bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical simulation of fluid flow, solidification and defects in high pressure die casting (HPDC) process
Authors: Dou K , Lordan E , Zhang Y J , Jacot A , Fan Z Y
Published: May 2019

The high pressure die casting process is extensively used to manufacture light metal parts with high productivity. A major drawback of the process is the relatively high variability in mechanical properties and poor repeatability between casting cycles, limiting the achievement of weight reduction through lighter design. Although it has been established that mechanical properties are adversely affected by casting defects, the origin of the relatively high randomness in the HPDC process is not well understood. Numerical simulation is a powerful and cost-effective tool to address this question, as it gives access to quantities that are difficult to obtain experimentally. A numerical simulation approach based on the finite element casting software ProCAST has been developed. The model was applied to the casting of aluminium tensile test samples, which were used to measure the tensile properties of the alloy. Simulation permitted the study of fluid flow, solidification and defect formation during each stage of the HPDC process: pouring, injection and cooling. Air entrapment and porosity distribution in the cast part were predicted. The results were compared with temperature measurements, porosity observations and solid distribution in the sleeve prior to injection. Although the results are still very preliminary, some trends could be established between the level of turbulence of the melt during injection and reduced elongation.
Microstructure evolution in an Al-Si piston alloy under ultrasonic melt processing
Authors: Chankitmunkong Suwaree , Eskin Dmitry G. , Limmaneevichitr Chaowalit
Published: May 2019

Piston Al-Si eutectic alloys are used to produce direct-chill cast billets for subsequent forging. Because of a very complex composition and multi-phase heterogeneous structure, it is necessary to control the formation of primary and eutectic compounds either through alloying or casting conditions (or both). In this study we used ultrasonic melt processing above or across the liquidus line to affect the occurrence and size distribution of primary Si as well as morphology of primary Al dendrites and high-temperature eutectic phases. The refinement of these particles has potential benefit for mechanical properties and formability during forging.
Evaluation of AHSS concepts with a focus on the product properties and appropriate casting characteristics of Arvedi ESP thin slab casters
Authors: Bernhard C. , Linzer B. , Presoly P. , Watzinger I. , Watzinger J.
Published: May 2019

The Arvedi ESP process and a variety of produced materials have been continuously developed since the opening of the Arvedi ESP plant in Cremona in 2009 to meet market demands for more sophisticated steel grades. The development of grades for more advanced applications such as advanced high strength steels and multiphase grades is of interest. Dual phase grades such as DP600 are already produced through an ESP line on an industrial scale; additional multi-phase grades such as TRIP are under development. High-strength steels for the automotive industry have especially high demands on material properties. In addition to the mechanical material properties, an excellent surface quality is required. The fundamental basis for such material properties on rolled coils needs to be provided from continuous casting. This paper deals with the classification of different – either Si - or Al-based – alloying concepts for TRIP steels with respect to their prospective behaviour in a thin slab caster.
Thermo-elasto-viscoplastic constitutive laws for metallic alloys during their solidification
Authors: Laschet G M , Behnken H
Published: May 2019

To describe the thermomechanical behaviour of the semi-solid state during alloy solidification, specific viscoplastic constitutive laws are derived for the coherent and non-coherent regime of the mush. For the coherent semi-solid regime an original viscoplastic flow potential is derived, which includes micro-structural parameters. This potential takes also isotropic hardening, pressure dependence of yielding and the strength difference in tension and compression into account. For the non-coherent mushy state of suspensions under shear loading, a simplified viscoplastic potential is adopted by neglecting pressure effects on the solid dendrites. Continuity at mechanical coherency is imposed and allows the reduction of the model parameters of the non-coherent regime. The developed constitutive laws are implemented in Abaqus via a user-defined CREEP routine. Simulations of uniaxial tension, compression or pure shear experiments allow identifying the model parameters of an A356 aluminium alloy.
Multiplicity of the saturated special fiber ring of height two perfect ideals
Authors: Cid-Ruiz Yairon
Published: May 2019

Let

R
R

be a polynomial ring and let

I
⊂
R

I \subset R

be a perfect ideal of height two minimally generated by forms of the same degree. We provide a formula for the multiplicity of the saturated special fiber ring of

I
I

. Interestingly, this formula is equal to an elementary symmetric polynomial in terms of the degrees of the syzygies of

I
I

. Applying ideas introduced by Busé, D’Andrea, and the author, we obtain the value of the

j
j

-multiplicity of

I
I

and an effective method for determining the degree and birationality of rational maps defined by homogeneous generators of

I
I

.
The closed ordinal Ramsey number 𝑅^{𝑐𝑙}(𝜔²,3)=𝜔⁶
Authors: Mermelstein Omer
Published: May 2019

Closed ordinal Ramsey numbers are a topological variant of the classical (ordinal) Ramsey numbers. We compute the exact value of the closed ordinal Ramsey number

R

c
l

(

ω
2

,
3
)
=

ω
6

R^{cl}(\omega ^2,3) = \omega ^6

.
Reverse orbifold construction and uniqueness of holomorphic vertex operator algebras
Authors: Lam Ching Hung , Shimakura Hiroki
Published: May 2019

In this article, we develop a general technique for proving the uniqueness of holomorphic vertex operator algebras based on the orbifold construction and its “reverse” process. As an application, we prove that the structure of a strongly regular holomorphic vertex operator algebra of central charge

24
24

is uniquely determined by its weight

1
1

Lie algebra if the Lie algebra has the type

E

6
,
3

G

2
,
1

3

E_{6,3}G_{2,1}^3

,

A

2
,
3

6

A_{2,3}^6

, or

A

5
,
3

D

4
,
3

A

1
,
1

3

A_{5,3}D_{4,3}A_{1,1}^3

.
Comparing Hecke coefficients of automorphic representations
Authors: Chiriac Liubomir , Jorza Andrei
Published: May 2019

We prove a number of unconditional statistical results of the Hecke coefficients for unitary cuspidal representations of

GL
(
2
)

\text {GL}(2)

over number fields. Using partial bounds on the size of the Hecke coefficients, instances of Langlands functoriality, and properties of Rankin–Selberg

L
L

-functions, we obtain bounds on the set of places where linear combinations of Hecke coefficients are negative. Under a mild functoriality assumption we extend these methods to

GL
(
n
)

\text {GL}(n)

. As an application, we obtain a result related to a question of Serre about the occurrence of large Hecke eigenvalues of Maass forms. Furthermore, in the cases where the Ramanujan conjecture is satisfied, we obtain distributional results of the Hecke coefficients at places varying in certain congruence or Galois classes.
Ssd1 and the cell wall integrity pathway promote entry, maintenance, and recovery from quiescence in budding yeast
Authors: Miles Shawna , Li Li Hong , Melville Zephan , Breeden Linda L.
Published: May 2019

Wild Saccharomyces cerevisiae strains are typically diploid. When faced with glucose and nitrogen limitation they can undergo meiosis and sporulate. Diploids can also enter a protective, nondividing cellular state or quiescence. The ability to enter quiescence is highly reproducible but shows broad natural variation. Some wild diploids can only enter cellular quiescence, which indicates that there are conditions in which sporulation is lost or selected against. Others only sporulate, but if sporulation is disabled by heterozygosity at the IME1 locus, those diploids can enter quiescence. W303 haploids can enter quiescence, but their diploid counterparts cannot. This is the result of diploidy, not mating type regulation. Introduction of SSD1 to W303 diploids switches fate, in that it rescues cellular quiescence and disrupts the ability to sporulate. Ssd1 and another RNA-binding protein, Mpt5 (Puf5), have parallel roles in quiescence in haploids. The ability of these mutants to enter quiescence, and their long-term survival in the quiescent state, can be rescued by exogenously added trehalose. The cell wall integrity pathway also promotes entry, maintenance, and recovery from quiescence through the Rlm1 transcription factor.
Illusory Gains from Chile's Targeted School Voucher Experiment
Authors: Feigenberg Benjamin , Yan Rui , Rivkin Steven
Published: May 2019

Chile implemented a targeted voucher programme in 2008 that increased funding for disadvantaged students at public and participating private schools by approximately 50%. This reform would be expected to raise average achievement in participating schools and to reduce the achievement gap related to socioeconomic status, and disadvantaged students did make fourth-grade test-score gains exceeding 0.2 standard deviations that other studies have attributed to the programme. However, we find only small increases in resources and school-switching and little evidence of competition-driven improvement, but a closing of the parental education and income gaps, raising doubts that the programme accounts for much of this convergence.
LION/web: a web-based ontology enrichment tool for lipidomic data analysis
Authors: Molenaar Martijn R , Jeucken Aike , Wassenaar Tsjerk A , van de Lest Chris H A , Brouwers Jos F , Helms J Bernd
Published: May 2019

Background

A major challenge for lipidomic analyses is the handling of the large amounts of data and the translation of results to interpret the involvement of lipids in biological systems.

Results

We built a new lipid ontology (LION) that associates >50,000 lipid species to biophysical, chemical, and cell biological features. By making use of enrichment algorithms, we used LION to develop a web-based interface (LION/web, www.lipidontology.com) that allows identification of lipid-associated terms in lipidomes. LION/web was validated by analyzing a lipidomic dataset derived from well-characterized sub-cellular fractions of RAW 264.7 macrophages. Comparison of isolated plasma membranes with the microsomal fraction showed a significant enrichment of relevant LION-terms including “plasma membrane", “headgroup with negative charge", "glycerophosphoserines", “above average bilayer thickness", and “below average lateral diffusion". A second validation was performed by analyzing the membrane fluidity of Chinese hamster ovary cells incubated with arachidonic acid. An increase in membrane fluidity was observed both experimentally by using pyrene decanoic acid and by using LION/web, showing significant enrichment of terms associated with high membrane fluidity ("above average", "very high", and "high lateral diffusion" and "below average transition temperature").

Conclusions

The results demonstrate the functionality of LION/web, which is freely accessible in a platform-independent way.
Export Crops and Civil Conflict
Authors: Crost Benjamin , Felter Joseph H
Published: May 2019

Many experts see a move toward high-value export crops, such as fruits and vegetables, as an important opportunity for economic growth and poverty reduction, but little is known about the effects of export crops in fragile and conflict-affected countries. We exploit movements in world market prices combined with geographic variation in crop production to show that increases in the value of bananas, the country’s biggest export crop, caused an increase in conflict violence and insurgent-controlled territory in the Philippines. This effect was concentrated in provinces where bananas are produced in large plantations with areas greater than 25 hectares. Our results are consistent with a mechanism in which insurgents fund their operations by extorting large agricultural export firms.
Effects of Constant and Fluctuating Low Temperatures on the Development of Aedes aegypti (Diptera: Culicidae) from a Temperate Region
Authors: De Majo María Sol , Zanotti Gabriela , Campos Raúl E , Fischer Sylvia
Published: May 2019

Most studies of the effects of low temperature on the development of immature stages of Aedes aegypti (L.) have been performed at constant temperatures in the laboratory, which may not accurately reflect the variable environmental conditions in the field. Thus, the aim of this study was to assess the effect of constant temperatures (CT) and fluctuating low temperatures (FT) on the fitness of Ae. aegypti of Buenos Aires, Argentina. Three CT treatments (12, 14, and 16°C) and three FT treatments (12, 14, and 16°C ± 4°C) were performed and then survival, development time, and size of adults analyzed for each treatment. The immature stages completed development in all the treatments, with an average survival of 88% at 16°C, 85% at 14°C, and 22% at 12°C, and showed no differences between the CT and FT treatments. Development times were similar between the CT and FT treatments at 16°C (average ± SD: 22.7 ± 2.0 d) and at 14°C (average ± SD: 30.5 ± 2.5 d), whereas at 12°C, they lasted longer under CT (average ± SD: 46.6 ± 5.1 d) than under FT (average ± SD: 37 ± 6.5 d). The sizes of the adults at 12 and 14°C were similar but larger than those at 16°C, and showed no differences between the CT and FT treatments. Compared to populations of other geographical regions assessed in previous studies, the shorter development times and the high survival at 14 and 16°C, and the ability to complete development at 12°C, a fact not previously reported, suggest that the Ae. aegypti population of Buenos Aires city has a higher tolerance to these conditions.
New steps in mucilage biosynthesis revealed by analysis of the transcriptome of the UDP-rhamnose/UDP-galactose transporter 2 mutant
Authors: Parra-Rojas Juan Pablo , Largo-Gosens Asier , Carrasco Tomás , Celiz-Balboa Jonathan , Arenas-Morales Verónica , Sepúlveda-Orellana Pablo , Temple Henry , Sanhueza Dayan , Reyes Francisca C , Meneses Claudio , Saez-Aguayo Susana , Orellana Ariel
Published: May 2019

Upon imbibition, epidermal cells of Arabidopsis thaliana seeds release a mucilage formed mostly by pectic polysaccharides. The Arabidopsis mucilage is composed mainly of unbranched rhamnogalacturonan-I (RG-I), with low amounts of cellulose, homogalacturonan, and traces of xylan, xyloglucan, galactoglucomannan, and galactan. The pectin-rich composition of the mucilage and their simple extractability makes this structure a good candidate to study the biosynthesis of pectic polysaccharides and their modification. Here, we characterize the mucilage phenotype of a mutant in the UDP-rhamnose/galactose transporter 2 (URGT2), which exhibits a reduction in RG-I and also shows pleiotropic changes, suggesting the existence of compensation mechanisms triggered by the lack of URGT2. To gain an insight into the possible compensation mechanisms activated in the mutant, we performed a transcriptome analysis of developing seeds using RNA sequencing (RNA-seq). The results showed a significant misregulation of 3149 genes, 37 of them (out of the 75 genes described to date) encoding genes proposed to be involved in mucilage biosynthesis and/or its modification. The changes observed in urgt2 included the up-regulation of UAFT2, a UDP-arabinofuranose transporter, and UUAT3, a paralog of the UDP-uronic acid transporter UUAT1, suggesting that they play a role in mucilage biosynthesis. Mutants in both genes showed changes in mucilage composition and structure, confirming their participation in mucilage biosynthesis. Our results suggest that plants lacking a UDP-rhamnose/galactose transporter undergo important changes in gene expression, probably to compensate modifications in the plant cell wall due to the lack of a gene involved in its biosynthesis.
miR828 and miR858 regulate VvMYB114 to promote anthocyanin and flavonol accumulation in grapes
Authors: Tirumalai Varsha , Swetha Chenna , Nair Ashwin , Pandit Awadhesh , Shivaprasad Padubidri V
Published: May 2019

miRNA-mediated silencing of R2R3 MYB transcription factor promotes the production of specific secondary metabolites in grapes.
Early Detection of Diabetic Ketoacidosis by Breathalyzer in a Sailor Reporting for Duty
Authors: Reinhart Jacob
Published: May 2019

Diabetic ketoacidosis (DKA) is a severe medical condition involving the uncontrolled hyperglycemia and ketoacidosis that results from impaired insulin utilization. The biochemical response to insulin resistance or deficiency is a ketotic state in which fatty acids are converted to ketone bodies for an alternative energy source. Patients in DKA acutely develop severe symptoms, typically over the course of 24–48 hours. Classic symptoms include nausea, vomiting, lethargy, altered mental status, and abdominal pain. As the time course of ketoacidosis is relatively rapid, it is rare to identify a developing case of DKA prior to symptom onset.

In this atypical case, the author presents an asymptomatic 37-year-old active duty male without a history of diabetes, whose DKA detection was inspired by an elevated breathalyzer reading. The Sailor underwent routine breath alcohol analysis per command instruction upon reporting for duty. In the absence of recent alcohol intake, the elevated breathalyzer reading is associated with the Sailor’s metabolic ketoacidosis. Acetone, one of three primary ketone bodies generated in DKA is notable as the cause of the hallmark fruity odor breath of DKA patients. In this case, it is converted to isopropanol, an agent that is detectable by breathalyzers.
The RNA-Binding Protein CsrA Controls Virulence in Erwinia amylovora by Regulating RelA, RcsB, and FlhD at the Posttranscriptional Level
Authors: Lee Jae Hoon , Ancona Veronica , Chatnaparat Tiyakhon , Yang Ho-wen , Zhao Youfu
Published: May 2019

CsrA, an RNA-binding protein, binds to target transcripts and alters their translation or stability. In Erwinia amylovora, CsrA positively regulates the expression of type III secretion system (T3SS), exopolysaccharide amylovoran, and motility. In this study, the global effect of CsrA and its noncoding small RNA (ncsRNA) csrB in E. amylovora was determined by RNA-seq, and potential molecular mechanisms of CsrA-dependent virulence regulation were examined. Transcriptomic analyses under the T3SS-inducing condition revealed that mutation in the csrA gene led to differential expression of more than 20% of genes in the genome. Among them, T3SS genes and those required for cell growth and viability were significantly downregulated. On the other hand, the csrB mutant exhibited significant upregulation of most major virulence genes, suggesting an antagonistic effect of csrB on CsrA targets. Direct interaction between CsrA protein and csrB was further confirmed through the RNA electrophoretic mobility shift assay (REMSA). However, no direct interaction between CsrA and hrpL and hrpS transcripts was detected, suggesting that HrpL and HrpS are not targets of CsrA, whereas three CsrA targets (relA, rcsB, and flhD) were identified and confirmed by REMSA, site-directed mutagenesis, and LacZ reporter gene assays. These findings might partially explain how CsrA positively controls E. amylovora virulence by targeting major regulators at the posttranscriptional level.
Deep Sequencing Reveals Early Reprogramming of Arabidopsis Root Transcriptomes Upon Ralstonia solanacearum Infection
Authors: Zhao Cuizhu , Wang Huijuan , Lu Yao , Hu Jinxue , Qu Ling , Li Zheqing , Wang Dongdong , He Yizhe , Valls Marc , Coll Núria S. , Chen Qin , Lu Haibin
Published: May 2019

Bacterial wilt caused by the bacterial pathogen Ralstonia solanacearum is one of the most devastating crop diseases worldwide. The molecular mechanisms controlling the early stage of R. solanacearum colonization in the root remain unknown. Aiming to better understand the mechanism of the establishment of R. solanacearum infection in root, we established four stages in the early interaction of the pathogen with Arabidopsis roots and determined the transcriptional profiles of these stages of infection. A total 2,698 genes were identified as differentially expressed genes during the initial 96 h after infection, with the majority of changes in gene expression occurring after pathogen-triggered root-hair development observed. Further analysis of differentially expressed genes indicated sequential activation of multiple hormone signaling cascades, including abscisic acid (ABA), auxin, jasmonic acid, and ethylene. Simultaneous impairment of ABA receptor genes promoted plant wilting symptoms after R. solanacearum infection but did not affect primary root growth inhibition or root-hair and lateral root formation caused by R. solanacearum. This indicated that ABA signaling positively regulates root defense to R. solanacearum. Moreover, transcriptional changes of genes involved in primary root, lateral root, and root-hair formation exhibited high temporal dynamics upon infection. Taken together, our results suggest that successful infection of R. solanacearum on roots is a highly programmed process involving in hormone crosstalk.
A Molecular Assay Allows the Simultaneous Detection of 12 Fungi Causing Fruit Rot in Cranberry
Authors: Conti Matteo , Cinget Benjamin , Vivancos Julien , Oudemans Peter , Bélanger Richard R.
Published: May 2019

Cranberry fruit rot (CFR) is arguably one of the most limiting factors of cranberry (Vaccinium macrocarpon) production throughout its growing areas. The disease is caused by a group of closely related fungi that require identification using long and cumbersome steps of isolation and microscopic observations of structural features. The objective of this study was to develop a molecular assay to simultaneously detect and discriminate 12 of the most important fungal species reported to be pathogenic on cranberry fruit to facilitate the diagnosis of CFR. As the first approach, internal transcribed spacers and large subunit regions of all fungi were sequenced and confirmed with sequences available in the NCBI database. These data were used to develop primers able to differentiate seven of the 12 species. The five remaining species, including three in the Phacidiaceae family and two in the Glomerellaceae family, were differentiated on the basis of a more discriminant marker, the translation elongation factor 1-α. Two PCR reactions were optimized to clearly delineate the 12 species. The multiplex test was first validated using pure fungal cultures; it was subsequently validated using fruit collected in cranberry beds in eastern Canada. In the latter case, the test was rigorous enough to clearly discriminate the fungal pathogens from contaminants. Within the tested samples, Physalospora vaccinii and Coleophoma empetri were most commonly found. This molecular test offers scientists, diagnosticians, and growers a powerful tool that can rapidly and precisely identify fungi causing CFR so they can implement appropriate control methods.
CE: Original Research: Errors in Postoperative Administration of Intravenous Patient-Controlled Analgesia: A Retrospective Study
Authors: Lee Yoonyoung , Kim Kisook , Kim Myounghee
Published: May 2019

Background: Intravenous patient-controlled analgesia (IV PCA), which typically involves opioids, has become widely used in clinical settings as an effective method of pain management. Identifying errors in the administration of these drugs is essential to improving patient outcomes. This study sought to describe and analyze the errors associated with postoperative IV PCA.

Methods: Relevant data were collected from the medical records of all patients who received IV PCA at a large academic medical center in South Korea during a three-year period. The study sample comprised 45,104 patients who used one of four types of IV PCA delivery devices.

Results: Errors occurred in 406 cases (0.9%). Operator error was the most common type of error (54.7%), followed by device malfunction (32.3%), prescription error (12.3%), and patient error (0.7%). Of the 222 operator errors, the most frequent type was failure to begin IV PCA drug administration (28.8%), followed by programming errors by non-anesthesia providers who weren't authorized to program the device (24.8%) and wrong infusion rates set by anesthesia providers who were so authorized (24.8%).

Conclusions: The findings provide valuable information that can aid in the development of policy and procedures for safer, more effective postoperative administration of IV PCA. They also suggest that it's necessary not only to improve the operation of acute pain services teams, but also to ensure ongoing provider and patient education specific to IV PCA use.
Implantable Pumps Require Specific Medications To Prevent Pump Failure And Risks To Patient Safety
Authors: Aschenbrenner Diane S.
Published: May 2019

The Food and Drug Administration has issued a Safety Communication regarding implantable pumps used for drug administration and the risks of using medications not approved for use with the pumps to treat or manage pain.

Nurses who work with patients receiving intrathecal delivery of pain medication via an implantable pump are urged to carefully read the pump's labeling to identify which medications are approved for use with the pump.
Examining human–carnivore interactions using a socio-ecological framework: sympatric wild canids in India as a case study
Authors: Srivathsa Arjun , Puri Mahi , Karanth Krithi K. , Patel Imran , Kumar N. Samba
Published: May 2019

Many carnivores inhabit human-dominated landscapes outside protected reserves. Spatially explicit assessments of carnivore distributions and livestock depredation patterns in human-use landscapes are crucial for minimizing negative interactions and fostering coexistence between people and predators. India harbours 23% of the world's carnivore species that share space with 1.3 billion people in approximately 2.3% of the global land area. We examined carnivore distributions and human–carnivore interactions in a multi-use forest landscape in central India. We focused on five sympatric carnivore species: Indian grey wolfCanis lupus pallipes, dholeCuon alpinus, Indian jackalCanis aureus indicus, Indian foxVulpes bengalensisand striped hyenaHyaena hyaena. Carnivore occupancy ranged from 12% for dholes to 86% for jackals, mostly influenced by forests, open scrublands and terrain ruggedness. Livestock/poultry depredation probability in the landscape ranged from 21% for dholes to greater than 95% for jackals, influenced by land cover and livestock- or poultry-holding. The five species also showed high spatial overlap with free-ranging dogs, suggesting potential competitive interactions and disease risks, with consequences for human health and safety. Our study provides insights on factors that facilitate and impede co-occurrence between people and predators. Spatial prioritization of carnivore-rich areas and conflict-prone locations could facilitate human–carnivore coexistence in shared habitats. Our framework is ideally suited for making socio-ecological assessments of human–carnivore interactions in other multi-use landscapes and regions, worldwide.
Functional amyloids promote retention of public goods in bacteria
Authors: Bruce John B. , West Stuart A. , Griffin Ashleigh S.
Published: May 2019

The growth and virulence of bacteria depends upon a number of factors that are secreted into the environment. These factors can diffuse away from the producing cells, to be either lost or used by cells that do not produce them (cheats). Mechanisms that act to reduce the loss of secreted factors through diffusion are expected to be favoured. One such mechanism may be the production of Fap fibrils, needle-like fibres on the cell surface observed inP. aeruginosa, which can transiently bind several secreted metabolites produced by cells. We test whether Fap fibrils help retain a secreted factor, the iron-scavenging molecule pyoverdine, and hence reduce the potential for exploitation by non-producing, cheating cells. We found that: (i) wild-type cells retain more iron-chelating metabolites than fibril non-producers; (ii) purified Fap fibrils can prevent the loss of the iron-chelators PQS (Pseudomonasquinolone signal) and pyoverdine; and (iii) pyoverdine non-producers have higher fitness in competition with fibril non-producers than with wild-type cells. Our results suggest that by limiting the loss of a costly public good, Fap fibrils may play an important role in stabilizing cooperative production of secreted factors.
Testosterone reduces the threat premium in competitive resource division
Authors: Geniole Shawn N. , Proietti Valentina , Bird Brian M. , Ortiz Triana L. , Bonin Pierre L. , Goldfarb Bernard , Watson Neil V. , Carré Justin M.
Published: May 2019

Like other animals, humans are sensitive to facial cues of threat. Recent evidence suggests that we use this information to dynamically calibrate competitive decision-making over resources, ceding more to high-threat individuals (who appear more willing/able to retaliate) and keeping more from low-threat individuals. Little is known, however, about the biological factors that support such threat assessment and decision-making systems. In a pre-registered, double-blind, placebo-controlled, cross-over testosterone administration study (
n
= 118 men), we show for the first time that testosterone reduces the effects of threat on decision-making: participants ceded more resources to high-threat (versus low-threat) individuals (replicating the ‘threat premium’), but this effect was blunted by testosterone, which selectively reduced the amount of resources ceded to those highest in threat. Thus, our findings suggest that testosterone influences competitive decision-making by recalibrating the integration of threat into the decision-making process.
Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in a Neocortical Microcircuit
Authors: Barros-Zulaica N , Rahmon J , Chindemi G , Perin R , Markram H , Ramaswamy S , Muller E
Published: May 2019

Previous studies based on the ‘Quantal Model’ for synaptic transmission suggested that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis and indicate that multi-vesicular release (MVR) could better explain the synaptic response variability observed in vitro. In this study we present a novel method to estimate the number of release sites per synapse, also known as the size of the readily-releasable pool (NRRP), from paired whole-cell recordings of layer 5 thick tufted pyramidal cell (L5_TTPC) connections in the somatosensory neocortex. Our approach extends the work of Loebel and colleagues to take advantage of a recently reported data-driven biophysical model of neocortical tissue. Using this approach, we estimated NRRP to be between two to three for connections between L5-TTPC. To constrain NRRP values for other connections in the microcircuit, we developed and validated a generalization approach using data on post-synaptic potential (PSP) coefficient of variations (CVs) from literature and matching to in silico experiments. Our study shows that synaptic connections in the neocortex generally are mediated by MVR and provides a data-driven approach to constrain the MVR model parameters of the microcircuit.
eIF3 associates with 80S ribosomes to promote translation elongation, mitochondrial homeostasis, and muscle health
Authors: Lin Yingying , Li Fajin , Huang Linlu , Duan Haoran , Fang Jianhuo , Sun Li , Xing Xudong , Tian Guiyou , Cheng Yabin , Yang Xuerui , Wolf Dieter A.
Published: May 2019

eIF3 is a multi-subunit complex with numerous functions in canonical translation initiation. eIF3 was also found to interact with 40S and 60S ribosomal proteins and translation elongation factors, but a direct involvement in translation elongation has never been demonstrated. We found that eIF3 deficiency reduced early ribosomal elongation speed between codons 25 and 75 on a set of ∼2,700 mRNAs encoding proteins associated with mitochondrial and membrane functions, resulting in defective synthesis of their encoded proteins. To promote elongation, eIF3 interacts with 80S ribosomes translating the first ∼60 codons and serves to recruit protein quality control factors, functions required for normal mitochondrial physiology. Accordingly, eIF3e+/-mice accumulate defective mitochondria in skeletal muscle and show a progressive decline in muscle strength. Hence, eIF3 interacts with 80S ribosomes to enhance, at the level of early elongation, the synthesis of proteins with membrane-associated functions, an activity that is critical for mitochondrial physiology and muscle health.
Biomass, abundances, and abundance and geographical range size relationship of birds along a rainforest elevational gradient in Papua New Guinea
Authors: Sam Katerina , Koane Bonny
Published: May 2019

The usually positive inter-specific relationship between geographical range size and the abundance of local bird populations comes with exceptions. On continents, the majority of these exceptions have been described from tropical montane areas in Africa, where geographically-restricted bird species are unusually abundant. We asked how the local abundances of passerine and non-passerine bird species along an elevational gradient on Mt. Wilhelm, Papua New Guinea relate to their geographical range size. We collected data on bird assemblages at eight elevations (200 – 3,700 m, at 500 m elevational increments). We used a standardized point-counts at 16 points at each elevational study site. We partitioned the birds into feeding guilds, and we obtained data on geographical range sizes from Bird-Life International data zone. We observed a positive relationship between abundance and geographical range size in the lowlands. This trend changed to a negative one towards higher elevations. The total abundances of the assemblage showed a hump-shaped pattern along the elevational gradient, with passerine birds, namely passerine insectivores, driving the observed pattern. In contrast to abundances, the mean biomass of the bird assemblages decreased with increasing elevation. Our results show that montane bird species maintain dense populations which compensate for the decreased available area near the top of the mountain.
Translational regulation of protrusion-localized RNAs involves silencing and clustering after transport
Authors: Moissoglu Konstadinos , Yasuda Kyota , Wang Tianhong , Chrisafis George , Mili Stavroula
Published: May 2019

Localization of RNAs to various subcellular destinations is a widely used mechanism that regulates a large proportion of transcripts in polarized cells. In many cases, such localized transcripts mediate spatial control of gene expression by being translationally silent while in transit and locally activated at their destination. Here, we investigate the translation of RNAs localized at dynamic cellular protrusions of human and mouse, migrating, mesenchymal cells. In contrast to the model described above, we find that protrusion-localized RNAs are not locally activated solely at protrusions, but can be translated with similar efficiency in both internal and peripheral locations. Interestingly, protrusion-localized RNAs are translated at extending protrusions, they become translationally silenced in retracting protrusions and this silencing is accompanied by coalescence of single RNAs into larger heterogeneous RNA clusters. This work describes a distinct mode of translational regulation of localized RNAs, which we propose is used to regulate protein activities during dynamic cellular responses.
Identification of a Mitofusin specificity region that confers unique activities to Mfn1 and Mfn2
Authors: Sloat SR , Whitley BN , Engelhart EA , Hoppins S
Published: May 2019

Mitochondrial structure can be maintained at steady state or modified in response to changes in cellular physiology. This is achieved by the coordinated regulation of dynamic properties including mitochondrial fusion, division and transport. Disease states, including neurodegeneration, are associated with defects in these processes. In vertebrates, two Mitofusin paralogs, Mfn1 and Mfn2, are required for efficient mitochondrial fusion. The Mitofusins share a high degree of homology and have very similar domain architecture, including an amino terminal GTPase domain and two extended helical bundles that are connected by flexible regions. Mfn1 and Mfn2 are non-redundant and are both required for mitochondrial outer membrane fusion. However, the molecular features that make these proteins functionally distinct are poorly defined. By engineering chimeric proteins composed of Mfn1 and Mfn2, we discovered a region that contributes to isoform-specific function (Mitofusin IsoformSpecificRegion – MISR). MISR confers unique fusion activity and Mitofusin specific nucleotide-dependent assembly properties. We propose that MISR functions in higher order oligomerization either directly, as an interaction interface, or indirectly through conformational changes.
Dock5 is a new regulator of microtubule dynamic instability through GSK3β inhibition in osteoclasts
Authors: Guimbal Sarah , Guérit David , Chardon Manon , Blangy Anne , Vives Virginie
Published: May 2019

Background information

Osteoclast resorption is dependent on a podosome-rich structure, called sealing zone, which is stabilized by acetylated microtubules. It tightly attaches the osteoclast to the bone creating a favorable acidic microenvironment for bone degradation. We already established that Rac activation by Dock5 is necessary for osteoclast resorption. Indeed, inhibition of Dock5 in osteoclasts results in Rac1 decreased activity associated to impaired podosome assembly into sealing zones and resorbing activity.

Results

In this report, we show that Dock5 knockout osteoclasts also present a reduced acetylated tubulin level leading to a decreased length and duration of microtubule growth phases whereas their growth speed remains unaffected. Dock5 does not act by direct interaction with the polymerized tubulin but through inhibition of the microtubules destabilizing kinase GSK3β downstream of Akt activation. Interestingly, we ruled out the implication of Rac1 in this process using specific inhibitors.

Conclusion

Our data involve Dock5 as a new regulator of microtubule dynamic instability in osteoclast.

Significance

The fact that Dock5 is a regulator of both actin cytoskeleton and microtubule dynamics makes it an interesting therapeutic target for osteolytic pathologies because of its dual role on sealing zone formation and stabilization.
SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events
Authors: Bergstrom Erik N. , Huang Mi Ni , Mahto Uma , Barnes Mark , Stratton Michael R. , Rozen Steven G. , Alexandrov Ludmil B.
Published: May 2019

Background

Cancer genomes are peppered with somatic mutations imprinted by different mutational processes. The mutational pattern of a cancer genome can be used to identify and understand the etiology of the underlying mutational processes. A plethora of prior research has focused on examining mutational signatures and mutational patterns from single base substitutions and their immediate sequencing context. We recently demonstrated that further classification of small mutational events (including substitutions, insertions, deletions, and doublet substitutions) can be used to provide a deeper understanding of the mutational processes that have molded a cancer genome. However, there has been no standard tool that allows fast, accurate, and comprehensive classification for all types of small mutational events

Results

Here, we present SigProfilerMatrixGenerator, a computational tool designed for optimized exploration and visualization of mutational patterns for all types of small mutational events. SigProfilerMatrixGenerator is written in Python with an R wrapper package provided for users that prefer working in an R environment. SigProfilerMatrixGenerator produces fourteen distinct matrices by considering transcriptional strand bias of individual events and by incorporating distinct classifications for single base substitutions, doublet base substitutions, and small insertions and deletions. While the tool provides a comprehensive classification of mutations, SigProfilerMatrixGenerator is also faster and more memory efficient than existing tools that generate only a single matrix.

Conclusions

SigProfilerMatrixGenerator provides a standardized method for classifying small mutational events that is both efficient and scalable to large datasets. In addition to extending the classification of single base substitutions, the tool is the first to provide support for classifying doublet base substitutions and small insertions and deletions. SigProfilerMatrixGenerator is freely available athttps://github.com/AlexandrovLab/SigProfilerMatrixGeneratorwith an extensive documentation athttps://osf.io/s93d5/wiki/home/.
A novel effect of the antigenic peptides position for presentation upon MHC class I
Authors: Imai Jun , Otani Mayu , Koike Eri , Yokoyama Yuuki , Maruya Mikako , Koyasu Shigeo , Sakai Takahiro
Published: May 2019

MHC-I molecules are expressed on the cell surface complexed with oligopeptides, most of which are generated from intracellular proteins by the ubiquitin-proteasome pathways and would be roughly proportional to the relative abundance of proteins and their rate of degradation. Thus MHC-I together with peptides function as immunological self-markers to exhibit the information about the repertoire of proteins expressed in a given cell to the immune system, and this process is called antigen (Ag) direct-presentation. Herein, we report a novel rule for the preference of peptides selected for the direct presentation; the N-terminally located antigenic peptides are more efficiently complexed with MHC-I than the C-terminally located peptides on the same protein. The superiority is largely dependent uponde novoproteins synthesis, degradation by proteasomes, and less dependent upon stabilities of proteins, indicating that this difference derived from rapidly degraded newly synthesized proteins such as defective ribosomal products (DRiPs). The effects of those N-terminal predominance was comparable with the enhanced MHC-I presentation by IFN-γ suggesting that they might play important roles in the adaptive immunity.
Extra-cellular matrix induced by steroids through a G-protein coupled receptor in a Drosophila model of renal fibrosis
Authors: Zheng Wenjing , Ocorr Karen , Tatar Marc
Published: May 2019

Aldosterone is produced by the mammalian adrenal cortex to modulate blood pressure and fluid balance, however excessive, prolonged aldosterone production promotes fibrosis and kidney failure. How aldosterone triggers disease may involve actions that are independent of its canonical mineralocorticoid receptor. Here we present aDrosophilamodel of renal pathology caused by excess extra-cellular matrix formation, stimulated by exogenous aldosterone and insect ecdysone steroids. Chronic administration of aldosterone or ecdysone induces expression and accumulation of collagen-like pericardin at adult nephrocytes – podocyte-like cells that filter circulating hemolymph. Excess pericardin deposition disrupts nephrocyte (glomerular) filtration and causes proteinuria in Drosophila, hallmarks of mammalian kidney failure. Steroid-induced pericardin arises from cardiomyocytes associated with nephrocytes, reflecting an analogous role of mammalian myofibroblasts in fibrotic disease. Remarkably, the canonical ecdysteroid nuclear hormone receptor, ecdysone receptor EcR, is not required for aldosterone or ecdysone to stimulate pericardin production or associated renal pathology. Instead, these hormones require a cardiomyocyte-associated G-protein coupled receptor, dopamine-EcR (dopEcR), a membrane-associated receptor previously characterized in the fly brain as affecting behavior. ThisDrosophilarenal disease model reveals a novel signaling pathway through which steroids may potentially modulate human fibrosis through proposed orthologs of dopEcR.

Significance Statement

Aldosterone regulates salt and fluid homeostasis, yet excess aldosterone contributes to renal fibrosis. Aldosterone acts through a nuclear hormone receptor, but an elusive, G-protein coupled receptor (GPCR) is thought to also mediate the hormone’s pathology. Here we introduce a Drosophila model of renal fibrosis. Flies treated with human aldosterone produce excess extra-cellular matrix and that causes kidney pathology. Flies treated with the insect steroid ecdysone produce similar pathology, and from this analogous response we identify an alternative receptor through which steroids mediate renal fibrosis -- the GPCR dopamine-Ecdysone Receptor (dopEcR). dopEcR functions in heart muscle cells associated with nephrocytes, analogous to the role of myofibroblasts in human fibrosis. This finding opens avenues to identify mammalian GPCR homologs of dopEcR through which aldosterone mediates renal fibrosis.
Hydrogel platform for in vitro three-dimensional assembly of human stem cell-derived β cells and endothelial cells
Authors: Augsornworawat Punn , Velazco-Cruz Leonardo , Song Jiwon , Millman Jeffrey R.
Published: May 2019

Differentiation of stem cells into functional replacement cells and tissues is a major goal of the regenerative medicine field. However, one limitation has been organization of differentiated cells into multi-cellular, three-dimensional assemblies. The islets of Langerhans contain many endocrine and non-endocrine cell types, such as insulin-producing β cells and endothelial cells. Transplantation of exogenous islets into diabetic patients can serve as a cell replacement therapy, replacing the need for patients to inject themselves with insulin, but the number of available islets from cadaveric donors is low. We have developed a strategy of assembling human embryonic stem cell-derived β cells with endothelial cells into three-dimensional aggregates on a hydrogel. The resulting islet organoids express β cell markers and are functional, capable of undergoing glucose-stimulated insulin secretion. These results provide a platform for evaluating the effects of the islet tissue microenvironment on human embryonic stem cell-derived β cells and other islet endocrine cells to develop tissue engineered islets.