bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation
Authors: Clay Delisa E. , Bretscher Heidi S. , Jezuit Erin A. , Bush Korie B. , Fox Donald T.
Published: October 2021

Cycling cells must respond to DNA double-strand breaks (DSBs) to avoid genome instability. Missegregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incompletely understood. We previously showed that Drosophilamelanogaster papillar cells lack DSB checkpoints (as observed in many cancer cells). Here, we show that papillar cells still recruit early acting repair machinery (Mre11 and RPA3) and the Fanconi anemia (FA) protein Fancd2 to DSBs. These proteins persist as foci on DSBs as cells enter mitosis. Repair foci are resolved in a stepwise manner during mitosis. DSB repair kinetics depends on both monoubiquitination of Fancd2 and the alternative end-joining protein DNA polymerase θ. Disruption of either or both of these factors causes micronuclei after DNA damage, which disrupts intestinal organogenesis. This study reveals a mechanism for how cells with inactive DSB checkpoints can respond to DNA damage that persists into mitosis.
Edge Raman enhancement at layered PbI2 platelets induced by laser waveguide effect
Authors: Ma Heyi , Wu Xianxin , Du Wenna , Zhao Liyun , Zhong Yangguang , Chen Shulin , Gao Peng , Yue Shuai , Zhang Qing , Liu Wei , Liu Xinfeng
Published: October 2021

As a two-dimensional (2D) layered semiconductor, lead iodide (PbI2) has been widely used in optoelectronics owing to its unique crystal structure and distinctive optical and electrical properties. A comprehensive understanding of its optical performance is essential for further application and progress. Here, we synthesized regularly shaped PbI2 platelets using the chemical vapor deposition method. Raman scattering spectroscopy of PbI2 platelets was predominantly enhanced when the laser radiated at the edge according to Raman mapping spectroscopy. Combining the outcome of polarized Raman scattering spectroscopy and finite-difference time domain simulation analysis, the Raman enhancement was proven to be the consequence of the enhancement effects inherent to the high refractive index contrast waveguide, which is naturally formed in well-defined PbI2 platelets. Because of the enlarged excited area determined by the increased propagation length of the laser in the PbI2 platelet formed waveguide, the total Raman enhancements are acquired rather than a localized point enhancement. Finally, the Raman enhancement factor is directly related to the thickness of the PbI2 platelet, which further confirms the waveguide-enhanced edge Raman. Our investigation of the optical properties of PbI2 platelets offers reference for potential 2D layered-related optoelectronic applications.
Agaciro, vernacular memory, and the politics of memory in post-genocide Rwanda
Authors: Mwambari David
Published: October 2021

Recent debates in post-genocide and post-war Rwanda have explored how official commemorations of the Genocide Against the Tutsi in many ways borrow and ‘mimic’ the Holocaust memory ‘paradigm’. The academic canon on post-1994 Rwanda focuses the mostly on politics around this official memory that has evolved into hegemonic memory and on how it has been mobilized to promote a selective memory of the past. However, there is little analysis of vernacular, bottom-up memory practices that have evolved alongside the official one. Using observation, semi-structured interviews, and secondary sources, this article examines vernacular memory practices of mourning the wartime missing in Rwanda. Through the concepts of ‘multidirectional’ and ‘traveling’ memory, this study examines how survivors of these interconnected violent histories that unfolded in two different countries claim multi-faceted Agaciro (dignity, self-respect, and self-worth) through two different memory approaches. The article argues that while actors in official memory approach claim Agaciro through borrowing from another global hegemonic memory, respondents in this study created vernacular avenues to remember their missing loved ones. The article finds that while hegemonic memory might appear to only compete with vernacular memory, there are also ‘knots’ that connect these two memory forms in Rwanda’s context and beyond. In its conclusion, the article proposes an Agaciro-centred approach to examine the relationships between official and unofficial memory practices that have been reenergized through protests both offline and online in Rwanda and beyond. The article contributes to scholarship on Rwanda’s post-genocide memory politics, transcultural memory, and decolonial perspectives on dignity.
Efficient production of isomaltose and isomaltooligosaccharides from starch using 1,4-α-glucan 6-α-glucosyltransferase and isopullulanase
Authors: Kitagawa Noriaki , Watanabe Hikaru , Mori Tetsuya , Nishimoto Tomoyuki , Aga Hajime , Ushio Shimpei , Yamamoto Koryu
Published: October 2021

We attempted to develop an efficient method for producing isomaltose, a disaccharide consisting of an α-(1→6)-linkage, from starch by combining enzymes of known activity. We found that the combination of 1,4-α-glucan 6-α-glucosyltransferase from Bacillus globisporus N75 and isopullulanase from Aspergillus brasiliensis ATCC 9642 led to the efficient synthesis of isomaltose. Inclusion of isoamylase and cyclomaltodextrin glucanotransferase resulted in increased efficiency, with production yields exceeding 70%. Furthermore, we considered that isomaltooligosaccharides could be synthesized from starch by combining 1,4-α-glucan 6-α-glucosyltransferase from Paenibacillus sp. PP710 and isopullulanase. In reactions that additionally utilized isoamylase and α-amylase, the total concentration of product, which included a series of isomaltooligosaccharides from isomaltose to isomaltodecaose, was 131 m m, and the ratio of 6-linked glucopyranosyl bonds to all bonds was 91.7% at a substrate concentration of 10%. The development of these manufacturing methods will accelerate the industrial production of isomaltose and isomaltooligosaccharides.
Mixed polysaccharides derived from shiitake mushroom, Poriacocos, Ginger, and Tangerine peel prevent the H1N1 virus infections in mice
Authors: Yang Diqi , Hu Minghua , Zhu Hongmei , Chen Jianguo , Wang Dehai , Ding Mingxing , Han Li
Published: October 2021

The pandemic influenza A (H1N1) virus spread globally and posed one of the most serious global public health challenges. The traditional Chinese medicine is served as a complementary treatment strategy with vaccine immunization. Here, we demonstrated that the mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger, and tyangerine peel prevent the H1N1 virus infections in mice. MP pretreatment attenuated H1N1 virus-induced weight loss, clinical symptoms, and death. The lymphocytes detection results showed that the CD3+, CD19+, and CD25+ cell proportions were upregulated in thymus under MP pretreatment. Besides, MP pretreatment reduced the inflammatory cell infiltration and increased the cell proportions of CD19+, CD25+, and CD278+ in lung. However, MP treatment have no effective therapeutic effect after H1N1 virus challenge. The current study suggested that pretreatment with MPs could attenuate H1N1 virus-induced lung injury and upregulate humoral and cellular immune responses in nonimmunized mice.
Natural tetramic acids elicit multiple inhibitory actions against mitochondrial machineries presiding over oxidative phosphorylation
Authors: Unten Yufu , Murai Masatoshi , Sakai Katsuyuki , Asami Yukihiro , Yamamoto Takenori , Masuya Takahiro , Miyoshi Hideto
Published: October 2021

The mitochondrial machineries presiding over ATP synthesis via oxidative phosphorylation are promising druggable targets. Fusaramin, a 3-acyl tetramic acid isolated from Fusarium concentricum FKI-7550, is an inhibitor of oxidative phosphorylation in Saccharomyces cerevisiae mitochondria, although its target has yet to be identified. Fusaramin significantly interfered with [3H]ADP uptake by yeast mitochondria at the concentration range inhibiting oxidative phosphorylation. A photoreactive fusaramin derivative (pFS-5) specifically labeled voltage-dependent anion channel 1 (VDAC1), which facilitates trafficking of ADP/ATP across the outer mitochondrial membrane. These results strongly suggest that the inhibition of oxidative phosphorylation by fusaramin is predominantly attributable to the impairment of VDAC1 functions. Fusaramin also inhibited FoF1-ATP synthase and ubiquinol-cytochrome c oxidoreductase (complex III) at concentrations higher than those required for the VDAC inhibition. Considering that other tetramic acid derivatives are reported to inhibit FoF1-ATP synthase and complex III, natural tetramic acids were found to elicit multiple inhibitory actions against mitochondrial machineries.
Faecal Calprotectin from Ileostomy Output Is Sensitive and Specific for the Prediction of Small Bowel Inflammation in Patients with Crohn’s Disease
Authors: Daoud Nader D , Hashash Jana G , Picco Michael F , Farraye Francis A
Published: October 2021

Background

Severe Crohn’s disease [CD] can result in extensive bowel resections and need for creation of an ileostomy. Faecal calprotectin [FC] is well studied in CD management, though its role in patients who have an ileostomy is unclear. Our aim is to understand if FC is a useful adjunct to radiographic or endoscopic studies in identifying recurrent CD after surgery in patients with an ileostomy.

Methods

Between January 1, 2017, and September 30, 2020, we searched the Mayo Clinic electronic medical record retrospectively for adult patients with ICD-10 code for CD, and a surgical history of an ileostomy. Patients were included in the analysis if they had at least one FC measured and a concomitant radiographic imaging and/or endoscopic procedure. An abnormal FC was defined as greater than 60 µg/g.

Results

Of 51 patients who met our inclusion criteria, 17 had an FC level >60 µg/g. Of these 17 patients, 14 had imaging and/or an ileoscopy confirming the presence of small bowel inflammation, with a sensitivity of 87.5%. Of the remaining 34 patients with an FC level ≤60 µg/g, 32 patients had imaging and/or ileoscopy demonstrating no small bowel inflammation, with a specificity of 91.4%. FC from an ileostomy effluent had a positive predictive value of 82.3%, a negative predictive value of 94.1% and test diagnostic accuracy of 90.1%.

Conclusion

FC from an ileostomy effluent is a highly sensitive and specific test for the assessment and monitoring of small bowel inflammation and disease recurrence in patients with CD.
An unusual case of dilated coronary sinus: case report and clinical implications
Authors: Cardi Thomas , Ohana Mickaël , Marzak Halim , Jesel Laurence
Published: October 2021

Background 

The presence of a dilated coronary sinus (CS) assessed by transthoracic echocardiography (TTE) is highly suggestive of inferior or superior vena cava (SVC) anomalies, in the absence of a shunt. The most frequent finding is the persistence of a left superior vena cava (LSVC): well-known feature to electrophysiologists. Abnormal inferior vena cava (IVC) drainage is another cause of CS dilatation.

Case summary 

An 83-year-old woman presented with heart failure symptoms, atrial fibrillation with rapid ventricular rate, and a dilated CS assessed by TTE. Atrioventricular (AV) node ablation was considered given the poor efficacy of a rate control strategy. Cardiac computed tomography (CT) revealed a double SVC with an LSVC draining directly into the dilated CS. Single-lead pacemaker implantation was performed using a right-sided vascular access with no technical difficulties. An aborted AV node ablation procedure was due to the impossibility of getting to the right atrium. Fluoroscopy and CT imaging at second look analysis confirmed the diagnosis of an abnormal IVC with an agenesia of its supra-hepatic segment directly drained into the CS.

Discussion 

Our clinical case illustrates an unusual and rare double venous abnormality: both LSVC and IVC directly drained into the CS and were responsible for its massive dilatation.
Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence
Authors: Fu Ci , Beattie Sarah R , Jezewski Andrew J , Robbins Nicole , Whitesell Luke , Krysan Damian J , Cowen Leah E
Published: October 2021

The opportunistic human fungal pathogen Cryptococcus neoformans has tremendous impact on global health, causing 181,000 deaths annually. Current treatment options are limited, and the frequent development of drug resistance exacerbates the challenge of managing invasive cryptococcal infections. In diverse fungal pathogens, the essential molecular chaperone Hsp90 governs fungal survival, drug resistance, and virulence. Therefore, targeting this chaperone has emerged as a promising approach to combat fungal infections. However, the role of Hsp90 in supporting C. neoformans pathogenesis remains largely elusive due to a lack of genetic characterization. To help dissect the functions of Hsp90 in C. neoformans, we generated a conditional expression strain in which HSP90 is under control of the copper-repressible promoter CTR4-2. Addition of copper to culture medium depleted Hsp90 transcript and protein levels in this strain, resulting in compromised fungal growth at host temperature; increased sensitivity to stressors, including the azole class of antifungals; altered C. neoformans morphology; and impaired melanin production. Finally, leveraging the fact that copper concentrations vary widely in different mouse tissues, we demonstrated attenuated virulence for the CTR4-2p-HSP90 mutant specifically in an inhalation model of Cryptococcus infection. During invasion and establishment of infection in this mouse model, the pathogen is exposed to the relatively high copper concentrations found in the lung as compared to blood. Overall, this work generates a tractable genetic system to study the role of Hsp90 in supporting the pathogenicity of C. neoformans and provides proof-of-principle that targeting Hsp90 holds great promise as a strategy to control cryptococcal infection.
Effect of Parenteral Energy or Amino Acid Doses on In-Hospital Mortality Among Patients With Aspiration Pneumonia: A Cohort Medical Claims Database Study
Authors: Maeda Keisuke , Murotani Kenta , Kamoshita Satoru , Horikoshi Yuri , Kuroda Akiyoshi
Published: October 2021

Background

This study examined the association between parenteral energy/amino acid doses and in-hospital mortality among inpatients on long-term nil per os (NPO) status, using a medical claims database in Japan.

Methods

Hospitalized patients with aspiration pneumonia, aged 65 and older, and on more than 7-day NPO status were identified in a medical claims database between January 2013 and December 2018. Using multivariate logistic regression and regression analyses, we examined the association between mean parenteral energy/amino acid doses and in-hospital mortality, and secondarily, the association between prognosis (in-hospital mortality, inability to receive full oral intake, readmission, and hospital stay length) and 4 groups of mean amino acid doses (no dose: 0 g/kg/day; very low dose: >0, ≤0.3 g/kg/day; low dose: >0.3, ≤0.6 g/kg/day; moderate dose: >0.6 g/kg/day).

Results

The analysis population included 20 457 inpatients (≥80 years: 78.3%). In total, 5 920 mortalities were recorded. Increased amino acid doses were significantly associated with reduced in-hospital mortality (p < .001). With a no dose reference level, the odds ratios (95% confidence interval) of in-hospital mortality adjusted for potential confounders were 0.78 (0.72–0.85), 0.74 (0.67–0.82), and 0.69 (0.59–0.81) for very low, low, and moderate amino acid doses, respectively. Additionally, patients prescribed amino acid dose levels more than 0.6 g/kg/day had shorter hospitalization periods than those prescribed none.

Conclusions

Increased amino acid doses were associated with reduced in-hospital mortality. Sufficient amino acid administration is recommended for patients with aspiration pneumonia requiring NPO status.
The Impact of Aging Policy on Societal Age Stereotypes and Ageism
Authors: Ng Reuben , Chow Ting Yu Joanne , Yang Wenshu
Published: October 2021

Background and Objectives

While studies have researched ageism in public policy, few investigated the impact of aging policy on ageism—typically, an unintended consequence. Ageism is linked to $63 billion in health care costs, so its antecedents are of interest. We test the association between Aging Policy Agenda Setting and Societal Age Stereotypes and hypothesize a mediating pathway via Medicalization of Aging, moderated by demographics.

Research Design and Methods

Scholars identified Singapore’s Pioneer Generation Policy (PGP) as one of the largest policy implementations in recent years, where the agenda was set by the Prime Minister at an equivalent State of the Union address in 2013, and US$7 billion allocated to fund outpatient health care costs for aged 65 years or older. More than 400,000 older adults received a PGP card and home visits by trained volunteers who co-devised a personalized utilization plan. We leveraged a 10-billion-word data set with more than 30 million newspaper and magazine articles to dynamically track Societal Age Stereotype scores over 8 years from pre- to postpolicy implementation.

Results

Societal Age Stereotypes followed a quadratic trend: Prior to the Aging Policy Agenda Setting from 2010 to 2014, stereotypes were trending positive; after 2014, it trended downward to become more negative. Medicalization of Aging mediated the relationship between Aging Policy Agenda Setting and Societal Age Stereotypes. Furthermore, Old-age Support Ratio moderated the mediational model, suggesting that the impact of policy on medicalization is stronger when a society is more aged.

Discussion and Implications

We provided a framework for policymakers to ameliorate the unintended consequences of aging policies on societal ageism—if unaddressed, it will exert an insidious toll on older adults, even if initial policies are well-intentioned.
Neurofilament Light Chain Is a Novel Biomarker for Major Depression and Related Executive Dysfunction
Authors: Chen Mu-Hong , Liu Yu-Li , Kuo Hsiang-Wei , Tsai Shih-Jen , Hsu Ju-Wei , Huang Kai-Lin , Tu Pei-Chi , Bai Ya-Mei
Published: October 2021

Background

Evidence suggests that major depressive disorder is related to neuroaxonal injury and that neurofilament light chain (NfL) is a biomarker of neuroaxonal injury. In addition, proinflammatory cytokines have been reported to be associated with major depression and neuroaxonal injury.

Methods

Forty patients with major depression and 40 age- and sex-matched healthy control participants were enrolled for the measurement of NfL and proinflammatory cytokines and assessment of executive function. General linear models were used to examine the association between NfL levels, proinflammatory cytokine levels, and executive function.

Results

Patients with major depressive disorder exhibited significantly higher NfL levels (P = .007) than the control participants. NfL levels were positively related to log-transformed levels of tumor necrosis factor-α (P = .004). Higher levels of NfL (P = .002) and tumor necrosis factor-α (P = .013) were associated with greater deficits in executive function.

Discussion

NfL was a novel biomarker for major depressive disorder and related executive dysfunction. Further studies are necessary to elucidate the role of NfL in the pathophysiology of major depression and related cognitive impairment.
Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care
Authors: Delory Tristan , Le Bel Josselin , Lariven Sylvie , Peiffer-Smadja Nathan , Lescure François-Xavier , Bouvet Elisabeth , Jeanmougin Pauline , Tubach Florence , Boëlle Pierre-Yves
Published: October 2021

Background

Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care.

Objectives

To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs.

Methods

We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections.

Results

We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%–42.2%) for amoxicillin, 16.6% (95% CI, 15.9%–17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%–7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%–6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001).

Conclusions

CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.
Detecting Autoantibodies by Multiparametric Assays: Impact on Prevention, Diagnosis, Monitoring, and Personalized Therapy in Autoimmune Diseases
Authors: Cinquanta Luigi , Infantino Maria , Bizzaro Nicola
Published: October 2021

Background

The introduction of multiparametric autoantibody tests has been proposed to improve the accuracy of the immunological diagnosis of autoimmune diseases (AID) and to accelerate time for completing the diagnostic process. Multiplex tests are capable of detecting many autoantibodies in a single run whereas a traditional immunoassay uses a single antigen to detect only a single specificity of autoantibodies. The reasons why multiplex tests could replace conventional immunoassays lie in the evidence that they allow for more efficient handling of large numbers of samples by the laboratory, while ensuring greater diagnostic sensitivity in AID screening.

Content

This review aims to highlight the important role that multiparametric tests could assume when designed for defined profiles they are used not only for diagnostic purposes but also to predict the onset of AID to identify clinical phenotypes and to define prognosis. Furthermore, differences in the antibody profile could identify which subjects will be responsive or not to a specific pharmacological treatment.

The use of autoantibody profiles, when specifically requested and performed with clinically validated technologies, can represent a significant step toward personalized medicine in autoimmunology.
The role of invasion and urbanization gradients in shaping avian community composition
Authors: Rogers Andrew M , Griffin Andrea S , Lermite Françoise , van Rensburg Berndt , Archibald Carla , Kark Salit
Published: October 2021

The extent to which native species utilize urban environments depends on species responses to multiple threatening processes. Here, we aimed to quantify changes in bird communities in response to changing habitat structure, invasive species and aggressive native species. We conducted surveys in two independently invaded regions with similar patterns of urban development. The study regions were New South Wales (NSW) and Queensland (QLD), Australia. We observed 127 species in NSW and 144 species in QLD. Most species (NSW 83 and QLD 84) are urban adapters making use of some or all urban sub-environments. Urban avoiders, species only found in remnant vegetation, were the second largest group (urban avoiders: NSW 23 and QLD 31). We found the lowest richness in the most urban sites (urban exploiters: NSW 10 and QLD 15). Using generalized linear mixed models, we found a non-significant relationship between species richness and the abundance of aggressive species like the common myna and noisy miners, Manorina melanocephala, but a significant positive correlation with the percentage of shrub cover at a site. As there is a gradual loss of species with increasing urbanization, retaining higher complexity in vegetation structure in urban areas will support large numbers of species and could help mitigate the potential impacts of aggressive urban-adapted species and habitat loss.
Glucose regulates cotton fiber elongation by interacting with brassinosteroid
Authors: Li Xinyang , Liu Wei , Ren Zhongying , Wang Xingxing , Liu Ji , Yang Zuoren , Zhao Junjie , Pei Xiaoyu , Liu Yangai , He Kunlun , Zhang Fei , Zhang Zhiqiang , Yang Daigang , Ma Xiongfeng , Li Wei
Published: October 2021

In plants, glucose (Glc) plays important roles, as a nutrient and signal molecule, in the regulation of growth and development. However, the function of Glc in fiber development of upland cotton (Gossypium hirsutum) is unclear. Here, using gas chromatography-mass spectrometry (GC-MS), we found that the Glc content in fibers was higher than that in ovules during the fiber elongation stage. In vitro ovule culture revealed that lower Glc concentrations promoted cotton fiber elongation, while higher concentrations had inhibitory effects. The hexokinase inhibitor N-acetylglucosamine (NAG) inhibited cotton fiber elongation in the cultured ovules, indicating that Glc-mediated fiber elongation depends on the Glc signal transduced by hexokinase. RNA sequencing (RNA-seq) analysis and hormone content detection showed that 150mM Glc significantly activated brassinosteroid (BR) biosynthesis, and the expression of signaling-related genes was also increased, which promoted fiber elongation. In vitro ovule culture clarified that BR induced cotton fiber elongation in a dose-dependent manner. In hormone recovery experiments, only BR compensated for the inhibitory effects of NAG on fiber elongation in a Glc-containing medium. However, the ovules cultured with the BR biosynthetic inhibitor brassinazole and from the BR-deficient cotton mutant pag1 had greatly reduced fiber elongation at all the Glc concentrations tested. This demonstrates that Glc does not compensate for the inhibition of fiber elongation caused by BR biosynthetic defects, suggesting that the BR signaling pathway works downstream of Glc during cotton fiber elongation. Altogether, our study showed that Glc plays an important role in cotton fibre elongation, and crosstalk occurs between Glc and BR signaling during modulation of fiber elongation.
The tidal evolution of the Fornax dwarf spheroidal and its globular clusters
Authors: Borukhovetskaya Alexandra , Errani Raphaël , Navarro Julio F , Fattahi Azadeh , Santos-Santos Isabel
Published: October 2021

The dark matter content of the Fornax dwarf spheroidal galaxy inferred from its kinematics is substantially lower than expected from LCDM cosmological simulations. We use N-body simulations to examine whether this may be the result of Galactic tides. We find that, despite improved proper motions from the Gaia mission, the pericentric distance of Fornax remains poorly constrained, mainly because its largest velocity component is roughly antiparallel to the solar motion. Translating Fornax’s proper motion into a Galactocentric velocity is, thus, sensitively dependent on Fornax’s assumed distance: the observed distance uncertainty, $\pm 8\,{{\rm per\,cent}}$, implies pericentric distances that vary between rperi ∼ 50 and ∼150 kpc. Our simulations show that for rperi in the lower range of that estimate, an LCDM subhalo with maximum circular velocity Vmax = 40 km s−1 (or virial mass $M_{200}\approx 10^{10}\, \rm M_\odot$, as expected from LCDM) would be tidally stripped to Vmax ∼ 23 km s−1 over 10 Gyr. This would reduce the dark mass within the Fornax stellar half-mass radius to about half its initial value, bringing it into agreement with observations. Tidal stripping affects mainly Fornax’s dark matter halo; its stellar component is affected little, losing less than $5\,{{\rm per\,cent}}$ of its initial mass in the process. We also explore the effect of Galactic tides on the dynamical friction decay times of Fornax’s population of globular clusters (GCs) and find little evidence for substantial changes, compared with models run in isolation. A population of GCs with initial orbital radii between 1 and 2 kpc is consistent with the present-day spatial distribution of Fornax GCs, despite assuming a cuspy halo. Neither the dark matter content nor the spatial distribution of GCs of Fornax seems inconsistent with a simple model where Fornax inhabits a tidally stripped cuspy cold dark matter halo.
Epoch of reionization power spectrum limits from Murchison Widefield Array data targeted at EoR1 field
Authors: Rahimi M , Pindor B , Line J L B , Barry N , Trott C M , Webster R L , Jordan C H , Wilensky M , Yoshiura S , Beardsley A , Bowman J , Byrne R , Chokshi A , Hazelton B J , Hasegawa K , Howard E , Greig B , Jacobs D , Joseph R , Kolopanis M , Lynch C , McKinley B , Mitchell D A , Murray S , Morales M F , Pober J C , Takahashi K , Tingay S J , Wayth R B , Wyithe J S B , Zheng Q
Published: October 2021

Current attempts to measure the 21 cm power spectrum of neutral hydrogen during the epoch of reionization (EoR) are limited by systematics that produce measured upper limits above both the thermal noise and the expected cosmological signal. These systematics arise from a combination of observational, instrumental, and analysis effects. In order to further understand and mitigate these effects, it is instructive to explore different aspects of existing data sets. One such aspect is the choice of observing field. To date, MWA EoR observations have largely focused on the EoR0 field. In this work, we present a new detailed analysis of the EoR1 field. The EoR1 field is one of the coldest regions of the southern radio sky, but contains the very bright radio galaxy Fornax-A. The presence of this bright extended source in the primary beam of the interferometer makes the calibration and analysis of EoR1 particularly challenging. We demonstrate the effectiveness of a recently developed shapelet model of Fornax-A in improving the results from this field. We also describe and apply a series of data quality metrics that identify and remove systematically contaminated data. With substantially improved source models, upgraded analysis algorithms and enhanced data quality metrics, we determine EoR power spectrum upper limits based on analysis of the best ∼14-h data observed during 2015 and 2014 at redshifts 6.5, 6.8, and 7.1, with the lowest 2σ upper limit at z = 6.5 of Δ2 ≤ (73.78 mK)2 at k = 0.13 h Mpc−1, improving on previous EoR1 measurement results.
AGN orientation through the spectroscopic correlations and model of dusty cone shell
Authors: Lakićević M , Kovačević-Dojčinović J , Popović L Č
Published: October 2021

The differences between Narrow Line Seyfert 1 galaxies (NLS1s) and Broad Line AGNs (BLAGNs) are not completely understood; it is thought that they may have different inclinations and/or physical characteristics. The FWHM(H β)–luminosities correlations are found for NLS1s and their origin is the matter of debate. Here we investigated the spectroscopic parameters and their correlations considering a dusty, cone model of AGN. We apply a simple conical dust distribution (spreading out of broad line region, BLR), assuming that the observed surface of the model is in a good correlation with MIR emission. The dusty cone model in combination with a BLR provides the possibility to estimate luminosity dependence on the cone inclination. The FWHM(H β)–luminosities correlations obtained from model in comparison with observational data show similarities which may indicate the influence of AGN inclination and structure to this correlation. An alternative explanation for FWHM(H β)–luminosities correlations is the selection effect by the black hole mass. These FWHM(H β)–luminosities correlations may be related to the starburst in AGNs, as well. The distinction between spectral properties of the NLS1s and BLAGNs could be caused by multiple effects: beside physical differences between NLS1s and BLAGNs (NLS1s have lighter black hole mass than BLAGNs), inclination of the conical AGN geometry may have important role as well, where NLS1s may be seen in lower inclination angles.
Concordance of multiple methods to define resiliency and vulnerability to sleep loss depends on Psychomotor Vigilance Test metric
Authors: Yamazaki Erika M , Casale Courtney E , Brieva Tess E , Antler Caroline A , Goel Namni
Published: October 2021

Study Objectives

Sleep restriction (SR) and total sleep deprivation (TSD) reveal well-established individual differences in Psychomotor Vigilance Test (PVT) performance. While prior studies have used different methods to categorize such resiliency/vulnerability, none have systematically investigated whether these methods categorize individuals similarly.

Methods

Forty-one adults participated in a 13-day laboratory study consisting of two baseline, five SR, four recovery, and one 36 h TSD night. The PVT was administered every 2 h during wakefulness. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and within each approach, six thresholds (±1 standard deviation and the best/worst performing 12.5%, 20%, 25%, 33%, and 50%) classified Resilient/Vulnerable groups. Kendall’s tau-b correlations examined the concordance of group categorizations of approaches within and between PVT lapses and 1/reaction time (RT). Bias-corrected and accelerated bootstrapped t-tests compared group performance.

Results

Correlations comparing the approaches ranged from moderate to perfect for lapses and zero to moderate for 1/RT. Defined by all approaches, the Resilient groups had significantly fewer lapses on nearly all study days. Defined by the Raw Score approach only, the Resilient groups had significantly faster 1/RT on all study days. Between-measures comparisons revealed significant correlations between the Raw Score approach for 1/RT and all approaches for lapses.

Conclusion

The three approaches defining vigilant attention resiliency/vulnerability to sleep loss resulted in groups comprised of similar individuals for PVT lapses but not for 1/RT. Thus, both method and metric selection for defining vigilant attention resiliency/vulnerability to sleep loss is critical.
An integrative omics approach reveals posttranscriptional mechanisms underlying circadian temperature compensation
Authors: Schmal Christoph , Maier Bert , Ashwal-Fluss Reut , Bartok Osnat , Finger Anna-Marie , Bange Tanja , Koutsouli Stella , Robles Maria S. , Kadener Sebastian , Herzel Hanspeter , Kramer Achim
Published: October 2021

A defining property of circadian clocks is temperature compensation, characterized by the resilience of circadian free-running periods against changes in environmental temperature. As an underlying mechanism, the balance or critical reaction hypothesis have been proposed. While the former supposes a temperature-dependent balancing of reactions with opposite effects on circadian period, the latter assumes an insensitivity of certain critical period determining regulations upon temperature changes. Posttranscriptional regulations such as temperature-sensitive alternative splicing or phosphorylation have been described as underlying reactions.

Here, we show that knockdown of cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a key regulator of 3’-end cleavage and polyadenylation, abolishes circadian temperature compensation in U-2 OS cells. We apply a combination of 3’-End-RNA-seq and mass spectrometry-based proteomics to globally quantify changes in 3’ UTR length as well as gene and protein expression between wild type and CPSF6 knock-down cells and their dependency on temperature. Analyzing differential responses upon temperature changes in wild type and CPSF6 knockdown cells reveals candidate genes underlying circadian temperature compensation. We identify that eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) is among these candidates. EIF2S1 is known as a master regulator of cellular stress responses that additionally regulates circadian rhythms. We show that knockdown of EIF2S1 furthermore impairs temperature compensation, suggesting that the role of CPSF6 in temperature compensation may be mediated by its regulation of EIF2S1.
A robust receptive field code for optic flow detection and decomposition during self-motion
Authors: Zhang Yue , Huang Ruoyu , Nörenberg Wiebke , Arrenberg Aristides B.
Published: October 2021

The perception of optic flow is essential for any visually guided behaviour of a moving animal. To mechanistically predict behaviour and understand the emergence of self-motion perception in vertebrate brains, it is essential to systematically characterize the motion receptive fields (RFs) of optic flow processing neurons. Here, we present the fine-scale RFs of thousands of motion-sensitive neurons studied in the diencephalon and the midbrain of zebrafish. We found neurons that serve as linear filters and robustly encode directional and speed information of translation-induced optic flow. These neurons are topographically arranged in pretectum according to translation direction. The unambiguous encoding of translation enables the decomposition of translational and rotational self-motion information from mixed optic flow. In behavioural experiments, we successfully demonstrated the predicted decomposition in the optokinetic and optomotor responses. Together, our study reveals the algorithm and the neural implementation for self-motion estimation in a vertebrate visual system.
Phylogenetic analyses for orthogroup-based classification of GDSL-type esterase/lipase (GELP) family in angiosperm representative species
Authors: Alberto Cenci , Mairenys Concepción-Hernández , Angenon Geert , Mathieu Rouard
Published: October 2021

GDSL-type esterase/lipase (GELP) enzymes have multiple functions in plants, spanning from developmental processes to the response to biotic and abiotic stresses. Genes encoding GELP belong to a large gene family with several tens to more than hundred members per angiosperm species.

Here, we applied iterative phylogenetic analyses to identify 10 main clusters subdivided into 44 expert-curated reference orthogroups (OGs) using three monocot and five dicot genomes. Our results show that some GELP OGs expanded while others were maintained as single copy genes.

This semi-automatic approach proves to be effective to characterize large gene families and provides a solid classification framework for the GELP members in angiosperms. The orthogroup-based reference will be useful to perform comparative studies, infer gene functions and better understand the evolutionary history of this gene family.
Application of machine learning methods in clinical trials for precision medicine
Authors: Wang Yizhuo , Carter Bing Z. , Li Ziyi , Huang Xuelin
Published: October 2021

Objective

A key component for precision medicine is a good prediction algorithm for patients’ response to treatments. We aim to implement machine learning (ML) algorithms into the response-adaptive randomization (RAR) design and improve the treatment outcomes.

Materials and Methods

We incorporated nine ML algorithms to model the relationship of patient responses and biomarkers in clinical trial design. Such a model predicted the response rate of each treatment for each new patient and provide guidance for treatment assignment. Realizing that no single method may fit all trials well, we also built an ensemble of these nine methods. We evaluated their performance through quantifying the benefits for trial participants, such as the overall response rate and the percentage of patients who receive their optimal treatments.

Results

Simulation studies showed that the adoption of ML methods resulted in more personalized optimal treatment assignments and higher overall response rates among trial participants. Compared with each individual ML method, the ensemble approach achieved the highest response rate and assigned the largest percentage of patients to their optimal treatments. For the real-world study, we successfully showed the potential improvements if the proposed design had been implemented in the study.

Conclusion

In summary, the ML-based RAR design is a promising approach for assigning more patients to their personalized effective treatments, which makes the clinical trial more ethical and appealing. These features are especially desirable for late-stage cancer patients who have failed all the FDA-approved treatment options and only can get new treatments through clinical trials.
Novelty detection in early olfactory processing of the honey bee, Apis mellifera
Authors: Lei H. , Haney S. , Jernigan C. , Guo X.J. , Cook C.N. , Bazhenov M. , Smith B.H.
Published: October 2021

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain – the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may assign a category of familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers.
In silico analysis for potential proteins and microRNAs in Glioblastoma and Parkinsonism
Authors: Banerjee Sayak , Chakraborty Souvik , Maiti Tarasankar , Bisawas Sristi
Published: October 2021

In today’s world, neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s Disease, Huntington’s Disease as well as brain cancers such as astrocytomas, ependymomas, glioblastomas have become a great threat to us. In this study, we are trying to find a probable molecular connection associated with two very much different diseases, Glioblastoma, also known as Glioblastoma Multiforme (cancers of microglial cells of our brain) and Parkinson’s disease. We at first downloaded the microarray datasets of these two diseases from Gene Expression Omnibus (GEO) and then analyzed them by the GEO2R tool. After analysis, we found 249 common upregulated differential expressed genes and 135 common downregulated differential expressed genes of these two diseases. Therefore the common differentially expressed genes, both upregulated and downregulated, were imported into STRING online tool to find out the protein-protein interactions. Now, this whole network was subjected to Cytoscape and the top ten hub genes were found by Cyto-Hubba plug-in. The top then hub genes are EGFR, CCNB1, CDK1, CCNA2, CHEK1, RAD51, MAD2L1, KIF20A, BUB1, and CCNB2. These all genes are upregulated in both diseases. To find out the biological processes, molecular functions, cellular components, and pathways associated with these hub genes Enrichr online software was used. We used miRNet software to determine the interactions of hub genes with microRNAs. This study will be useful in the future for drug targets discovery for these diseases.
Aberrant Functional Connectivity between Reward and Inhibitory Control Networks in Pre-Adolescent Binge Eating Disorder
Authors: Murray Stuart B. , Alba Celina , Duval Christina J. , Nagata Jason M. , Cabeen Ryan P. , Lee Darrin J. , Toga Arthur W. , Siegel Steven J. , Jann Kay
Published: October 2021

Background

Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied.

Methods

58 pre-adolescent children (aged 9-10-years) with BED and 66 age, BMI and developmentally-matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI (rs-fMRI) functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward (orbitofrontal cortex, nucleus accumbens, amygdala) and inhibitory control (dorsolateral prefrontal cortex, anterior cingulate cortex) networks via hypothesis-driven seed-to- seed analyses, and secondary seed-to-voxel analyses.

Results

Our findings revealed reduced FC between the dlPFC and amygdala, and between the anterior cingulate cortex and orbitofrontal cortex in pre-adolescent children with BED, relative to age, gender, BMI and developmentally matched controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses.

Conclusions

Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.