bluuebunny/crossref_metadata_2025_split huggingface dataset:
ID1 functions as an autonomous phosphate (Pi) regulator upstream of the miR399-ZmPHO2 signaling module in maize
Authors: Wang Xufeng , Yuan Dan , Liu Yanchun , Liang Yameng , He Juan , Yang Xiaoyu , Hang Runlai , Jia Hong , Mo Beixin , Tian Feng , Chen Xuemei , Liu Lin 
Published: July 2022

AbstractThe macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of Pi acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 in maize induced a premature aging syndrome after pollination. Knockout of ZmPHO2, one of the miR399 targets, resulted in a similar premature aging phenotype. Strikingly, we found that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression is independent of the Pi status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we found that ZmPHO2 was under selection during maize domestication, resulting in a more sensitive response to phosphate starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.
Sex-biased infections scale to population impacts for an emerging wildlife disease
Authors: Kailing Macy J. , Hoyt Joseph R. , White J. Paul , Kaarakka Heather M. , Redell Jennifer A. , Leon Ariel E. , Rocke Tonie E. , DePue John E. , Scullon William H. , Parise Katy L. , Foster Jeffrey T. , Kilpatrick A. Marm , Langwig Kate E. 
Published: August 2022

ABSTRACTDemographic factors are fundamental in shaping infectious disease dynamics. Aspects of populations that create structure, like age and sex, can affect patterns of transmission, infection intensity and population outcomes. However, studies rarely link these processes from individual to population-scale effects. Moreover, the mechanisms underlying demographic differences in disease are frequently unclear. Here, we explore sex-biased infections for a multi-host fungal disease of bats, white-nose syndrome, and link disease-associated mortality between sexes, the distortion of sex ratios, and the potential mechanisms underlying sex differences in infection. We collected data on host traits, infection intensity, and survival of five bat species at 42 sites across seven years. We found females were more infected than males for all five species. Females also had lower apparent survival over winter and accounted for a smaller proportion of populations over time. Notably, female-biased infections were evident by early hibernation and likely driven by sex-based differences in autumn mating behavior. Male bats were more active during autumn which likely reduced replication of the cool-growing fungus. Higher disease impacts in female bats may have cascading effects on bat populations beyond the hibernation season by limiting recruitment and increasing the risk of Allee effects.
Obesity promotes breast epithelium DNA damage in BRCA mutation carriers
Authors: Bhardwaj Priya , Iyengar Neil M. , Zahid Heba , Carter Katharine M. , Byun Dong Jun , Choi Man Ho , Sun Qi , Savenkov Oleksandr , Louka Charalambia , Liu Catherine , Piloco Phoebe , Acosta Monica , Bareja Rohan , Elemento Olivier , Foronda Miguel , Dow Lukas E. , Oshchepkova Sofya , Giri Dilip D. , Pollak Michael , Zhou Xi Kathy , Hopkins Benjamin D. , Laughney Ashley M. , Frey Melissa K. , Ellenson Lora Hedrick , Morrow Monica , Spector Jason A. , Cantley Lewis C. , Brown Kristy A. 
Published: August 2022

AbstractObesity is an established risk factor for breast cancer among women in the general population after menopause. Whether elevated bodyweight is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less clear due to inconsistent findings from epidemiological studies and lack of mechanistic studies in this population. Here, we show that DNA damage in normal breast epithelium of BRCA mutation carriers is positively correlated with body mass index and with biomarkers of metabolic dysfunction. Additionally, RNA-sequencing reveals significant obesity-associated alterations to the breast adipose microenvironment of BRCA mutation carriers, including activation of estrogen biosynthesis, which impacts neighboring breast epithelial cells. We found that blockade of estrogen biosynthesis or estrogen receptor activity decreases DNA damage, whereas treatment with leptin or insulin increases DNA damage in BRCA heterozygous epithelial cells. Furthermore, we show that increased adiposity is associated with mammary gland DNA damage and increased penetrance of mammary tumors in Brca1+/- mice. Overall, our results provide mechanistic evidence in support of a link between bodyweight and breast cancer development in BRCA mutation carriers and suggests that maintaining a healthy bodyweight or pharmacologically targeting estrogen or metabolic dysfunction may reduce the risk of breast cancer in this population.One Sentence SummaryElevated bodyweight is positively associated with DNA damage in breast epithelium of BRCA mutation carriers
Spatial distribution and predictive factors of antenatal care in Burundi: a multilevel analysis and spatial baseline for the third Burundian demographic health survey
Authors: Barankanira Emmanuel , Iradukunda Arnaud , Ntakaburimvo Nestor , Ahishakiye Willy , Nsavyimana Jean Claude , Odjidja Emmanuel Nene 
Published: August 2022

AbstractBackgroundThe use of antenatal care by pregnant women enables them to receive good pregnancy monitoring. This monitoring includes counseling, health instructions, examinations and tests to avoid pregnancy-related complications or death during childbirth. To avoid these complications, the World Health Organization (WHO) recommends at least four antenatal visits. Therefore, this study sought to understand the spatial distribution and predictive factors of antenatal care (ANC) among women aged 15 to 49 years with a medical doctor in Burundi.MethodsWe used data from the Second Burundi Demographic and Health Survey (DHS). A descriptive and spatial analysis of ANC prevalence were done. The ANC prevalence was mapped by region and by province. In unsampled data points, a cluster based interpolation of ANC prevalence was done using the kernel method with an adaptive window. Predictive factors of ANC were assessed using a fixed effects binary logistic regression. The dependent variable was antenatal care with a medical doctor and the explanatory variables were place of residence, age, education level, religion, marital status of the woman, household wealth index and delivery place of the woman. Data processing and data analysis were done using R software, version 3.5.0.ResultsThe ANC prevalence varied from 0.0 to 16.2% with a median of 0.5%. A highest predicted ANC prevalence was observed at Muyinga and Kirundo provinces’ junction. Low prevalence was observed in several locations in all regions and provinces. The woman’s education level and delivery place were significantly associated with antenatal care with a medical doctor.ConclusionGlobally, the ANC prevalence is low in Burundi. It varies across the country. There is an intra-regional or intra-provincial heterogeneity in term of ANC prevalence. Woman’s education level and delivery place are significantly associated antenatal care.
Short report: A trend analysis of attitudes towards early diagnosis of dementia in Germany
Authors: Zülke Andrea E. , Luppa Melanie , Luck Tobias , Riedel-Heller Steffi G. 
Published: August 2022

AbstractBackgroundEarly detection of dementia provides numerous benefits for those living with dementia and their relatives and healthcare systems at large. Methods available for early diagnosis have improved significantly over the past years. Therefore, we examined whether openness towards early diagnosis for dementia and preferred sources of support have changed in Germany over the last decade.MethodWe compared findings from two representative telephone surveys conducted among older adults in Germany (≥ 60 years of age) in 2011 and 2022, assessing attitudes towards and willingness to pursue an early diagnosis of dementia in a sample of n = 879 individuals (mean age: 72.9, % female: 58.8). Group comparisons using Chi2- and t-tests and multivariable regression analyses were conducted, assessing factors linked to willingness to be examined for an early diagnosis of dementia.ResultsOpenness towards early diagnosis of dementia was high both in 2011 and 2022, but slightly declined over time (b=.62; 95% CI: .45; .86). Belief in preventability of dementia was linked to greater openness towards an early diagnosis of dementia (b=1.52; 95% CI: 1.12; 2.07).ConclusionWillingness to pursue an early diagnosis of dementia is high in the older German public, but slightly lower than reported previously. Improving knowledge on modifiable risk factors and better understanding of individual motives underlying endorsement or refusal of an early diagnosis may further increase acceptance in the general public.
Comprehensive analysis using DNA metabarcoding, PCR, and HPLC unveils the adulteration in Brahmi herbal products
Authors: Shah Abhi P. , Travadi Tasnim , Sharma Sonal , Pandit Ramesh , Joshi Chaitanya , Joshi Madhvi 
Published: August 2022

AbstractBackgroundThe herbal products market is expanding and creating a bottleneck for raw materials. Hence, economically motivated adulteration has a high prevalence. DNA barcoding and species-specific PCR assays are now revolutionising the molecular identification of herbal products and are included in a number of pharmacopoeias for the identification of raw materials. High-throughput sequencing with barcoding advances toward metabarcoding, which enables the identification of unintentionally or intentionally unlabelled plant material present in herbal products. Brahmi is one of the most commercially significant and nootropic botanicals, with great controversy over the terms “Brahmi” being used to describe both Bacopa monneri (BM) and Centella asiatica (CA) species.PurposeThis study evaluates DNA-based methods for Brahmi herbal products with the traditional HPLC-based analytical approach in order to assess their effectiveness.MethodsWe employed a species-specific PCR assay, DNA metabarcoding using rbcL minibarcode, and HPLC to detect the presence of the Brahmi (either BM or CA) in eighteen market samples. All the methods have been validated using in-house blended formulations.ResultsComprehensive analysis of all three methods revealed the presence of 22.2%, 55.6%, and 50.0% of Brahmi by PCR assay, DNA metabarcoding, and HPLC, respectively, in Brahmi market formulations, whereas blended formulations only exhibited targeted plant species with all three methods.ConclusionSpecies-specific PCR can be used as a cost-effective and rapid method to detect the presence of the Brahmi, while in high-throughput methods, DNA metabarcoding can be used to detect the presence of widespread adulterated botanicals, and further, bioactive compounds could be detected by HPLC. These results emphasise the need for quality control of the marketed Brahmi herbal products as well as the implementation of all methodologies in accordance with fit for purpose.
Recombinant Human ACE2-Fc : A promising therapy for SARS-CoV2 infection
Authors: Smitha P.K , Shandil R.K. , Suresh Pushkarni , Biswas Kunal , Rudramurthy G.R. , Naveenkumar C.N. , Bharathkumar K. , Battula Naga Puspha , Chowdhury Suprabuddha Datta , Sinha Sakshi , Dutta Sarmistha , Dhar Sujan K. , Narayanan Shridhar , Das Manjula 
Published: August 2022

AbstractSARS-CoV2 entry is mediated by binding of viral spike-protein(S) to the transmembrane Angiotensin-Converting Enzyme-2 (ACE2) of the host cell. Thus, to prevent transmission of disease, strategies to abrogate the interaction are important. However, ACE2 cannot be blocked since its normal function is to convert the Angiotensin II peptide to Angiotensin(1-7) to reduce hypertension. This work reports a recombinant cell line secreting soluble ACE2-ectopic domain (MFcS2), modified to increase binding and production efficacy and fused to human immunoglobulin-Fc. While maintaining its enzymatic activity, the molecule trapped and neutralized SARS CoV2 virus in vitro with an IC50 of 64 nM. In vivo, with no pathology in the vital organs, it inhibited the viral load in lungs in SARS-CoV2 infected Golden-Syrian-hamster. The Intravenous pharmacokinetic profiling of MFcS2 in hamster at a dose of 5 mg/Kg presented a maximum serum concentration of 23.45 µg/mL with a half-life of 29.5 hrs. These results suggest that MFcS2 could be used as an effective decoy based therapeutic strategy to treat COVID19. This work also reports usage of a novel oral-cancer cell line as in vitro model of SARS-Cov2 infection, validated by over expressing viral-defence pathways upon RNA-seq analysis and over-expression of ACE2 and TMPRSS upon growth in hyperglycaemic condition.
Altered global modular organization of intrinsic functional connectivity in autism arises from atypical node-level processing
Authors: Sigar Priyanka , Uddin Lucina Q. , Roy Dipanjan 
Published: August 2022

ABSTRACTAutistic spectrum disorder (ASD) is a neurodevelopmental condition characterized by restricted interests and repetitive behaviors as well as social-communication deficits. These traits are associated with atypicality of functional brain networks. Modular organization in the brain plays a crucial role in network stability and adaptability for neurodevelopment. Previous neuroimaging research demonstrates discrepancies in studies of functional brain modular organization in ASD. These discrepancies result from the examination of mixed age groups. Furthermore, recent findings suggest while much attention has been given to deriving atlases and measuring the connections between nodes, the within nodes information may be crucial in determining altered modular organization in ASD compared with TD. However, altered modular organization originating from systematic nodal changes are yet to be explored in younger children with ASD. Here, we used graph-theoretical measures to fill this knowledge gap. To this end, we utilized multicenter resting-state BOLD fMRI data collected from 5–10-year-old children - 34 ASD and 40 typically developing obtained from the Autism Brain Image Data Exchange (ABIDE) I and II. We demonstrated alterations in the topological roles and modular cohesiveness are the two key properties of the brain regions anchored in default mode, sensorimotor, and salience networks primarily relates to social and sensory deficits in ASD children. These results demonstrate atypical global network organization in ASD children arise from nodal role changes and contribute to the growing body of literature suggesting that there is interesting information within nodes providing critical marker of functional brain networks in Autistic children.
Engram Stability and Maturation During Systems Consolidation Underlies Remote Memory
Authors: Refaeli Ron , Kreisel Tirzah , Groysman Maya , Adamsky Adar , Goshen Inbal 
Published: August 2022

AbstractRemote memories play an important role in how we perceive the world and are rooted in ensembles in the CA1 and ACC, however the evolution of these components during systems consolidation has not yet been comprehensively addressed. By applying transgenic approaches for ensemble identification, CLARITY, retro-AAV and rabies virus for circuit mapping, and chemogenetics for functional interrogation, we addressed the dynamics of CA1-ACC ensembles and their connectivity as well as the contribution of astrocytes to the process. We found that the CA1 engrams remain stable between recent and remote recall, and, the inhibition of the engram for recent recall during remote recall functionally impairs memory. We also found that the new cells in the remote recall engram in the CA1 are not added randomly, but differ according to their connections: First, the anterograde CA1 → ACC engram cell projection grows larger. Second, in the retrograde projections, the ACC reduces input to CA1 engram cells, while input from the entorhinal cortex and paraventricular nucleus of the thalamus increases. Finally, we found that activating CA1 astrocytes during acquisition improves recent but not remote recall, and that CA1 → ACC projecting cells are recruited earlier when the astrocytes are stimulated. Our results shine fresh light on systems consolidation by providing a deeper understanding of engram stability and maturation in the transition from recent to remote memory.
Why slow axonal transport is bidirectional – can axonal transport of tau protein rely only on motor-driven anterograde transport?
Authors: Kuznetsov Ivan A. , Kuznetsov Andrey V. 
Published: August 2022

AbstractSlow axonal transport (SAT) moves multiple proteins from the soma, where they are synthesized, to the axon terminal. Due to the great lengths of axons, SAT almost exclusively relies on active transport, which is driven by molecular motors. The puzzling feature of slow axonal transport is its bidirectionality. Although the net direction of SAT is anterograde, from the soma to the terminal, experiments show that it also contains the retrograde component. One of the proteins transported by SAT is microtubule-associated protein tau. To better understand why the retrograde component in tau transport is needed, we used the perturbation technique. We analyzed the simplification of the full tau SAT model for the case when retrograde motor-driven transport and diffusion-driven transport of tau are negligible, and tau is driven only by anterograde (kinesin) motors. The solution of the simplified equations shows that the tau concentration along the axon length stays almost uniform (decreases very slightly), which is inconsistent with the tau concentration at the outlet boundary (at the axon tip). Thus kinesin-driven transport alone is not enough to explain the experimentally observed distribution of tau, and the retrograde motor-driven component in SAT is needed.
Molecular origins of asymmetric proton conduction in the influenza M2 channel
Authors: Lazaridis Themis 
Published: August 2022

AbstractThe M2 proton channel of influenza A is embedded into the viral envelope and allows acidification of the virion when the external pH is lowered. In contrast, no outward proton conductance is observed when the internal pH is lowered, although outward current is observed at positive voltage. Residues Trp41 and Asp44 are known to play a role in preventing pH-driven outward conductance but the mechanism for this is unclear. We investigate this issue using classical molecular dynamics simulations with stochastic proton hops. When all key His37 residues are neutral, inward proton movement is much more facile than outward movement if the His are allowed to shuttle the proton. The preference for inward movement increases further as the charge on the His37 increases. Analysis of the trajectories reveals three factors accounting for this asymmetry. First, the Asp44 trap the hydronium by strong electrostatic interactions. Secondly, Asp44 and Trp41 orient the hydronium with the protons pointing inward, hampering outward Grotthus hopping. The Trp41 add to the barrier by weakly H-bonding to potential H+ acceptors. Finally, for charged His, the H3O+ in the inner vestibule tends to get trapped at lipid-lined fenestrations of the cone-shaped channel. Simulations qualitatively reproduce the experimentally observed higher outward conductance of mutants. The ability of positive voltage, unlike proton gradient, to induce outward current appears to arise from its ability to bias H3O+ and the waters around it toward more H-outward orientations.SignificanceThe M2 proton channel of influenza A, the best-studied viral ion channel and a proven drug target, conducts protons asymmetrically in response to a pH gradient. That is, protons flow inward when the external pH is low, but not outward when the internal pH is low. Experiments identified residues that play a role in this behavior, but how they do it has not been clear. This work identifies three molecular mechanisms that explain qualitatively the experimentally observed preference for inward conduction. These insights could improve our understanding of proton channels and possibly other key biological systems that exhibit vectorial proton transport.
Pharmacologic Stabilization of Retromer Rescues Endosomal Pathology Induced by Defects in the Alzheimer’s geneSORL1
Authors: Mishra Swati , Knupp Allison , Kinoshita Chizuru , Williams C. Andrew , Rose Shannon E. , Martinez Refugio , Theofilas Panos , Young Jessica E. 
Published: August 2022

SUMMARYThe Sortilin-related receptor 1 gene (SORL1,SORLA) is strongly associated with risk of developing Alzheimer’s disease (AD). SORLA is a regulator of endosomal trafficking in neurons and interacts with retromer, a complex that is a ‘master conductor’ of endosomal trafficking. Pharmacological chaperones stabilize retromerin vitro, enhancing its function. Here we used an isogenic series of human induced pluripotent stem cell (hiPSC) lines with either one or two copies ofSORL1or harboring one copy of aSORL1variant linked to increased risk for AD. We treated hiPSC-derived cortical neurons with the established retromer chaperone, TPT-260, and tested whether indicators of AD’s defining endosomal, amyloid, and Tau pathologies were corrected. We observed that the degree of rescue by TPT-260 treatment varied, depending on the number of copies of functionalSORL1and whichSORL1variant was expressed. Using a disease-relevant preclinical model, our work illuminates how theSORL1-retromer pathway can be therapeutically harnessed.
Protein N-Terminomics Reveals Major Proteases in Regulating Beige Adipocyte Differentiation
Authors: Chang Hsin-Yi , Chang Chih-Hsiang , Nishida Hiroshi , Takamuro Kaho , Ogata Kosuke , Peng Kuan-Chieh , Lin Li-Chun , Lo Yii-Jwu , Huang Tsui-Chin , Ishihama Yasushi 
Published: August 2022

SummaryIn this comprehensive study, we present an innovative analytical platform designed to capture the temporal shifts in both the proteome and protein N-terminome during beige adipocyte differentiation. Employing a refined N-terminomics technique, we achieved a high purity of 97% in isolating protein N-terminal peptides. Our data encompassed 7,171 unique N-terminal peptides, with 3,043 from canonical proteins and 4,129 with neo-N-termini. Strikingly, nearly half (44%) of the proteins revealed distinct temporal trajectories between the global proteome and the N-terminome. This underscores the central role of proteolysis in beige adipocyte differentiation. Experimentally, knockdown of either Pmpcb, Plg, or Cstd in preadipocytes attenuated thermogenesis, manifested by reduced levels of beige adipocyte markers like Cidea, Pgc1a, Ucp1, and Tbx1 and an increase in adipogenic proteins, thereby hampering beige adipocyte maturation. A salient discovery was the non-apoptotic role of caspase 8 protease; inhibiting its proteolytic action amplified Ucp1 expression levels. Collectively, our findings spotlight proteases and their proteolytic by-products as vital regulators in beige adipocyte differentiation.