bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics single-cell analysis of human pancreatic islets reveals novel cellular states in health and type 1 diabetes
Authors: Fasolino Maria , Schwartz Gregory W. , Golson Maria L. , Wang Yue J. , Morgan Ashleigh , Liu Chengyang , Schug Jonathan , Liu Jinping , Wu Minghui , Traum Daniel , Kondo Ayano , May Catherine L. , Goldman Naomi , Wang Wenliang ,   the HPAP Consortium, Feldman Michael , Moore Jason H. , Japp Alberto S. , Betts Michael R. , Faryabi Robert B. , Naji Ali , Kaestner Klaus H. , Vahedi Golnaz 
Published: January 2021

AbstractType 1 diabetes (T1D) is an autoimmune disease of only partially defined etiology in which immune cells destroy insulin-producing beta cells. Using single-cell transcriptomics and an advanced analytical strategy to assess pancreatic islets of T1D, autoantibody-positive, and non-diabetic organ donors, we identified both canonical cell types and rare insulin-expressing cells with a hybrid mixture of endocrine and exocrine gene signatures within all donors. We further found elevated expression of MHC Class II pathway genes in exocrine ductal cells of T1D donors, which we confirmed through CyTOF, in situ imaging mass cytometry, and immunofluorescence analysis. Taken together, our multimodal analyses identify novel cell types and processes that may contribute to T1D immunopathogenesis and provide new cellular and molecular insights into human pancreas function.
Encephalitis patient derived monoclonal GABAAreceptor antibodies cause catatonia and epileptic seizures
Authors: Kreye Jakob , Wright Sukhvir K. , van Casteren Adriana , Machule Marie-Luise , Reincke S. Momsen , Nikolaus Marc , Stöffler Laura , van Hoof Scott , Sanchez-Sendin Elisa , Kornau Hans-Christian , Kaindl Angela M. , Wilson Max A. , Greenhill Stuart , Woodhall Gavin , Turko Paul , Vida Imre , Garner Craig C. , Wickel Jonathan , Geis Christian , Fukata Yuko , Fukata Masaki , Prüss Harald 
Published: January 2021

AbstractAutoantibodies targeting the GABAAreceptor (GABAAR) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given the common overlap with further autoantibodies and the lack of patient derived monoclonal antibodies (mAbs). We cloned and recombinantly produced five affinity-maturated GABAAR IgG1 mAbs from cerebrospinal fluid cells, which bound to various epitopes involving α1 and γ2 receptor subunits, with variable binding strength and partial competition. mAbs selectively reduced GABAergic currents in neuronal cultures without causing receptor internalization. Cerebroventricular infusion of GABAAR mAbs and Fab fragments into rodents induced a severe phenotype with catatonia, seizures and increased mortality, reminiscent of encephalitis patients’ symptoms. Our results prove direct functional effects of autoantibodies on GABAARs and provide an animal model for GABAAR encephalitis. They further provide the scientific rationale for clinical treatments using antibody depletion and pave the way for future antibody-selective immunotherapies.
Genome-wide DNA methylation predicts environmentally-driven life history variation in a marine fish
Authors: Cayuela Hugo , Rougeux Clément , Laporte Martin , Mérot Claire , Normandeau Eric , Leitwein Maëva , Dorant Yann , Præbel Kim , Kenchington Ellen , Clément Marie , Sirois Pascal , Bernatchez Louis 
Published: January 2021

AbstractThe molecular mechanisms underlying intraspecific variation in life history strategies are still poorly understood, despite the importance of this question for understanding of organism’s responses to environmental variability. Theoretical work proposed that epigenetic mechanisms such as DNA methylation might regulate intraspecific variation in life history strategies, however this assumption has rarely been verified empirically in wild populations. We examined associations between genome-wide methylation changes and environmentally-driven life history variation in two lineages of a marine fish that diverged approximatively 2.5 Mya, the capelin (Mallotus villosus), from North America and Europe. In both lineages, capelin harbour two contrasted life history strategies: some are strictly semelparous, experience fast actuarial senescence, but benefit from high hatching success by spawning on demersal sites where water temperature is low and relatively stable. In contrast, others are facultative iteroparous, have slower actuarial senescence, and suffer from lower hatching success by breeding in the intertidal zone where temperature is warmer, thermohaline parameters are less stable, and egg desiccation risk is high. Performing whole genome and epigenome sequencing, we showed that these contrasted life history strategies are more likely governed by epigenetic changes than by differences in DNA sequence. While genetic differentiation between the capelin harbouring different life history strategies was negligible, we detected parallel genome-wide methylation changes across lineages. We identified 1,067 differentially methylated regions (DMRs) comprising 15,818 CpGs, with 22% of them located within 5-kb around genes comprising promotor regions. We found that all DMRs were hypermethylated in demersal-spawning individuals. This striking result suggests that lower water temperature at demersal sites leads to an overall hypermethylation of the genome determined during the epigenetic reprogramming occurring over embryonic development. Our study emphasizes that parallel epigenetics changes in lineages with divergent genetic background could have a functional role in the regulation of intraspecific life history variation.
The coral symbiontCandidatusAquarickettsia is variably abundant in threatened Caribbean acroporids and transmitted horizontally
Authors: Baker Lydia J. , Reich Hannah G. , Kitchen Sheila A. , Klinges J. Grace , Koch Hanna R. , Baums Iliana B. , Muller Erinn , Thurber Rebecca Vega 
Published: January 2021

AbstractThe aquatic symbiont “Candidatus Aquarickettsia rohweri” infects a diversity of non-bilaterian metazoan phyla. In the threatened coralAcropora cervicornis,Aquarickettsiaproliferates in response to increased nutrient exposure, resulting in suppressed growth and increased disease susceptibility and mortality. This study evaluated the extent, as well as the ecology and evolution ofAquarickettsiainfecting the Caribbean corals:Ac. cervicornisandAc. palmataand their hybrid (‘Ac. prolifera’). The bacterial parasiteAquarickettsiawas found in all acroporids, with host and sampling location impacting infection magnitude. Phylogenomic and genome-wide single nucleotide variant analysis foundAquarickettsiaclustering by region, not by coral taxon. Fixation analysis suggested within coral colonies,Aquarickettsiaare genetically isolated to the extent that reinfection is unlikely. Relative to other Rickettsiales,Aquarickettsiais undergoing positive selection, with Florida populations experiencing greater positive selection relative to the other Caribbean locations. This may be due toAquarickettsiaresponse to increased nutrient stress in Florida, as indicated by greaterin situreplication rates in these corals.Aquarickettsiadid not significantly codiversify with either coral animal nor algal symbiont, and qPCR analysis of gametes and juveniles from susceptible coral genotypes indicated absence in early life stages. Thus, despite being an obligate parasite,Aquarickettsiamust be horizontally transmitted via coral mucocytes, an unidentified secondary host, or a yet unexplored environmentally mediated mechanism. Importantly, the prevalence ofAquarickettsiainAc. cervicornisand high abundance in Florida populations suggests that disease mitigation efforts in the US and Caribbean should focus on preventing early infection via horizontal transmission.
RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry
Authors: Cucinotta Christine E. , Dell Rachel H. , Braceros Keean C.A. , Tsukiyama Toshio 
Published: January 2021

AbstractQuiescence is a reversible G0state essential for differentiation, regeneration, stem cell renewal, and immune cell activation. Necessary for long-term survival, quiescent chromatin is compact, hypoacetylated, and transcriptionally inactive. How transcription activates upon cell-cycle re-entry is undefined. Here we report robust, widespread transcription within the first minutes of quiescence exit. During quiescence, the chromatin-remodeling enzyme RSC was already bound to the genes induced upon quiescence exit. RSC depletion caused severe quiescence exit defects: a global decrease in RNA polymerase II (Pol II) loading, Pol II accumulation at transcription start sites, initiation from ectopic upstream loci, and aberrant antisense transcription. These phenomena were due to a combination of highly robust Pol II transcription and severe chromatin defects in the promoter regions and gene bodies. Together, these results uncovered multiple mechanisms by which RSC facilitates initiation and maintenance of large-scale, rapid gene expression despite a globally repressive chromatin state.
Selectivity of Protein Interactions along the Aggregation Pathway of α-Synuclein
Authors: Leitão André D. G. , Soto Paulina Rudolffi , Chappard Alexandre , Bhumkar Akshay , Hunter Dominic J. B. , Sierecki Emma , Gambin Yann 
Published: January 2021

AbstractThe aggregation of α-SYN follows a cascade of oligomeric, prefibrillar and fibrillar forms, culminating in the formation of Lewy Bodies (LB), the pathological hallmarks of Parkinson’s Disease in neurons. Whilst α-synuclein is a major contributor to LB, these dense accumulations of protein aggregates and tangles of fibrils contain over 70 different proteins. However, the potential for interactions between these proteins and the different aggregated species of α-SYN is largely unknown. We hypothesized that the proteins present in the Lewy Bodies are trapped or pulled into the aggregates in a hierarchical manner, by binding at specific stages of the aggregation of α-SYN.In this study we uncover a map of interactions of a total of 65 proteins, against different species formed by α-SYN. We measured binding to monomeric α-SYN using AlphaScreen, a sensitive nano-bead assay for detection of protein-protein interactions. To access different oligomeric species, we made use of the pathological mutants of α-SYN (A30P, G51D and A53T), which form oligomeric species with distinct properties. Finally, we used bacterially expressed recombinant α-SYN to generate amyloid fibrils and measure interactions with a pool of GFP-tagged potential partners. Binding to oligomers and fibrils was measured by two-color coincidence detection (TCCD) on a single molecule spectroscopy setup. Overall, we demonstrate that LB components are selectively recruited to specific steps in the formation of the LB, explaining their presence in the inclusions. Only a few proteins were found to interact with α-SYN monomers at detectable levels, and only a subset recognizes the oligomeric α-SYN including autophagosomal proteins. We therefore propose a new model for the formation of Lewy Bodies, where selectivity of protein partners at different steps drives the arrangement of these structures, uncovering new ways to modulate aggregation.Significance StatementThe molecular complexity of the Lewy Bodies has been a major hindrance to a bottom-up reconstruction of these inclusions, protein by protein. This work presents an extensive dataset of protein-protein interactions, showing that despite its small size and absence of structure, α-SYN binds to specific partners in the LB, and that there is a clear selectivity of interactions between the different α-SYN species along the self-assembly pathway. We use single-molecule methods to deconvolute number and size of the co-aggregates, to gain detailed information about the mechanisms of interaction. These observations constitute the basis for the elaboration of a global interactome of α-SYN.
Synchronization of seasonal acclimatization and short‐term heat hardening improves physiological resilience in a changing climate
Authors: Zhang Wen‐yi , Storey Kenneth B. , Dong Yun‐wei 
Published: January 2021

Abstract

Animal survival and species distribution in the face of global warming and increasing occurrences of heatwave largely depend on how heat tolerance shifts with plastic responses at different spatiotemporal scales, including long‐term acclimation/acclimatization and short‐term heat hardening. However, knowledge about the interaction of these plastic responses is still unclear.

To understand how plastic responses at different time‐scales work together to adjust heat tolerance of organisms, we examined the effect of heat hardening on the upper thermal limits of an intertidal mudflat bivalve, the razor clam Sinonovacula constricta, for different seasons using heart rate as a proxy.

We observed a stronger heat hardening response of S. constricta in warm seasons, implying that heat hardening worked synchronously with seasonal acclimatization to increase resistance of the clams to high temperatures in warm seasons. In warm seasons, heat hardening increased heat tolerance by 2–4°C and showed a 24‐hr temporal dependence, suggesting an adaptation to the diel fluctuation of thermal regimes in summer.

Furthermore, thermal stress resembling seasonal maximum environmental temperature induced stronger heat hardening effects, indicating that heat hardening is an essential plastic response to extreme hot weather, complementing seasonal acclimatization.

Our results suggest that high temperature risk can be alleviated jointly by seasonal acclimatization and heat hardening, and emphasize the importance of considering physiological plasticity on both long‐term and short‐term temporal scales in evaluating and forecasting vulnerability of organisms to climate change.

A free Plain Language Summary can be found within the Supporting Information of this article.
Functional diversity and trait composition of vascular plant and Sphagnum moss communities during peatland succession across land uplift regions
Authors: Laine Anna M. , Lindholm Tapio , Nilsson Mats , Kutznetsov Oleg , Jassey Vincent E. J. , Tuittila Eeva‐Stiina 
Published: January 2021

Abstract

Most of the carbon accumulated into peatlands is derived from Sphagnum mosses. During peatland development, the relative share of vascular plants and Sphagnum mosses in the plant community changes, which impacts ecosystem functions. Little is known on the successional development of functional plant traits or functional diversity in peatlands, although this could be a key for understanding the mechanisms behind peatland resistance to climate change. Here we aim to assess how functionality of successive plant communities change along the autogenic peatland development and the associated environmental gradients, namely peat thickness and pH, and to determine whether trait trade‐offs during peatland succession are analogous between vascular plant and moss communities.

We collected plant community and trait data on successional peatland gradients from post‐glacial rebound areas in coastal Finland, Sweden and Russia, altogether from 47 peatlands. This allowed us to analyse the changes in community‐weighted mean trait values and functional diversity (diversity of traits) during peatland development.

Our results show comparative trait trade‐offs from acquisitive species to conservative species in both vascular plant and Sphagnum moss communities during peatland development. However, mosses had higher resistance to environmental change than vascular plant communities. This was seen in the larger proportion of intraspecific trait variation than species turnover in moss traits, while the proportions were opposite for vascular plants. Similarly, the functional diversity of Sphagnum communities increased during the peatland development, while the opposite occurred for vascular plants. Most of the measured traits showed a phylogenetic signal. More so, the species common to old successional stages, namely Ericacae and Sphagna from subgroup Acutifolia were detected as most similar to their phylogenetic neighbours.

Synthesis. During peatland development, vegetation succession leads to the dominance of conservative plant species accustomed to high stress. At the same time, the autogenic succession and ecological engineering of Sphagna leads to higher functional diversity and intraspecific variability, which together indicate higher resistance towards environmental perturbations.
Overyielding in young tree communities does not support the stress‐gradient hypothesis and is favoured by functional diversity and higher water availability
Authors: Belluau Michaël , Vitali Valentina , Parker William C. , Paquette Alain , Messier Christian 
Published: January 2021

Abstract

Biodiversity effects on productivity and other ecosystem functions are strongly dependent on climate and resource availability. Based on the stress‐gradient hypothesis, under conditions of greater abiotic stress, diversity effects on plant performance are intensified due to the increased relative importance of positive plant interactions. However, whether this hypothesis is consistently applicable in forest systems remains unclear. A field trial was established to test the stress‐gradient hypothesis and examine diversity effects on above‐ground biomass production of young trees in mixtures exposed to different water availability.

Six native tree species of northern temperate forests (Acer saccharum, Betula papyrifera, Larix laricina, Picea glauca, Pinus strobus and Quercus rubra) were planted as monocultures and as mixtures of two, four and six species. For five growing seasons, four replicates of each community were exposed to conditions of either low‐ or high‐water availability created by rainfall exclusion and weekly irrigation, respectively. Growth‐years 4 and 5 were significantly different when the climatic water balance of the growing seasons was compared. We tested the effects of functional diversity on: (a) total growth of mixtures under low‐ and high‐water availability, and (b) annual growth in years 4 (higher water availability, 2017) and 5 (lower water availability, 2018).

Annual growth of most species in both years was greater under high‐ versus low‐water availability. Functional diversity had a significant positive effect on total biomass production and annual growth, and this effect was more strongly expressed under high‐water availability. Functional diversity effects on annual growth did not differ between years 4 and 5 regardless of their climatic water balance. Functional and species identity were key to understanding productivity responses to mixture and treatment effects.

Synthesis. Contrary to the stress‐gradient hypothesis, the positive effects of functional diversity on productivity were enhanced by high‐water availability and were independent of seasonal water balance.
Dynamic feedbacks among tree functional traits, termite populations and deadwood turnover
Authors: Guo Chao , Tuo Bin , Ci Hang , Yan En‐Rong , Cornelissen Johannes H. C. 
Published: January 2021

Abstract

Changes in the composition of plant functional traits may affect ecosystem processes through influencing trophic interactions. Bottom‐up control by plant species through food availability to animals may vary with time. However, such dynamics and their consequences for deadwood turnover are poorly known for detrital food webs.

We introduce a dynamic conceptual model of the feedback of tree functional traits, (deadwood‐feeding) termite populations and deadwood decomposition. We hypothesized that tree functional diversity (in terms of a wood resource economic spectrum [WES]) supports the sustenance of termite populations via complementary food supplied through time, as deadwood varies in traits both initially across species and because of different decomposition rates. Simultaneously, driven by this temporal dynamics of food quality, the consumption of deadwood by termites should hypothetically sustain deadwood turnover in a functionally diverse forest over time.

We tested our hypothesis through an 18‐month termite‐exclusion decomposition experiment by incubating coarse (i.e. 5 cm diameter) deadwood of 34 woody species in two subtropical forests in East China. One site still sustained a healthy population of pangolins as the keystone termite predator, whereas another had lost its pangolins due to hunting and illegal wildlife trade.

The results supported our hypothesis: in the first 12 months, termites amplified the positive linear relationship between % wood mass loss and initial wood quality (WES). In contrast, between 12 and 18 months, termite‐mediated consumption, and associated wood mass loss, showed a humpback relation with the initial WES. This shift in termite preference of deadwood species along the WES reflects complementary food availability to termites through time.

Synthesis. Our findings imply that tree functional composition, with variation in deadwood quality through decomposition time, can help to sustain termite populations and thereby forest carbon turnover. Future studies need to test whether and how our conceptual model may apply to other detrital systems and food webs. In general, food web research would benefit from a stronger focus on temporal patterns for better understanding the interactions of basal resource functional traits and consumers on ecosystem functions.
Subsurface and surface halophile communities of the chaotropic Salar de Uyuni
Authors: Martínez José M. , Escudero Cristina , Rodríguez Nuria , Rubin Sergio , Amils Ricardo 
Published: January 2021

SummarySalar de Uyuni (SdU) is the biggest athalosaline environment on Earth, holding a high percentage of the known world Li reserves. Due to its hypersalinity, temperature and humidity fluctuations, high exposure to UV radiation, and its elevated concentration of chaotropic agents like MgCl2, LiCl and NaBr, SdU is considered a polyextreme environment. Here, we report the prokaryotic abundance and diversity of 46 samples obtained in different seasons and geographical areas. The identified bacterial community was found to be more heterogeneous than the archaeal community, with both communities varying geographically. A seasonal difference has been detected for archaea. Salinibacter, Halonotius and Halorubrum were the most abundant genera in Salar de Uyuni. Different unclassified archaea were also detected. In addition, the diversity of two subsurface samples obtained at 20 and 80 m depth was evaluated and compared with the surface data, generating an evolutionary record of a multilayer hypersaline ecosystem.
‘Banner of an Atomic Regiment’: Morris Louis, Greenberg's Modernism, and Science, c. 1962
Authors: Curley John J. 
Published: January 2021

AbstractAround 1962, ‘formalism’ could indicate methodological purity in the realms of both art and science. With camps in both disciplines attempting to minimize human intervention in the realm of decision‐making, ‘formalism’ could take on mechanical overtones, thereby linking art and science in profound ways. This essay considers the ways in which the austere abstract paintings of Morris Louis from the years surrounding 1960 bring these dual formalisms into focus. When viewed through the criticism of Clement Greenberg and the near‐unwavering faith President Kennedy's administration placed in new technocratic ways of waging war, Louis's paintings can be seen as beatified expressions of a mechanical rationality that also brought the world to the brink of nuclear apocalypse. Through deep engagement with Greenberg's criticism and media archives, the essay forges links between Greenberg's version of Louis and the dark sides of this rationality. The article concludes by locating ways to consider Louis's paintings outside of the Greenbergian straitjacket – recapturing the strangeness and chaotic nature of the painter's practice.