bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal form for maps with nilpotent linear part
Authors: Mokhtari Fahimeh , Roell Ernst , Sanders Jan A.
Published: May 2022

The normal form for an

n

-dimensional map with irreducible nilpotent linear part is determined using

s
l

2

-representation theory. We sketch by example how the reducible case can also be treated in an algorithmic manner. The construction (and proof) of the

s
l

2

-triple from the nilpotent linear part is more complicated than one would hope for, but once the abstract

s
l

2

theory is in place, both the description of the normal form and the computational splitting to compute the generator of the coordinate transformation can be handled explicitly in terms of the nilpotent linear part without the explicit knowledge of the triple. If one wishes one can compute the normal form such that it is guaranteed to lie in the kernel of an operator and one can be sure that this is really a normal form with respect to the nilpotent linear part; one can state that the normal form is in

s
l

2

-style. Although at first sight the normal form theory for maps is more complicated than for vector fields in the nilpotent case, it turns out that the final result is much better. Where in the vector field case one runs into invariant theoretical problems when the dimension gets larger if one wants to describe the general form of the normal form, for maps we obtain results without any restrictions on the dimension. In the literature only the two-dimensional nilpotent case has been described so far, as far as we know.
Selective and tunable excitation of topological non-Hermitian quasi-edge modes
Authors: Longhi Stefano
Published: May 2022

Non-Hermitian lattices under semi-infinite boundary conditions sustain an extensive number of exponentially localized states, dubbed non-Hermitian quasi-edge modes. Quasi-edge states arise rather generally in systems displaying the non-Hermitian skin effect and can be predicted from the non-trivial topology of the energy spectrum under periodic boundary conditions via a bulk-edge correspondence. However, the selective excitation of the system in one among the infinitely many topological quasi-edge states is challenging both from practical and conceptual viewpoints. In fact, in any realistic system with a finite lattice size most of the quasi-edge states collapse and become metastable states. Here we suggest a route toward the selective and tunable excitation of topological quasi-edge states that avoids the collapse problem by emulating semi-infinite lattice boundaries via tailored on-site potentials at the edges of a finite lattice. We illustrate such a strategy by considering a non-Hermitian topological interface obtained by connecting two Hatano–Nelson chains with opposite imaginary gauge fields, which is amenable for a full analytical treatment.
A micromechanical model for phase-change composites
Authors: Li Xiying , Wang Shuang , Lu Lu , Lv Pengyu , Duan Huiling
Published: May 2022

Phase-change composites have a wide range of tunable mechanical properties caused by temperature-driven phase transition, and have been widely applied in many cutting-edge fields like soft robotics. Previous studies on the effective mechanical properties of phase-change composites mostly use experimental methods, and there have been few theoretical approaches. In this work, we develop a micromechanical framework capable of tracking the effective mechanical properties of phase-change composites throughout the entire phase transition. The phase-change materials embedded in the composites are modelled as inclusions, and the non-phase-change materials are modelled as the matrix. This allows us to determine the effective mechanical properties of phase-change composites via the energy equivalency approach. Moreover, since the new phase will be generated inside the phase-change inclusions in the form of sub-inclusions during the phase transition, the inclusions are modelled as two-phase composites, and their effective mechanical properties are then determined using the Mori–Tanaka method. Finally, by comparing theoretical predictions with experimental data, the accuracy and reliability of the present model are verified. We believe that the proposed model can serve as a powerful tool for evaluating the effective mechanical properties of phase-change composites and provide theoretical guidelines for the design of advanced devices with tunable mechanical performance.
Clock-linked genes underlie seasonal migratory timing in a diurnal raptor
Authors: Bossu Christen M. , Heath Julie A. , Kaltenecker Gregory S. , Helm Barbara , Ruegg Kristen C.
Published: May 2022

Seasonal migration is a dynamic natural phenomenon that allows organisms to exploit favourable habitats across the annual cycle. While the morphological, physiological and behavioural changes associated with migratory behaviour are well characterized, the genetic basis of migration and its link to endogenous biological time-keeping pathways are poorly understood. Historically, genome-wide research has focused on genes of large effect, whereas many genes of small effect may work together to regulate complex traits like migratory behaviour. Here, we explicitly relax stringent outlier detection thresholds and, as a result, discover how multiple biological time-keeping genes are important to migratory timing in an iconic raptor species, the American kestrel (Falco sparverius). To validate the role of candidate loci in migratory timing, we genotyped kestrels captured across autumn migration and found significant associations between migratory timing and genetic variation in metabolic and light-input pathway genes that modulate biological clocks (top1, phlpp1, cpne4andpeak1). Further, we demonstrate that migrating individuals originated from a single panmictic source population, suggesting the existence of distinct early and late migratory genotypes (i.e. chronotypes). Overall, our results provide empirical support for the existence of a within-population-level polymorphism in genes underlying migratory timing in a diurnally migrating raptor.
Geographically diverse canid sampling provides novel insights into pre-industrial microbiomes
Authors: Yarlagadda K. , Zachwieja A. J. , de Flamingh A. , Phungviwatnikul T. , Rivera-Colón A. G. , Roseman C. , Shackelford L. , Swanson K. S. , Malhi R. S.
Published: May 2022

Canine microbiome studies are often limited in the geographic and temporal scope of samples studied. This results in a paucity of data on the canine microbiome around the world, especially in contexts where dogs may not be pets or human associated. Here, we present the shotgun sequences of fecal microbiomes of pet dogs from South Africa, shelter and stray dogs from India, and stray village dogs in Laos. We additionally performed a dietary experiment with dogs housed in a veterinary medical school, attempting to replicate the diet of the sampled dogs from Laos. We analyse the taxonomic diversity in these populations and identify the underlying functional redundancy of these microbiomes. Our results show that diet alone is not sufficient to recapitulate the higher diversity seen in the microbiome of dogs from Laos. Comparisons to previous studies and ancient dog fecal microbiomes highlight the need for greater population diversity in studies of canine microbiomes, as modern analogues can provide better comparisons to ancient microbiomes. We identify trends in microbial diversity and industrialization in dogs that mirror results of human studies, suggesting future research can make use of these companion animals as substitutes for humans in studying the effects of industrialization on the microbiome.
Plasticity in social behaviour varies with reproductive status in an avian cooperative breeder
Authors: Little Jasmine , Rubenstein Dustin R. , Guindre-Parker Sarah
Published: May 2022

Cooperatively breeding vertebrates are common in unpredictable environments where the costs and benefits of providing offspring care fluctuate temporally. To balance these fitness outcomes, individuals of cooperatively breeding species often exhibit behavioural plasticity according to environmental conditions. Although individual variation in cooperative behaviours is well-studied, less is known about variation in plasticity of social behaviour. Here, we examine the fitness benefits, plasticity and repeatability of nest guarding behaviour in cooperatively breeding superb starlings (
Lamprotornis superbus
). After demonstrating that the cumulative nest guarding performed at a nest by all breeders and helpers combined is a significant predictor of reproductive success, we model breeder and helper behavioural reaction norms to test the hypothesis that individuals invest more in guarding in favourable seasons with high rainfall. Variation in nest guarding behaviour across seasons differed for individuals of different reproductive status: breeders showed plastic nest guarding behaviour in response to rainfall, whereas helpers did not. Similarly, we found that individual breeders show repeatability and consistency in their nest guarding behaviour while individual helpers did not. Thus, individuals with the potential to gain direct fitness benefits exhibit greater plasticity and individual-level repeatability in cooperative behaviour.
Genetic architecture of adaptive radiation across two trophic levels
Authors: Feller Anna F. , Seehausen Ole
Published: May 2022

Evolution of trophic diversity is a hallmark of adaptive radiation. Yet, transitions between carnivory and herbivory are rare in young adaptive radiations. Haplochromine cichlid fish of the African Great Lakes are exceptional in this regard. Lake Victoria was colonized by an insectivorous generalist and in less than 20 000 years, several clades of specialized herbivores evolved. Carnivorous versus herbivorous lifestyles in cichlids require many different adaptations in functional morphology, physiology and behaviour. Ecological transitions in either direction thus require many traits to change in a concerted fashion, which could be facilitated if genomic regions underlying these traits were physically linked or pleiotropic. However, linkage/pleiotropy could also constrain evolvability. To investigate components of the genetic architecture of a suite of traits that distinguish invertivores from algae scrapers, we performed quantitative trait locus (QTL) mapping using a second-generation hybrid cross. While we found indications of linkage/pleiotropy within trait complexes, QTLs for distinct traits were distributed across several unlinked genomic regions. Thus, a mixture of independently segregating variation and some pleiotropy may underpin the rapid trophic transitions. We argue that the emergence and maintenance of associations between the different genomic regions underpinning co-adapted traits that evolved and persist against some gene flow required reproductive isolation.
No major cost of evolved survivorship in
Drosophila melanogaster
populations coevolving with
Pseudomonas entomophila
Authors: Ahlawat Neetika , Maggu Komal , Jigisha  , Arun Manas Geeta , Meena Abhishek , Agarwala Amisha , Prasad Nagaraj Guru
Published: May 2022

Rapid exaggeration of host and pathogen traits via arms race dynamics is one possible outcome of host–pathogen coevolution. However, the exaggerated traits are expected to incur costs in terms of resource investment in other life-history traits. The current study investigated the costs associated with evolved traits in a host–pathogen coevolution system. We used the
Drosophila melanogaster
(host)
–Pseudomonas entomophila
(pathogen) system to experimentally derive two selection regimes, one where the host and pathogen both coevolved, and the other, where only the host evolved against a non-evolving pathogen. After 17 generations of selection, we found that hosts from both selected populations had better post-infection survivorship than controls. Even though the coevolving populations tended to have better survivorship post-infection, we found no clear evidence that the two selection regimes were significantly different from each other. There was weak evidence for the coevolving pathogens being more virulent than the ancestral pathogen. We found no major cost of increased post-infection survivorship. The costs were not different between the coevolving hosts and the hosts evolving against a non-evolving pathogen. We found no evolved costs in the coevolving pathogens. Thus, our results suggest that increased host immunity and pathogen virulence may not be costly.
RNA-based stable isotope probing provides no indication for rapid α-synuclein assimilation by murine gut bacteria
Authors: Brandau Lena , Weis Severin , Weyland Maximilian , Berger Fabian K. , Schnell Sylvia , Schäfer Karl-Herbert , Egert Markus
Published: May 2022

In Parkinson’s disease (PD), α-synuclein is a key protein in the process of neurodegeneration. Besides motor symptoms, most PD patients additionally suffer from gastrointestinal tract (GIT) dysfunctions, even several years before the onset of motor disabilities. Studies have reported a dysbiosis of gut bacteria in PD patients compared to healthy controls and have suggested that the enteric nervous system (ENS) can be involved in the development of the disease. As α-synuclein was found to be secreted by neurons of the ENS, we used RNA-based stable isotope probing (RNA-SIP) to identify gut bacteria that might be able to assimilate this protein. The gut contents of 24 mice were pooled and incubated with isotopically labelled (13C) and unlabelled (12C) α-synuclein. After incubation for 0, 4 and 24 h, RNA was extracted from the incubations and separated by density gradient centrifugation. However, RNA quantification of density-resolved fractions revealed no incorporation of the 13C isotope into the extracted RNA, suggesting that α-synuclein was not assimilated by the murine gut bacteria. Potential reasons and consequences for follow-up-studies are discussed.
Auditory spatial analysis in reverberant audio-visual multi-talker environments with congruent and incongruent visual room information
Authors: Ahrens Axel , Lund Kasper Duemose
Published: May 2022

In multi-talker situation, listeners have the challenge to identify a target speech source out of a mixture of interfering background noises. In the current study it was investigate how listeners analyze audio-visual scenes with varying complexity in terms of number of talkers and reverberation. Furthermore, the visual information of the room was either coherent with the acoustic room or incoherent. The listeners’ task was to locate an ongoing speech source in a mixture of other speech sources. The 3D audio-visual scenarios were presented using a loudspeaker array and virtual reality glasses. It was shown that room reverberation as well as the number of talkers in a scene influence the ability to analyze an auditory scene in terms of accuracy and response time. Incongruent visual information of the room did not affect this ability. When few talkers were presented simultaneously, listeners were able to quickly and accurately detect a target talker even in adverse room acoustical conditions. Reverberation started to affect the response time when four or more talkers were presented. The number of talkers became a significant factor for five or more simultaneous talkers.
Genotyping and population structure of the China Kadoorie Biobank
Authors: Walters Robin G , Millwood Iona Y , Lin Kuang , Valle Dan Schmidt , McDonnell Pandora , Hacker Alex , Avery Daniel , Cai Na , Kretzschmar Warren W , Ansari M Azim , Lyons Paul A , Collins Rory , Donnelly Peter , Hill Michael , Peto Richard , Shen Hongbing , Jin Xin , Nie Chao , Xu Xun , Guo Yu , Yu Canqing , Lv Jun , Clarke Robert J , Li Liming , Chen Zhengming ,   the China Kadoorie Biobank Collaborative Group
Published: May 2022

China Kadoorie Biobank is a population-based prospective cohort of >512,000 adults recruited in 2004-2008 from 10 geographically diverse regions across China. Detailed data from questionnaire and physical measurements were collected at baseline, with additional measurements at three resurveys involving approximately 5% of surviving participants. Incident disease events are captured through electronic linkage to death and disease registries and to the national health insurance system. Genome-wide genotyping has been conducted for >100,000 participants using custom-designed Axiom® arrays. Analysis of these data reveals extensive relatedness within the CKB cohort, signatures of recent consanguinity, and principal component signatures reflecting large-scale population movements from recent Chinese history. In addition to numerous CKB studies of candidate drug targets and disease risk factors, CKB has made substantial contributions to many international genetics consortia. Collected biosamples are now being used for high-throughput ‘omics assays which, together with planned whole genome sequencing, will continue to enhance the scientific value of this biobank.
FoxP3-mediated blockage of ryanodine receptor 2 is the molecular basis for the contact-based suppression by regulatory T cells
Authors: Wang Xiaobo , Geng Shuang , Meng Junchen , Kang Ning , Liu Xinyi , Xu Yanni , Lv Huiyun , Xu Ying , Xu Xun , Song Xinrong , Zhang Bin , Wang Xin , Nuerbulati Nuerdida , Zhang Ze , Zhai Di , Mao Xin , Sun Ruya , Wang Xiaoting , Wang Ruiwu , Guo Jie , Chen S. R. Wayne , Zhou Xuyu , Xia Tie , Qi Hai , Hu Xiaoyu , Shi Yan
Published: May 2022

The suppression mechanism of regulatory T cells is an intensely investigated topic. As our focus has shifted towards a model centered on indirect inhibition of dendritic cells, a universally applicable effector mechanism controlled by FoxP3 expression has not been found. Here, we report that FoxP3 blocks the transcription of ER Ca2+-release channel ryanodine receptor 2. Reduced RyR2 shuts down basal Ca2+oscillation in Tregs, which reduces m-Calpain activities that is needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency renders the CD4+T cell pool to become immune suppressive, and behave in the same manner as FoxP3+Tregs in viral infection, asthma, hypersensitivity, colitis and tumor development. In the absence of FoxP3, RyR2-deficient CD4+T cells rescue the systemic autoimmunity associated with Scurfy mice. Therefore, FoxP3-mediated Ca2+signaling inhibition may be a central effector mechanism of Treg immune suppression.

One Sentence Summary

Calcium channel RyR2 dictates Treg adhesion-based suppression
A neural mechanism for terminating decisions
Authors: Stine Gabriel M , Trautmann Eric M , Jeurissen Danique , Shadlen Michael N
Published: May 2022

The brain makes decisions by accumulating evidence until there is enough to stop and choose. Neural mechanisms of evidence accumulation are well established in association cortex, but the site and mechanism of termination is unknown. Here, we elucidate a mechanism for termination by neurons in the primate superior colliculus. We recorded simultaneously from neurons in lateral intraparietal cortex (LIP) and the superior colliculus (SC) while monkeys made perceptual decisions, reported by eye-movements. Single-trial analyses revealed distinct dynamics: LIP tracked the accumulation of evidence on each decision, and SC generated one burst at the end of the decision, occasionally preceded by smaller bursts. We hypothesized that the bursts manifest a threshold mechanism applied to LIP activity to terminate the decision. Focal inactivation of SC produced behavioral effects diagnostic of an impaired threshold sensor, requiring a stronger LIP signal to terminate a decision. The results reveal the transformation from deliberation to commitment.
High-efficiency HDR in immortalized cell lines by crude rAAV mediated donor template delivery
Authors: Mehta Stuti , Buyanbat Altantsetseg , Zheng Ge , Liu Nan , Orkin Stuart H.
Published: May 2022

Owing to low efficiency of homology-directed repair (HDR), precise knock-in (KI) of large DNA fragments is a challenge in genome editing. High-efficiency HDR has been reported for primary cells in preclinical gene therapy by combining CRISPR/Cas9 mediated induction of double-strand breaks (DSB) with delivery of a single-stranded DNA HDR-donor-template via highly purified recombinant adeno-associated virus (rAAV). Due in part to the labor and expense of rAAV particle purification, rAAV-mediated HDR-template delivery has been underutilized used to generate large KIs in cultured cell lines. Here, we report application of crude preparations of rAAV to deliver HDR-templates for the KI of large ∼2kb fragments at various genomic loci in several -human as well as mouse cell lines at high efficiency. Our approach should facilitate experiments necessitating KI of large DNA fragments to tag endogenous loci for visualization and/or conditional protein degradation.
KINOMO: A non-negative matrix factorization framework for recovering intra- and inter-tumoral heterogeneity from single-cell RNA-seq data
Authors: Tagore Somnath , Wang Yiping , Biermann Jana , Rabadan Raul , Azizi Elham , Izar Benjamin
Published: May 2022

Single-cell RNA-sequencing (scRNA-seq) is a powerful technology to uncover cellular heterogeneity in tumor ecosystems. Due to differences in underlying gene load, direct comparison between patient samples is challenging, and this is further complicated by the sparsity of data matrices in scRNA-seq. Here, we present a factorization method called KINOMO (Kernel dIfferentiability correlation-based NOn-negative Matrix factorization algorithm using Kullback-Leibler divergence loss Optimization). This tool uses quadratic approximation approach for error correction and an iterative multiplicative approach, which improves the quality assessment of NMF-identified factorization, while mitigating biases introduced by inter-patient genomic variability. We benchmarked this new approach against nine different methods across 15 scRNA-seq experiments and find that KINOMO outperforms prior methods when evaluated with an adjusted Rand index (ARI), ranging 0.82-0.91 compared to 0.68-0.77. Thus, KINOMO provides an improved approach for determining coherent transcriptional programs (and meta-programs) from scRNA-seq data of cancer tissues, enabling comparison of patients with variable genomic backgrounds.

Classification

Physical Sciences (Applied Mathematics; Biophysics and Computational Biology), Biological Sciences (Applied Biological Sciences; Biophysics and Computational Biology; Medical Sciences; Systems Biology.).

Significance Statement

Identification of shared or distinct cell programs in single-cell RNA-seq data of patient cancer cells is challenging due to underlying variability of gene load which determines transcriptional output. We developed an analytical approach to define transcriptional variability more accurately across patients and therefore enable comparison of program expression despite inherent genetic heterogeneity. Thus, this method overcomes challenges not adequately addressed by other methods broadly used for the analysis of single-cell genomics data.
Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2D6/CYP2C19 genes play a role? A UK population-based study
Authors: Richards-Belle Alvin , Austin-Zimmerman Isabelle , Wang Baihan , Zartaloudi Eirini , Cotic Marius , Gracie Caitlin , Khani Noushin Saadullah , Wannasuphoprasit Yanisa , Wronska Marta , Dawda Yogita , Osborn David P.J. , Bramon Elvira
Published: May 2022

Background

Dyslipidaemia is an important risk factor for cardiovascular morbidity in people with severe mental illness and which contributes to premature mortality in this population. The link between antipsychotics and dyslipidaemia is well-established, whilst evidence on antidepressants is mixed.

Aims

To investigate (1) if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants, and (2) if CYP2D6 and CYP2C19 genetic variation plays a role.

Methods

Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein (L/HDL-C) cholesterol and triglycerides derived from blood samples. CYP2D6 and CYP2C19 metabolic phenotypes were assigned from genetic data. Linear regression investigated study aims.

Results

Of 469,739 participants, 36,043 took antidepressants and 3,255 antipsychotics. Significant associations were found between use of amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine, and venlafaxine with worse levels of each lipid parameter (i.e., higher total cholesterol, LDL-C, and triglycerides and lower HDL-C). Venlafaxine was associated with the worst lipid profile (total cholesterol, mean difference: 0·21 mmol/L, 95% confidence interval [CI]: 0·17 to 0·26, p<0·001). Antipsychotic use was associated with lower HDL-C and higher triglycerides (0·31 mmol/L, 95% CI 0·28 to 0·35, p<0·001). In participants taking sertraline, the CYP2C19 intermediate metaboliser phenotype was associated with higher HDL-C (0·05 mmol/L 95% CI: 0·01 to 0·09, p=0·007) and lower triglycerides (-0·17 mmol/L 95% CI: -0·29 to -0·05, p=0·007).

Conclusions

Antidepressants are significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring of lipids. Further research should investigate why the CYP2C19 intermediate metaboliser phenotype may be protective for HDL-C and triglycerides in people taking sertraline.
Solid fuel use in relation to dementia risk in middle-aged and older adults: A prospective cohort study
Authors: Pu Fan , Hu Yingying , Li Chenxi , Cao Xingqi , Yang Zhenqing , Liu Yi , Zhang Jingyun , Li Xueqin , Yang Yongli , Wang Wei , Liu Xiaoting , Hu Kejia , Ma Yanan , Liu Zuyun
Published: May 2022

Objectives

It remains unknown whether household air pollution is associated with dementia risk. This study examined the associations between solid fuel use for cooking and heating (the main source of household air pollution) and dementia risk.

Methods

This analysis included data on 11,352 participants (aged 45+ years) from the 2011 wave of China Health and Retirement Longitudinal Study, with follow-up to 2018. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM) and then standardized for analysis. Household fuel types of cooking and heating were categorized as solid (e.g., coal, crop residue) and clean (e.g., central heating, solar). Multivariable analyses were performed using generalized estimating equations. Moreover, we examined the joint associations of solid fuel use for cooking and heating with the BDRM score.

Results

We found an independent and significant association of solid (vs. clean) fuel use for cooking and heating with a higher BDRM score after adjusting for potential confounders (e.g., ß = 0.14 for solid fuel for cooking; 95% CI: 0.12, 0.17). Participants who used solid (vs. clean) fuel for both cooking and heating had the highest BDRM score (ß = 0.20; 95%CI: 0.16, 0.23). Subgroup analysis suggested stronger associations in participants living in rural areas.

Conclusions

Solid fuel use for cooking and heating was independently associated with increased dementia risk in Chinese middle-aged and older adults, particularly among those living in rural areas. Our findings call for more efforts to facilitate universal access to clean energy for dementia prevention.
Characteristics of patients with positional OSA according to ethnicity and the identification of a novel phenotype – Lateral Positional Patients (Lateral PP): A MESA study
Authors: Sason Yuval Ben , Oksenberg Arie , Sobel Jonathan A. , Behar Joachim A.
Published: May 2022

Study Objectives

To investigate the characteristics of Obstructive Sleep Apnea (OSA) positional patients’ (PP) phenotypes among different ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA) dataset. Moreover, we hypothesized the existence of a new OSA PP phenotype we coined “Lateral PP”, for whom the lateral apneas hypopnea index (AHI) is at least double the supine AHI.

Methods

From 2,273 adults with sleep information, we analyzed data of 1,323 subjects that slept more than 4 hours and had at least 30 minutes of sleep in both the supine and the non-supine positions. Demographics and clinical information were compared for the different PP, and ethnic groups.

Results

861 (65.1%) patients had OSA and 35 (4.1%) were Lateral PP. Lateral PP patients were mainly females (62.9%), obese (31.4 median body mass index), had mild to moderate OSA (94.3%), and mostly were non-Chinese American (97.1%). Among all OSA patients, 550 (63.9%) were Supine PP, and 17.7% were supine-isolated OSA (siOSA). Supine PP and Lateral PP were present in 73.1% and 1.0% of Chinese Americans, 61.0% and 3.4% of Hispanics, 68.3% and 4.7% of White-Caucasian, and 56.2% and 5.2% of Black-African American OSA patients.

Conclusion

Chinese-American have the highest prevalence of Supine PP, whereas Black-African American patients lean towards less Supine PP and higher Lateral PP. Lateral PP appears as a novel OSA phenotype. However, it was found for a small group of OSA patients and thus its presence should be further validated.

Brief Summary

We studied prevalence of obstructive sleep apnea (OSA) positional phenotypes among Black African-American, Caucasian, Hispanic, and Chinese American patients and described their demographic and polysomnographic characteristics. Despite similar levels of OSA severity in the four ethnic groups, Chinese American had a higher prevalence of Supine PP, whereas Black-African American patients were significantly less Supine PP, as compared to other ethnic groups.

In addition, we identify a novel OSA PP phenotype we named “Lateral positional patients (Lateral-PP)”. These OSA patients had apnea and hypopnea events mainly in the lateral position. This was a small group of OSA patients (4.1%) that were mainly obese, female, with mild-moderate OSA, and more prevalent in Black-African American.
Mendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk
Authors: Zollner Linda , Boekstegers Felix , Ponce Carol Barahona , Scherer Dominique , Marcelain Katherine , Gárate-Calderón Valentina , Waldenberger Melanie , Morales Erik , Rojas Armando , Munoz César , Müller Bettina , Retamales Javier , de Toro Gonzalo , Kortmann Allan Vera , Barajas Olga , Teresa Rivera María , Cortés Analía , Loader Denisse , Saavedra Javiera , Gutiérrez Lorena , Ortega Alejandro , Bertrán Maria Enriqueta , Bartolotti Leonardo , Gabler Fernando , Campos Mónica , Alvarado Juan , Moisán Fabricio , Spencer Loreto , Nervi Bruno , Carvajal Daniel , Losada Héctor , Almau Mauricio , Fernández Plinio , Olloquequi Jordi , Carter Alice R. , Miquel Poblete Juan Francisco , Bustos Bernabe Ignacio , Guajardo Macarena Fuentes , Gonzalez-Jose Rolando , Cátira Bortolini Maria , Acuña-Alonzo Victor , Gallo Carla , Linares Andres Ruiz , Rothhammer Francisco , Bermejo Justo Lorenzo
Published: May 2022

Background

A strong association between the proportion of Native American ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association.

Methods

Markers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses.

Result

We found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6×10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0×10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4×10-5).

Conclusions

The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient.
Hunter-gatherer oral microbiomes are shaped by contact network structure
Authors: Musciotto Federico , Dobon Begoña , Greenacre Michael , Mira Alex , Chaudhary Nikhil , Salali Gul Deniz , Gerbault Pascale , Schlaepfer Rodolph , Astete Leonora H. , Ngales Marilyn , Gomez-Gardenes Jesus , Latora Vito , Battiston Federico , Bertranpetit Jaume , Vinicius Lucio , Migliano Andrea Bamberg
Published: May 2022

Ancestral humans evolved a complex social structure still observed in extant hunter-gatherers. Here we investigate the effects of extensive sociality and mobility on the oral microbiome of 138 Agta hunter-gatherers from the Philippines. Comparisons of microbiome composition showed that the Agta are more similar to Central African Bayaka hunter-gatherers than to neighboring farmers. We also defined the Agta social microbiome as a set of 137 oral bacteria (only 7% of 1980 amplicon sequence variants) significantly influenced by social contact (quantified through wireless sensors of short-range interactions). We show that interaction networks covering large areas, and their strong links between close kin, spouses, and even unrelated friends, can significantly predict bacterial transmission networks across Agta camps. Finally, more central individuals to social networks are also bacterial supersharers. We conclude that hunter-gatherer social microbiomes, which are predominantly pathogenic, were shaped by evolutionary tradeoffs between extensive sociality and disease spread.
Organic Convolution in The Ventral Visual Pathway Can Explain the Variety of Shape Tuning in Area V4
Authors: Gold Carl
Published: May 2022

This modeling study proposes a novel theory for how V4 neurons embody selectivity to the varying degrees of curvature in diverse receptive field arrangements reported in previous recording studies. The model shows that a simple, unsupervised approach to curvature selectivity can explain a wide variety of past observations: V1 aggregates points into selectivity for lines and edges at a variety of rotations; V2 aggregates orientated segments into selectivity for corners at a variety of angles and rotations; V4 aggregates corners into curvature selectivity in a variety of degrees, rotations and positions. The model is implemented in 900,000 integrate and fire units in standard cortical micro-circuits obeying Dale’s law. The unit model and spike timing and transmission use realistic biophysical parameters. A novel method for simulating large numbers of integrate and fire units with tensor programming and GPU hardware is employed: By combining convolution with the time course of post-synaptic potentials, computation occurs in a feedforward cascade of loosely synchronized spikes. The model has relatively few parameters which are tuned by stochastic search with manual fine tuning. A synthesis of hierarchical and convolutional network models, this study adds novel elements to both: In comparison to previous hierarchical models there is a novel V4 mechanism and a biologically realistic computation based on single spikes using tensor convolution as the simulation engine. In comparison to previous convolution models there is a much higher degree of biological realism and a novel unsupervised approach to connection formation.
Privacy-Aware Kinship Inference in Admixed Populations using Projection on Reference Panels
Authors: Wang Su , Kim Miran , Li Wentao , Jiang Xiaoqian , Chen Han , Harmanci Arif
Published: May 2022

Estimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in 3rd party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization. Here, we make use of existing reference panels with a projection-based approach that simplifies kinship estimation in the admixed populations. We use simulated and real datasets to demonstrate the accuracy and efficiency of kinship estimation. We present a secure federated kinship estimation framework and implement a secure kinship estimator using homomorphic encryption-based primitives for computing relatedness between samples in 2 different sites while genotype data is kept confidential.
Motor and Visual Plasticity interact in Adult Humans
Authors: Sarı Izel D. , Lunghi Claudia
Published: May 2022

Neuroplasticity is maximal during development and declines in adulthood, especially for sensory cortices. On the contrary, the motor cortex retains plasticity throughout the lifespan. This difference has led to a modular view of plasticity in which different brain regions have their own plasticity mechanisms that do not depend or translate on others. Recent evidence indicates that visual and motor plasticity share common neural mechanisms (e.g. GABAergic inhibition), indicating a possible link between these different forms of plasticity, however the interaction between visual and motor plasticity has never been tested directly. Here we show that when visual and motor plasticity are elicited at the same time in adult humans, visual plasticity is impaired, while motor plasticity is spared. This unilateral interaction between visual and motor plasticity demonstrates a clear link between these two forms of plasticity. We conclude that local neuroplasticity in separate systems might be regulated globally, to preserve overall homeostasis in the brain.
The LEPIS-HuR-TMOD4 axis regulates hepatic cholesterol homeostasis and accelerates atherosclerosis
Authors: Lv Ping , Pan Hangyu , Hu Kexin , Li Qinxian , Lin Rongzhan , Zheng Shaoyi , Guo Zhigang , Guo Kai
Published: May 2022

Long noncoding RNAs (lncRNAs) play an important role in the entire progression of atherosclerosis. In this study, we identified an uncharacterized lncRNA, Liver Expressions by PSRC1 Induce Specifically (LEPIS). The expression of LEPIS and its potential target tropomodulin 4 (TMOD4) in the liver of ApoE-/- mice fed a high-fat diet was increased. An ApoE-/- mouse model with the overexpression of LEPIS or TMOD4 in liver was established, and we found that both LEPIS and TMOD4 increased the burden of atherosclerosis and reduced hepatic cholesterol levels. Further study revealed that LEPIS and TMOD4 affect the expression of genes related to hepatic cholesterol homeostasis, including proprotein convertase subtilisin/kexin type9 (PCSK9) and low-density lipoprotein receptor (LDLR), which are closely related to hypercholesterolemia. Mechanistically, human antigen R (HuR), an RNA-binding protein, was shown to be critical for the regulation of TMOD4 by LEPIS. Further, we found that overexpression of LEPIS promoted the shuttling of HuR from the nucleus to the cytoplasm, enhanced the stability of TMOD4 mRNA, and in turn promoted the expression of TMOD4. In addition, TMOD4 was found to affect intracellular cholesterol levels through PCSK9. These results suggest that the LEPIS-HuR-TMOD4 axis is a potential intervention target for hepatic cholesterol homeostasis and atherosclerosis.

Graphical abstract
Rank concordance of polygenic indices: Implications for personalised intervention and gene-environment interplay
Authors: Muslimova Dilnoza , Pereira Rita Dias , Hinke Stephanie von , van Kippersluis Hans , Rietveld Cornelius A. , Meddens S. Fleur W.
Published: May 2022

Polygenic indices (PGIs) are increasingly used to identify individuals at high risk of developing diseases and disorders and are advocated as a screening tool for personalised intervention in medicine and education. The performance of PGIs is typically assessed in terms of the amount of phenotypic variance they explain in independent prediction samples. However, the correct ranking of individuals in the PGI distribution is a more important performance metric when identifying individuals at high genetic risk. We empirically assess the rank concordance between PGIs that are created with different construction methods and discovery samples, focusing on cardiovascular disease (CVD) and educational attainment (EA). We find that the rank correlations between the constructed PGIs vary strongly (Spearman correlations between 0.17 and 0.94 for CVD, and between 0.40 and 0.85 for EA), indicating highly unstable rankings across different PGIs for the same trait. Simulations show that measurement error in PGIs is responsible for a substantial part of PGI rank discordance. Potential consequences for personalised medicine in CVD and research on gene-environment (G×E) interplay are illustrated using data from the UK Biobank.
The making of the oral microbiome in Agta hunter-gatherers
Authors: Dobon Begoña , Musciotto Federico , Mira Alex , Greenacre Michael , Schlaepfer Rodolph , Aguileta Gabriela , Astete Leonora H. , Ngales Marilyn , Latora Vito , Battiston Federico , Vinicius Lucio , Migliano Andrea B. , Bertranpetit Jaume
Published: May 2022

Ecological and genetic factors have influenced the composition of the human microbiome during our evolutionary history. We analyzed the oral microbiota of the Agta, a hunter-gatherer population where part of its members is adopting an agricultural diet. We show that age is the strongest factor modulating the microbiome, likely through immunosenescence as there is an increase of pathogenicity with age. Biological and cultural processes generate sexual dimorphism in the oral microbiome. A small subset of oral bacteria is influenced by the host genome, linking host collagen genes to bacterial biofilm formation. Our data also suggests that shifting from a fish/meat to a rice-rich diet transforms their microbiome, mirroring the Neolithic transition. All these factors have implications in the epidemiology of oral diseases. Thus, the human oral microbiome is multifactorial, and shaped by various ecological and social factors that modify the oral environment.
AI inspired discovery of new biomarkers for clinical prognosis of liver cancer
Authors: Liang Junhao , Zhang Weisheng , Yang Jianghui , Wu Meilong , Dai Qionghai , Yin Hongfang , Xiao Ying , Kong Lingjie
Published: May 2022

Tissue biomarkers are crucial for cancer diagnosis, prognosis assessment, and treatment planning. However, few of current biomarkers used in clinics are robust enough to show a true analytical and clinical value. Thus the search for additional tissue biomarkers, including the strategies to identify them, is imperative. Recently, the capabilities of deep learning (DL)-based computational pathology in cancer diagnosis and prognosis have been explored, but the limited interpretability and generalizability make the results difficult to be accepted in clinical practice. Here we present an interpretable human-centric DL-guided framework—PathFinder (Pathological-biomarker-finder)— that can inspire pathologists to discover new tissue biomarkers from well-performing DL models, which bridges the gap between DL and clinical prognosis. By combining sparse multi-class tissue spatial distribution information of whole slide images (WSIs) with attribution methods, PathFinder can achieve localization, characterization, and verification of potential biomarkers, while guaranteeing state-of-the-art prognostic performance. With the inspiration of PathFinder, we discovered that tumor necrosis in liver cancer, a long-neglected factor, has a strong relationship with patient prognosis. Thus we proposed two clinically independent indicators, including necrosis area fraction and tumor necrosis distribution, for practical prognosis, and verified their potentials in clinical prognosis according to Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)-derived criteria. Our work demonstrates a successful example of introducing artificial intelligence (AI) into clinical practice in a knowledge discovery way, which can be adopted in identifying biomarkers in various cancer types and modalities.
Insights into the microbial strain mediated impact on pest insect development
Authors: Gurung Kiran , Salles Joana Falcão , Wertheim Bregje
Published: May 2022

Molecular analyses of host-associated microorganisms have demonstrated the essential role that the microbiome plays in host development. Approaches targeting the sequencing of ribosomal genes have successfully identified key species of the host-associated microbiome. However, it remains unclear to what extent the strain-specific characteristics influence the outcome of the host-microbiome interactions. This is particularly important for insect pests, where microbial species might be used as targets for biocontrol purposes. Understanding strain-level variation represents thus a crucial step in determining the microbial impact on hosts. To investigate the microbial strain-level effects on an invasive insect pest, Drosophila suzukii, we compared the impact of monocultures and cocultures of different bacterial and yeast strains. We investigated whether different strains of Gluconobacter and Pichia differentially influenced the larval development of the pest. Fly trait measurements demonstrated beneficial, although variable, impact of these microbial strains on the fitness of suzukii. Using cocultures of microbial strains, we found that in some combinations, the beneficial effects were intermediate between those of the respective monocultures. In contrast, in other cases, strong inhibitory effects were observed. Hence, our study reports that strain-level effects within species are present in D. suzukii, reinforcing the importance of assessing the impact of associated microbiota on pest insects at the strain level.

Highlights

Microbial strains make up an essential part of the diversity of an insect host’s

Characterizing and accounting for strain-specific impact on a pest’s life-history traits and different combinations of strains constitute an important step in our understanding of the pest management strategies.

We investigated whether there was any strain-specific impact of bacteria and yeasts on the larval development of a frugivorous pest.

We observed that strains varied in their impact, both as monocultures and cocultures, indicating their importance in modifying the host ecology.

Our study adds to the growing literature on the importance of strains in pest insects.