bluuebunny/crossref_metadata_2025 huggingface dataset:
Cone-Beam CT With Augmented Fluoroscopy Combined With Electromagnetic Navigation Bronchoscopy for Biopsy of Pulmonary Nodules
Authors: Pritchett Michael A. , Schampaert Stéphanie , de Groot Joris A.H. , Schirmer Charles C. , van der Bom Imramsjah
Published: September 2018

Background:

Electromagnetic navigation bronchoscopy (ENB) has been widely adopted as a guidance technique for biopsy of peripheral lung nodules. However, ENB is limited by the lack of real-time confirmation of the biopsy devices. Intraprocedural cone-beam computed tomography (CBCT) imaging can be utilized to assess or confirm the location of biopsy devices. The aim of this study is to determine the safety and diagnostic yield (DY) of image fusion of intraprocedural CBCT data with live fluoroscopy (augmented fluoroscopy) during ENB-guided biopsy of peripheral lung nodules.

Methods:

Data from 75 consecutive patients who underwent biopsy with ENB was collected retrospectively. Patients underwent CBCT imaging while temporarily suspending mechanical ventilation. CBCT data were acquired and 3-dimensional segmentation of nodules was performed using commercially available software (OncoSuite). During ENB, the segmented lesions were projected and fused with live fluoroscopy enabling real-time 3-dimensional guidance.

Results:

A total of 93 lesions with a median size of 16.0 mm were biopsied in 75 consecutive patients. The overall DY by lesion was 83.7% (95% confidence interval, 74.8%-89.9%). Multivariate regression analysis showed no independent correlation between lesion size, lesion location, lesion visibility under standard fluoroscopy, and the presence of a bronchus sign with DY. Pneumothorax occurred in 3 patients (4%).

Conclusion:

Intraprocedural CBCT imaging with augmented fluoroscopy is feasible and effective and is associated with high DY during ENB-guided biopsies.
Prolonged Late Permian–Early Triassic hyperthermal: failure of climate regulation?
Authors: Kump Lee R.
Published: September 2018

The extreme warmth associated with the mass extinction at the Permian–Triassic boundary was likely produced by a rapid build-up of carbon dioxide in the atmosphere from the eruption and emplacement of the Siberian Traps. In comparison to another hyperthermal event, the Palaeocene–Eocene Thermal Maximum, the Permian–Triassic event, while leaving a similar carbon isotope record, likely had larger amounts of CO
2
emitted and did not follow the expected time scale of climate recovery. The quantities and rates of CO
2
emission likely exhausted the capacity of the long-term climate regulator associated with silicate weathering. Failure was enhanced by slow rock uplift and high continentality associated with the supercontinental phase of global tectonics at the time of the Siberian Traps eruption.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
Greenhouse- and orbital-forced climate extremes during the early Eocene
Authors: Kiehl Jeffrey T. , Shields Christine A. , Snyder Mark A. , Zachos James C. , Rothstein Mathew
Published: September 2018

The Palaeocene–Eocene Thermal Maximum (PETM) was a significant global warming event in Earth's deep past (56 Mya). The warming across the PETM boundary was driven by a rapid rise in greenhouse gases. The event also coincided with a time of maximum insolation in Northern Hemisphere summer. There is increased evidence that the mean warming was accompanied by enhanced seasonality and/or extremes in precipitation (and flooding) and drought. A high horizontal resolution (50 km) global climate model is used to explore changes in the seasonal cycle of surface temperature, precipitation, evaporation minus precipitation and river run-off for regions where proxy data are available. Comparison for the regions indicates the model accurately simulates the observed changes in these climatic characteristics with North American interior warming and drying, and warming and increased river run-off at other regions. The addition of maximum insolation in Northern Hemisphere summer leads to a drier North America, but wetter conditions at most other locations. Long-range transport of atmospheric moisture plays a critical role in explaining regional changes in the water cycle. Such high-frequency variations in precipitation might also help explain discrepancies or misinterpretation of some climate proxies from the same locations, especially where sampling is coarse, i.e. at or greater than the frequency of precession.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
Strategies in times of crisis—insights into the benthic foraminiferal record of the Palaeocene–Eocene Thermal Maximum
Authors: Schmidt Daniela N. , Thomas Ellen , Authier Elisabeth , Saunders David , Ridgwell Andy
Published: September 2018

Climate change is predicted to alter temperature, carbonate chemistry and oxygen availability in the oceans, which will affect individuals, populations and ecosystems. We use the fossil record of benthic foraminifers to assess developmental impacts in response to environmental changes during the Palaeocene–Eocene Thermal Maximum (PETM). Using an unprecedented number of µ-computed tomography scans, we determine the size of the proloculus (first chamber), the number of chambers and the final size of two benthic foraminiferal species which survived the extinction at sites 690 (Atlantic sector, Southern Ocean, palaeodepth 1900 m), 1210 (central equatorial Pacific, palaeodepth 2100 m) and 1135 (Indian Ocean sector, Southern Ocean, palaeodepth 600–1000 m). The population at the shallowest site, 1135, does not show a clear response to the PETM, whereas those at the other sites record reductions in diameter or proloculus size. Temperature was similar at all sites, thus it is not likely to be the reason for differences between sites. At site 1210, small size coincided with higher chamber numbers during the peak event, and may have been caused by a combination of low carbonate ion concentrations and low food supply. Dwarfing at site 690 occurred at lower chamber numbers, and may have been caused by decreasing carbonate saturation at sufficient food levels to reproduce. Proloculus size varied strongly between sites and through time, suggesting a large influence of environment on both microspheric and megalospheric forms without clear bimodality. The effect of the environmental changes during the PETM was more pronounced at deeper sites, possibly implicating carbonate saturation.

This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
An essential role for dNTP homeostasis following CDK-induced replication stress
Authors: Pai Chen-Chun , Hsu Kuo-Feng , Durley Samuel. C. , Keszthelyi Andrea , Kearsey Stephen E. , Rallis Charalampos , Folkes Lisa K. , Deegan Rachel , Wilkins Sarah E. , Pfister Sophia X. , León Nagore De , Schofield Christopher J. , Bähler Jürg , Carr Antony M. , Humphrey Timothy C.
Published: September 2018

Replication stress is a common feature of cancer cells, and thus a potentially important therapeutic target. Here we show that CDK-induced replication stress is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads to increased dNTP demand and replication stress through CDK-induced firing of dormant replication origins. Subsequent dNTP depletion leads to inefficient DNA replication, Mus81-dependent DNA damage, and to genome instability. Cells respond to this replication stress by increasing dNTP supply through Set2-dependent MBF-induced expression of Cdc22, the catalytic subunit of ribonucleotide reductase (RNR). Disrupting dNTP synthesis following Wee1 inactivation, through abrogating Set2-dependent H3K36 tri-methylation or DNA integrity checkpoint inactivation results in critically low dNTP levels, replication collapse and cell death, which can be rescued by increasing dNTP levels. These findings support a ‘dNTP supply and demand’ model in which maintaining dNTP homeostasis is essential to prevent replication catastrophe in response to CDK-induced replication stress.
Endopeptidase regulation as a novel function of the Zur-dependent zinc starvation response
Authors: Murphy Shannon G. , Alvarez Laura , Adams Myfanwy C. , Liu Shuning , Chappie Joshua S. , Cava Felipe , Dörr Tobias
Published: September 2018

The cell wall is a strong, yet flexible, meshwork of peptidoglycan (PG) that gives a bacterium structural integrity. To accommodate a growing cell, the wall is remodeled by both PG synthesis and degradation.Vibrio choleraeencodes a group of three nearly identical zinc-dependent endopeptidases (EPs) that hydrolyze PG to facilitate cell growth. Two of these (shyAandshyC) are housekeeping genes and form a synthetic lethal pair, while the third (shyB) is not expressed under standard laboratory conditions. To investigate the role of ShyB, we conducted a transposon screen to identify mutations that activateshyBtranscription. We found thatshyBis induced as part of the Zur-mediated zinc starvation response, a mode of regulation not previously reported for cell wall lytic enzymes.In vivo, ShyB alone was sufficient to sustain cell growth in low-zinc environments.In vitro, ShyB retained its D,D-endopeptidase activity against purified sacculi in the presence of the metal chelator EDTA at a concentration that inhibits ShyA and ShyC. This suggests that ShyB can substitute for the other EPs during zinc starvation, a condition that pathogens encounter while infecting a human host. Our survey of transcriptomic data from diverse bacteria identified other candidate Zur-regulated endopeptidases, suggesting that this adaptation to zinc starvation is conserved in other Gram-negative bacteria.

Importance

The human host sequesters zinc and other essential metals in order to restrict growth of potentially harmful bacteria. In response, invading bacteria express a set of genes enabling them to cope with zinc starvation. InVibrio cholerae, the causative agent of the diarrheal disease cholera, we have identified a novel member of this zinc starvation response: a cell wall hydrolase that retains function in low-zinc environments and is conditionally essential for cell growth. Other human pathogens contain homologs that appear to be under similar regulatory control. These findings are significant because they represent, to our knowledge, the first evidence that zinc homeostasis influences cell wall turnover. Anti-infective therapies commonly target the bacterial cell wall and, therefore, an improved understanding of how the cell wall adapts to host-induced zinc starvation could lead to new antibiotic development. Such therapeutic interventions are required to combat the rising threat of drug resistant infections.
A sex-stratified genome-wide association study of tuberculosis using a multi-ethnic genotyping array
Authors: Schurz Haiko , Kinnear Craig J , Gignoux Chris , Wojcik Genevieve , van Helden Paul D , Tromp Gerard , Henn Brenna , Hoal Eileen G , Möller Marlo
Published: September 2018

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a complex disease with a known human genetic component. Males seem to be more affected than females and in most countries the TB notification rate is twice as high in males as in females. While socio-economic status, behaviour and sex hormones influence the male bias they do not fully account for it. Males have only one copy of the X chromosome, while diploid females are subject to X chromosome inactivation. In addition, the X chromosome codes for many immune-related genes, supporting the hypothesis that X-linked genes could contribute to TB susceptibility in a sex-biased manner. We report the first TB susceptibility genome-wide association study (GWAS) with a specific focus on sex-stratified autosomal analysis and the X chromosome. Individuals from an admixed South African population were genotyped using the Illumina Multi Ethnic Genotyping Array, specifically designed as a suitable platform for diverse and admixed populations. Association testing was done on the autosome and X chromosome in a sex stratified and combined manner. SNP association testing was not statistically significant using a stringent cut-off for significance but revealed likely candidate genes that warrant further investigation. A genome wide interaction analysis detected 16 significant interactions. Finally, the results highlight the importance of sex-stratified analysis as strong sex-specific effects were identified on both the autosome and X chromosome.
Heterochrony of puberty in the European Badger (Meles meles) can be explained by growth rate and group-size: Evidence for two endocrinological phenotypes
Authors: Sugianto Nadine Adrianna , Newman Chris , Macdonald David Whyte , Buesching Christina Dagmar
Published: September 2018

Puberty is a key stage in mammalian ontogeny, involving endocrinological, physiological and behavioural changes, moderated by intrinsic and extrinsic factors. Thus, not all individuals within one population achieve sexual maturity simultaneously. Here, using the European badger (Meles meles) as a model, we describe male testosterone and female oestrone profiles (using Enzyme-immunoassays) from first capture (3 months, post-weaning) until 28 months (attaining sexual maturity and final body size), along with metrics of somatic growth, scent gland development and maturation of external reproductive organs as well as intra-specific competition. In both sexes, endocrinological puberty commenced at ca. 11 months. Thereafter, cub hormone levels followed adult seasonal hormone patterns but at lower levels, with the majority of cubs reaching sexual maturity during their second mating season (22-28 months). Interestingly, there was evidence for two endocrinological phenotypes among male cubs (less evident in females), with early developers reaching sexual maturity at 11 months (first mating season) and late developers reaching sexual maturity at 22-26 months (second mating season). Early developers also attained a greater proportion of their ultimate adult size by 11 months, exhibiting faster growth rates than late developers (despite having similar adult size). Male cubs born into larger social groups tended to follow the late developer phenotype. Our results support the hypothesis that a minimum body size is required to reach sexual maturity, which may be achieved at different ages, even within a single population, where early maturity can confer individual fitness advantages and enhance population growth rate.
Mutant screen for reproduction unveils depression-associated Piccolo’s control over reproductive behavior
Authors: Medrano Gerardo A. , Singh Manvendra , Plautz Erik J. , Good Levi B. , Chapman Karen M. , Chaudhary Jaideep , Jaichander Priscilla , Powell Heather M. , Pudasaini Ashutosh , Shelton John M. , Richardson James A. , Xie Xian-Jin , Ivics Zoltán , Braun Christine , Ackermann Frauke , Garner Craig C. , Izsvák Zsuzsanna , Hamra F. Kent
Published: September 2018

Successful sexual reproduction involves complex, genetically encoded interplay between animal physiology and behavior. The rat provides a highly fecund mammalian model for studying how the brain impacts reproduction. Here, we report a forward genetics screen in rats to identify genes that affect reproduction. A panel of 18 distinct rat strains harboring Sleeping Beauty gene trap mutations were analyzed for the ability to reproduce. As expected, our mutant screen identified genes where reproductive failure was connected to gametogenesis (Btrc, Pan3, Spaca6, Ube2k) and embryogenesis (Alk3, Exoc6b, Slc1a3, Tmx4, Zmynd8). In addition, we identified Ata13 (longevity) and Pclo (neuronal disorders), previously not associated with an inability to conceive. Neurologically, Pclo is known to regulate the size of presynaptic vesicle pools. Here, dominant traits in Pclo mutant rats caused epileptiform activity and affected genes supporting GABAergic synaptic transmission (Gabra6, Gabrg3). Recessive traits in Pclo mutant rats transmitted altered reproductive behavior, as homozygous Pclo mutant rats produced gametes but neither sex would mate with wildtype rats. Pclo mutant rat behavior was linked to endophenotypes signifying compromised brain-gonad crosstalk via disturbed GnRH signaling and allelic markers for major depressive disorder in humans (Grm5, Htr2a, Sorcs3, Negr1, Drd2). Thus, by rat genetics, we identified Pclo as a candidate presynaptic factor required for reproduction.

Author Summary

Piccolo gene mutations have previously been identified in human cohorts diagnosed with behavioral syndromes that impact one’s emotions, including depression and bipolar disorder. Although studies in human populations implicate changes to Piccolo’s DNA sequence to enhanced susceptibility for behavioral disorders, studies in mouse models have yet to link Piccolo mutations to altered behavior. Here, by a novel genetics approach, we report Piccolo mutation-dependent effects on reproductive behavior in rats, a finding that may turn out to be relevant to the behavioral effects that are associated with human Piccolo gene mutations. Thus, research aimed at understanding how Piccolo functions to regulate reproduction in rats could prove pivotal in our ability to understand neurological mechanisms that influence human emotions.
The ER chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasites
Authors: Kudyba Heather M. , Cobb David W. , Fierro Manuel A. , Florentin Anat , Ljolje Dragan , Singh Balwan , Lucchi Naomi W. , Muralidharan Vasant
Published: September 2018

The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the red blood cell is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathways. In this study, we tested the role of an uncharacterized ER protein, PfGRP170, in regulating these key functions by generating conditional mutants. Our data show that PfGRP170 localizes to the ER and is essential for asexual growth, specifically required for proper development of schizonts. PfGRP170 is essential for surviving heat shock, suggesting a critical role in cellular stress response. The data demonstrate that PfGRP170 interacts with the Plasmodium orthologue of the ER chaperone, BiP. Finally, we found that loss of PfGRP170 function leads to the activation of the Plasmodium eIF2α kinase, PK4, suggesting a specific role for this protein in this parasite stress response pathway.
Harnessing Avidity: Quantifying Entropic and Energetic Effects of Linker Length and Rigidity Required for Multivalent Binding of Antibodies to HIV-1 Spikes
Authors: Einav Tal , Yazdi Shahrzad , Coey Aaron , Bjorkman Pamela J. , Phillips Rob
Published: September 2018

Due to the low density of envelope (Env) spikes on the surface of HIV-1, neutralizing IgG antibodies rarely bind bivalently using both antigen-binding arms (Fabs) to crosslink between spikes (inter-spike crosslinking), instead resorting to weaker monovalent binding that is more sensitive to Env mutations. Synthetic antibodies designed to bivalently bind a single Env trimer (intra-spike crosslinking) were previously shown to exhibit increased neutralization potencies. In initial work, diFabs joined by varying lengths of rigid double-stranded DNA (dsDNA) were considered. Anticipating future experiments to improve synthetic antibodies, we investigate whether linkers with different rigidities could enhance diFab potency by modeling DNA-Fabs containing different combinations of rigid dsDNA and flexible single-stranded DNA (ssDNA) and characterizing their neutralization potential. Model predictions suggest that while a long flexible polymer may be capable of bivalent binding, it exhibits weak neutralization due to the large loss in entropic degrees of freedom when both Fabs are bound. In contrast, the strongest neutralization potencies are predicted to require a rigid linker that optimally spans the distance between two Fab binding sites on an Env trimer, and avidity can be further boosted by incorporating more Fabs into these constructs. These results inform the design of multivalent anti-HIV-1 therapeutics that utilize avidity effects to remain potent against HIV-1 in the face of the rapid mutation of Env spikes.

Significance

IgG antibodies utilize avidity to increase their apparent affinities through simultaneous binding of two antigen-binding Fabs – if one Fab dissociates from an antigen, the other Fab can remain attached, allowing rebinding. HIV-1 foils this strategy by having few, and highly-separated, Envelope spike targets for antibodies, forcing most IgGs to bind monovalently. Here we develop a statistical mechanics model of synthetic diFabs joined by DNA linkers of different lengths and flexibilities. This framework enables us to translate the energetic and entropic effects of the linker into the neutralization potency of a diFab. We demonstrate that the avidity of multivalent binding is enhanced by using rigid linkers or including additional Fabs capable of simultaneous binding, providing the means to quantitatively predict the potencies of other antibody designs.
Fatigue induces long lasting detrimental changes in motor skill learning
Authors: Branscheidt Meret , Kassavetis Panagiotis , Rogers Davis , Lindquist Martin A. , Celnik Pablo
Published: September 2018

Fatigue due to physical exertion is a ubiquitous phenomenon in everyday life and especially common in a range of neurological diseases. While the effect of fatigue on limiting skill execution are well known, its influence on learning new skills is unclear. This is of particular interest as it is common practice to train athletes, musicians or perform rehabilitation exercises up to and beyond a point of fatigue. In a series of experiments, we describe how fatigue impairs motor skill learning beyond its effects on task execution. The negative effects on learning are evidenced by impaired task acquisition on subsequent practice days even in the absence of fatigue. Further, we found that this effect is in part mediated centrally and can be alleviated by altering motor cortex function. Thus, the common practice of training while, or beyond, fatigue levels should be carefully reconsidered, since this affects overall long-term skill learning.
Species abundance information improves sequence taxonomy classification accuracy
Authors: Kaehler Benjamin D. , Bokulich Nicholas A. , McDonald Daniel , Knight Rob , Gregory Caporaso J. , Huttley Gavin A.
Published: September 2018

Popular naive Bayes taxonomic classifiers for amplicon sequences assume that all species in the reference database are equally likely to be observed. We demonstrate that classification accuracy degrades linearly with the degree to which that assumption is violated, and in practice it is always violated. By incorporating environment-specific taxonomic abundance information, we demonstrate that species-level resolution is attainable.
Comprehensive analysis of human hookworm secreted proteins using a proteogenomic approach
Authors: Logan J , Manda SS , Choi YJ , Field M , Eichenberger RM , Mulvenna J , Nagaraj SH , Fujiwara RT , Gazzinelli-Guimaraes P , Bueno L , Mati V , Mitreva M , Sotillo J , Loukas A
Published: September 2018

The human hookworm Necator americanus infects more than 400 million people worldwide, contributing substantially to the poverty in these regions. Adult stage N. americanus live in the small intestine of the human host where they inject excretory/secretory (ES) products into the mucosa. ES products have been characterized at the proteome level for a number of animal hookworm species, but until now, the difficulty in obtaining sufficient live N. americanus has been an obstacle in characterizing the secretome of this important human pathogen. Herein we describe the ES proteome of N. americanus and utilize this information to conduct the first proteogenomic analysis of a parasitic helminth, significantly improving the available genome and thereby generating a robust description of the parasite secretome. The genome annotation resulted in a a revised prediction of 3,425 fewer genes than initially reported, accompanied by a significant increase in the number of exons and introns, total gene length and the percentage of the genome covered by genes. Almost 200 ES proteins were identified by LC-MS/MS with SCP/TAPS proteins, ‘hypothetical’ proteins and proteases among the most abundant families. These proteins were compared to commonly used model species of human parasitic infections, including Ancylostoma caninum, Nippostrongylus brasiliensis and Heligmosomoides polygyrus. Our findings provide valuable information on important families of proteins with both known and unknown functions that could be instrumental in host-parasite interactions, including protein families that might be key for parasite survival in the onslaught of robust immune responses, as well as vaccine and drug targets.
Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated α-Synuclein
Authors: Birol Melissa , Wojcik Slawomir P. , Miranker Andrew D. , Rhoades Elizabeth
Published: September 2018

Cell-to-cell transmission of toxic forms of α-Synuclein (αS) is thought to underlie disease progression in Parkinson’s disease. αS in humans is constitutively N-terminally acetylated (αSacetyl), although the impact of this modification is relatively unexplored. Here we report that αSacetylis more effective at inducing intracellular aggregation in primary neurons than unmodified αS (αSun). We identify complex N-linked glycans as binding partners for αSacetyl, and demonstrate that cellular internalization of αSacetylis reduced significantly upon cleavage of extracellular N-linked glycans, but not other carbohydrates. We verify binding of αSacetylto N-linked glycansin vitro, using both isolated glycans and cell-derived proteoliposomes. Finally, we identify neurexin lβ, a neuronal glycoprotein, as capable of driving glycan-dependent uptake of αSacetyl. Importantly, our results are specific to αSacetylas αSundoes not demonstrate sensitivity for N-linked glycans. Our study identifies extracellular N-linked glycans, and neurexin lβ specifically, as key modulators of neuronal uptake of physiological αSacetyldrawing attention to the potential therapeutic value of αSacetyl-glycan interactions.
Insights into the molecular features of the von Hippel-Lindau like protein
Authors: Quaglia Federica , Minervini Giovanni , Tabaro Francesco , Tosatto Silvio C.E.
Published: September 2018

We present an in silico characterization of the von Hippel-Lindau like protein (VLP), the only known human paralogue of the von Hippel-Lindau tumor suppressor protein (pVHL). Phylogenetic investigation showed VLP to be mostly conserved in upper mammals and specifically expressed in brain and testis. Structural analysis and molecular dynamics simulation show VLP to be very similar to pVHL three-dimensional organization and binding dynamics. In particular, conservation of elements at the protein interfaces suggests VLP to be a functional pVHL homolog potentially possessing multiple functions beyond HIF-1α-dependent binding activity. Our findings show that VLP may share at least seven interactors with pVHL, suggesting novel functional roles for this under-studied human protein. These may occur at precise hypoxia levels where functional overlap with pVHL may permit a finer modulation of pVHL functions.
New cheloniellid arthropod with large raptorial appendages from the Silurian of Wisconsin, USA
Authors: Wendruff Andrew J. , Babcock Loren E. , Mikulic Donald G. , Kluessendorf Joanne
Published: September 2018

Cheloniellids comprise a small, distinctive group of Paleozoic arthropods of whose phylogenetic relationships within the Arthropoda remain unresolved. A new form,Xus yus, n. gen, n. sp. is reported from the Waukesha Lagerstatte in the Brandon Bridge Formation (Silurian: Telychian), near Waukesha, Wisconsin, USA. Exceptionally preserved specimens show previously poorly known features including biramous appendages; this is the first cheloniellid to show large, anterior raptorial appendages. We emend the diagnosis of Cheloniellida; cephalic appendages are uniramous and may include raptorial appendages; trunk appendages are biramous.
The effect of varied exercise intensity on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats
Authors: Ruan Ling , Neil.A. Smart , Li Fanghui
Published: September 2018

Exercise and diet may improve cardio-metabolic health in non-alcoholic fatty liver disease, but the optimal exercise prescription remains unclear. We aimed to compare the effects of diet and exercise at different intensities on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats. Fifty Sprague Dawley rats (180-220g) were randomly divided into two experimental groups and fed either standard rodent chow diet or a high-fat diet. After16 weeks, these animals that received the HFD were randomly separated into a high fat control group or three exercise training groups: HF and low intensity exercise, HF and moderate intensity exercise, HF and incremental intensity exercise, these experimental rats keep sedentary or training for the next 6 weeks. Markers of Aortic Oxidative stress were detected using assay kit. Immunohistochemical analysis was performed to determine the expression level of eNOS and ET-1. Lipid metabolism parameters were detected with an automatic analyzer. Exercise at different intensities improved lipid metabolism, enhanced anti-oxidation function, reduced MDA, increased NO, and improved the expression of eNOS and ET-1 protein levels. Decreased blood lipids were exhibited in all exercise groups. Notably, moderate intensity exercise demonstrated more effect on increasing GSH contents, and decreased the expression of ET-1 protein levels.
RAFTS3G – An efficient and versatile clustering software to analyses in large protein datasets
Authors: Lima Nichio Bruno Thiago de , de Oliveira Aryel Marlus Repula , de Pierri Camilla Reginatto , Costa Santos Leticia Graziela , Vialle Ricardo Assunção , Marchaukoski Jeroniza Nunes , Oliveira Pedrosa Fabio de , Raittz Roberto Tadeu
Published: September 2018

The need to develop computational tools and techniques that can predict efficiently consistent groups of family proteins in large volume of biological information is still a great perspective in Bioinformatic studies. Besides that, it is difficult to increase speed demanding low computational processing to minimize the information complexity. Tools already consolidated as the CD-HIT and UCLUST generates very compact data that makes the Data Mining difficult and have low efficiency when used for detect homology among proteins requiring manual intervention, therefore it is necessary a tool that is also efficient in low similarity. Here we present a new approach for the Data Mining and analysis of homology in large dataset of protein sequences, the RAFTS3G. We used the UniProtKB/Swiss-Prot database with the most popular clustering tools and RAFTS3G proved to be more than 10 times faster than CD-HIT and its strategy increases the performance in low similarity to detect protein families.

Contact:raittz@ufpr.br
Sex Differences in Aggression: Differential Roles of 5-HT2, Neuropeptide F and Tachykinin
Authors: Bubak Andrew N. , Watt Michael J. , Renner Kenneth J. , Luman Abigail A. , Costabile Jamie D. , Sanders Erin J. , Grace Jaime L. , Swallow John G.
Published: September 2018

Despite the conserved function of aggression across taxa in obtaining critical resources such as food and mates, serotonin’s (5-HT) modulatory role on aggressive behavior appears to be largely inhibitory for vertebrates but stimulatory for invertebrates. However, critical gaps exist in our knowledge of invertebrates that need to be addressed before definitively stating opposing roles for 5-HT and aggression. Specifically, the role of 5-HT receptor subtypes are largely unknown, as is the potential interactive role of 5-HT with other neurochemical systems known to play a critical role in aggression. Similarly, the influence of these systems in driving sex differences in aggressive behavior of invertebrates is not well understood. Here, we investigated these questions by employing complementary approaches in a novel invertebrate model of aggression, the stalk-eyed fly. A combination of altered social conditions, pharmacological manipulation and 5-HT2receptor knockdown by siRNA revealed an inhibitory role of this receptor subtype on aggression. Additionally, we provide evidence for 5-HT2’s involvement in regulating neuropeptide F activity, a suspected inhibitor of aggression. However, this function appears to be stage-specific, altering only the initiation stage of aggressive conflicts. Alternatively, pharmacologically increasing systemic concentrations of 5-HT significantly elevated the expression of the neuropeptide tachykinin, which did not affect contest initiation but instead promoted escalation via production of high intensity aggressive behaviors. Notably, these effects were limited solely to males, with female aggression and neuropeptide expression remaining unaltered by any manipulation that affected 5-HT. Together, these results demonstrate a more nuanced role for 5-HT in modulating aggression in invertebrates, revealing an important interactive role with neuropeptides that is more reminiscent of vertebrates. The sex-differences described here also provide valuable insight into the evolutionary contexts of this complex behavior.

Significance Statement

Serotonin’s (5-HT) modulatory role in aggression is generally reported as inhibitory in vertebrates but stimulatory in invertebrates. Using a novel invertebrate model system, we provide evidence of common pathways of aggression at the 5-HT receptor subtype level as well as 5-HT’s interactive role with other neurochemical systems namely neuropeptide F and tachykinin. Additionally, we found that these effects were sex-dependent as well as stage-dependent affecting either the initiation or escalation stage of an aggressive contest. Our results reveal the impressive level of conservation with respect to neurochemical mechanisms among species as diverse as vertebrates and invertebrates, and highlights the need to consider multiple factors when determining potential taxonomic differences in how 5-HT mediates aggression.
Absence of SIV-specific CD8+ T cells in germinal centers may set the stage for persistent infection
Authors: Li Shengbin , Folkvord Joy M. , Kovacs Katalin J , Wagstaff Reece K. , Mwakalundwa Gwantwa , Rendahl Aaron K. , Rakasz Eva G. , Connick Elizabeth , Skinner Pamela J.
Published: September 2018

CD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection.

Author Summary

A paucity of SIV-specific CD8+ T cells in lymphoid follicles and complete absence within most follicular germinal centers during early infection may set the stage for the establishment of persistent chronic infection.
Fast analytical evaluation of intermolecular electrostatic interaction energies using the pseudoatom representation of the electron density. I. The Löwdin α-function method
Authors: Nguyen Daniel , Kisiel Zbigniew , Volkov Anatoliy
Published: September 2018

The previously reported [Volkovet al.(2004).Chem. Phys. Lett.391, 170–175] exact potential and multipole moment (EP/MM) method for evaluation of intermolecular electrostatic interaction energies using the nuclei-centered pseudoatom representation of electron densities is significantly improved in terms of both speed and accuracy by replacing the numerical quadrature integration of the exact potential with a fully analytical technique. The resulting approach, incorporated in theXDPROPmodule of the software packageXD, has been tested on several molecular systems ranging in size from water–water to dodecapeptide–dodecapeptide dimers using electron densities constructedviathe University at Buffalo Aspherical Atom Databank. The improved hybrid method provides electrostatic interaction energies within the uncertainty of ≤0.2 kJ mol−1for all benchmark systems. The running time for a dimer of a sizable, 225-atom dodecapeptide is under 4 s on a 2012 central processing unit (2.8 GHz AMD Opteron 6348) and under 3 s on a relatively modern processor (2.8 GHz Intel Xeon E3-1505M v5).
The phase problem for two-dimensional crystals. II. Simulations
Authors: Arnal Romain D. , Zhao Yun , Mitra Alok K. , Spence John C. H. , Millane Rick P.
Published: September 2018

Phasing of diffraction data from two-dimensional crystals using only minimal molecular envelope information is investigated by simulation. Two-dimensional crystals are an attractive target for studying membrane proteins using X-ray free-electron lasers, particularly for dynamic studies at room temperature. Simulations using an iterative projection algorithm show that phasing is feasible with fairly minimal molecular envelope information, supporting recent uniqueness results for this problem [Arnal & Millane (2017).Acta Cryst.A73, 438–448]. The effects of noise and likely requirements for structure determination using X-ray free-electron laser sources are investigated.
Energy flow of Bloch waves in X-ray dynamical diffraction in the Laue case for perfect crystals
Authors: Saka Takashi
Published: September 2018

The direction of energy flow for Bloch waves during X-ray dynamical diffraction in perfect crystals is investigated. The energy flow is spread uniformly within the Borrmann fan in the conventional Laue case where the imaginary part of the crystal structure factor is much smaller than the real part. However, when the imaginary part is large, as in the case of X-rays with energies close to the absorption edge for single atoms in crystals, the energy flow direction is found to be restricted, and the results are discussed in relation to the Bragg case.
Intensive X-ray standing-wave-like fields localized near a surface of a crystalline superlattice
Authors: Prudnikov I. R.
Published: September 2018

A peculiar kind of intensive X-ray standing wave is analytically shown to exist. Such an X-ray interference field is localized in the vicinity of a surface of a crystalline superlattice and its amplitude decays exponentially in both directions perpendicular to the surface. The appearance of the standing wave is accompanied by a deep dip in a chosen Bragg peak of the superlattice.
A structural equation model for enhancing effectiveness of engineering, procurement and construction (EPC) major projects
Authors: Aldhaheri Mohamed , Bakchan Amal , Sandhu Maqsood Ahmad
Published: September 2018

Purpose

The purpose of this paper is to define and analyze causal factors shaping the effectiveness of engineering, procurement and construction (EPC) major projects in meeting the product objectives, from the end-user’s perspective.

Design/methodology/approach

An online survey questionnaire was developed and administered to end-users working in major oil and gas projects. Data collection process was initiated on, around 275 end-users, and 213 responses were received, achieving a high response rate of 77 percent.

Findings

The results indicate that both alignment of objectives and end-user’s engagement factors exhibit a positive influence on effectiveness of EPC, with the former having higher contribution than the latter. In this context, the product success triangle reveals higher preference of the end-user’s team toward quality than schedule and cost objectives.

Research limitations/implications

Shifting the efforts of involving the end-user forward in time, starting from the planning stage, alleviates the adverse impacts of design changes as well as increases the ability to save cost, improve performance and increase end-user’s satisfaction.

Practical implications

The model raises the awareness of oil and gas industry practitioners toward the critical factors influencing the project effectiveness and proposes useful techniques for maintaining proper alignment between project and product objectives as well as facilitating end-user’s engagement at the site level. As such, it can serve as a motivation tool for aligning the objectives and acknowledging the engagement, with the aim of achieving the product success.

Originality/value

The effectiveness of EPC structural model was developed and tested using PLS–structural equation modeling statistical technique. The interpretation of the structural model demonstrated that both end-user’s engagement and alignment of objectives are essential to successfully achieve project effectiveness.
The fabric of digital life
Authors: Iliadis Andrew , Pedersen Isabel
Published: September 2018

Purpose

This paper aims to examine how metadata taxonomies in embodied computing databases indicate context (e.g. a marketing context or an ethical context) and describe ways to track the evolution of the embodied computing industry over time through digital media archiving.

Design/methodology/approach

The authors compare the metadata taxonomies of two embodied computing databases by providing a narrative of their top-level categories. After identifying these categories, they describe how they structure the databases around specific themes.

Findings

The growing wearables market often hides complex sociotechnical tradeoffs. Marketing products like Vandrico Inc.’s Wearables Database frame wearables as business solutions without conveying information about the various concessions users make (about giving up their data, for example). Potential solutions to this problem include enhancing embodied computing literacy through the construction of databases that track media about embodied computing technologies using customized metadata categories. Databases such as FABRIC contain multimedia related to the emerging embodied computing market – including patents, interviews, promotional videos and news articles – and can be archived through user-curated collections and tagged according to specific themes (privacy, policing, labor, etc.). One of the benefits of this approach is that users can use the rich metadata fields to search for terms and create curated collections that focus on tradeoffs related to embodied computing technologies.

Originality/value

This paper describes the importance of metadata for framing the orientation of embodied computing databases and describes one of the first attempts to comprehensively track the evolution of embodied computing technologies, their developers and their diverse applications in various social contexts through media archiving.
Crisis response team decision‐making as a bureau‐political process
Authors: Kalkman Jori Pascal , Kerstholt José H. , Roelofs Maaike
Published: September 2018

Given their different views and interests, how do liaisons in interorganizational crisis response teams negotiate collective decisions? We conducted an experiment with eight crisis response teams to answer this question. Taking a bureau‐political view, we find that liaisons make decisions by following one of two decision‐making pathways. First, liaisons claim some decisions as subject to their authority and make crisis response decisions independently. Second, when such authority claims are rejected or when no liaison claims decision‐making authority, deliberative consensus‐seeking takes place. Additionally, we find that crisis response team negotiations are primarily prompted by liaisons’ different views, although clashing organizational interests are nor irrelevant. We conclude that a bureau‐political perspective helps to understand how liaisons reach collective crisis response decisions.
Decomposing Human Blood: Canine Detection Odor Signature and Volatile Organic Compounds
Authors: Rendine Marcello , Fiore Carmela , Bertozzi Giuseppe , De Carlo Dania , Filetti Vera , Fortarezza Palmira , Riezzo Irene
Published: September 2018

The admissibility of human “odor mortis” discrimination in courts depends on the lack of comprehension of volatile organic compounds (VOCs) during the human decay process and of the lack in standardized procedures in training cadaver dogs. Blood was collected from four young people who died from traffic accidents and analyzed using HS‐SPME/GC‐MS at different decompositional stages. Two dogs, professionally trained, were tested to exactly locate blood samples, for each time point of the experiment. We found a long list of VOCs which varied from fresh to decomposed blood samples, showing differences in specific compounds. Dog performance showed a positive predictive value between 98.96% and 100% for DOG A, and between 99.47% and 100% for DOG B. Our findings demonstrated that decomposing human blood is a good source of VOCs and a good target for canine training.
Emotional Communication in Long‐Term Abstained Alcoholics
Authors: Harmsworth Chelsea , Paulmann Silke
Published: September 2018

Background

Alcoholism is associated with difficulties in perceiving emotions through nonverbal channels including prosody. The question whether these difficulties persist to long‐term abstinence has, however, received little attention.

Methods

In a 2‐part investigation, emotional prosody production was investigated in long‐term abstained alcoholics and age‐ and education‐matched healthy controls. First, participants were asked to produce semantically neutral sentences in different emotional tones of voice. Samples were then acoustically analyzed. Next, naïve listeners were asked to recognize the emotional intention of speakers from a randomly collected subset. Voice quality indicators were also assessed by the listeners.

Results

Findings revealed emotional prosody production differences between the 2 groups. Differences were particularly apparent when looking at pitch use. Alcoholics’ mean and variability of pitch differed significantly from controls’ use. The use of loudness was affected to a lesser extent. Crucially, naïve raters confirmed that the intended emotion was more difficult to recognize from exemplars produced by alcoholics. Differences between the 2 groups were also found with regard to voice quality.

Conclusions

These results suggest that emotional communication difficulties can persist long after alcoholics have quit drinking.