bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analysis reveals geography rather than culture as the predominant factor shaping genetic variation in northern Kenyan human populations
Authors: Taravella Oill Angela M. , Handley Carla , Howell Emma K. , Stone Anne C. , Mathew Sarah , Wilson Melissa A. 
Published: November 2021

AbstractObjectivesThe aim of this study was to characterize the genetic relationships within and among four neighboring populations in northern Kenya in light of cultural relationships to understand the extent to which geography and culture shape patterns of genetic variation.Materials and MethodsWe collected DNA and demographic information pertaining to aspects of social identity and heritage from 572 individuals across the Turkana, Samburu, Waso Borana, and Rendille of northern Kenya. We sampled individuals across a total of nine clans from these four groups and, additionally, three territorial sections within the Turkana and successfully genotyped 376 individuals.ResultsHere we report that geography predominately shapes genetic variation within and among human groups in northern Kenya. We observed a clinal pattern of genetic variation that mirrors the overall geographic distribution of the individuals we sampled. We also found relatively higher rates of intermarriage between the Rendille and Samburu and evidence of gene flow between them that reflect these higher rates of intermarriage. Among the Turkana, we observed strong recent genetic substructuring based on territorial section affiliation. Within ethnolinguistic groups, we found that Y chromosome haplotypes do not consistently cluster by natal clan affiliation. Finally, we found that sampled populations that are geographically closer have lower genetic differentiation, and that cultural similarity does not predict genetic similarity as a whole across these northern Kenyan populations.DiscussionOverall, the results from this study highlight the importance of geography, even on a local geographic scale, in shaping observed patterns of genetic variation in human populations.
A biosafety level 2 surrogate for studying SARS-CoV-2 survival in food processing environmental biofilms
Authors: Featherstone Austin B. , Dass Sapna Chitlapilly 
Published: November 2021

AbstractMeat processing plants have been at the center of the SARS-CoV-2 pandemic. There are several factors that contribute to the persistence of SARS-CoV-2 in meat processing plants and one of the factors is the formation of a multi-species biofilm with virus. Biofilm can act as a reservoir in protecting, harboring, and dispersing SARS-CoV-2 from biofilm to the meat processing facility environment. We used Murine Hepatitis Virus (MHV) as a surrogate for SARS-CoV-2 virus and meat processing facility drain samples to develop mixed-species biofilms on commonly found materials in processing facilities (Stainless-Steel (SS), PVC and tiles). The results showed that MHV was able to integrate into the environmental biofilm and survived for a period of 5 days at 7°C. There was no significate difference between the viral-environmental biofilm biovolumes developed on different materials SS, PVC, and tiles. There was a 2-fold increase in the virus-environmental biofilm biovolume when compared to environmental biofilm by itself. These results indicate a complex virus-environmental biofilm interaction which is providing enhanced protection for the survival of viral particles with the environmental biofilm community.
Diverse operant control of different motor cortex populations during learning
Authors: Vendrell-Llopis Nuria , Fang Ching , Qü Albert J. , Costa Rui M. , Carmena Jose M. 
Published: November 2021

AbstractDuring motor learning, as well as during neuroprosthetic learning, animals learn to control motor cortex activity in order to generate behavior. Two different population of motor cortex neurons, intra-telencephalic (IT) and pyramidal tract (PT) neurons, convey the resulting cortical signals within and outside the telencephalon. Although a large amount of evidence demonstrates contrasting functional organization among both populations, it is unclear whether the brain can equally learn to control the activity of either class of motor cortex neurons. To answer this question, we used a Calcium imaging based brain-machine interface (CaBMI) and trained different groups of mice to modulate the activity of either IT or PT neurons in order to receive a reward. We found that animals learn to control PT neuron activity faster and better than IT neuron activity. Moreover, our findings show that the advantage of PT neurons is the result of characteristics inherent to this population as well as their local circuitry and cortical depth location. Taken together, our results suggest that motor cortex is optimized to control the activity of pyramidal track neurons, embedded deep in cortex, and relaying motor commands outside of the telencephalon.
The emergence of a collective sensory response threshold in ant colonies
Authors: Gal Asaf , Kronauer Daniel J. C. 
Published: November 2021

AbstractThe sensory response threshold is a fundamental biophysical property of biological systems that underlies many physiological and computational functions, and its systematic study has played a pivotal role in uncovering the principles of neural computation. Here, we show that ant colonies, which perform computational tasks at the group level, have emergent collective sensory response thresholds. Colonies respond collectively to step changes in temperature and evacuate the nest during severe perturbations. This response is characterized by a group-size dependent threshold, and the underlying dynamics are dominated by social feedback between the ants. Using a binary network model, we demonstrate that a balance between short-range excitatory and long-range inhibitory interactions can explain the emergence of the collective response threshold and its size dependency. Our findings illustrate how simple social dynamics allow insect colonies to integrate information about the external environment and their internal state to produce adaptive collective responses.
Bimodal Remapping of Visual Grids
Authors: Long Xiaoyang , Cai Jing , Deng Bin , Chen Zhe Sage , Zhang Sheng-Jia 
Published: November 2021

AbstractSpatially modulated neurons from the rat secondary visual cortex (V2) show grid-like firing patterns during freely foraging in open-field enclosures. However, the remapping of the V2 grid cells is not well understood. Here we report two classes of V2 grid cell populations with distinct remapping properties: one regular class with invariant grid field patterns, and the other bimodal class that has remapping induced by environmental manipulations such as changes in enclosure shape, size, orientation and lighting in a familiar environment. The bimodal V2 grid cell pattern remains stable regardless of the follow-up manipulations, but restores to the original firing pattern upon animal’s re-entry into the familiar environment on the next day or from the novel environment. The bimodal V2 grid cells are modulated with theta frequency during the course of remapping and stabilize quickly. We also found conjunctive bistable V2 grid cells with invariant head directional tuning. Overall, our results suggest a new grid cell mechanism in V2 that is different from the medial entorhinal cortex (MEC) grid cells.HighlightsBistable V2 grid cells display bimodal or bistable remappingV2 grid cell firing patterns are not disrupted in darknessV2 grid cells preserve theta frequency modulation during remapping
An arachnid’s guide to be an ant: morphological and behavioural mimicry in ant-mimicking spiders
Authors: Subramaniam Nimish , Tamma Krishnapriya , Uma Divya 
Published: November 2021

AbstractBatesian mimicry imposes several challenges to mimics and evokes adaptations in multiple sensory modalities. Myrmecomorphy, morphological and behavioral resemblance to ants, is seen in over 2000 arthropod species. Ant-like resemblance is observed in at least 13 spider families despite spiders having a distinct body plan compared to ants. Quantifying the extent to which spiders’ shape, size, and behavior resemble model ants will allow us to comprehend the evolutionary pressures that have facilitated myrmecomorphy. Myrmaplata plataleoides are ‘accurate’ mimics of the weaver ants, Oecophylla smaragdina. In this study, we quantify the speed of movement of model, mimic, and non-mimetic jumping spiders. We use traditional and geometric morphometrics to quantify traits such as foreleg and hindleg size, body shape between the model ant, mimic, and non-mimics. Our results suggest that while the mimics closely resemble the model ants in speed of movement, they occupy an intermediate morphological space compared to the model ants and non-mimics. We suggest that ant-mimicking spiders are better at mimicking ants’ locomotory movement than morphology and overall body shape. Our study provides a framework to understand the multimodal nature of mimicry and helps discern the relative contributions of such traits that drive mimetic accuracy in ant-mimicking spiders.
Identification of marker-trait associated SNPs for fruit weight and plant height in a wild and domesticated jujube fruit tree (Ziziphus spp.) collection using genotyping-by-sequencing
Authors: Uddin Nisar , Shinde Harshraj , Tesfamicael Kiflu , Ali Niaz , Tricker Penny J. , Rodríguez López Carlos M. 
Published: November 2021

AbstractZiziphus are economically and nutritionally important fruiting plants that were domesticated in China around 7000 years ago. We identified genetic diversity in 141 accessions of four, different species collected in Pakistan and in China, including wild species of Ziziphus mauritiana, Z. nummularia and Z. oxyphllya, and both wild and domesticated Z. jujuba Mill. Population structure, phylogenetic analysis and principal coordinates analysis based on 10,889 high-quality SNPs derived from genotyping-by-sequencing indicated that the accessions clustered into two major groups. The wild Pakistani Z. jujuba and Z. nummularia exhibited higher genetic diversity and polymorphic information content (0.37 and 0.23 respectively) than other species. We further conducted a genome-wide association study and discovered six highly significant marker-trait associations for fruit weight and plant height in this population. Our study provides important information for future breeding of Ziziphus species.
Type 1 interferon supports B cell responses to polysaccharide antigens but is not required for MPL/TDCM adjuvant effects on innate B cells
Authors: Spurrier M. Ariel , Jennings-Gee Jamie E. , Haas Karen M. 
Published: November 2021

AbstractWe previously described monophosphoryl lipid A (MPL) and synthetic cord factor, trehalose-6,6’-dicorynomycolate (TDCM) significantly increases antibody (Ab) responses to T cell independent type 2 antigens (TI-2 Ags) in a manner dependent on B cell-intrinsic TLR4 expression as well as MyD88 and TRIF adapter proteins. Given the requirement for TRIF in optimal MPL/TDCM adjuvant effects and the capacity of MPL to drive type I IFN production, we aimed to investigate the extent to which adjuvant effects on TI-2 Ab responses depend on type I IFN receptor (IFNAR) signaling. We found IFNAR−/−mice had impaired early TI-2 Ag-induced B cell activation and expansion and that B cell-intrinsic type I IFN signaling on B cells was essential for normal antibody responses to TI-2 Ags, including haptenated Ficoll and the pneumococcal vaccine, Pneumovax23. However, MPL/TDCM significantly increased TI-2 IgM and IgG responses in IFNAR−/−mice. MPL/TDCM enhanced TI-2 Ab production primarily by activating innate B cells (B-1b and splenic CD23−B cells) as opposed to CD23+enriched follicular B cells. In summary, our study highlights an important role for type I IFN in supporting early B cell responses to TI-2 Ags through B cell-expressed IFNAR, but nonetheless demonstrates an MPL/TDCM adjuvant significantly increases TI-2 Ab responses independently of type I IFN signaling and does so by predominantly supporting increased polysaccharide-specific Ab production by innate B cell populations.Key pointsB cell-intrinsic IFNAR expression promotes TI-2 Ab responses.MPL/TDCM adjuvant effects are independent of type 1 IFN.MPL/TDCM promotes TI-2 Ab responses by innate B cells.
Improving the Virtual Trichrome Assessment through Bridge Category Models
Authors: Levy Joshua , Bobak Carly , Azizgolshani Nasim , Liu Xiaoying , Ren Bing , Lisovsky Mikhail , Suriawinata Arief , Christensen Brock , O’Malley James , Vaickus Louis 
Published: November 2021

AbstractNon-alcoholic steatohepatitis (NASH) is a liver disease characterized by excessive lipid accumulation and disease progression is typically assessed through inspection of a Trichrome stain for Fibrosis staging. As the public health burden of NASH worsens due to evolving lifestyle habits, pathology laboratory resources will become increasingly strained due to rising demand for specialized stains. Virtual staining processes, computational methods which can synthesize the application of chemical staining reagents, can potentially provide resource savings by obviating the need to acquire specialized stains. Virtual staining technologies are assessed by comparing virtual and real tissue stains for their realism and ability to stage. However, these assessment methods are rife with statistical mistreatment of observed phenomena that are difficult to account for. Bridge category ratings represent a phenomenon where a pathologist may assign two adjacent stages simultaneously, which may bias and/or reduce the power of research findings. Such stage assignments were frequently reported in a large-scale assessment of Virtual Trichrome technologies yet were unaccounted for since no statistical adjustment procedures existed. In this work, we provide an updated assessment of Virtual Trichrome technologies using Bridge Category Models, which account for these bridge ratings. We report that two of four pathologists tended to assign lower Fibrosis stages to virtually stained tissue while the other two pathologists assigned similar stages. These research findings differ when bridge ratings are not accounted for. While promising, these results indicate further room for algorithmic finetuning of Virtual Trichrome technologies.
Air plasma-activated medium exerts tumor-specific cytotoxicity via the oxidative stress-induced perinuclear mitochondrial clustering
Authors: Suzuki-Karasaki Manami , Ando Takashi , Ochiai Yushi , Kawahara Kenta , Suzuki-Karasaki Miki , Nakayama Hideki , Suzuki-Karasaki Yoshihiro 
Published: November 2021

AbstractIntractable cancers such as osteosarcoma (OS) and oral cancer (OC) are highly refractory, recurrent, and metastatic once developed, and their prognosis is still disappointing. Tumor-targeted therapy eliminating cancers effectively and safely is the current clinical choice. Since aggressive tumors have inherent or acquired resistance to multidisciplinary therapies targeting apoptosis, tumor-specific induction of another cell death modality is a promising avenue to meet the goal. Here, we report that a cold atmospheric air plasma-activated medium (APAM) can induce cell death in OS and OC via a unique mitochondrial clustering. This event was named monopolar perinuclear mitochondrial clustering (MPMC) because of the characteristic unipolar mitochondrial perinuclear aggregation. APAM had potent antitumor activity both in vitro and in vivo. APAM caused apoptosis, necrotic cell death, and autophagy. APAM contained hydrogen peroxide and increased mitochondrial ROS (mROS), while the antioxidant N-acetylcysteine (NAC) prevented cell death. MPMC occurred following mitochondrial fragmentation coinciding with nuclear damages. MPMC was accompanied by the tubulin network remodeling and mitochondrial lipid peroxide (mLPO) accumulation and prevented by NAC and the microtubule inhibitor, Nocodazole. Increased Cardiolipin (CL) oxidation was also seen, and NAC and the peroxy radical scavenger Ferrostatin-1 prevented it. In contrast, in fibroblasts, APAM induced minimal cell death, mROS generation, mLPO accumulation, CL oxidation, and MPMC. These results suggest that MPMC is a tumor-specific cause of cell death via mitochondrial oxidative stress and microtubule-driven mitochondrial motility. MPMC might serve as a promising target for exerting tumor-specific cytotoxicity.
Graphical abstract
When Yeast Cells Change their Mind: Cell Cycle “Start” is Reversible under Starvation
Authors: Irvali Deniz , Schlottmann Fabian P. , Muralidhara Prathibha , Nadelson Iliya , Wood N. Ezgi , Doncic Andreas , Ewald Jennifer C. 
Published: November 2021

AbstractEukaryotic cells decide in late G1 whether to commit to another round of genome duplication and division. This point of irreversible cell cycle commitment is a molecular switch termed “Restriction Point” in mammals and “Start” in budding yeast. At Start, yeast cells integrate multiple signals such as pheromones, osmolarity, and nutrients. If sufficient nutrients are lacking, cells will not pass Start. However, how the cells respond to nutrient depletion after they have made the Start decision, remains poorly understood.Here, we analyze by live cell imaging how post-Start yeast cells respond to nutrient depletion. We monitor fluorescently labelled Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 back into the nucleus. This occurs when cells are faced with starvation up to 20 minutes after Start. In these cells, the positive feedback loop is interrupted, Whi5 re-binds DNA, and CDK activation occurs a second time once nutrients are replenished. Cells which re-import Whi5 also become sensitive to mating pheromone again, and thus behave like pre-Start cells. In summary, we show that upon starvation the commitment decision at Start can be reversed. We therefore propose that in yeast, as has been suggested for mammalian cells, cell cycle commitment is a multi-step process, where irreversibility in face of nutrient signaling is only reached approximately 20 minutes after CDK activation at Start.
Quantitative Measurement of Diffusion-weighted Imaging Signal Using Expression-controlled Aquaporin-4 Cells: Comparative Study of 2-compartment and Diffusion Kurtosis Imaging Models
Authors: Imaizumi Akiko , Obata Takayuki , Kershaw Jeff , Tachibana Yasuhiko , Abe Yoichiro , Shibata Sayaka , Nitta Nobuhiro , Aoki Ichio , Yasui Masato , Higashi Tatsuya 
Published: November 2021

AbstractPurposeThe purpose of this study was to compare parameter estimates for the 2-compartment (2Comp) and diffusion kurtosis imaging (DKm) models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability.MethodsDWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2Comp and DKm models. For the 2Comp model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff=1-Fs) of the fast and slow compartments were estimated. For the DKm model, estimates of the diffusion kurtosis (K) and corrected diffusion coefficient (D) were obtained.ResultsFor the 2Comp model, Ds and Fs showed clear differences between AQP4-expressing and non-expressing cells. Fs was also sensitive to cell density. There was no clear relationship with the cell type for the DKm parameters.ConclusionsChanges to cell membrane water permeability due to AQP4 expression affected DWI of cell suspensions. For the 2Comp and DKm models, Ds was the parameter most sensitive to differences in AQP4 expression.
Everyday functioning in a community-based volunteer population: Differences between participant- and study partner-report
Authors: Verrijp M. , Dubbelman M.A. , Visser L.N.C. , Jutten R.J. , Nijhuis E.W. , Zwan M.D. , van Hout H.P.J. , Scheltens P. , van der Flier W.M. , Sikkes S.A.M. 
Published: November 2021

AbstractINTRODUCTIONImpaired awareness in dementia due to Alzheimer’s disease and related disorders, made study partner-report the preferred method of measuring interference in ‘instrumental activities of daily living’ (IADL). However, with a shifting focus towards earlier disease stages and prevention, the question arises whether self-report might be equally or even more appropriate. This study aims to investigate how participant and study partner report IADL perform in a community-based volunteer population without dementia, and which factors relate to differences between participant and study partner report.METHODSParticipants (N=3288; 18–97 years, 70.4% females) and their study partners (N=1213; 18–88 years, 45.8% females) were recruited from the Dutch brain research registry. IADL was measured using the Amsterdam IADL Questionnaire. Concordance between participant and study partner-reported IADL difficulties was examined using intraclass correlation coefficient (ICC). Multinomial logistic regressions were used to investigate which demographic, cognitive and psychosocial factors related to participant and study partner differences, by looking at the over- and underreport of IADL difficulties by the participant, relative to their study partner.RESULTSThe vast majority of A-IADL-Q scores represented no difficulties for both participants (87.9%) and study partners (89.4%). Concordance between participants and study partners was moderate (ICC=.55, 95%CI=[.51, .59]), 24.5% (N=297) of participants overreported their IADL difficulties compared to study partners, and 17.8% (N=216) underreported difficulties. The presence of depressive symptoms (odds ratio (OR)=1.31, 95%CI=[1.12, 1.54]), as well as memory complaints (OR=2.45, 95%CI=[1.80, 3.34]), increased the odds of participants overreporting their IADL difficulties. Higher IADL ratings decreased the odds of participant underreport (OR=0.71, 95%CI=[0.67, 0.74]).CONCLUSIONIn this sample of community-based volunteers, the majority of participants and study partners reported no major IADL difficulties. Differences between participant and study partner were, however, quite prevalent, with subjective factors indicative of increased report of IADL difficulties by the participant in particular. These findings suggest that self- and study partner-report measures may not be interchangeable, and that the level of awareness needs to be taken into account, even in cognitively healthy individuals.
Reversal of lineage plasticity in RB1/TP53-deleted prostate cancer through FGFR and Janus kinase inhibition
Authors: Karthaus Wouter R. , Chan Joseph , Setty Manu , Love Jillian R. , Zaidi Samir , Choo Zi-ning , Persad Sitara , LaClair Justin , Lawrence Kayla E , Chaudhary Ojasvi , Xu Tianhao , Masilionis Ignas , Mazutis Linas , Chaligne Ronan , Pe’er Dana , Sawyers Charles L 
Published: November 2021

AbstractThe inherent plasticity of tumor cells provides a mechanism of resistance to many molecularly targeted therapies, exemplified by adeno-to-neuroendocrine lineage transitions seen in prostate and lung cancer. Here we investigate the root cause of this lineage plasticity in a primary murine prostate organoid model that mirrors the lineage transition seen in patients. These cells lose luminal identity within weeks following deletion ofTrp53andRb1, ultimately acquiring an Ar-negative, Syp+ phenotype after orthotopicin vivotransplantation. Single-cell transcriptomic analysis revealed progressive mixing of luminal-basal lineage features after tumor suppressor gene deletion, accompanied by activation of Jak/Stat and Fgfr pathway signaling and interferon-a and -g gene expression programs prior to any morphologic changes. Genetic or pharmacologic inhibition of Jak1/2 in combination with FGFR blockade restored luminal differentiation and sensitivity to antiandrogen therapy in models with residual AR expression. Collectively, we show lineage plasticity initiates quickly as a largely cell-autonomous process and, through newly developed computational approaches, identify a pharmacological strategy that restores lineage identity using clinical grade inhibitors.