bluuebunny/crossref_metadata_2025 huggingface dataset:
Building protoplanetary disks from the molecular cloud: redefining the disk timeline
Authors: Baillié K. , Marques J. , Piau L.
Published: March 2019

Context. Planetary formation models are necessary to understand the characteristics of the planets that are the most likely to survive. Their dynamics, their composition and even the probability of their survival depend on the environment in which they form. We therefore investigate the most favorable locations for planetary embryos to accumulate in the protoplanetary disk: the planet traps.

Aims. We study the formation of the protoplanetary disk by the collapse of a primordial molecular cloud, and how its evolution leads to the selection of specific types of planets.

Methods. We use a hydrodynamical code that accounts for the dynamics, thermodynamics, geometry and composition of the disk to numerically model its evolution as it is fed by the infalling cloud material. As the mass accretion rate of the disk onto the star determines its growth, we can calculate the stellar characteristics by interpolating its radius, luminosity and temperature over the stellar mass from pre-calculated stellar evolution models. The density and midplane temperature of the disk then allow us to model the interactions between the disk and potential planets and determine their migration.

Results. At the end of the collapse phase, when the disk reaches its maximum mass, it pursues its viscous spreading, similarly to the evolution from a minimum mass solar nebula (MMSN). In addition, we establish a timeline equivalence between the MMSN and a “collapse-formed disk” that would be older by about 2 Myr.

Conclusions. We can save various types of planets from a fatal type-I inward migration: in particular, planetary embryos can avoid falling on the star by becoming trapped at the heat transition barriers and at most sublimation lines (except the silicates one). One of the novelties concerns the possible trapping of putative giant planets around a few astronomical units from the star around the end of the infall. Moreover, trapped planets may still follow the traps outward during the collapse phase and inward after it. Finally, this protoplanetary disk formation model shows the early possibilities of trapping planetary embryos at disk stages that are anterior by a few million years to the initial state of the MMSN approximation.
Astrophysical detections and databases for the mono deuterated species of acetaldehyde CH2DCOH and CH3COD
Authors: Coudert L. H. , Margulès L. , Vastel C. , Motiyenko R. , Caux E. , Guillemin J.-C.
Published: March 2019

Context. Detection of deuterated species may provide information on the evolving chemistry in the earliest phases of star-forming regions. For molecules with two isomeric forms of the same isotopic variant, gas-phase and solid-state formation pathways can be differentiated using their abundance ratio.

Aims. Spectroscopic databases for astrophysical purposes are built for the two mono deuterated isomeric species CH2DCOH and CH3COD of the complex organic molecule acetaldehyde. These databases can be used to search and detect these two species in astrophysical surveys, retrieving their column density and therefore abundances.

Methods. Submillimeter wave and terahertz transitions were measured for mono deuterated acetaldehyde CH2DCOH which is a non-rigid species displaying internal rotation of its asymmetrical CH2D methyl group. An analysis of a dataset consisting of previously measured microwave data and the newly measured transition was carried out with a model accounting for the large amplitude torsion.

Results. The frequencies of 2556 transitions are reproduced with a unitless standard deviation of 2.3 yielding various spectroscopic constants. Spectroscopic databases for astrophysical purposes were built for CH2DCOH using the results of the present analysis and for CH3COD using the results of a previous spectroscopic investigation. These two species were both searched for and are detected toward a low-mass star-forming region.

Conclusions. We report the first detection of CH2DCOH (93 transitions) and the detection of CH3COD (43 transitions) species in source B of the IRAS 16293−2422 young stellar binary system located in the ρ Ophiuchus cloud region, using the publicly available ALMA Protostellar Interferometric Line Survey.
Management of Pathologic Fractures Around the Hip: Part 2–Acetabulum
Authors: Auran Richard L. , Duran Michael D. , de Comas Amalia M. , Jacofsky David J.
Published: March 2019

Metastatic disease to the periacetabular region of the pelvis is a complex and challenging problem to treat. Similar to the proximal femur, this area of the skeleton has a high proportion of involvement when primary tumors metastasize to bone. Surgical intervention to treat this patient population is significantly more difficult than treating lesions of the proximal femur. There tends to be higher rates of intraoperative blood loss and postoperative complications, as well as poorer prognoses. It is important for the operating surgeon to evaluate the patient's medical status using a multidisciplinary approach and fully understand their prognosis before planning and performing surgical intervention. Given the complex nature of these surgeries, they are best performed by orthopaedic oncologists or experienced revision arthroplasty specialists. The clinical evaluation, workup, and perioperative adjuncts to treatment for periacetabular metastatic disease are similar to those for disease of the proximal femur as discussed in part 1 of this article series. This review focuses on aspects specific to acetabular disease and surgical intervention in these patients.
An Unusual Case of Infantile Spasms Due to a Pathogenic Variant in the MECP2 Gene
Authors: Charkhand Behshad , Liu Natarie , Barrett Karlene T. , Al-Hertani Walla , Scantlebury Morris H.
Published: March 2019

The infantile spasms (IS) syndrome is a developmental epileptic encephalopathy disorder characterized by epileptic spasms occurring in infancy, hypsarrhythmia on the electroencephalography (EEG) and developmental arrest or regression. The etiologies include structural, metabolic, and genetic causes. We report an unusual case of IS due to a de novo variant in the MECP2 gene. The patient also had variants of uncertain significance in the SCN9A and SCN5A genes inherited from the father and mother, respectively. This report highlights the need for broad genetic testing in MECP2-related disorders with atypical presentations to better understand the disease etiology.
Immunization of Vγ2Vδ2 T cells programs sustained effector memory responses that control tuberculosis in nonhuman primates
Authors: Shen Ling , Frencher James , Huang Dan , Wang Wandang , Yang Enzhuo , Chen Crystal Y. , Zhang Zhuoran , Wang Richard , Qaqish Arwa , Larsen Michelle H. , Shen Hongbo , Porcelli Steven A. , Jacobs William R. , Chen Zheng W.
Published: March 2019

Significance

Despite the urgent need for a better tuberculosis (TB) vaccine, relevant protective mechanisms remain unknown. We previously defined protective phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP)–specific Vγ2Vδ2 T cells as a unique subset in primates, and, here, we immunized them selectively for protection against TB. A single respiratory vaccination of macaques with attenuated HMBPP-producing
Listeria monocytogenes
(Lm
ΔactA prfA
*), but not an HMBPP-lacking
ΔgcpE Listeria
strain, expanded Vγ2Vδ2 T cells, elicited Th1-like Vγ2Vδ2 T cell responses, and reduced TB infection/pathology after moderate-dose TB challenge. Such protection correlated with rapid memory-like, Th1-like Vγ2Vδ2 T cell responses, the presence of tissue-resident Vγ2Vδ2 T effectors coproducing IFN-γ/perforin and inhibiting intracellular
Mycobacterium tuberculosis
growth, and enhanced CD4
+
/CD8
+
T cell responses. These findings establish a concept incorporating immunization of human Vγ2Vδ2 T cells for TB vaccine development.
Mechanisms for achieving high speed and efficiency in biomolecular machines
Authors: Wagoner Jason A. , Dill Ken A.
Published: March 2019

Significance

Molecular machines are cellular proteins that transduce energy. They can convert energy to motion, recharge ATP stores by harnessing ion flows, and pump ions energetically uphill. Molecular machines are able to be both fast and efficient at the same time. How do they achieve high speeds at high efficiency? Here we explore mechanisms of evolution or synthetic design that can optimize these properties, such as a conformationally driven mechanical step, which varies the conformational free-energy landscape to mitigate large kinetic barriers, and mechanical substeps, which split one large kinetic barrier into multiple smaller ones.
Regulation of T cell expansion by antigen presentation dynamics
Authors: Mayer Andreas , Zhang Yaojun , Perelson Alan S. , Wingreen Ned S.
Published: March 2019

Significance

Antigen-specific T cells proliferate multiple times during an immune reaction to fight against disease. This expansion of T cells must be carefully regulated to ensure an effective defense while avoiding autoimmunity. One challenge to regulation is that the initial size of antigen-specific T cell clones can be quite variable. Intriguingly, a recent study in mice found that the fold expansion of a T cell clone depends as an inverse power law on its initial size. We propose a simple mathematical model that naturally yields the observed power law relation. Our model accounts for multiple experiments on T cell proliferation, suggests optimal vaccination protocols, and highlights dynamics of presented antigen as a key regulator of the size of an immune response.
Array atomic force microscopy for real-time multiparametric analysis
Authors: Yang Qingqing , Ma Qian , Herum Kate M. , Wang Chonghe , Patel Nirav , Lee Joon , Wang Shanshan , Yen Tony M. , Wang Jun , Tang Hanmei , Lo Yu-Hwa , Head Brian P. , Azam Farooq , Xu Sheng , Cauwenberghs Gert , McCulloch Andrew D. , John Scott , Liu Zhaowei , Lal Ratnesh
Published: March 2019

Significance

High-resolution multipoint simultaneous structure–function analysis is becoming of great interest in a broad spectrum of fields for deciphering multiscale dynamics, especially in biophysics and materials science. However, current techniques are limited in terms of versatility, resolution, throughput, and biocompatibility. Here, a multifunctional imaging platform is introduced that shows high sensitivity, minimum cross-talk, and a variety of probe-based sensing. This is demonstrated by parallel multiparametric studies in air and liquid, including mechanical wave propagation in a soft polymer film, imaging of live neurons, and cooperative activities of living coupled cardiac muscle cells. As an experimental demonstration of array atomic force microscopy for multiparametric analysis in dynamic systems this work sheds light on the study of emergent properties in wide-ranging fields.
Antibiotic treatment affects the expression levels of copper transporters and the isotopic composition of copper in the colon of mice
Authors: Miller Kerri A. , Vicentini Fernando A. , Hirota Simon A. , Sharkey Keith A. , Wieser Michael E.
Published: March 2019

Significance

Isotopic analysis has the ability to detect changes in metal homeostasis in vivo. Using this advanced technique to investigate metal metabolism, we identified a significant change in copper processing in the gut of mice with depleted gut microbiota. In addition, we observed changes in the expression of copper transporters in the colon. The role of intestinal microbiota in copper processing in the gastrointestinal tract was previously unknown. Using the unique ability of isotopic analyses to detect changes in metal processing has enabled the identification of the intestinal microbiota as a significant influence on copper metabolism in the gut.
Discovery of novel carbohydrate-active enzymes through the rational exploration of the protein sequences space
Authors: Helbert William , Poulet Laurent , Drouillard Sophie , Mathieu Sophie , Loiodice Mélanie , Couturier Marie , Lombard Vincent , Terrapon Nicolas , Turchetto Jeremy , Vincentelli Renaud , Henrissat Bernard
Published: March 2019

Significance

In the context of genome and metagenome sequencing, the assignment of function to sequences is a serious issue. In the case of enzymes of strong substrate specificity, such as those involved in the breakdown of polysaccharides (e.g., glycoside hydrolases and polysaccharide lyases), assignments become unreliable when sequence similarity to experimentally studied enzymes is low. To better explore the sequence-to-function relationships of these enzymes, we successfully applied a strategy based on a rational bioinformatic selection of enzyme targets, synthetic gene synthesis, and screening of recombinant proteins on a wide diversity of carbohydrate substrates. Seventy-nine of our 564 targets exhibited enzymatic activity, including three activities that have not been described previously, and 13 novel enzyme families could be defined.
Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon
Authors: Xia Chuanwu , Fu Zhuji , Battaile Kevin P. , Kim Jung-Ja P.
Published: March 2019

Membrane-bound mitochondrial trifunctional protein (TFP) catalyzes β-oxidation of long chain fatty acyl-CoAs, employing 2-enoyl-CoA hydratase (ECH), 3-hydroxyl-CoA dehydrogenase (HAD), and 3-ketothiolase (KT) activities consecutively. Inherited deficiency of TFP is a recessive genetic disease, manifesting in hypoketotic hypoglycemia, cardiomyopathy, and sudden death. We have determined the crystal structure of human TFP at 3.6-Å resolution. The biological unit of the protein is α
2
β
2
. The overall structure of the heterotetramer is the same as that observed by cryo-EM methods. The two β-subunits make a tightly bound homodimer at the center, and two α-subunits are bound to each side of the β
2
dimer, creating an arc, which binds on its concave side to the mitochondrial innermembrane. The catalytic residues in all three active sites are arranged similarly to those of the corresponding, soluble monofunctional enzymes. A structure-based, substrate channeling pathway from the ECH active site to the HAD and KT sites is proposed. The passage from the ECH site to the HAD site is similar to those found in the two bacterial TFPs. However, the passage from the HAD site to the KT site is unique in that the acyl-CoA intermediate can be transferred between the two sites by passing along the mitochondrial inner membrane using the hydrophobic nature of the acyl chain. The 3′-AMP-PPi moiety is guided by the positively charged residues located along the “ceiling” of the channel, suggesting that membrane integrity is an essential part of the channel and is required for the activity of the enzyme.
Cell-free gene-regulatory network engineering with synthetic transcription factors
Authors: Swank Zoe , Laohakunakorn Nadanai , Maerkl Sebastian J.
Published: March 2019

Gene-regulatory networks are ubiquitous in nature and critical for bottom-up engineering of synthetic networks. Transcriptional repression is a fundamental function that can be tuned at the level of DNA, protein, and cooperative protein–protein interactions, necessitating high-throughput experimental approaches for in-depth characterization. Here, we used a cell-free system in combination with a high-throughput microfluidic device to comprehensively study the different tuning mechanisms of a synthetic zinc-finger repressor library, whose affinity and cooperativity can be rationally engineered. The device is integrated into a comprehensive workflow that includes determination of transcription-factor binding-energy landscapes and mechanistic modeling, enabling us to generate a library of well-characterized synthetic transcription factors and corresponding promoters, which we then used to build gene-regulatory networks de novo. The well-characterized synthetic parts and insights gained should be useful for rationally engineering gene-regulatory networks and for studying the biophysics of transcriptional regulation.
Mitochondrial UPR repression during
Pseudomonas aeruginosa
infection requires the bZIP protein ZIP-3
Authors: Deng Pan , Uma Naresh Nandhitha , Du Yunguang , Lamech Lilian T. , Yu Jun , Zhu Lihua Julie , Pukkila-Worley Read , Haynes Cole M.
Published: March 2019

Mitochondria generate most cellular energy and are targeted by multiple pathogens during infection. In turn, metazoans employ surveillance mechanisms such as the mitochondrial unfolded protein response (UPR
mt
) to detect and respond to mitochondrial dysfunction as an indicator of infection. The UPR
mt
is an adaptive transcriptional program regulated by the transcription factor ATFS-1, which induces genes that promote mitochondrial recovery and innate immunity. The bacterial pathogen
Pseudomonas aeruginosa
produces toxins that disrupt oxidative phosphorylation (OXPHOS), resulting in UPR
mt
activation. Here, we demonstrate that
Pseudomonas aeruginosa
exploits an intrinsic negative regulatory mechanism mediated by the
Caenorhabditis elegans
bZIP protein ZIP-3 to repress UPR
mt
activation. Strikingly, worms lacking
zip-3
were impervious to
Pseudomonas aeruginosa
-mediated UPR
mt
repression and resistant to infection. Pathogen-secreted phenazines perturbed mitochondrial function and were the primary cause of UPR
mt
activation, consistent with these molecules being electron shuttles and virulence determinants. Surprisingly,
Pseudomonas aeruginosa
unable to produce phenazines and thus elicit UPR
mt
activation were hypertoxic in
zip-3
–deletion worms. These data emphasize the significance of virulence-mediated UPR
mt
repression and the potency of the UPR
mt
as an antibacterial response.
Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer’s-associated amyloid beta peptide
Authors: Cater Jordan H. , Kumita Janet R. , Zeineddine Abdallah Rafaa , Zhao Guomao , Bernardo-Gancedo Ana , Henry Amanda , Winata Wendy , Chi Mengna , Grenyer Brin S. F. , Townsend Michelle L. , Ranson Marie , Buhimschi Catalin S. , Charnock-Jones D. Stephen , Dobson Christopher M. , Wilson Mark R. , Buhimschi Irina A. , Wyatt Amy R.
Published: March 2019

Significance

Pregnancy is a unique physiological state involving biological stresses that promote protein damage (misfolding) within the maternal body. Currently, little is known regarding how the maternal body copes with elevated protein misfolding in pregnancy. This is important, because the accumulation of misfolded proteins underlies many human disorders, including preeclampsia, a serious complication of pregnancy. In this study, we show that pregnancy zone protein (PZP) efficiently inhibits the aggregation of misfolded proteins, including the amyloid beta peptide, which forms plaques in preeclampsia and in Alzheimer’s disease. We propose that up-regulation of PZP is a major maternal adaptation that helps to maintain protein homeostasis during pregnancy. Moreover, pregnancy-independent up-regulation of PZP indicates that its chaperone function could be broadly important in humans.
Organic enantiomeric high-
T
c
ferroelectrics
Authors: Li Peng-Fei , Liao Wei-Qiang , Tang Yuan-Yuan , Qiao Wencheng , Zhao Dewei , Ai Yong , Yao Ye-Feng , Xiong Ren-Gen
Published: March 2019

For nearly 100 y, homochiral ferroelectrics were basically multicomponent simple organic amine salts and metal coordination compounds. Single-component homochiral organic ferroelectric crystals with high-Curie temperature (
T
c
) phase transition were very rarely reported, although the first ferroelectric Rochelle salt discovered in 1920 is a homochiral metal coordination compound. Here, we report a pair of single-component organic enantiomorphic ferroelectrics, (
R
)-3-quinuclidinol and (
S
)-3-quinuclidinol, as well as the racemic mixture (
Rac
)-3-quinuclidinol. The homochiral (
R
)- and (
S
)-3-quinuclidinol crystallize in the enantiomorphic-polar point group 6 (
C
6
) at room temperature, showing mirror-image relationships in vibrational circular dichroism spectra and crystal structure. Both enantiomers exhibit 622
F
6-type ferroelectric phase transition with as high as 400 K [above that of BaTiO
3
(
T
c
= 381 K)], showing very similar ferroelectricity and related properties, including sharp step-like dielectric anomaly from 5 to 17, high saturation polarization (7 μC/cm
2
), low coercive field (15 kV/cm), and identical ferroelectric domains. Their racemic mixture (
Rac
)-3-quinuclidinol, however, adopts a centrosymmetric point group 2/
m
(
C
2h
), undergoing a nonferroelectric high-temperature phase transition. This finding reveals the enormous benefits of homochirality in designing high-
T
c
ferroelectrics, and sheds light on exploring homochiral ferroelectrics with great application.
Intracellular cargo transport by single-headed kinesin motors
Authors: Schimert Kristin I. , Budaitis Breane G. , Reinemann Dana N. , Lang Matthew J. , Verhey Kristen J.
Published: March 2019

Significance

Intracellular transport is driven by molecular motors that carry cargoes along cytoskeletal tracks. Molecular motors, such as kinesin-1, contain two motor domains so they can walk processively (take many steps per encounter) along a microtubule track. The two motor domains alternate their catalytic activities so that one of them is always attached to the track. Here we show that kinesins with one motor domain are not processive as individuals but can work collectively to drive continuous transport in cells. However, their transport is most efficient when the motor-to-cargo distance is short and the cargo imposes little load on the motor. These results lend insight into the minimal requirements for kinesin transport and the synergies gained through teamwork and coordination.
Energy conservation by a hydrogenase-dependent chemiosmotic mechanism in an ancient metabolic pathway
Authors: Schoelmerich Marie Charlotte , Müller Volker
Published: March 2019

Significance

Acetogenic bacteria are the most primordial living organisms. They can live solely on inorganic compounds by using carbon monoxide or molecular hydrogen as energy sources to fix carbon dioxide to acetate and rely on a chemiosmotic mechanism for energy conservation. Most microorganisms possess a complex respiratory chain that is composed of many different components to establish the chemiosmotic gradient. Here, we dissect the bioenergetics in a chemolithoautotrophic thermophilic acetogenic bacterium. This living fossil uses a simple respiration comprising only a hydrogenase and an ATP synthase for energy conservation. This two-module respiration system is sufficient to sustain primordial microbial life.
Online learning with an almost perfect expert
Authors: Brânzei Simina , Peres Yuval
Published: March 2019

Significance

Online learning is a prominent learning paradigm where data become available over time. The main challenge is to predict future events using past observations and any domain-specific knowledge available, such as expert advice. We study multiclass online learning, where a forecaster is choosing each day one of

d

options based on the advice of

n

experts and learns the correct choice in hindsight, incurring a unit cost for each mistake. This problem is intermediate between binary prediction and the general hedge setting, and our conceptual contribution is showing that multiclass decision making is not harder than binary decision making.
Interplay between DNA sequence and negative superhelicity drives R-loop structures
Authors: Stolz Robert , Sulthana Shaheen , Hartono Stella R. , Malig Maika , Benham Craig J. , Chedin Frederic
Published: March 2019

Significance

Three-stranded R-loop structures form during transcription when the nascent RNA transcript rehybridizes to the template DNA strand. This creates an RNA:DNA hybrid and forces the nontemplate DNA strand into a single-stranded, looped-out state. R-loops form universally over conserved hotspot regions. To date, the physicochemical bases underlying R-loop formation remain unclear. Using a “first-principle” mathematical approach backed by experimental validation, we elucidated the relative contributions of DNA sequence and DNA topology to R-loop formation. Our work provides a quantitative assessment of the energies underlying R-loop formation and of their interplay. It further reveals these structures as important regulators of the DNA topological state.
Mechanism for autoinhibition and activation of the MORC3 ATPase
Authors: Zhang Yi , Klein Brianna J. , Cox Khan L. , Bertulat Bianca , Tencer Adam H. , Holden Michael R. , Wright Gregory M. , Black Joshua , Cardoso M. Cristina , Poirier Michael G. , Kutateladze Tatiana G.
Published: March 2019

Microrchidia 3 (MORC3) is a human protein linked to autoimmune disorders, Down syndrome, and cancer. It is a member of a newly identified family of human ATPases with an uncharacterized mechanism of action. Here, we elucidate the molecular basis for inhibition and activation of MORC3. The crystal structure of the MORC3 region encompassing the ATPase and CW domains in complex with a nonhydrolyzable ATP analog demonstrates that the two domains are directly coupled. The extensive ATPase:CW interface stabilizes the protein fold but inhibits the catalytic activity of MORC3. Enzymatic, NMR, mutational, and biochemical analyses show that in the autoinhibited, off state, the CW domain sterically impedes binding of the ATPase domain to DNA, which in turn is required for the catalytic activity. MORC3 autoinhibition is released by disrupting the intramolecular ATPase:CW coupling through the competitive interaction of CW with histone H3 tail or by mutating the interfacial residues. Binding of CW to H3 leads to a marked rearrangement in the ATPase–CW cassette, which frees the DNA-binding site in active MORC3 (on state). We show that ATP-induced dimerization of the ATPase domain is strictly required for the catalytic activity and that the dimeric form of ATPase–CW might cooperatively bind to dsDNA. Together, our findings uncovered a mechanism underlying the fine-tuned regulation of the catalytic domain of MORC3 by the epigenetic reader, CW.
GSAP modulates γ-secretase specificity by inducing conformational change in PS1
Authors: Wong Eitan , Liao George P. , Chang Jerry C. , Xu Peng , Li Yue-Ming , Greengard Paul
Published: March 2019

Significance

γ-Secretase cleaves multiple transmembrane proteins, but little is known about how it controls its substrate specificity. γ-Secretase activating protein (GSAP) has been reported to differentially activate γ-secretase for APP and Notch cleavages. The mechanism by which GSAP regulates γ-secretase specificity is elusive. Here, we demonstrate that GSAP directly regulates γ-secretase activity and specificity. Furthermore, GSAP functions as a switch between two forms of γ-secretase that have different activities for APP and Notch substrates, leading to different specificities. These findings open a new avenue for drug development through targeting the specificity of modifying proteins. This work also suggests that the association of GSAP with aging, Alzheimer’s disease, and Down syndrome could be attributed to the function of GSAP in the regulation of γ-secretase.
Stretchable materials of high toughness and low hysteresis
Authors: Wang Zhengjin , Xiang Chunping , Yao Xi , Le Floch Paul , Mendez Julien , Suo Zhigang
Published: March 2019

Significance

Many applications in engineering require stretchable materials that dissipate little energy during normal operation of cyclic loads (low hysteresis), but dissipate much energy to resist rupture (high toughness), and survive prolonged cyclic loads (fatigue resistant). However, existing stretchable materials cannot meet these requirements simultaneously. Here we present a principle to achieve this goal, and demonstrate the principle by a composite of two stretchable materials of low hysteresis, with large modulus contrast and strong adhesion. The composite retains the low hysteresis, but is much tougher and more fatigue resistant than the constituents. The same principle applies to elastomers, gels, and elastomer–gel hybrids. This class of materials provides opportunities to create high-cycle and low-dissipation soft robots and soft human–machine interfaces.
Lipoprotein lipase is active as a monomer
Authors: Beigneux Anne P. , Allan Christopher M. , Sandoval Norma P. , Cho Geoffrey W. , Heizer Patrick J. , Jung Rachel S. , Stanhope Kimber L. , Havel Peter J. , Birrane Gabriel , Meiyappan Muthuraman , Gill John E. , Murakami Masami , Miyashita Kazuya , Nakajima Katsuyuki , Ploug Michael , Fong Loren G. , Young Stephen G.
Published: March 2019

Significance

Lipoprotein lipase (LPL) plays a central role in plasma lipid metabolism, hydrolyzing the triglycerides in lipoproteins and releasing fatty acid nutrients for vital tissues. LPL is synthesized by adipocytes and myocytes and secreted into the interstitial spaces, whereupon it is captured by an endothelial cell protein, GPIHBP1, and transported to its site of action within the capillary lumen. For decades, LPL has been assumed to be a homodimer, with dimerization thought to be required for both secretion and catalytic activity. In the present study, we revisited the notion that LPL is a homodimer. Our findings indicate that LPL and GPIHBP1-bound LPL are active in a monomeric state.
Improving the Retention Rate of Fat Grafts in Recipient Areas via Botulinum Toxin A Treatment
Authors: Shi Nian , Su Yingjun , Guo Shuzhong , Zhang Zhaoxiang , Qiu Lihong , Yi Chenggang
Published: March 2019

Background

Improving the retention rate of transplanted fat is, currently, of great concern. Partial immobilization, angiogenesis, and adipose tissue-derived stem cells, all proven to be influenced by botulinum toxin A (BTX-A), are significant in fat graft retention.

Objectives

The authors sought to determine the impact of BTX-A on fat grafts.

Methods

Our study included 12 Sprague Dawley rats and each rat’s hind limbs were randomly designated as the BTX-A side and control side. We injected 0.2 mL of BTX-A-treated fat into the quadriceps femoris and subcutaneous space of the BTX-A sides. This was also done for the control sides but with untreated fat. We performed electroneuromyography of recipient muscles at 1 week post-operation. The rats were euthanized at 12 weeks post-operation and we observed the fat retention rate, the fat’s histologic characteristics, and the density of vessels and mature adipocytes.

Results

The amplitudes of electroneuromyography were smaller for the BTX-A sides than the control sides. For intramuscularly injected fat, the BTX-A sides had better retention rates and histologic characteristics and a higher density of vessels and mature adipocytes than the control sides. For subcutaneously injected fat, the BTX-A sides had better histologic characteristics and a higher density of vessels and mature adipocytes than the control sides, but the retention rates were not significantly different between the 2 sides.

Conclusions

Injecting BTX-A-treated fat grafts can immobilize the surrounding muscles. BTX-A can improve the density of vessels and mature adipocytes, histologic characteristics of fat grafts, and retention rate of fat grafts transplanted into muscles.
Maintenance of deceptive gifts in a natural spider population: ecological and demographic factors
Authors: Albo Maria J , Franco-Trecu Valentina , Wojciechowski Filip J , Toft Søren , Bilde Trine
Published: March 2019

Alternative mating tactics are expected to occur predominantly when mate competition is intense, resources are in short supply, or as a result of asymmetric power relationships between individuals. Males of the nuptial gift-giving spider Pisaura mirabilis use a prevailing tactic of offering a nutritive gift (insect prey) and a deceptive tactic of offering a worthless gift (consumed prey) to prospective mates. If the male’s tactic depends on precopulatory male–male competition, worthless gifts should occur primarily late in the season, when the operational sex ratio (OSR) becomes male-biased. If it depends on resource availability and/or postcopulatory sexual selection (sperm competition), worthless gifts should occur mostly early in the mating season, when prey availability is low and most females are unmated (i.e., postcopulatory sexual selection is weak). Nuptial gift construction correlated positively with prey availability and negatively with OSR, suggesting that males increase reproductive effort when resource and mate availability increase. We did not find evidence for body condition affecting male tactic use. Male size had a marked effect on the reproductive tactic employed. Males that matured early in the season were very small and employed mostly the nutritive gift tactic during their short life. Among the males that matured later and persisted through the season, relatively small males employed the worthless gift tactic whereas large males employed the nutritive gift tactic. We suggest that the existence of 2 distinct life-history strategies among males (early small and late large size) interacts with environmental and demographic conditions to maintain the deceptive tactic.
GREP: genome for REPositioning drugs
Authors: Sakaue Saori , Okada Yukinori
Published: March 2019

Making use of accumulated genetic knowledge for clinical practice is our next goal in human genetics. Here we introduce GREP (Genome for REPositioning drugs), a standalone python software to quantify an enrichment of the user-defined set of genes in the target of clinical indication categories and to capture potentially repositionable drugs targeting the gene set. We show that genes identified by the large-scale genome-wide association studies were robustly enriched in the approved drugs to treat the trait of interest. This enrichment analysis was also highly applicable to other sets of biological genes such as those identified by gene expression studies and genes somatically mutated in cancers. This software should accelerate investigators to reposition drugs to other indications with the guidance of known genomics.

Availability and implementation

GREP is available at https://github.com/saorisakaue/GREP as a python source code.

Supplementary information

Supplementary data are available at Bioinformatics online.
Holistic optimization of an RNA-seq workflow for multi-threaded environments
Authors: Hung Ling-Hong , Lloyd Wes , Agumbe Sridhar Radhika , Athmalingam Ravishankar Saranya Devi , Xiong Yuguang , Sobie Eric , Yeung Ka Yee
Published: March 2019

For many next generation-sequencing pipelines, the most computationally intensive step is the alignment of reads to a reference sequence. As a result, alignment software such as the Burrows-Wheeler Aligner is optimized for speed and is often executed in parallel on the cloud. However, there are other less demanding steps that can also be optimized to significantly increase the speed especially when using many threads. We demonstrate this using a unique molecular identifier RNA-sequencing pipeline consisting of 3 steps: split, align, and merge. Optimization of all three steps yields a 40% increase in speed when executed using a single thread. However, when executed using 16 threads, we observe a 4-fold improvement over the original parallel implementation and more than an 8-fold improvement over the original single-threaded implementation. In contrast, optimizing only the alignment step results in just a 13% improvement over the original parallel workflow using 16 threads.

Availability and implementation

Code (M.I.T. license), supporting scripts and Dockerfiles are available at https://github.com/BioDepot/LINCS_RNAseq_cpp and Docker images at https://hub.docker.com/r/biodepot/rnaseq-umi-cpp/

Supplementary information

Supplementary data are available at Bioinformatics online.
A novel mouse model of sporadic colon cancer induced by combination of conditional Apc genes and chemical carcinogen in the absence of Cre recombinase
Authors: Souris Jeffrey S , Zhang Hannah J , Dougherty Urszula , Chen Nai-Tzu , Waller Joseph V , Lo Leu-Wei , Hart John , Chen Chin-Tu , Bissonnette Marc
Published: March 2019

Although valuable insights into colon cancer biology have been garnered from human colon cancer cell lines and primary colonic tissues, and animal studies using human colon cancer xenografts, immunocompetent mouse models of spontaneous or chemically induced colon cancer better phenocopy human disease. As most sporadic human colon tumors present adenomatous polyposis coli (APC) gene mutations, considerable effort has gone into developing mice that express mutant Apc alleles that mimic human colon cancer pathogenesis. A serious limitation of many of these Apc-mutant murine models, however, is that these mice develop numerous tumors in the small intestine but few, if any, in the colon. In this work, we examined three spontaneous mouse models of colon tumorigenesis based upon the widely used multiple intestinal neoplasia (Min) mouse: mice with either constitutive or conditional Apc mutations alone or in combination with caudal-related homeobox transcription factor CDX2P-Cre transgene — either with or without exposure to the potent colon carcinogen azoxymethane. Using the CDX2 promoter to drive Cre recombinase transgene expression effectively inactivated Apc in colonocytes, creating a model with earlier tumor onset and increased tumor incidence/burden, but without the Min mouse model’s small intestine tumorigenesis and susceptibility to intestinal perforation/ulceration/hemorrhage. Most significantly, azoxymethane-treated mice with conditional Apc expression, but absent the Cre recombinase gene, demonstrated nearly 50% tumor incidence with two or more large colon tumors per mouse of human-like histology, but no small intestine tumors — unlike the azoxymethane-resistant C57BL/6J-background Min mouse model. As such this model provides a robust platform for chemoprevention studies.
Variation in ribosomal DNA copy number is associated with lung cancer risk in a prospective cohort study
Authors: Hosgood H Dean , Hu Wei , Rothman Nathaniel , Klugman Madelyn , Weinstein Stephanie J , Virtamo Jarmo R , Albanes Demetrius , Cawthon Richard , Lan Qing
Published: March 2019

Disruption of ribosomal DNA (rDNA) has been linked to a variety of diseases in humans, including carcinogenesis. To evaluate the associations between rDNA copy number (CN) and risk of lung cancer, we measured 5.8S and 18S rDNA CN in the peripheral blood of 229 incident lung cancer cases and 1:1 matched controls from a nested case–control study within a prospective cohort of male smokers. There was a dose–response relationship between quartiles of both 18S and 5.8S rDNA CN and risk of lung cancer (odds ratio [OR], 95% confidence interval [CI]: 18S: 1.0 [ref]; 1.2 [0.6–2.1]; 1.8 [1.0–3.4]; 2.3 [1.3–4.1; Ptrend = 0.0002; 5.8S: 1.0 [ref]; 1.6 [0.8–2.9]; 2.2 [1.1–4.2]; 2.6 [1.3–5.1]; Ptrend = 0.0001). The associations between rDNA CN and lung cancer risk were similar when excluding cases diagnosed within 5 years of follow-up, and when stratifying by heavy (>20 cigarettes per day) and light smokers (≤20 cigarettes per day).

We are the first to report that rDNA CN may be associated with future risk of lung cancer. To further elucidate the relationship between rDNA and lung cancer, replication studies are needed in additional populations, particularly those that include non-smokers.
Improving the robustness of scale-free networks by maintaining community structure
Authors: Mozafari Marzieh , Khansari Mohammad
Published: March 2019

Scale-free networks, which play an important role in modelling human activities, are always suffering from intentional attacks which have serious consequences on their functionality. Degree distribution and community structure are two distinguishing characteristics of these networks considered in optimizing network robustness process recently. Since community structure is known as functional modules in some networks, modifying them during the improving network robustness process may affect network performance. We propose a preferential rewiring method to improve network robustness which not only keeps degree distribution unchanged but also preserves community structure and decreases the number of rewired edges at the same time. At first, the robustness of each community is improved by applying a smart rewiring method based on the neighbourhood of nodes. Then, relations between communities are gotten more robust with a preferential rewiring based on degree and betweenness hybrid centrality of nodes. This method was applied to several types of networks including Dolphins, WU-PowerGrid and US-Airline as real-world networks and Lancichinetti–Fortunato–Radicchi benchmark model as an artificial network with the scale-free property. The results show that the proposed method enhances the robustness of all networks against degree centrality attacks between 50% and 80% and betweenness centrality attacks between 30% and 70%. Whereas, in all cases, community structure preserved more than 50%. In comparison with previous studies, the proposed method can improve network robustness more significantly and decrease the number of rewires. It also is not dependent on the attack strategy.
Genetic variation and cryptic lineage diversity of the Nigerian red-headed rock agama Agama agama associate with eco-geographic zones
Authors: Nneji Lotanna M , Adeola Adeniyi C , Yan Fang , Okeyoyin Agboola O , Oladipo Ojo C , Saidu Yohanna , Samuel Dinatu , Nneji Ifeanyi C , Adeyi Akindele O , Onadeko Abiodun B , Olagunju Temidayo E , Omotoso Olatunde , Oladipo Segun O , Iyiola Oluyinka A , Usongo John Y , Auta Timothy , Usman Abbas D , Abdullahi Halima , Ikhimiukor Odion O , Zhou Wei-Wei , Jin Jie-Qiong , Ugwumba Obih A , Ugwumba Adiaha A A , Peng Min-Sheng , Murphy Robert W , Che Jing
Published: March 2019

Nigeria is an Afrotropical region with considerable ecological heterogeneity and levels of biotic endemism. Among its vertebrate fauna, reptiles have broad distributions, thus, they constitute a compelling system for assessing the impact of ecological variation and geographic isolation on species diversification. The red-headed rock agama, Agama agama, lives in a wide range of habitats and, thus, it may show genetic structuring and diversification. Herein, we tested the hypothesis that ecology affects its genetic structure and population divergence. Bayesian inference phylogenetic analysis of a mitochondrial DNA (mtDNA) gene recovered four well-supported matrilines with strong evidence of genetic structuring consistent with eco-geographic regions. Genetic differences among populations based on the mtDNA also correlated with geographic distance. The ecological niche model for the matrilines had a good fit and robust performance. Population divergence along the environmental axes was associated with climatic conditions, and temperature ranked highest among all environmental variables for forest specialists, while precipitation ranked highest for the forest/derived savanna, and savanna specialists. Our results cannot reject the hypothesis that niche conservatism promotes geographic isolation of the western populations of Nigerian A. agama. Thus, ecological gradients and geographic isolation impact the genetic structure and population divergence of the lizards. This species might be facing threats due to recent habitat fragmentation, especially in western Nigeria. Conservation actions appear necessary.
Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study
Authors: Sood Ajit , Mahajan Ramit , Singh Arshdeep , Midha Vandana , Mehta Varun , Narang Vikram , Singh Tarundeep , Singh Pannu Anmol
Published: March 2019

Objectives

To study the role of faecal microbiota transplantation [FMT] in maintenance of remission in ulcerative colitis [UC].

Methods

In this pilot study, patients with UC in clinical remission achieved after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care [SOC] therapy was continued in all patients. The primary endpoint was maintenance of steroid-free clinical remission [Mayo score ≤2, all subscores ≤1] at Week 48. Secondary endpoints were achievement of endoscopic remission [endoscopic Mayo score 0] and histological remission [Nancy grade 0, 1] at Week 48.

Results

In all, 61 patients in clinical remission were randomised to receive either FMT [n = 31] or placebo [n = 30]. The primary outcome was achieved in 27/31 [87.1%] patients allocated FMT versus 20/30 [66.7%] patients assigned placebo [p = 0.111]. Secondary endpoints of endoscopic remission (FMT: 18/31 [58.1%] versus placebo: 8/30 [26.7%], p = 0.026) and histological remission (FMT: 14/31 [45.2%] versus placebo: 5/30 [16.7%], p = 0. 033) were achieved in a significantly higher number of patients with FMT. Three patients receiving FMT [9.7%] and 8 patients on placebo [26.7%] relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT; one patient who relapsed on placebo required colectomy.

Conclusions

Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC.
Network topology inference using information cascades with limited statistical knowledge
Authors: Ji Feng , Tang Wenchang , Tay Wee Peng , Chong Edwin K P
Published: March 2019

We study the problem of inferring network topology from information cascades, in which the amount of time taken for information to diffuse across an edge in the network follows an unknown distribution. Unlike previous studies, which assume knowledge of these distributions, we only require that diffusion along different edges in the network be independent together with limited moment information (e.g. the means). We introduce the concept of a separating vertex set for a graph, which is a set of vertices in which for any two given distinct vertices of the graph there exists a vertex whose distance to them is different. We show that a necessary condition for reconstructing a tree perfectly using distance information between pairs of vertices is given by the size of an observed separating vertex set. We then propose an algorithm to recover the tree structure using infection times whose differences have means corresponding to the distance between two vertices. To improve the accuracy of our algorithm, we propose the concept of redundant vertices, which allows us to perform averaging to better estimate the distance between two vertices. Though the theory is developed mainly for tree networks, we demonstrate how the algorithm can be extended heuristically to general graphs. Simulations using synthetic and real networks and experiments using real-world data suggest that our proposed algorithm performs better than some current state-of-the-art network reconstruction methods.
Adaptive control parameterization method by density functions for optimal control problems
Authors: Ejlali Nastaran , Hosseini Seyed Mohammad
Published: March 2019

This paper proposes an efficient adaptive control parameterization method for solving optimal control problems. In this method, mesh density functions are used to generate mesh points. In the first step, the problem is solved by control parameterization on uniform mesh points. Then at each step, the approximate control obtained from the previous step is applied to construct a mesh density function, and consequently a new adapted set of mesh points. Several numerical examples are included to demonstrate that the adaptive control parameterization method is more accurate than a uniform control parameterization one.