fagerland Morten W. , McTiernan Anne , Schlichting Ellen , Hjartåker Anette
Published: August 2020

The time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients’ dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.
Salt taste perception and blood pressure levels in population-based samples: the Circulatory Risk in Communities Study (CIRCS)
Authors: Kudo Asako , Kitamura Akihiko , Imano Hironori , Cui Renzhe , Umesawa Mitsumasa , Yamagishi Kazumasa , Ohira Tetsuya , Muraki Isao , Hayama-Terada Mina , Kiyama Masahiko , Iso Hiroyasu ,   for CIRCS Investigators
Published: August 2020

To examine the associations of salt perception with salt intake and blood pressure levels in general populations, we performed a cross-sectional study in two communities where salt intake level is different, Akita and Osaka in Japan. Taste perception (detection for certain taste and recognition for salt taste) was determined using a Na-impregnated test strip for 1024 Akita and 1199 Osaka adults aged 30–74 years. The proportions of detection for 0·1 % salt were 61, 62, 79, and 79 % in Akita men, Osaka men, Akita women and Osaka women, respectively. The corresponding proportions of not recognising of 1·6 % salt taste (>1·6 %) were 34, 30, 16 and 21 %. Detection threshold was higher in Akita than in Osaka for women aged 60–74 years, and recognition threshold was lower in Akita than in Osaka for women aged 30–59 and 60–74 years. The high detection (≥0·4 %) and recognition (>1·6 %) thresholds of salt taste were associated with higher salt intake scores for Akita men aged 30–59 years, whose detection and recognition thresholds tended be positively associated with systolic and diastolic blood pressures (SBP and DBP) after adjustment for potential confounders. Among Akita elderly men, detection threshold tended to be positively associated with SBP and DBP, while among Akita middle-aged women, recognition threshold was associated with SBP. In conclusion, the high thresholds of salt perception were inversely associated with salt intake for Akita middle-aged men and with blood pressure levels for Akita middle-aged and elderly men and middle-aged women.
Pandemic Response as Border Politics
Authors: Kenwick Michael R. , Simmons Beth A.
Published: August 2020

Pandemics are imbued with the politics of bordering. For centuries, border closures and restrictions on foreign travelers have been the most persistent and pervasive means by which states have responded to global health crises. The ubiquity of these policies is not driven by any clear scientific consensus about their utility in the face of myriad pandemic threats. Instead, we show they are influenced by public opinion and preexisting commitments to invest in the symbols and structures of state efforts to control their borders, a concept we callborder orientation. Prior to the COVID-19 pandemic, border orientation was already generally on the rise worldwide. This trend has made it convenient for governments to “contain” the virus by externalizing it, rather than taking costly but ultimately more effective domestic mitigation measures. We argue that the pervasive use of external border controls in the face of the coronavirus reflects growing anxieties about border security in the modern international system. To a great extent, fears relating to border security have become a resource in domestic politics—a finding that does not bode well for designing and implementing effective public health policy.
Dementia-related psychosis and the potential role for pimavanserin
Authors: Cummings Jeffery L. , Devanand D. P. , Stahl Stephen M.
Published: August 2020

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2Areceptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2Areceptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.
AI Evaluation in Selection
Authors: Mirowska Agata
Published: August 2020

Abstract. This study investigates how information provided prior to the application stage of the selection process affects application intentions toward the job and organization. Existing research has focused on applicants who have already entered into the selection process; however, information revealed prior to application may cause candidates to self-select themselves out of the process. Utilizing a randomized experimental design, participants read a job ad specifying that their prerecorded interviews would be reviewed by a human or an artificial intelligence-based evaluator. The results show increased intentions to apply and pursue the job in the human evaluation condition.
Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential in renal cell carcinoma
Authors: Ruan Hailong , Li Sen , Bao Lin , Zhang Xiaoping
Published: August 2020

VHL mutations are the most common tumorigenic lesions in clear cell renal cell carcinoma (ccRCC) and result in continued activation of the HIF/VEGF pathway and uncontrolled cancer progression. Receptor tyrosine kinase (RTK) inhibitors such as sunitinib have been demonstrated to target tumorigenic signaling pathways, delay tumor progression, and improve patient prognosis in metastatic renal cell carcinoma (mRCC). Although several mechanisms of sunitinib resistance have been reported, the solutions to overcome this resistance remain unclear. In our study, we found that increased expression of Y-box binding protein 1 (YB1, a multidrug resistance associated protein) and EphA2 (a member of the erythropoietin-producing hepatocellular (Eph) receptor family, belonging to the RTK family) mediated sunitinib resistance and mRCC exhibited a large phenotypic dependence on YB1 and EphA2. In addition, our findings confirm that YB1 promotes the invasion, metastasis and sunitinib resistance of ccRCC by regulating the EphA2 signaling pathway. Furthermore, pharmacological inhibition of EphA2 through the small molecule inhibitor ALW-II-41-27 reduced the proliferation of sunitinib-resistant tumor cells, suppressed tumor growth in vivo, and restored the sensitivity of sunitinib-resistant tumor cells to sunitinib in vitro and in vivo. Mechanistically, YB1 increases the protein levels of EphA2 by maintaining the protein stability of EphA2 through inhibition of the proteasomal degradation pathway. Collectively, our findings provide the theoretical rationale that ccRCC metastasis and RTK-directed therapeutic resistance could be prospectively and purposefully targeted.
Bidirectional C and N transfer and a potential role for sulfur in an epiphytic diazotrophic mutualism
Authors: Stuart Rhona K , Pederson Eric R A , Weyman Philip D , Weber Peter K , Rassmussen Ulla , Dupont Christopher L
Published: August 2020

In nitrogen-limited boreal forests, associations between feathermoss and diazotrophic cyanobacteria control nitrogen inputs and thus carbon cycling, but little is known about the molecular regulators required for initiation and maintenance of these associations. Specifically, a benefit to the cyanobacteria is not known, challenging whether the association is a nutritional mutualism. Targeted mutagenesis of the cyanobacterial alkane sulfonate monooxygenase results in an inability to colonize feathermosses by the cyanobacterium Nostoc punctiforme, suggesting a role for organic sulfur in communication or nutrition. Isotope probing paired with high-resolution imaging mass spectrometry (NanoSIMS) demonstrated bidirectional elemental transfer between partners, with carbon and sulfur both being transferred to the cyanobacteria, and nitrogen transferred to the moss. These results support the hypothesis that moss and cyanobacteria enter a mutualistic exosymbiosis with substantial bidirectional material exchange of carbon and nitrogen and potential signaling through sulfur compounds.
A cosmopolitan fungal pathogen of dicots adopts an endophytic lifestyle on cereal crops and protects them from major fungal diseases
Authors: Tian Binnian , Xie Jiatao , Fu Yanping , Cheng Jiasen , Li Bo , Chen Tao , Zhao Ying , Gao Zhixiao , Yang Puyun , Barbetti Martin J , Tyler Brett M , Jiang Daohong
Published: August 2020

Fungal pathogens are seriously threatening food security and natural ecosystems; efficient and environmentally friendly control methods are essential to help safeguard such resources for increasing human populations on a global scale. Here, we find that Sclerotinia sclerotiorum, a widespread pathogen of dicotyledons, can grow endophytically in wheat, rice, barley, maize, and oat, providing protection against Fusarium head blight, stripe rust, and rice blast. Protection is also provided by disabled S. sclerotiorum strains harboring a hypovirulence virus. The disabled strain DT-8 promoted wheat yields by 4–18% in the field and consistently reduced Fusarium disease by 40–60% across multiple field trials. We term the host-dependent trophism of S. sclerotiorum, destructively pathogenic or mutualistically endophytic, as schizotrophism. As a biotroph, S. sclerotiorum modified the expression of wheat genes involved in disease resistance and photosynthesis and increased the level of IAA. Our study shows that a broad-spectrum pathogen of one group of plants may be employed as a biocontrol agent in a different group of plants where they can be utilized as beneficial microorganisms while avoiding the risk of in-field release of pathogens. Our study also raises provocative questions about the potential role of schizotrophic endophytes in natural ecosystems.
Correction: Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability
Authors: Bertan Fabio , Wischhof Lena , Sosulina Liudmila , Mittag Manuel , Dalügge Dennis , Fornarelli Alessandra , Gardoni Fabrizio , Marcello Elena , Di Luca Monica , Fuhrmann Martin , Remy Stefan , Bano Daniele , Nicotera Pierluigi
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression
Authors: Zhang Dandan , Ni Ni , Wang Yuyao , Tang Zhimin , Gao Huiqin , Ju Yahan , Sun Na , He Xiaoyu , Gu Ping , Fan Xianqun
Published: August 2020

Adipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.
On-target versus off-target effects of drugs inhibiting the replication of SARS-CoV-2
Authors: Sauvat Allan , Ciccosanti Fabiola , Colavita Francesca , Di Rienzo Martina , Castilletti Concetta , Capobianchi Maria Rosaria , Kepp Oliver , Zitvogel Laurence , Fimia Gian Maria , Piacentini Mauro , Kroemer Guido
Published: August 2020

The current epidemic of coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) calls for the development of inhibitors of viral replication. Here, we performed a bioinformatic analysis of published and purported SARS-CoV-2 antivirals including imatinib mesylate that we found to suppress SARS-CoV-2 replication on Vero E6 cells and that, according to the published literature on other coronaviruses is likely to act on-target, as a tyrosine kinase inhibitor. We identified a cluster of SARS-CoV-2 antivirals with characteristics of lysosomotropic agents, meaning that they are lipophilic weak bases capable of penetrating into cells. These agents include cepharentine, chloroquine, chlorpromazine, clemastine, cloperastine, emetine, hydroxychloroquine, haloperidol, ML240, PB28, ponatinib, siramesine, and zotatifin (eFT226) all of which are likely to inhibit SARS-CoV-2 replication by non-specific (off-target) effects, meaning that they probably do not act on their ‘official’ pharmacological targets, but rather interfere with viral replication through non-specific effects on acidophilic organelles including autophagosomes, endosomes, and lysosomes. Imatinib mesylate did not fall into this cluster. In conclusion, we propose a tentative classification of SARS-CoV-2 antivirals into specific (on-target) versus non-specific (off-target) agents based on their physicochemical characteristics.
WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner
Authors: Chen Shijie , Li Yuezhan , Zhi Shuang , Ding Zhiyu , Wang Weiguo , Peng Yi , Huang Yan , Zheng Ruping , Yu Haiyang , Wang Jianlong , Hu Minghua , Miao Jinglei , Li Jinsong
Published: August 2020

N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m6A modification at the 3′UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m6A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.
Dead cells release a ‘necrosignal’ that activates antibiotic survival pathways in bacterial swarms
Authors: Bhattacharyya Souvik , Walker David M. , Harshey Rasika M.
Published: August 2020

Swarming is a form of collective bacterial motion enabled by flagella on the surface of semi-solid media. Swarming populations exhibit non-genetic or adaptive resistance to antibiotics, despite sustaining considerable cell death. Here, we show that antibiotic-induced death of a sub-population benefits the swarm by enhancing adaptive resistance in the surviving cells. Killed cells release a resistance-enhancing factor that we identify as AcrA, a periplasmic component of RND efflux pumps. The released AcrA interacts on the surface of live cells with an outer membrane component of the efflux pump, TolC, stimulating drug efflux and inducing expression of other efflux pumps. This phenomenon, which we call ‘necrosignaling’, exists in other Gram-negative and Gram-positive bacteria and displays species-specificity. Given that adaptive resistance is a known incubator for evolving genetic resistance, our findings might be clinically relevant to the rise of multidrug resistance.
A molecular assembler that produces polymers
Authors: Engwerda Anthonius H. J. , Fletcher Stephen P.
Published: August 2020

Molecular nanotechnology is a rapidly developing field, and tremendous progress has been made in developing synthetic molecular machines. One long-sought after nanotechnology is systems able to achieve the assembly-line like production of molecules. Here we report the discovery of a rudimentary synthetic molecular assembler that produces polymers. The molecular assembler is a supramolecular aggregate of bifunctional surfactants produced by the reaction of two phase-separated reactants. Initially self-reproduction of the bifunctional surfactants is observed, but once it reaches a critical concentration the assembler starts to produce polymers instead of supramolecular aggregates. The polymer size can be controlled by adjusting temperature, reaction time, or introducing a capping agent. There has been considerable debate about molecular assemblers in the context of nanotechnology, our demonstration that primitive assemblers may arise from simple phase separated reactants may provide a new direction for the design of functional supramolecular systems.
Author Correction: The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding
Authors: Windler F. , Bönigk W. , Körschen H. G. , Grahn E. , Strünker T. , Seifert R. , Kaupp U. B.
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Tobacco smoke and morphine alter peripheral and CNS inflammation following HIV infection in a humanized mouse model
Authors: Cornwell William D. , Sriram Uma , Seliga Alecia , Zuluaga-Ramirez Viviana , Gajghate Sachin , Rom Slava , Winfield Malika , Heldt Nathan A. , Ambrose David , Rogers Thomas J. , Persidsky Yuri
Published: August 2020

Tobacco smoking is common in HIV-infected patients, and is prevalent among intravenous opiate abusers. Conversely, intravenous opiate abusers are more likely HIV-infected, and opiate abuse is associated with more severe neuroinflammation. Given the coincident use of tobacco smoking among HIV-infected intravenous drug users (IVDUs), we set out to study the effects of smoke exposure, chronic morphine administration, and HIV infection using the NSG humanized mouse model. Our results show that smoke, morphine, and the combination promotes the decline in CD4+ T cells in HIV-infected mice. Further, chronic morphine administration increases the numbers of circulating CD8+ T cells which express the inhibitory receptor PD-1, as well as the cytolytic proteins perforin and granzyme B in the infected mice. We also found that the combination of smoke and morphine inhibited the expression of IL-1α, IL-4 and IL-17A. Finally, the combination of smoke and morphine exposure induces microglial activation following infection, as well as in the absence of HIV infection. To our knowledge, this is the first report to assess the combined effects of smoke and chronic morphine exposure on the inflammation associated with HIV infection, and demonstrate that these two insults exert significant neuroinflammatory activity.
Core design principles for nurturing organization-level selection
Authors: Wilson David Sloan , Philip Melvin M. , MacDonald Ian F. , Atkins Paul W. B. , Kniffin Kevin M.
Published: August 2020

Dynamic relationships between individuals and groups have been a focus for evolutionary theorists and modelers for decades. Among evolutionists, selfish gene theory promotes reductionist approaches while multilevel selection theory encourages a context-sensitive approach that appreciates that individuals and groups can both matter. Among economists, a comparable contrast is found wherein the reductionist shareholder primacy theory most associated with Nobel laureate Milton Friedman is very different from the context-sensitive focus on managing common resources that Nobel laureate Elinor Ostrom pioneered. In this article, we examine whether the core design principles that Ostrom advanced can cultivate selection at supra-individual levels across different domains. We show that Ostrom’s design principles that were forged in the context of managing natural resources are associated with positive outcomes for human social groups across a variety of functional domains.