bluuebunny/crossref_metadata_2025 huggingface dataset:
Extended and cumulative effects of experimentally induced intergroup conflict in a cooperatively breeding mammal
Authors: Morris-Drake Amy , Linden Jennifer F. , Kern Julie M. , Radford Andrew N.
Published: December 2021

Conflict between rival groups is rife in nature. While recent work has begun exploring the behavioural consequences of this intergroup conflict, studies have primarily considered just the 1–2 h immediately after single interactions with rivals or their cues. Using a habituated population of wild dwarf mongooses (Helogale parvula), we conducted week-long manipulations to investigate longer-term impacts of intergroup conflict. Compared to a single presentation of control herbivore faeces, one rival-group faecal presentation (simulating a territorial intrusion) resulted in more within-group grooming the following day, beyond the likely period of conflict-induced stress. Repeated presentations of outsider cues led to further changes in baseline behaviour by the end of the week: compared to control weeks, mongooses spent less time foraging and foraged closer to their groupmates, even when there had been no recent simulated intrusion. Moreover, there was more baseline territorial scent-marking and a higher likelihood of group fissioning in intrusion weeks. Consequently, individuals gained less body mass at the end of weeks with repeated simulated intrusions. Our experimental findings provide evidence for longer-term, extended and cumulative, effects of an elevated intergroup threat, which may lead to fitness consequences and underpin this powerful selective pressure.
Invasive snake causes massive reduction of all endemic herpetofauna on Gran Canaria
Authors: Piquet Julien C. , López-Darias Marta
Published: December 2021

Invasive snakes represent a serious threat to island biodiversity, being responsible for far-reaching impacts that are noticeably understudied, particularly regarding native reptiles. We analysed the impact of the invasive California kingsnake,Lampropeltis californiae—recently introduced in the Canary Islands—on the abundance of all endemic herpetofauna of the island of Gran Canaria. We quantified the density in invaded and uninvaded sites for the Gran Canaria giant lizard,Gallotia stehlini, the Gran Canaria skink,Chalcides sexlineatus, and Boettger's wall gecko,Tarentola boettgeri. We used spatially explicit capture-recapture and distance-sampling methods forG. stehliniand active searches under rocks for the abundance of the other two reptiles. The abundance of all species was lower in invaded sites, with a reduction in the number of individuals greater than 90% forG. stehlini, greater than 80% forC. sexlineatusand greater than 50% forT. boettgeriin invaded sites. Our results illustrate the severe impact ofL. californiaeon the endemic herpetofauna of Gran Canaria and highlight the need for strengthened measures to manage this invasion. We also provide further evidence of the negative consequences of invasive snakes on island reptiles and emphasize the need for further research on this matter on islands worldwide.
A lack of repeatability creates the illusion of a trade-off between basal and plastic cold tolerance
Authors: O'Neill Erica , Davis Hannah E. , MacMillan Heath A.
Published: December 2021

The thermotolerance–plasticity trade-off hypothesis predicts that ectotherms with greater basal thermal tolerance have a lower acclimation capacity. This hypothesis has been tested at both high and low temperatures but the results often conflict. If basal tolerance constrains plasticity (e.g. through shared mechanisms that create physiological constraints), it should be evident at the level of the individual, provided the trait measured is repeatable. Here, we used chill-coma onset temperature and chill-coma recovery time (CCO and CCRT; non-lethal thermal limits) to quantify cold tolerance ofDrosophila melanogasteracross two trials (pre- and post-acclimation). Cold acclimation improved cold tolerance, as expected, but individual measurements of CCO and CCRT in non-acclimated flies were not (or only slightly) repeatable. Surprisingly, however, there was still a strong correlation between basal tolerance and plasticity in cold-acclimated flies. We argue that this relationship is a statistical artefact (specifically, a manifestation of regression to the mean; RTM) and does not reflect a true trade-off or physiological constraint. Thermal tolerance trade-off patterns in previous studies that used similar methodology are thus likely to be impacted by RTM. Moving forward, controlling and/or correcting for RTM effects is critical to determining whether such a trade-off or physiological constraint exists.
Handgrip strength and 2D : 4D in women: homogeneous samples challenge the (apparent) gender paradox
Authors: Bäck Nora , Schaefer Katrin , Windhager Sonja
Published: December 2021

The length ratio between the second and the fourth digit (2D : 4D) is a retrospective, non-invasive biomarker for prenatal androgen exposure. It was found to be negatively correlated with handgrip strength (HGS) in men, but the evidence for women is mixed. Such studies in women call for increased detection sensitivity. The present study was designed to reduce potential confounding factors, especially age and ethnicity variation. We measured the digit ratios and HGS of 125 healthy women between 19 and 31 years of age from a remote region in Austria. 2D : 4D of both hands was significantly and negatively correlated with HGS (
n
= 125, right hand:
r
= –0.255,
p
= 0.002, left hand:
r
= –0.206,
p
= 0.011). Size, direction and significance of correlation coefficients remained stable when statistically controlling for age, body weight, body height, body mass index or hours of exercise per week. This yields theory-consistent evidence that HGS and 2D : 4D are clearly associated in women—when sufficiently reducing genetic variation (confounding 2D : 4D), the ontogenetic environment and age ranges (confounding HGS) in the study population. This finding implies similar organizing effects of prenatal androgens as in men, pointing to a more parsimonious developmental mechanism and a new look into its proximate and ultimate causes.
Mycolicibacterium baixiangningiae sp. nov. and Mycolicibacterium mengxianglii sp. nov., two new rapidly growing mycobacterial species
Authors: Cheng Yanpeng , Lei Wenjing , Wang Xiaoxia , Tian Zhi , Liu Haican , Yang Jing , Lu Shan , Lai Xin-He , Pu Ji , Huang Ying , Zhang Sihui , Yang Caixin , Lian Xingxing , Bai Yibo , Wan Kanglin , Wang Suping , Xu Jianguo
Published: December 2021

Four bacterial strains (LJ126T/S18 and Z-34T/S20) recovered from faecal samples of Tibetan antelopes on the Qinghai–Tibet Plateau of China were analysed using a polyphasic approach. All four isolates were aerobic, short rod-shaped, non-motile, Gram-stain-positive, acid-fast and fast-growing. Phylogenetic analyses based upon 16S rRNA and whole-genome sequences showed that the two pair of strains formed two distinct branches within the evolutionary radiation of the genus

Mycolicibacterium

. Strains LJ126T/S18 and Z-34T/S20 were most closely related to

Mycolicibacterium austroafricanum

CCUG 37667T,

Mycobacterium aurum

NCTC 10437T,

Mycobacterium pyrenivorans

DSM 44605T,

Mycobacterium monacense

JCM 15658T,

Mycolicibacterium sarraceniae

JCM 30395T,

Mycolicibacterium tokaiense

JCM 6373T and

Mycobacterium murale

JCM 13392T, but readily distinguished from the known species by a combination of chemotaxonomic and phenotypic features and by low average nucleotide identity values (74.4–84.9 %). Consequently, the two strain pairs are considered to represent different novel species of

Mycolicibacterium

for which the names Mycolicibacterium baixiangningiae sp. nov. and Mycolicibacterium mengxianglii sp. nov. are proposed, with LJ126T (=CGMCC 1.1992T=KCTC 49535T) and Z-34T (=CGMCC 1.1993T=DSM 106172T) as the respective type strains.
Parvimonas parva sp. nov., derived from a human genito-urinary lesion
Authors: Jansson Moritz K. , Hering Silvio , Buhl Michael E. J.
Published: December 2021

A strain of obligately anaerobically growing Gram-positive cocci was isolated from a human genito-urinary sample and characterized by a polyphasic approach. Analyses of 16S rRNA gene and whole-genome sequences of this strain S3374T indicated that it belonged to the genus

Parvimonas

. Overall genome relatedness index calculations confirmed it to be phylogenetically distinct from

Parvimonas micra

(NCTC 11808T) as its most closely related species with standing in nomenclature, with average nucleotide identity and genome-to-genome distance values of 85.8 and 30.2 %, respectively. Biochemically, strain S3374T was strongly proteolytic and can be differentiated from

P. micra

(DSM 20468T) by absence of phosphatase activity. The DNA G+C content of strain S3374T was 28.6 mol%. Based on the phenotypical, biochemical and genetic findings, strain S3374T is considered to represent a novel species within the genus

Parvimonas

, for which the name Parvimonas parva sp. nov. is proposed. The type strain is S3374T (=DSM 110786T=CCOS 1934T=CCUG 74294T). This description adds strain S3374T as a second species to the genus

Parvimonas

which has so far been monotypic. While the type strain of this genus,

P. micra

, has a long standing in nomenclature and its role in human health and disease has been studied to some extent, this description of the proposed novel species represented by strain S3374T will allow microbiologists worldwide to identify isolates of P. parva sp. nov., a prerequisite for further investigation of its relevance in the clinical context and beyond.
Antifungal susceptibility profile of invasive Candida glabrata isolates (2009–2020) from a tertiary care hospital laboratory in Pakistan
Authors: Memon Saba , Farooqi Joveria , Zafar Urooj , Naqvi Syed Faheem , Zafar Afia , Jabeen Kauser
Published: December 2021

Introduction. Invasive infections with Candida glabrata are a global concern due to poor clinical outcomes and propensity to acquire resistance to antifungal agents.

Hypothesis/Gap Statement. Monitoring emerging resistance and trends in Candida glabrata, an important agent of candidemia in Pakistan, is critical for patient management; data that is missing from Pakistan.

Aim. Thus, this study evaluated antifungal resistance and MICs) distribution in invasive C. glabrata isolates from Pakistan.

Methods. This cross-sectional and retrospective study was conducted from January 2009 to March 2020 at a clinical laboratory in Pakistan that has a nation-wide network. Antifungal susceptibility data of 277 candidemia, deep organ and soft tissue (invasive) C. glabrata sensu lato isolates against fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, caspofungin and amphotericin B was retrieved. Susceptibility testing was performed using colorimetric broth microdilution and interpreted using CLSI criteria. Demographics, clinical history and outcome were studied. Chi-square test was used to demonstrate association between antifungal resistance and clinical characteristics of the patients.

Results. We identified 277 patients with invasive C. glabrata infection. Of which 48 (18.4%) isolates were resistant to fluconazole (MIC ≥64 mg l−1), one isolate each was resistant to amphotericin (MIC=2 mg l−1), anidulafungin (MIC=1 mg l−1) and micafungin (MIC=0.5 mg l−1). MIC90 for fluconazole was 64 mg l−1 and other triazoles 2 mg l−1, caspofungin 0.12 mg l−1, anidulafungin 0.06 mg l−1, micafungin 0.03 mg l−1 and amphotericin 0.5 mg l−1. Fluconazole MIC ≥64 mg l−1, caspofungin MIC >0.06 mg l−1 and amphotericin MIC >0.25 mg l−1 (above MIC50) were significantly associated with patient being alive at the time of reporting, no use of healthcare devices, nor infection with other fungi. Fluconazole resistance was significantly associated with prior antifungal use by the patient.

Conclusion. Surveillance data of antifungal resistance among common Candida species should be monitored closely for identification of resistant strains.
The prognostic and diagnostic value of intraleukocytic malaria pigment: an individual patient data pooled meta-analysis of 32,000 patients with severe falciparum malaria in Africa and Asia
Authors: Srinamon Ketsanee , Watson James A , Silamut Kamolrat , Intharabut Benjamas , Phu Nguyen Hoan , Diep Pham Thi , Lyke Kirsten E , Fanello Caterina , Seidlein Lorenz von , Chotivanich Kesinee , Dondorp Arjen M , Day Nicholas PJ , White Nicholas J
Published: December 2021

Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Accurate diagnosis and prognostic assessment are critical to clinical management. In 6,027 prospectively studied patients diagnosed with severe malaria we assessed the prognostic value of peripheral blood film counts of malaria pigment containing polymorphonu-clear leukocytes (PMNs) and monocytes. We combined these results with previously published data and show, in an individual patient data meta-analysis (n=32,035), that the proportion of pigment containing PMNs is predictive of in-hospital mortality. In African children the proportion of pigment containing PMNs is a strong indicator that the primary diagnosis is severe malaria, and it adds to the prognostic assessment from simple bedside examination, and to the conventional malaria parasite count. Microscopy assessment of pigment containing PMNs is simple and rapid, and should be performed in all patients hospitalised with suspected severe malaria.
Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation
Authors: James Jaime , Chen Yifei , Hernandez Clara M. , Forster Florian , Dagnell Markus , Cheng Qing , Saei Amir A. , Gharibi Hassan , Lahore Gonzalo Fernandez , Åstrand Annika , Malhotra Rajneesh , Malissen Bernard , Zubarev Roman A. , Arnér Elias S.J. , Holmdahl Rikard
Published: December 2021

Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor signaling. As with all protein tyrosine phosphatases the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T cell-dependent inflammatory response and development of T cell dependent autoimmune arthritis due to enhanced TCR signaling and activation of T cells, an effect neutralized by a mutation in Ncf1, a component of the NOX2 complex. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show that PTPN22 functionally interacts with Ncf1 and is regulated by oxidation via the non-catalytic C129 residue and oxidation-prone PTPN22 leads to increased severity in the development of T cell-dependent autoimmunity.

Significance statement

A hitherto unstudied aspect of PTPN22 biology is its regulation by cell redox states. Here we created a mouse model where PTPN22 was mutated to respond differentially to redox levels in vivo and found that PTPN22 function is regulated by reactive oxygen species and that redox regulation of PTPN22 impacts T-cell-dependent autoimmune inflammation.
Harmonizing Functional Connectivity Reduces Scanner Effects in Community Detection
Authors: Chen Andrew A. , Srinivasan Dhivya , Pomponio Raymond , Fan Yong , Nasrallah Ilya M. , Resnick Susan M. , Beason-Held Lori L. , Davatzikos Christos , Satterthwaite Theodore D. , Bassett Dani S. , Shinohara Russell T. , Shou Haochang
Published: December 2021

Community detection on graphs constructed from functional magnetic resonance imaging (fMRI) data has led to important insights into brain functional organization. Large studies of brain community structure often include images acquired on multiple scanners across different studies. Differences in scanner can introduce variability into the downstream results, and these differences are often referred to as scanner effects. Such effects have been previously shown to significantly impact common network metrics. In this study, we identify scanner effects in data-driven community detection results and related network metrics. We assess a commonly employed harmonization method and propose new methodology for harmonizing functional connectivity that leverage existing knowledge about network structure as well as patterns of covariance in the data. Finally, we demonstrate that our new methods reduce scanner effects in community structure and network metrics. Our results highlight scanner effects in studies of brain functional organization and provide additional tools to address these unwanted effects. These findings and methods can be incorporated into future functional connectivity studies, potentially preventing spurious findings and improving reliability of results.
DARTS: an Algorithm for Domain-Associated RetroTransposon Search in Genome Assemblies
Authors: Biryukov Mikhail , Ustyantsev Kirill
Published: December 2021

Retrotransposons comprise a substantial fraction of eukaryotic genomes reaching the highest proportions in plants. Therefore, identification and annotation of retrotransposons is an important task in studying regulation and evolution of plant genomes. A majority of computational tools for mining transposable elements (TEs) are designed for subsequent genome repeat masking, often leaving aside the element lineage classification and its protein domain composition. Additionally, studies focused on diversity and evolution of a particular group of retrotransposons often require substantial customization efforts from researchers to adapt existing software to their needs. Here, we developed a computational pipeline to mine sequences of protein-coding retrotransposons based on the sequences of their conserved protein domains - DARTS. Using the most abundant group of TEs in plants - long terminal repeat (LTR) retrotransposons (LTR-RTs), we show that DARTS has radically higher sensitivity of LTR-RTs identification compared to a widely accepted LTRharvest tool. DARTS can be easily customized for specific user needs. As a result, DARTS returns a set of structurally annotated nucleotide and amino acid sequences which can be readily used in subsequent comparative and phylogenetic analyses. DARTS should facilitate researchers interested in discovery and in-detail analysis of diversity and evolution of retrotransposons, LTR-RTs, and other protein-coding TEs.
Cortical tracking of voice pitch in the presence of multiple speakers depends on selective attention
Authors: Brodbeck Christian , Simon Jonathan Z.
Published: December 2021

Voice pitch carries linguistic as well as non-linguistic information. Previous studies have described cortical tracking of voice pitch in clean speech, with responses reflecting both pitch strength and pitch value. However, pitch is also a powerful cue for auditory stream segregation, especially when competing streams have pitch differing in fundamental frequency, as is the case when multiple speakers talk simultaneously. We therefore investigated how cortical speech pitch tracking is affected in the presence of a second, task-irrelevant speaker. We analyzed human magnetoencephalography (MEG) responses to continuous narrative speech, presented either as a single talker in a quiet background, or as a two-talker mixture of a male and a female speaker. In clean speech, voice pitch was associated with a right-dominant response, peaking at a latency of around 100 ms, consistent with previous EEG and ECoG results. The response tracked both the presence of pitch as well as the relative value of the speaker’s fundamental frequency. In the two-talker mixture, pitch of the attended speaker was tracked bilaterally, regardless of whether or not there was simultaneously present pitch in the speech of the irrelevant speaker. Pitch tracking for the irrelevant speaker was reduced: only the right hemisphere still significantly tracked pitch of the unattended speaker, and only during intervals in which no pitch was present in the attended talker’s speech. Taken together, these results suggest that pitch-based segregation of multiple speakers, at least as measured by macroscopic cortical tracking, is not entirely automatic but strongly dependent on selective attention.
Impostor Phenomenon in the Nutrition and Dietetics Profession: An Online Cross-Sectional Survey
Authors: Landry Matthew J. , Bailey Dylan A. , Lee MinJi , Van Gundy Samuel , Ervin Audrey
Published: December 2021

Background

Impostor phenomenon (IP) (also known as impostor syndrome) describes high-achieving individuals who, despite their objective successes, fail to internalize their accomplishments and have persistent self-doubt and fear of being exposed as a fraud or impostor. Despite robust literature describing the effects of IP in other health care professions, there is an absence of research within the nutrition and dietetics profession.

Objective

To assess the prevalence and predictors of IP within the nutrition and dietetics students and practitioners.

Design

An online cross-sectional survey was conducted.

Participants/setting

1,015 students, dietetic interns, and currently practicing and retired nutrition and dietetic technicians registered, and registered dietitian nutritionists provided complete responses.

Main outcome measures

Impostor phenomenon was assessed with the Clance Impostor Phenomenon Scale (CIPS). Self-reported Job satisfaction and well-being were assessed using validated scales.

Statistical analyses

Descriptive statistics were summarized and reported using frequency counts and percentages. Unadjusted logistic regression models were used to assess the relationship between IP and sociodemographic outcomes, job satisfaction, and well-being.

Results

Respondents were primarily female, non-Hispanic White, and practicing dietitians. The average CIPS score was 66.0 ± 16.3 (range 22-99). 64% of survey respondents (n=655) experience intense or frequent IP and 62% (n=628) had a CIPS score ≥62. Older age, educational attainment, professional level, and membership in Academy groups were associated with lower IP scores. Greater Social media use was associated with higher IP scores. Job satisfaction and overall well-being were inversely correlated with impostor phenomenon (p<0.001).

Conclusions

Findings from an online survey suggest that a majority of nutrition and dietetics students and practitioners experience IP. Our results reinforce the need to recognize and address this issue by raising awareness, using early prevention methods, and supporting individuals who are younger and/or new to the profession.
Predicted CTL responses from pressured epitopes in SARS-CoV-2 correlate with COVID-19 severity
Authors: Rao Vishal , Banerjee Ushashi , Sambaturu Narmada , Chunchanur Sneha , Ambica R , Chandra Nagasuma
Published: December 2021

Heterogeneity in susceptibility among individuals to COVID-19 has been evident through the pandemic worldwide. Protective cytotoxic T lymphocyte (CTL) responses generated against pathogens in certain individuals are known to impose selection pressure on the pathogen, thus driving emergence of new variants. In this study, we focus on the role played by host genetic heterogeneity in terms of HLA-genotypes in determining differential COVID-19 severity in patients and dictating mechanisms of immune evasion adopted by SARS-CoV-2 due to the imposed immune pressure at global and cohort levels. We use bioinformatic tools for CTL epitope prediction to identify epitopes under immune pressure. Using HLA-genotype data of COVID-19 patients from a local cohort, we observe that asymptomatic individuals recognize a larger number of pressured epitopes which could facilitate emergence of mutations at these epitopic regions to overcome the protectivity they offer to the host. Based on the severity of COVID-19, we also identify HLA-alleles and epitopes that offer higher protectivity against severe disease in infected individuals. Finally, we shortlist a set of pressured and protective epitopes that represent regions in the viral proteome that are under higher immune pressure across SARS-CoV-2 variants due to the protectivity they offer. Identification of such epitopes could potentially aid in prediction of indigenous variants of SARS-CoV-2 and other pathogens, defined by the distribution of HLA-genotypes among members of a population.
Systematic review of cardiac adverse effects in children and young people under 18 years of age after SARS-CoV-2 vaccination
Authors: Cruz Joana , Duret Amedine , Harwood Rachel , Fraser Lorna K. , Jones Caroline B. , Ward Joseph , Whittaker Elizabeth , Kenny Simon E. , Viner Russell M.
Published: December 2021

Background

Reports of myocarditis and pericarditis following vaccination with mRNA vaccines for SARS-CoV-2 have occurred after countries began vaccinating adolescents. We undertook a systematic review of cardiac adverse effects associated with SARS-CoV-2 vaccine in children and young people (CYP)< 18 years.

Methods

Systematic review with protocol prospectively registered with PROSPERO (CRD42021275380).

Six electronic databases were searched from 1 December 2019 to 14 September 2021. Eligible studies were those reporting on CYP with reported or proven myocarditis, pericarditis and/or myopericarditis associated with vaccination against SARS-CoV-2. We summarized findings across all clinical cases reported in case report / case series studies. As a number of studies reported data from two publicly available vaccine surveillance systems, we updated estimates of reporting rates for cardiac adverse events up to 31 October for the US Vaccine Adverse Event Reporting System (VAERS) and 13 November for EudraVigilance covering European Union and European Economic Area (EUEA) countries.

Results

Twenty-one studies were included from 338 identified records. Seventeen were case reports/series describing a total of 127 CYP. Three studies described reporting rates from passive surveillance databases (VAERS, EudraVigilance, and the WHO VigiBase) and one described 22 cases from the US Vaccine Safety Datalink (VSD).

Clinical series reported that 99.2% presented with chest pain, 100% had raised troponin and 73.8% had an abnormal ECG. Cardiovascular magnetic resonance (CMR) in 91 cases identified myocardial injury in 61.5%, with 90.1% showing late gadolinium enhancement. NSAIDs were the most common treatment (76.0%).

One US dataset (VSD) estimated a significant excess of 29.6 events per million vaccine doses across both sexes and doses. There were 1129 reports of myocarditis and 358 reports of pericarditis from across the USA and EU/EEA. The VAERS reporting rate per million for myocarditis was 12.4 for boys and 1.4 for girls after the first dose, and 49.6 for boys and 6.1 for girls after the second dose. There was a marked trend for VAERS reporting to be highest soon after initiation of the vaccine schedule, suggesting reporting bias.

Conclusions

Cardiac adverse effects are very rare after mRNA vaccination for COVID-19 in CYP <18 years. The great majority of cases are mild and self-limiting without significant treatment. No data are yet available on children under 12 years. Larger detailed longitudinal studies are urgently needed from active surveillance sources.
Global Assessment of IRF8 as a Novel Cancer Biomarker
Authors: McQuaid Daniel C. , Panse Gauri , Wang Wei-Lien , Katz Samuel G. , Xu Mina L.
Published: December 2021

Interferon regulatory factor 8 (IRF8) is a member of the IRF family that is specific to the hematopoietic cell and is involved in regulating the development of human monocytic and dendritic-lineage cells, as well as B cells. Since its utility as a sensitive and specific monoblast marker in the context of acute monocytic leukemias has been recently demonstrated, we hypothesized that it may also be useful as a novel immunohistochemical marker in myeloid sarcomas and blastic plasmacytoid dendritic cell neoplasms (BPDCN) with respect to their differential diagnoses. In this retrospective study, we analyzed the IHC expression pattern of IRF8 in 385 patient samples across 30 types of cancers, referenced to their mRNA expression data available through TCGA. In addition, we assessed IRF8 in 35 myeloid sarcomas, and 13 BPDCNs. Twenty-four of 35 cases of myeloid sarcomas (68.5%) showed positivity for IRF8, with six cases (17.1%) demonstrating IRF8 expression in the absence of CD34 and MPO. All 13 of 13 BPDCNs (100%) showed strong uniform expression of IRF8 and was occasionally more definitive than CD123. IRF8 was negative in all desmoplastic small round cell tumors, Ewing sarcomas, synovial sarcomas, and undifferentiated pleomorphic sarcomas, as well as all epithelial malignancies tested except for 2 triple negative breast cancers that showed subset weak staining. In conclusion, IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers.
Polygenic risk score from a multi-ancestry GWAS uncovers susceptibility of heart failure
Authors: Wu Kuan-Han H. , Douville Nicholas J. , Konerman Matthew C. , Mathis Michael R. , Hummel Scott L. , Wolford Brooke N. , Surakka Ida , Graham Sarah E. , Joo Hyeon , Hirbo Jibril , Cox Nancy J. , Lee Simon , Preuss Michael , Loos Ruth J.F. , Daly Mark J. , Neale Benjamin M. , Zhou Wei , Hornsby Whitney E. , Willer Cristen. J.
Published: December 2021

Identifying individuals at high risk of heart failure during precursor stages could allow for earlier initiation of treatments to modify disease progression. We performed a GWAS meta- analysis to generate a heart failure (HF) polygenic risk score (PRS) then tested the association with phenotypic subtypes (reduced ejection fraction [HFrEF] and preserved ejection fraction [HFpEF]) to evaluate the value of polygenic risk prediction. Results from the European-ancestry analysis showed that an ancestry-matched PRS, calculated from GBMI meta-analysis outperformed the previous HF GWAS (HERMES), yielding an adjusted odds ratio (aOR) of 2.27 (95% CI: 2.05-2.51; p: 1.76×10−56) from GBMI compared to 1.30 (95% CI: 1.18-1.44; p: 1.42×10− 7) from HERMES, and 1.49 (95% CI: 1.33-1.66; p: 8.38×10−13) compared to 1.17 (95% CI: 1.05- 1.31; p: 0.004) for HFrEF and HFpEF, respectively. Next, we evaluated the performance differences between ancestry-matched and multi-ancestry PRS in the African American cohort. The GBMI multi-ancestry GWAS-based PRS had a significant aOR of 1.49 (p: 0.006). Findings suggest that a PRS for heart failure derived from the GBMI multi-ancestry study is useful in predicting HFrEF, but less powerful in predicting HFpEF in an independent cohort. The difficulty in predicting HFpEF could result from the GBMI HF phenotype, preferencing HFrEF over HFpEF, and/or greater genetic heterogeneity in the HFpEF phenotype.
Cohesin modulates DNA replication to preserve genome integrity
Authors: Wu Jinchun , Liu Yang , Zhangding Zhengrong , Liu Xuhao , Ai Chen , Gan Tingting , Liu Yiyang , Yin Jianhang , Zhang Weiwei , Hu Jiazhi
Published: December 2021

Cohesin participates in loop formation by extruding DNA fibers from its ring-shaped structure. Cohesin dysfunction eliminates chromatin loops but only causes modest transcription perturbation, which cannot fully explain the frequently observed mutations of cohesin in various cancers. Here, we found that DNA replication initiates at more than one thousand extra dormant origins after acute depletion of RAD21, a core subunit of cohesin, resulting in earlier replicating timing at approximately 30% of the human genomic regions. In contrast, CTCF is dispensable for suppressing the early firing of dormant origins that are distributed away from the loop boundaries. Furthermore, greatly elevated levels of gross DNA breaks and genome-wide chromosomal translocations arise in RAD21-depleted cells, accompanied by dysregulated replication timing at dozens of hotspot genes. Thus, we conclude that cohesin coordinates DNA replication initiation to ensure proper replication timing and safeguards genome integrity.
AP-1 transcription factor network explains diverse patterns of cellular plasticity in melanoma cells
Authors: Comandante-Lou Natacha , Baumann Douglas G. , Fallahi-Sichani Mohammad
Published: December 2021

Cellular plasticity associated with fluctuations in transcriptional programs allows individual cells in a tumor to adopt heterogeneous differentiation states and switch phenotype during their adaptive responses to therapies. Despite increasing knowledge of such transcriptional programs, the molecular basis of cellular plasticity remains poorly understood. Here, we combine multiplexed transcriptional and protein measurements at population and single-cell levels with multivariate statistical modeling to show that the state of AP-1 transcription factor network plays a unifying role in explaining diverse patterns of plasticity in melanoma. We find that a regulated balance between AP-1 factors cJUN, JUND, FRA2, FRA1 and cFOS determines the intrinsic diversity of differentiation states and adaptive responses to MAPK inhibitors in melanoma cells. Perturbing this balance through genetic depletion of specific AP-1 proteins, or by MAPK inhibitors, shifts cellular heterogeneity in a predictable fashion. Thus, AP-1 may serve as a critical node for manipulating cellular plasticity with potential therapeutic implications.
Brain–heart dynamics during emotional processing under uncertain conditions: An index of depression risk
Authors: Chan Hui-Ling , Kanayama Noriaki , Mizuochi Ryohei , Yamawaki Shigeto , Machizawa Maro G.
Published: December 2021

Recent studies have highlighted the essential role of interoception in healthy emotional processing and the pathology of major depressive disorder. However, it is unclear how individual differences in healthy people with high depression risk (HDR; i.e., individual differences in depression risk) are related to the neurophysiological underpinnings of interoception and emotional reactions under different degrees of certainty. We examined whether an individual’s depression risk mediates the relationships of heartbeat-evoked potentials (HEPs), a neurophysiological marker of cardiac interoception, with heart rate (HR) and heart rate variability (HRV), indices for cardiac reactivity. In a concurrent electroencephalogram-electrocardiogram (EEG-ECG) experiment, 26 healthy participants completed an emotion-evoking picture-evaluation task. Each trial began with a differential auditory cue that was associated with the certainty of subsequently seeing a pleasant or unpleasant picture. The results showed the following: after participants saw a cue of uncertainty, HDR was associated with 1) reduced neural activity when anticipating upcoming pictures and 2) enhanced physiological reactions tounexpected, unpleasant pictures. These results suggest that weaker predictions and augmented prediction errors for negative emotional stimuli reflect depression risk. Moreover, depression risk significantly mediated the relationships between HEPs and HR and between HEPs and HRV for unexpected, unpleasant stimuli. This study provides evidence that interoception and autonomic cardiac regulation may be altered by depression risk. This highlights the insights provided by specific indices of brain–heart interactions, such as HEPs, into the underlying activity of the autonomic nervous system and unique interoceptive disturbances associated with depression risk.
Meet me in the middle: median temperatures impact cyanobacteria and photoautotrophy in eruptive Yellowstone hot springs
Authors: Hamilton Trinity L. , Havig Jeff
Published: December 2021

Geographic isolation can be a main driver of microbial evolution in hot springs while temperature plays a role on local scales. For example, cyanobacteria, particularly high temperature Synechococcus spp., have undergone ecological diversification along temperature gradients in hot spring outflow channels. While water flow, and thus temperature, is largely stable in many hot springs, flow can vary in geysing/eruptive hot springs resulting in large temperature fluctuations (sometimes more than 40°C). However, the role of large temperature fluctuations in driving diversification of cyanobacteria in eruptive hot springs has not been explored. Here, we examined phototroph community composition and potential photoautotrophic activity in two alkaline eruptive hot springs with similar geochemistry in the Lower Geyser Basin in Yellowstone National Park, WY. We observed distinct cyanobacterial amplicon sequencing variants (ASVs) consistent with allopatry and levels of light-dependent inorganic carbon uptake rates similar to other hot springs, despite large temperature fluctuations. Our data suggests median temperatures may drive phototroph fitness in eruptive hot springs while future studies are necessary to determine the evolutionary consequences of thriving under continuously fluctuating temperatures. We propose that large temperature swings in eruptive hot springs offer unique environments to examine the role of allopatry vs. physical and chemical characteristics of ecosystems in driving cyanobacteria evolution and add to the debate regarding the ecology of thermal adaptation and the potential for narrowing niche breadth with increasing temperature.

Importance

Hot spring cyanobacteria have long been model systems for examining ecological diversification as well as characterizing microbial adaptation and evolution to extreme environments. These studies have reported cyanobacterial diversification in hot spring outflow channels that can be defined by distinct temperature ranges. Our study builds on these previous studies by examining cyanobacteria in geysing hot springs. Geysing hot springs result in outflow channel that experience regular and large temperature fluctuations. While community composition is similar between geysing and nongeysing hot spring outflow channels, our data suggests median, rather than high temperature, drive the fitness of cyanobacteria in geysing hot springs. We propose that large temperature swings may result in patterns of ecological diversification that are distinct from more stable outflows.
Decoding the absolute stoichiometric composition and structural plasticity of α-carboxysomes
Authors: Sun Yaqi , Harman Victoria M. , Johnson James R. , Chen Taiyu , Dykes Gregory F. , Lin Yongjun , Beynon Robert J. , Liu Lu-Ning
Published: December 2021

Carboxysomes are anabolic bacterial microcompartments that play an essential role in carbon fixation in cyanobacteria and some chemoautotrophs. This self-assembling organelle encapsulates the key CO2-fixing enzymes, Rubisco, and carbonic anhydrase using a polyhedral protein shell that is constructed by hundreds of shell protein paralogs. The α-carboxysome from the chemoautotroph Halothiobacillus neapolitanus serves as a model system in fundamental studies and synthetic engineering of carboxysomes. Here we adopt a QconCAT-based quantitative mass spectrometry to determine the absolute stoichiometric composition of native α-carboxysomes from H. neapolitanus. We further performed an in-depth comparison of the protein stoichiometry of native and recombinant α-carboxysomes heterologously generated in Escherichia coli to evaluate the structural variability and remodeling of α-carboxysomes. Our results provide insight into the molecular principles that mediate carboxysome assembly, which may aid in rational design and reprogramming of carboxysomes in new contexts for biotechnological applications.
SIR Modeling the Dual Disaster Impacts of Omicron B.1.1.529 and Natural Disaster Events on Simulated 6 Months (December 2021 – May 2022) Healthcare System Resiliences in Fragile SE Asia Ring of Fire Ecosystems
Authors: Wibowo Andri
Published: December 2021

For some countries that have experienced numerous natural disasters, including massive earthquakes and tsunamis, managing the COVID-19 pandemic can be very challenging. This situation arises considering that the disaster can directly and indirectly affect the healthcare system’ s capacity to serve the COVID-19 cases. With severely damaged healthcare facilities due to the disaster, there will be severely ill COVID-19 cases unmanaged. The coupling and interplay between these two phenomena can indeed be catastrophic. One of the regions where this issue becomes concerned is in Southeast Asia, where most of the Asian countries lie in the fragile ring of fire ecosystem, contributing to the high tsunami and earthquake disasters in the world. At the same time, Asia is one of the regions that have been severely impacted due to the current COVID-19 Delta Variant. Recently, a more contagious Omicron Variant has emerged and put a more massive burden on the healthcare facilities that are impacted by disasters. Then, in this situation, this paper aims to assess healthcare resilience in managing the Omicron pandemic amid disaster impacts. SIR simulation was used to determine whether severely ill Omicron cases were below or above healthcare and ICU capacity under different vaccination coverage. Our result confirms that vaccination coverage was the imminent factor in reducing the severely ill cases in every healthcare facility, whether the facilities were damaged or not. Increasing vaccination coverage from 30% to 60% will significantly reduce the number of severely ill cases that fall below the capacity of healthcare. Based on the current SIR model on the Omicron epidemic variables and Ro, it is estimated that the Omicron will reach its peak after 180 days in February 2022 and will totally disappear in May 2022 in this modeled area. When healthcare system facilities were fully operational and no disaster happened, combined with 60% vaccination rates, all Omicron case numbers were below and under the available hospital beds and even available ICU beds. While the situation is changed when a disaster occurs and causes 30% damage or reduction to healthcare facilities. In this situation, there are portions of Omicron cases that cannot be managed by the healthcare system since the cases have exceeded the available beds. The situations become more apparent where the healthcare facilities are severely damaged and lose 60% of their functionality. In this situation, all modeled Omicron cases and even the severe cases have exceeded the ICU capacity.
DALI (Diversity AnaLysis Interface): a novel tool for the integrated analysis of multimodal single cell RNAseq data and immune receptor profiling
Authors: Verstaen Kevin , Ibech Kevin , Lammens Inés , Roels Jana , Saeys Yvan , Lambrecht Bart N , Vandamme Niels , Vanhee Stijn
Published: December 2021

Single-cell RNA sequencing is instrumental to unravel the cellular and transcriptomic heterogeneity of T and B cells in health and disease. Recent technological advances add additional layers of information allowing researchers to simultaneously explore the transcriptomic, surface protein and immune receptor diversity during adaptive immune responses. The increasing data complexity poses a burden on the workload for bioinformaticians, who are often not familiar with the specificities and biology of immune receptor profiling. The wet-lab modalities and sequencing capabilities currently have outpaced bioinformatics solutions, which forms an ever-increasing barrier for many biologists to analyze their datasets. Here, we present DALI (Diversity AnaLysis Interface), a software package to identify and analyze T cell and B cell receptor diversity in high-throughput single-cell sequencing data. DALI aims to support bioinformaticians with a functional toolbox, allowing seamless integration of multimodal scRNAseq and immune receptor profiling data generated through 10X Genomics Cell Ranger software. The R-based package builds further on workflows using the Seurat package and other existing tools for BCR/TCR analyses. In addition, DALI is designed to engage immunologists having limited coding experience with their data, using a browser-based interactive graphical user interface. The implementation of DALI can effectively lead to a two-way communication between wet-lab scientists and bioinformaticians to advance the analysis of complex datasets.
A target capture approach for phylogenomic analyses at multiple evolutionary timescales in rosewoods (Dalbergiaspp.) and the legume family (Fabaceae)
Authors: Crameri Simon , Fior Simone , Zoller Stefan , Widmer Alex
Published: December 2021

Understanding the genetic changes associated with the evolution of biological diversity is of fundamental interest to molecular ecologists. The assessment of genetic variation at hundreds or thousands of unlinked genetic loci forms a sound basis to address questions ranging from micro-to macro-evolutionary timescales, and is now possible thanks to advances in sequencing technology. Major difficulties are associated with i) the lack of genomic resources for many taxa, especially from tropical biodiversity hotspots, ii) scaling the numbers of individuals analyzed and loci sequenced, and iii) building tools for reproducible bioinformatic analyses of such datasets. To address these challenges, we developed a set of target capture probes for phylogenomic studies of the highly diverse, pantropically distributed and economically significant rosewoods (Dalbergiaspp.), explored the performance of an overlapping probe set for target capture across the legume family (Fabaceae), and built a general-purpose bioinformatics pipeline. Phylogenomic analyses ofDalbergiaspecies from Madagascar yielded highly resolved and well supported hypotheses of evolutionary relationships. Population genomic analyses identified differences between closely related species and revealed the existence of a potentially new species, suggesting that the diversity of MalagasyDalbergiaspecies has been underestimated. Analyses at the family level corroborated previous findings by the recovery of monophyletic subfamilies and many well-known clades, as well as high levels of gene tree discordance, especially near the root of the family. The new genomic and bioinformatics resources will hopefully advance systematics and ecological genetics research in legumes, and promote conservation of the highly diverse and endangeredDalbergiarosewoods.
Magnesium Force Fields for OPC Water with Accurate Solvation, Ion-Binding, and Water-Exchange Properties: Successful Transfer from SPC/E
Authors: Grotz Kara K. , Schwierz Nadine
Published: December 2021

Magnesium plays a vital role in a large variety of biological processes. To model such processes by molecular dynamics simulations, researchers rely on accurate force field parameters for Mg2+ and water. OPC is one of the most promising water models yielding an improved description of biomolecules in water. The aim of this work is to provide force field parameters for Mg2+ that lead to accurate simulation results in combination with OPC water. Using twelve different Mg2+ parameter sets, that were previously optimized with different water models, we systematically assess the transferability to OPC based on a large variety of experimental properties. The results show that the Mg2+ parameters for SPC/E are transferable to OPC and closely reproduce the experimental solvation free energy, radius of the first hydration shell, coordination number, activity derivative, and binding affinity toward the phosphate oxygens on RNA. Two optimal parameter sets are presented: MicroMg yields water exchange in OPC on the microsecond timescale in agreement with experiments. NanoMg yields accelerated exchange on the nanosecond timescale and facilitates the direct observation of ion binding events for enhanced sampling purposes.