bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the factors influencing citizens’ willingness-to-accept the use of insects to feed poultry, cattle, pig and fish in Brazil
Authors: de Faria Domingues Carla Heloisa , Borges João Augusto Rossi , Ruviaro Clandio Favarini , Guidolin Diego Gomes Freire , Carrijo Juliana Rosa Mauad 
Published: October 2019

AbstractThe increase in world’s population will cause a high demand of animal-sourced food, which will require a boost in the production of protein, because protein is an important component of animal feed. A higher production of protein, however, might contribute for the depletion of environmental resources. In this scenario, the use of insects as an alternative source of protein to feed animals could be a solution. However, citizens’ willingness-to-accept insect as a source of protein to feed animals is unknown, particularly in developing countries, such as Brazil. The aim of this study was to investigate the factors influencing citizens’ willingness-to-accept the use of insects to feed poultry, cattle, pig and fish. To reach this aim, we conducted an online survey with Brazilian citizens. We analyzed the data using descriptive statistics and four logistic regression models. In each of logistic models, the dependent variable was citizens’ willingness-to-accept the use of insects to feed either poultry, or cattle, or pig or fish. A set of independent variables including socio-demographic characteristics, attitudes, perceived benefits, perceived risks, and perceived concerns were used to explain citizens' willingness-to-accept the use of insect to feed animals. Results showed that most citizens would accept that poultry, pig, and fish receive insect-based diets, and half of the citizens would accept and half would not accept that cattle receive such diet. Results of the logistic regression models showed that citizens who had a positive attitude about using insects to feed animals were more willing-to-accept the use of insect to feed poultry, cattle, pig, and fish compared to those who had a negative attitude. Citizens who perceived the benefits of using insect to feed animals were less willing-to-accept the use of insects to feed poultry compared to those who didn’t perceive the benefits. Citizens who perceived the benefits of using insects to feed animals were more willing-to-accept the use of insect to feed fish compared to those who didn’t perceive the benefits. Citizens who were more concerned about using insect to feed animals were more willing-to-accept the use of insects to feed poultry compared to those who were less concerned. Finally, citizens who were more concerned about using insects to feed animals were less willing-to-accept the use of insect to feed pigs compared to those who were less concerned. These results revealed important insights that can be used to design strategies to increase the acceptance of the use of insects to feed poultry, cattle, pig, and fish.
Early conservation benefits of a de facto marine protected area at San Clemente Island, California
Authors: Esgro Michael W. , Lindholm James , Nickols Kerry J. , Bredvik Jessica 
Published: October 2019

AbstractDe facto marine protected areas (DFMPAs) are regions of the ocean where human activity is restricted for reasons other than conservation. Although DFMPAs are widespread globally, their potential role in the protection of marine habitats, species, and ecosystems has not been well studied. In 2012 and 2013, we conducted remotely operated vehicle (ROV) surveys of marine communities at a military DFMPA and an adjacent fished reference site at San Clemente Island, the southernmost of California’s Channel Islands. We used data extracted from ROV imagery to compare density and biomass of focal species, as well as biodiversity and community composition, between the two sites. Generalized linear modeling indicated that both density and biomass of California sheephead (Semicossyphus pulcher) were significantly higher inside the DFMPA. Biomass of ocean whitefish (Caulolatilus princeps) was also significantly higher inside the DFMPA. However, species richness and Shannon-Weaver diversity were not significantly higher inside the DFMPA, and overall fish community composition did not differ significantly between sites. Demonstrable differences between the DFMPA and fished site for two highly sought-after species hint at early potential benefits of protection, though the lack of differences in the broader community suggests that a longer trajectory of recovery may be required for other species. A more comprehensive understanding of the potential conservation benefits of DFMPAs is important in the context of marine spatial planning and global marine conservation objectives.
Microscaled Proteogenomic Methods for Precision Oncology
Authors: Satpathy Shankha , Jaehnig Eric J. , Krug Karsten , Kim Beom-Jun , Saltzman Alexander B. , Chan Doug , Holloway Kimberly R. , Anurag Meenakshi , Huang Chen , Singh Purba , Gao Ari , Namai Noel , Dou Yongchao , Wen Bo , Vasaikar Suhas , Mutch David , Watson Mark , Ma Cynthia , Ademuyiwa Foluso O. , Rimawi Mothaffar , Hoog Jeremy , Jacobs Samuel , Malovannaya Anna , Hyslop Terry , Clauser Karl C. , Mani D. R. , Perou Charles , Miles George , Zhang Bing , Gillette Michael A. , Carr Steven A. , Ellis Matthew J. 
Published: October 2019

AbstractCancer proteogenomics integrates genomics, transcriptomics and mass spectrometry (MS)-based proteomics to gain insights into cancer biology and treatment efficacy. A proteogenomics approach was therefore developed for frozen core biopsies using tissue-sparing specimen processing with a “microscaled” proteomics workflow. For technical proof-of-principle, biopsies from ERBB2 positive breast cancers before and 48-72 hours after the first dose of neoadjuvant trastuzumab-based chemotherapy were analyzed. ERBB2 protein and phosphosite levels, as well as mTOR target phosphosites, were significantly more suppressed upon treatment in cases associated with pathological complete response, suggesting MS-based pharmacodynamics is achievable. Furthermore, integrated analyses indicated potential causes of treatment resistance including the absence of ERBB2 amplification (false-ERBB2 positive) and insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification (pseudo-ERBB2 positive). Candidate resistance features in true-ERBB2+ cases, including androgen receptor signaling, mucin expression and an inactive immune microenvironment were observed. Thus, proteogenomic analysis of needle core biopsies is feasible and clinical utility should be investigated.
Discovery and Optimization of Inhibitors for the Pup Proteasome System in Mycobacterium tuberculosis
Authors: Janssen Guido V. , Zhang Susan , Merkx Remco , Schiesswohl Christa , Chatterjee Champak , Darwin K. Heran , Ovaa Huib 
Published: October 2019

AbstractTuberculosis is a global health problem with the existence and spreading of multidrug resistant and extensive drug resistant strains. The development of new drugs for tuberculosis that inhibit different activities than the current drugs is thus urgent. The prokaryotic ubiquitin like protein proteasome system is an attractive target for the development of new drugs. Using a Pup-based fluorogenic substrate, we screened for inhibitors of Dop, a depupylase, and identified I-OMe-Tyrphostin AG538 (1) and Tyrphostin AG53 (2). The hits were validated and determined to be fast reversible non-ATP competitive inhibitors. The SAR was established by testing 27 synthesized analogs of 1 and 2. Several of the synthesized compounds also inhibited the depupylation of a native substrate, FabD∼Pup. Importantly, the pupylation and depupylation activities of PafA, the sole Pup ligase in M. tuberculosis, was also inhibited by some of these compounds. With the identification of the first described lead compounds for Dop and PafA inhibition, this study shows that high throughput screening can be a successful strategy for this purpose.
Multicentric tracking of multiple agents by anterior cingulate cortex during pursuit and evasion
Authors: Yoo Seng Bum Michael , Tu Jiaxin Cindy , Hayden Benjamin Yost 
Published: October 2019

SUMMARYSuccessful pursuit and evasion require rapid and precise coordination of navigation with adaptive motor control. We hypothesized that the dorsal anterior cingulate cortex (dACC), which communicates bidirectionally with both the hippocampal complex and premotor/motor areas, would serve a mapping role in this process. We recorded responses of dACC ensembles in two macaques performing a joystick-controlled continuous pursuit/evasion task. We found that dACC multiplexes two sets of signals, (1) world-centric variables that together form a representation of the position and velocity of all relevant agents (self, prey, and predator) in the virtual world, and (2) avatar-centric variables, i.e. self-prey distance and angle. Both sets of variables are multiplexed within an overlapping set of neurons. Our results suggest that dACC may contribute to pursuit and evasion by computing and continuously updating a multicentric representation of the unfolding task state, and support the hypothesis that it plays a high-level abstract role in the control of behavior.
Intersubject consistent dynamic connectivity during natural vision revealed by functional MRI
Authors: Di Xin , Biswal Bharat B 
Published: October 2019

AbstractThe functional communications between brain regions are thought to be dynamic. However, it is usually difficult to elucidate whether the observed dynamic connectivity is functionally meaningful or simply due to noise during unconstrained task conditions such as resting-state. During naturalistic conditions, such as watching a movie, it has been shown that local brain activities, e.g. in the visual cortex, are consistent across subjects. Following similar logic, we propose to study intersubject correlations of the time courses of dynamic connectivity during naturalistic conditions to extract functionally meaningful dynamic connectivity patterns. We analyzed a functional MRI (fMRI) dataset when the subjects watched a short animated movie. We calculated dynamic connectivity by using sliding window technique, and quantified the intersubject correlations of the time courses of dynamic connectivity. Although the time courses of dynamic connectivity are thought to be noisier than the original signals, we found similar level of intersubject correlations of dynamic connectivity to those of regional activity. Most importantly, highly consistent dynamic connectivity could occur between regions that did not show high intersubject correlations of regional activity, and between regions with little stable functional connectivity. The analysis highlighted higher order brain regions such as the default mode network that dynamically interacted with posterior visual regions during the movie watching, which may be associated with the understanding of the movie.HighlightsIntersubject consistency may provide a complementary approach to study brain dynamic connectivityWidespread brain regions showed highly consistent dynamic connectivity during movie watching, while these regions themselves did not show highly consistent regional activityConsistent dynamic connectivity often occurred between regions from different functional systems
Human iPSC modeling reveals mutation-specific responses to gene therapy in Best disease
Authors: Sinha Divya , Steyer Benjamin , Shahi Pawan K. , Mueller Katherine , Valiauga Rasa , Edwards Kimberly L. , Bacig Cole , Steltzer Stephanie S. , Srinivasan Sandhya , Abdeen Amr , Cory Evan , Periyasamy Viswesh , Siahpirani Alireza Fotuhi , Stone Edwin M. , Tucker Budd A , Roy Sushmita , Pattnaik Bikash R. , Saha Krishanu , Gamm David M. 
Published: October 2019

AbstractDominantly inherited disorders are not typically considered therapeutic candidates for gene augmentation. Here, we utilized patient-specific induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) to test the potential of gene augmentation to treat Best disease, a dominant macular dystrophy caused by over 200 missense mutations in BEST1. Gene augmentation in iPSC-RPE fully restored BEST1 calcium-activated chloride channel activity and improved rhodopsin degradation in iPSC-RPE models of recessive bestrophinopathy and dominant Best disease caused by two different ion binding domain mutations. A dominant Best disease iPSC-RPE model that did not respond to gene augmentation showed normalization of BEST1 channel activity following CRISPR-Cas9 editing of the mutant allele. We then tested gene editing in all three dominant Best disease iPSC-RPE models, which produced premature stop codons exclusively within the mutant BEST1 alleles. Single-cell profiling demonstrated no adverse perturbation of RPE transcriptional programs in any model, although off-target analysis detected a silent genomic alteration in one model. These results suggest that gene augmentation is a viable first-line approach for some dominant Best disease patients and that non-responders are candidates for alternate approaches such as genome editing. However, testing genome editing strategies for on-target efficiency and off-target events using patient-matched iPSC-RPE model systems is warranted. In summary, personalized iPSC-RPE models can be used to select among a growing list of gene therapy options to maximize safety and efficacy while minimizing time and cost. Similar scenarios likely exist for other genotypically diverse channelopathies, expanding the therapeutic landscape for affected patients.SignificanceDominantly inherited disorders pose distinct challenges for gene therapies, particularly in the face of extreme mutational diversity. We tested whether a broad gene replacement strategy could reverse the cellular phenotype of Best disease, a dominant blinding condition that targets retinal pigment epithelium (RPE). Using RPE generated from patient-specific induced pluripotent stem cells (iPSCs), we show that gene replacement functionally overcomes some, but not all, of the tested mutations. In comparison, all dominant Best disease models tested were phenotypically corrected after mutation-specific genome editing, although one off-target genomic alteration was discovered. Our results support a two-tiered approach to gene therapy for Best disease, guided by safety and efficacy testing in iPSC-RPE models to maximize personal and public health value.
The transcriptional response of genes to RpoS concentration in Escherichia coli is not determined by core promoter sequences
Authors: Beeler Suzannah M. , Doering Christopher R. , Tran Sarena , Stoebel Daniel M. 
Published: October 2019

ABSTRACTThe alternative sigma factor RpoS is an important regulatory protein in Escherichia coli, responsible for mediating the general stress response. RpoS levels vary continuously in response to different stresses. Previous work has shown that genes vary in their responsiveness to increasing RpoS concentrations, with some genes being “sensitive,” requiring only a low level of RpoS to be relatively highly expressed, while other genes are “insensitive,” only being highly expressed in the presence of high levels of RpoS. In other systems, this type of variation is caused by interactions between the regulatory protein and the DNA it binds. To see if this is the case for RpoS, we measured twelve RpoS binding site mutants for their effects on maximal expression and responsiveness to increasing RpoS concentration. While maximal expression varied over an order of magnitude across these twelve constructs, the responsiveness to increasing RpoS concentration was largely unaffected, suggesting that the RpoS binding site alone is not responsible for a genes’ sensitivity or insensitivity to RpoS. In addition, we swapped the RpoS binding region between sensitive and insensitive promoters and found no change in the behavior of the promoter. Taken together, these results argue that differences in sensitivity of the RpoS-dependent promoters are not due to interactions between RpoS and the various DNA sites it binds.
A Novel Optimization-Based Tool to Automate Infeasible Cycle-Free Gapfilling of Genome-Scale Metabolic Models
Authors: Schroeder Wheaton L. , Saha Rajib 
Published: October 2019

SUMMARYStoichiometric metabolic modeling, particularly Genome-Scale Models (GSMs), is now an indispensable tool for systems biology. The model reconstruction process typically involves collecting information from public databases; however, incomplete systems knowledge leaves gaps in any reconstruction. Current tools for addressing gaps use databases of biochemical functionalities to address gaps on a per-metabolite basis and can provide multiple solutions, but cannot avoid Thermodynamically Infeasible Cycles (TICs), invariably requiring lengthy manual curation. To address these limitations, this work introduces an optimization-based multi-step method named OptFill which performs TIC-avoiding whole-model gapfilling. We applied OptFill to three fictional prokaryotic models of increasing sizes and to a published GSM of Escherichia coli, iJR904. This application resulted in holistic and infeasible cycle free gapfilling solutions. Part of OptFill can, in addition, be adapted to automate inherent TICs identification in any GSM, such as iJR904. Overall, OptFill can address critical issues in automated development of high-quality GSMs.In BriefStoichiometric models of metabolism are useful in studying metabolic interactions in biological systems, but are labor-intensive to create, particularly when addressing gaps or cycles in metabolic reconstruction process. Introduced here is a novel tool, OptFill, which can be used to address both gaps and cycles in model reconstruction, increasing automation.HighlightsThis work presents an alternative to state-of-the-art methods for gapfilling.Unlike current methods, this method is holistic and infeasible cycle free.This method is applied to three test and one published model.This method might also be used to address infeasible cycling.
Selectivity and engineering of the sialoglycan-binding spectrum in Siglec-like adhesins
Authors: Bensing Barbara A. , Loukachevitch Lioudmila V. , Agarwal Rupesh , Yamakawa Izumi , Luong Kelvin , Hadadianpour Azadeh , Yu Hai , Fialkowski Kevin P. , Castro Manuel A , Wawrzak Zdzislaw , Chen Xi , Baudry Jerome , Smith Jeremy C. , Sullam Paul M , Iverson T M 
Published: October 2019

The Siglec-like Serine-Rich Repeat (SRR) adhesins mediate bacterial attachment to mammalian hosts via sialoglycan receptors. Here, we combine structural, computational, biochemical, and phylogenetic approaches to elucidate the determinants of the sialoglycan-binding spectrum across the family of Siglec-like SRR adhesins. We further identified mutable positions that disproportionately affect sialoglycan selectivity, as demonstrated by increases in binding to alternative ligands of 2- to 3-orders of magnitude. Biologically, these studies highlight how bacteria nimbly modulate the receptor interaction during coevolution of host and pathogen. These studies additionally created binding proteins specific for sialyl-T antigen or 6S-sialyl LewisX that can recognize glycosylation of human plasma proteins. The engineered binding proteins can facilitate the characterization of normal cellular glycan modifications or may be used as diagnostic tools in disease states with altered glycosylation.SignificanceThe ability of bacteria to bind selectively to host receptors underlies both commensalism and pathogenesis. Here, we identify the molecular basis for receptor selectivity in streptococci that bind to sialoglycan receptors. This revealed how to convert these adhesins into selective probes that measure triand tetrasacharides within the context of larger glycosylations. These probes that can be used in a laboratory with no specialized equipment and can be used to address biological questions relating to sialoglycan-dependent signaling and adhesion.
A neural circuit basis for context-modulation of individual locomotor behavior
Authors: Skutt-Kakaria Kyobi , Reimers Pablo , Currier Timothy A. , Werkhoven Zach , de Bivort Benjamin L. 
Published: October 2019

AbstractDefying the cliche that biological variation arises from differences in nature or nurture, genetically identical animals reared in the same environment exhibit striking differences in their behaviors. Innate behaviors can be surprisingly flexible, for example by exhibiting context-dependence. The intersection of behavioral individuality and context-dependence is largely unexplored, particularly at the neural circuit level. Here, we show that individual flies’ tendencies to turn left or right (locomotor handedness) changes when ambient illumination changes. This change is itself a stable individual behavioral characteristic. Silencing output neurons of the central complex (a premotor area that mediates goal-directed navigation) blocks this change. These neurons respond to light with idiosyncratic changes to their baseline calcium levels, and idiosyncratic morphological variation in their presynaptic arbors correlates with idiosyncratic sensory-context-specific turn biases. These findings provide a circuit mechanism by which individual locomotor biases arise and are modulated by sensory context.
Genomic Polymorphisms in Toxin-Antitoxin Systems and Identification of Novel Phylo-SNPs and Polymorphisms Associated with Drug Resistance/Susceptibility in Clinical Isolates of Mycobacterium tuberculosis from Mumbai, India
Authors: Nilgiriwala Kayzad , Chitalia Vidushi , Shah Sanchi , Papewar Akshata 
Published: October 2019

ABSTRACTToxin-antitoxin (TA) modules are one of the prominent determinants that triggers a persistent state aiding Mycobacterium tuberculosis evasion to host generated stresses. The 79 characterized and putative TA systems described in M. tuberculosis are dominated by the VapBC, MazEF, HigAB, RelBE and ParDE TA families, largely involved in persistence and cell arrest. Hence, there is a need to maintain and conserve the TA loci in the chromosome of the pathogen. It is essential to study the genomic differences of the TA systems in clinical isolates along with its association to drug susceptibility patterns and lineage. In the current study, the TA loci and their promoter sequences were analysed from the whole genome sequence data of 74 clinical isolates. Mykrobe Predictor was used for lineage identification and drug resistance predictions in the clinical isolates. Polymorphisms associated with 79.8% (63/79) TA systems were observed across 72 clinical isolates. Among the TA systems, the isolates had a varying number of polymorphisms localised primarily in the toxin genes (58.7%), antitoxin genes (40.7%) and chaperones (0.6%), due to Single Nucleotide Polymorphism (SNP) resulting in transition (67.3%), transversion or frameshift mutations. Our analysis suggests the presence of novel Phylo-SNPs by establishing high confidence association of specific lineages to polymorphisms in the TA systems. Notably, association of polymorphisms in Rv1838c-1839c (VapBC13), Rv3358-3357 (YefM/YoeB) and Rv0240-0239 (VapBC24) to Delhi/Central Asia lineage. The polymorphic loci of the 3 TA systems is localised in the antitoxin gene of the Delhi/Central Asia strains, with a resultant silent mutation. The assessment of correlation between TA polymorphisms and the drug resistance profile revealed correlation of SNPs in VapBC35 with drug resistant M. tuberculosis strains and SNPs in VapBC24, VapBC13 and YefM/YoeB to drug sensitive strains.