bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily ranging and den usage patterns structure fission-fusion dynamics and social associations in spotted hyenas
Authors: Strauss Eli D. , Jensen Frants H. , Gersick Andrew S. , Thomas Mara , Holekamp Kay E. , Strandburg-Peshkin Ariana 
Published: October 2021

ABSTRACTEnvironment structure often shapes social interactions. Spatial attractors that draw multiple individuals may play a particularly important role in dispersed groups, where individuals must first encounter one another to interact. We use GPS data recorded simultaneously from five spotted hyenas (Crocuta crocuta) within a single clan to investigate how communal dens and daily ranging patterns shape fission-fusion dynamics (subgroup splits and merges). We introduce a species-general framework for identifying and characterizing dyadic fission-fusion events and describe a taxonomy of ten possible configurations of these events. Applying this framework to the hyena data illuminates the spatiotemporal structure of social interactions within hyenas’ daily routines. The most common types of fission-fusion events involve close approaches between individuals, do not involve co-travel together, and occur at the communal den. Comparison to permutation-based reference models suggests that den usage structures broad-scale patterns of social encounters, but that other factors influence how those encounters unfold. We discuss the dual role of communal dens in hyenas as physical and social resources, and suggest that dens are an example of a general “social piggybacking” process whereby environmental attractors take on social importance as reliable places to encounter conspecifics, causing social and spatial processes to become fundamentally intertwined.
Study of Metyltetraprole, an unusual agrofungicide targeting the Qo-site of cytochrome bc1 complex
Authors: Serot Claudia , Michel Thomas , Lucas Valentine , Meunier Brigitte 
Published: October 2021

AbstractThe mitochondrial respiratory chain bc1 complex is a proven target of agrofungicides. Most of them are Qo-site antagonists (i.e QoIs), competing with the substrate ubiquinol, and likely share the same binding mode as the widespread Qo-site resistance mutation G143A confers cross-resistance. Metyltetraprole (MTP) presents an exception as studies with phytopathogenic fungi showed that the inhibitor was unaffected by G143A. Here, we used the yeast model to investigate its mode of action. Analysis of bc1 complex mutants supports a Qo-site binding for MTP. However the compound seems distinct to other QoIs, such as azoxystrobin, in various ways, namely; 1) G143A was without effect on MTP, as previously reported. 2) The level of MTP resistance of mutants was higher in bc1 complex activity assays than in growth assays while the opposite was observed with azoxystrobin. 3) Steady-state kinetics used to characterise the mode of action of MTP also revealed differences compared to other QoIs.
INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury
Authors: Calabrese Barbara , Jones Steven , Yamaguchi-Shiraishi Yoko , Lingelbach Michael , Manor Uri , Svitkina Tatyana M , Higgs Henry N , Shih Andy Y , Halpain Shelley 
Published: October 2021

ABSTRACTDuring early stages of ischemic brain injury, glutamate receptor hyperactivation mediates neuronal death via osmotic cell swelling. Here we show that ischemia and excess NMDA receptor activation – conditions that trigger neuronal swelling -- cause actin filaments to undergo a rapid and extensive reorganization within the somatodendritic compartment. Normally, F-actin is concentrated within dendritic spines, with relatively little F-actin in the dendrite shaft. However, beginning <5 min after incubation of neurons with NMDA, F-actin depolymerizes within dendritic spines and polymerizes into long, stable filament bundles within the dendrite shaft and soma. A similar “actinification” of the somatodendritic compartment occurs after oxygen/glucose deprivation in vitro, and in mouse brain after photothrombotic stroke in vivo. Following transient, sub-lethal NMDA exposure these actin changes spontaneously reverse within 1-2 hours. A combination of Na+, Cl-, water, and Ca2+ entry are all necessary, but not individually sufficient, for induction of actinification. Spine F-actin depolymerization is also required. Actinification is driven by activation of the F-actin polymerization factor inverted formin-2 (INF2). Silencing of INF2 renders neurons more vulnerable to NMDA-induced membrane leakage and cell death, and formin inhibition markedly increases ischemic infarct severity in vivo. These results show that ischemia-induced actin filament reorganization within the dendritic compartment is an intrinsic pro-survival response that protects neurons from death induced by swelling.
Dcp2 C-terminal Cis-Binding Elements Control Selective Targeting of the Decapping Enzyme by Forming Distinct Decapping Complexes
Authors: He Feng , Wu Chan , Jacobson Allan 
Published: October 2021

SUMMARYA single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs for decapping-dependent 5’ to 3’ decay, but the molecular mechanisms controlling selective mRNA targeting by the enzyme remain elusive. Through extensive genetic analyses we uncover cis-regulatory elements in the Dcp2 C-terminal domain that control selective targeting of the decapping enzyme by forming distinct decapping complexes. Two Upf1-binding motifs target the decapping enzyme to NMD substrates, and a single Edc3-binding motif targets both Edc3 and Dhh1 substrates. Pat1-binding leucine-rich motifs target Edc3 and Dhh1 substrates under selective conditions. Although it functions as a unique targeting component of specific complexes, Edc3 is a common component of multiple complexes. Xrn1 also has a specific Dcp2 binding site, allowing it to be directly recruited to decapping complexes. Collectively, our results demonstrate that Upf1, Edc3, and Pat1 function as regulatory subunits of the holo-decapping enzyme, controlling both its targeting specificity and enzymatic activation.HighlightsLoss of Dcp2 cis-binding elements causes selective stabilization of distinct decapping substratesDcp2 cis-binding elements promote the assembly of target-specific decapping complexes in vivoXrn1 binds to Dcp2, and both Edc3 and Xrn1 are common components of multiple decapping complexesUpf1, Edc3, and Pat1 function as unique targeting subunits of the yeast holo-decapping enzyme
Improving Martini 3 for disordered and multidomain proteins
Authors: Thomasen F. Emil , Pesce Francesco , Roesgaard Mette Ahrensback , Tesei Giulio , Lindorff-Larsen Kresten 
Published: October 2021

AbstractCoarse-grained molecular dynamics simulations are a useful tool to determine conformational ensembles of proteins. Here, we show that the coarse-grained force field Martini 3 underestimates the global dimensions of intrinsically disordered proteins (IDPs) and multidomain proteins when compared with small angle X-ray scattering (SAXS) data, and that increasing the strength of protein-water interactions favours more expanded conformations. We find that increasing the strength of interactions between protein and water by ca. 10% results in improved agreement with the SAXS data for IDPs and multi-domain proteins. We also show that this correction results in a more accurate description of self-association of IDPs and folded proteins and better agreement with paramagnetic relaxation enhancement data for most IDPs. While simulations with this revised force field still show deviations to experiments for some systems our results suggest that it is overall a substantial improvement for coarse-grained simulations of soluble proteins.
IMPROVED SSRs-BASED GENETIC DIVERSITY ASSESSMENT OF COCONUTS (COCOS NUCIFERA L) ALONG THE COAST OF KENYA
Authors: Masha Justus C. , Muhammed Najya , Njung’e Vincent , Oyoo Maurice E. , Miheso Manfred 
Published: October 2021

ABSTRACTCoconut is the most important cash crop along the Coast of Kenya, yet its genetic diversity has not been fully established. A genetic diversity study of 48 coconut genotypes that were collected along the Coast of Kenya was conducted with 13 polymorphic short sequence repeats (SSRs) markers. SSR analysis was performed using GeneMapper while data analysis was done with PowerMarker and DARwin softwares.The results revealed a total of 68 alleles ranging from 2 to 11 per locus with a mean of 5.23 per marker. Gene diversity and polymorphic information content (PIC) ranged between 0.41 to 0.83 and 0.33 to 0.79, respectively. A neighbour-joining dendrogram grouped the genotypes into three major clusters containing distinct sub-clusters. This study underscored that capillary electrophoresis is a more accurate and informative technique for SSRs allele scoring than agarose gels, which was reported in a previous study with the same SSRs markers and coconut genotypes in Kenya. The clusters observed forms the basis to isolate conservation blocks, which are the key to establishing a genebank, since there is no documented coconut genebank for ex-situ conservation in Kenya.
Effects of productive management of an agroforestry system on the associated diversity of parasitoids (Hymenoptera: Braconidae)
Authors: Pech Cutis Cecilia Marisol , Castillo Sánchez Luis Enrique , Canul Solís Jorge Rodolfo , López Coba Ermilo , Ruz Febles Nery Maria , Campos-Navarrete Maria Jose 
Published: October 2021

SummaryTropical agroecosystems have emerged from the continuous modification of natural environments, as a sustainability alternative for food production and biodiversity conservation. This work explores how the diversity of parasitoids is modified in environments where plant diversity is limited e.g. crops and when these are adjacent to secondary vegetation, i.e. a scenario fragmented continuously in a limited space. It was found that there is no direct effect of plant diversity in the group of parasitoids studied; but the number of specialist species is high, which indicates that in diversified agroecosystems these probably function as remnants of natural habitat or as a refuge for parasitoids that disperse to different types of management within the agroecosystem. Therefore, it is necessary to consider in future studies the controls exerted by the plant diversity effects bottom-up and consumer top-down. Adding to this the context of the interactions that occur in agroecosystems.
The structure balance of gene-gene networks beyond pairwise interactions
Authors: Allahyari Nastaran , Kargaran Amir , Hosseiny Ali , Jafari G. R. 
Published: October 2021

AbstractDespite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared with the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles the nonessential gene network is more balanced compared to the essential network.
Structural basis of ATP-dependent high-fidelity epigenome maintenance
Authors: Wang Juncheng , Catania Sandra , Wang Chongyuan , de la Cruz M. Jason , Rao Beiduo , Madhani Hiten D. , Patel Dinshaw J. 
Published: October 2021

SUMMARYEpigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance-type cytosine methyltransferase identified in the fungal or protist kingdoms. DNMT5 requires ATP and displays exquisite hemimethyl-DNA specificity. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out the DNA duplex. ATP binding then triggers a striking structural reconfiguration of the methyltransferase catalytic pocket that enables cofactor binding, completion of base-flipping, and catalysis. Unmethylated DNA binding fails to open cofactor pocket and subsequent ATP binding triggers its ejection to ensure fidelity. This chaperone-like, enzyme-remodeling role of the SNF2 domain illuminates how energy can be used to enable faithful epigenetic memory.HighlightsStructures of DNMT5 reveal mechanism of ATP-dependent DNA methylationHemimethylated CpG recognition triggers partial base flipping of the target cytosineHemimethylated DNA induces rigid body rotation to activate the SNF2 ATPase domainMTase catalytic pocket is remodeled by the SNF2 ATPase to achieve specificity
Targeting MLL methyltransferases enhance the anti-tumor effects of PI3K inhibition in hormone receptor-positive breast cancer
Authors: Jones RB. , Farhi J. , Adams M. , Parwani K. , Zecevic M. , Cooper G. , Lee RS. , Hong AL. , Spangle JM 
Published: October 2021

AbstractThe high frequency of aberrant PI3K pathway activation in hormone receptor-positive (HR+) breast cancer has led to the development, clinical testing, and approval of the p110α-selective PI3K inhibitor alpelisib. The limited clinical efficacy of alpelisib and other PI3K inhibitors is partially attributed to the functional antagonism between PI3K and estrogen receptor (ER) signaling, which is mitigated via combined PI3K inhibition and endocrine therapy. We and others have previously demonstrated a chromatin-associated mechanism by which PI3K supports cancer development and antagonizes ER signaling through the modulation of H3K4 methylation. Here we show that inhibition of the H3K4 histone methyltransferase MLL1 in combination with PI3K inhibition impairs HR+ breast cancer clonogenicity and cell proliferation. While combined PI3K/MLL1 inhibition reduces AKT effector signaling and H3K4 methylation, MLL1 inhibition increases PI3K effector signaling and upregulates the expression of receptor tyrosine kinase signaling cascades upstream of and including AKT. These data reveal a feedback loop between MLL1 and AKT in which MLL1 inhibition reactivates AKT. We additionally show that combined PI3K and MLL1 inhibition synergizes to cause cell death in in vitro and in vivo models of HR+ breast cancer, which is enhanced by the additional genetic ablation of the H3K4 methyltransferase and AKT target MLL4. Together, our data provide evidence of a feedback mechanism connecting histone methylation with AKT and may support the preclinical development and testing of pan-MLL inhibitors.Significance StatementPharmacological inhibition of PI3K provides limited efficacy in PIK3CA-mutated, HR+ breast cancers. Here the authors leverage PI3K/AKT-driven chromatin modification to identify MLL histone methyltransferases as a therapeutic target. Dual PI3K and MLL inhibition synergize to reduce clonogenicity and cell proliferation while enhancing apoptosis in in vitro models, and induces tumor regression in xenograft models of PI3K-activated, HR+ breast cancer. Furthermore, MLL1 inhibition reveals a feedback loop leading to AKT hyperactivation, which is relieved with combined PI3K/MLL inhibition. These findings demonstrate the utility of MLL inhibitors for the treatment of some solid cancers, as patients with HR+ breast cancer characterized by PIK3CA mutation may derive clinical benefit from combined PI3K/MLL inhibition.
Deafening‐induced rapid changes to spine synaptic connectivity in the adult avian vocal basal ganglia
Authors: ZHOU Xiaojuan , CHEN Yalan , PENG Jikan , ZUO Mingxue , SUN Yingyu 
Published: October 2021

AbstractThe basal ganglia have been implicated in auditory‐dependent vocal learning and plasticity in human and songbirds, but the underlying neural phenotype remains to be clarified. Here, using confocal imaging and three‐dimensional electron microscopy, we investigated striatal structural plasticity in response to hearing loss in Area X, the avian vocal basal ganglia, in adult male zebra finch (Taeniopygia guttata). We observed a rapid elongation of dendritic spines, by approximately 13%, by day 3 after deafening, and a considerable increase in spine synapse density, by approximately 61%, by day 14 after deafening, compared with the controls with an intact cochlea. These findings reveal structural sensitivity of Area X to auditory deprivation and suggest that this striatal plasticity might contribute to deafening‐induced changes to learned vocal behavior.
Seed traits and rodent community interact to determine seed fate: evidence from both enclosure and field experiments
Authors: HOU Xiang , ZHANG Bo , STEELE Michael A. , HAN Ning , FENG Tuo , WANG Jing , CHEN Xiaoning , AN Xiaolei , CHANG Gang 
Published: October 2021

AbstractAnimal‐mediated seed dispersal is an important ecological process in which a strong mutualism between animals and plants can arise. However, few studies have examined how a community of potential seed dispersers interacts with sympatric seed trees. We employed a series of experiments in the Qinling Mountains in both semi‐natural enclosure and the field to assess the interactions among 3 sympatric rodent species and 3 Fagaceae tree seeds. Seed traits all showed similar tannin levels but markedly different physical traits and nutritional contents. We found that seeds with heavy weight, thick coat, and high nutritional contents were less likely to be eaten in situ but more often to be eaten after dispersal or hoarded by rodents. These results support both the handling time hypothesis and the high nutrition hypothesis. Surprisingly, we also found that rodents, maybe, preferred to consume seeds with low levels of crude fiber in situ, and to harvest and hoard those with high levels of crude fiber for later consumption. The sympatric rodent species, Cansumys canus, the largest rodent in our study, harvested and hoarded more Quercus variabilis seeds with high physical and nutritional traits, while Apodemus draco, the smallest rodent, harvested more Q. serrata seeds with low physical and nutritional traits, and Niviventer confucianus harvested and hoarded more Q. aliena seeds with medium physical and nutritional traits. Our study demonstrates that different seed traits play different roles in influencing the seed fate and the shaping of mutualism and predation interactions within a community of rodent species.
Are current cut‐off values of 11‐DOC in children useful for assessing suspected nonclassical congenital adrenal hyperplasia due to 11β‐hydroxylase deficiency?
Authors: Barash Galia , Drach Lior , Naugolni Larisa , Yacoel Tamar , Bistritzer Tzvi , Rachmiel Marianna 
Published: October 2021

AbstractObjectiveA nonclassic form of 11β‐hydroxylase deficiency (NC11β‐OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11‐deoxycortisol (11‐DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11‐DOC level cutoffs. One of the accepted references for 11‐DOC levels for the paediatric population was published in 1991 by Lashansky et al.AimTo determine the correlation between 11‐DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β‐OHD.DesignA retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients’ medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11‐DOC cut‐off levels according to Lashansky for sex and age, and according to commercial kit cut‐offs.ResultsData were complete at presentation for 136 patients. Long‐term clinical data were documented for 98 patients, mean follow‐up duration of 3.1 years (1.37–5.09). There was no statistically significant difference in the number of cases with elevated 11‐DOC according to both cut‐offs and early puberty, premature adrenarche nor acne. Follow‐up data demonstrated no statistically significant difference in the number of cases with elevated 11‐DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism.ConclusionsBasal and corticotropin stimulated 11‐DOC levels were not significantly elevated above the 1.5 times cut‐offs according to paediatric‐specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β‐OHD.
Breaking down “harassment” to characterize trends in human interaction cases in Maine's pinnipeds
Authors: Newcomb Emma , Walk Dominique , Haverkamp Holland , Doughty Lynda , Todd Sean , Seton Rosemary , Jones Lindsey , Cammen Kristina 
Published: October 2021

AbstractRecent marine mammal recovery and growth of human populations in coastal areas has led to increased human harassment of protected pinniped populations. Yet, current monitoring approaches lack the necessary resolution to describe this emerging issue. We therefore propose a new classification scheme for monitoring of marine mammal–human interaction (HI), which defines categories based on the type of human behavior and associated risks to the animal. Among harbor, harp, and gray seal strandings (N = 3,525) from 2007 to 2019 in Maine, United States, evidence of HI was reported in 14.72% of strandings, with the majority (75.34%) of these cases involving harassment. The number of HI reports increased over time, particularly in the southern region of the state, and an analysis of geographic hotspots further identifies emerging areas of concern. Variation in the rate and type of HI among species, age classes, and seasons reflect differences in pinniped life history. The most commonly observed types of harassment included human approach, physical contact, and displacement. By breaking down harassment, we aim to inform ongoing mitigation efforts and contribute to our understanding of the impact of HI on marine mammal health, as well as offer a transferable methodological approach to monitoring human–wildlife interaction.