bluuebunny/crossref_metadata_2025 huggingface dataset:
Global cooling and enhanced Eocene Asian mid-latitude interior aridity
Authors: Li J. X. , Yue L. P. , Roberts A. P. , Hirt A. M. , Pan F. , Guo Lin , Xu Y. , Xi R. G. , Guo Lei , Qiang X. K. , Gai C. C. , Jiang Z. X. , Sun Z. M. , Liu Q. S.
Published: July 2018

Tibetan Plateau uplift has been suggested as the main driving force for mid-latitude Asian inland aridity (AIA) and for deposition of thick aeolian sequences in northern China since the Miocene. However, the relationship between earlier AIA and Tibetan Plateau mountain building is uncertain because of a lack of corresponding thick aeolian sequences with accurate age constraints. We here present results for a continuous aeolian sequence that spans the interval from >51 to 39 Ma from the eastern Xorkol Basin, Altun Shan, northeastern Tibetan Plateau. The basal age of the studied sequence postdates initial uplift of the Tibetan Plateau by several million years. Our results indicate that the local palaeoclimate was teleconnected strongly to the overall global cooling pattern, so that local enhanced aridification recorded by the studied aeolian sequence is dominantly a response to global climatic forcing rather than plateau uplift.
Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy
Authors: Fledrich R. , Abdelaal T. , Rasch L. , Bansal V. , Schütza V. , Brügger B. , Lüchtenborg C. , Prukop T. , Stenzel J. , Rahman R. U. , Hermes D. , Ewers D. , Möbius W. , Ruhwedel T. , Katona I. , Weis J. , Klein D. , Martini R. , Brück W. , Müller W. C. , Bonn S. , Bechmann I. , Nave K. A. , Stassart R. M. , Sereda M. W.
Published: July 2018

In patients with Charcot–Marie–Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.
Multimodal neuromarkers in schizophrenia via cognition-guided MRI fusion
Authors: Sui Jing , Qi Shile , van Erp Theo G. M. , Bustillo Juan , Jiang Rongtao , Lin Dongdong , Turner Jessica A. , Damaraju Eswar , Mayer Andrew R. , Cui Yue , Fu Zening , Du Yuhui , Chen Jiayu , Potkin Steven G. , Preda Adrian , Mathalon Daniel H. , Ford Judith M. , Voyvodic James , Mueller Bryon A. , Belger Aysenil , McEwen Sarah C. , O’Leary Daniel S. , McMahon Agnes , Jiang Tianzi , Calhoun Vince D.
Published: July 2018

Cognitive impairment is a feature of many psychiatric diseases, including schizophrenia. Here we aim to identify multimodal biomarkers for quantifying and predicting cognitive performance in individuals with schizophrenia and healthy controls. A supervised learning strategy is used to guide three-way multimodal magnetic resonance imaging (MRI) fusion in two independent cohorts including both healthy individuals and individuals with schizophrenia using multiple cognitive domain scores. Results highlight the salience network (gray matter, GM), corpus callosum (fractional anisotropy, FA), central executive and default-mode networks (fractional amplitude of low-frequency fluctuation, fALFF) as modality-specific biomarkers of generalized cognition. FALFF features are found to be more sensitive to cognitive domain differences, while the salience network in GM and corpus callosum in FA are highly consistent and predictive of multiple cognitive domains. These modality-specific brain regions define—in three separate cohorts—promising co-varying multimodal signatures that can be used as predictors of multi-domain cognition.
JNK regulates muscle remodeling via myostatin/SMAD inhibition
Authors: Lessard Sarah J. , MacDonald Tara L. , Pathak Prerana , Han Myoung Sook , Coffey Vernon G. , Edge Johann , Rivas Donato A. , Hirshman Michael F. , Davis Roger J. , Goodyear Laurie J.
Published: July 2018

Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor, SMAD2, at specific linker region residues leading to inhibition of the growth suppressor, myostatin. In human skeletal muscle, this JNK/SMAD signaling axis is activated by resistance exercise, but not endurance exercise. We conclude that JNK acts as a key mediator of muscle remodeling during exercise via regulation of myostatin/SMAD signaling.
Cysteine-mediated decyanation of vitamin B12 by the predicted membrane transporter BtuM
Authors: Rempel S. , Colucci E. , de Gier J. W. , Guskov A. , Slotboom D. J.
Published: July 2018

Uptake of vitamin B12 is essential for many prokaryotes, but in most cases the membrane proteins involved are yet to be identified. We present the biochemical characterization and high-resolution crystal structure of BtuM, a predicted bacterial vitamin B12 uptake system. BtuM binds vitamin B12 in its base-off conformation, with a cysteine residue as axial ligand of the corrin cobalt ion. Spectroscopic analysis indicates that the unusual thiolate coordination allows for decyanation of vitamin B12. Chemical modification of the substrate is a property other characterized vitamin B12-transport proteins do not exhibit.
Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids
Authors: Jung Kwang Bo , Lee Hana , Son Ye Seul , Lee Mi-Ok , Kim Young-Dae , Oh Soo Jin , Kwon Ohman , Cho Sunwha , Cho Hyun-Soo , Kim Dae-Soo , Oh Jung-Hwa , Zilbauer Matthias , Min Jeong-Ki , Jung Cho-Rok , Kim Janghwan , Son Mi-Young
Published: July 2018

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.
Wildfire as a major driver of recent permafrost thaw in boreal peatlands
Authors: Gibson Carolyn M. , Chasmer Laura E. , Thompson Dan K. , Quinton William L. , Flannigan Mike D. , Olefeldt David
Published: July 2018

Permafrost vulnerability to climate change may be underestimated unless effects of wildfire are considered. Here we assess impacts of wildfire on soil thermal regime and rate of thermokarst bog expansion resulting from complete permafrost thaw in western Canadian permafrost peatlands. Effects of wildfire on permafrost peatlands last for 30 years and include a warmer and deeper active layer, and spatial expansion of continuously thawed soil layers (taliks). These impacts on the soil thermal regime are associated with a tripled rate of thermokarst bog expansion along permafrost edges. Our results suggest that wildfire is directly responsible for 2200 ± 1500 km2 (95% CI) of thermokarst bog development in the study region over the last 30 years, representing ~25% of all thermokarst bog expansion during this period. With increasing fire frequency under a warming climate, this study emphasizes the need to consider wildfires when projecting future circumpolar permafrost thaw.
Cross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy
Authors: Regla-Nava Jose Angel , Elong Ngono Annie , Viramontes Karla M. , Huynh Anh-Thy , Wang Ying-Ting , Nguyen Anh-Viet T. , Salgado Rebecca , Mamidi Anila , Kim Kenneth , Diamond Michael S. , Shresta Sujan
Published: July 2018

As Zika virus (ZIKV) emerges into Dengue virus (DENV)-endemic areas, cases of ZIKV infection in DENV-immune pregnant women may rise. Here we show that prior DENV immunity affects maternal and fetal ZIKV infection in pregnancy using sequential DENV and ZIKV infection models. Fetuses in ZIKV-infected DENV-immune dams were normal sized, whereas fetal demise occurred in non-immune dams. Moreover, reduced ZIKV RNA is present in the placenta and fetuses of ZIKV-infected DENV-immune dams. DENV cross-reactive CD8+ T cells expand in the maternal spleen and decidua of ZIKV-infected dams, their depletion increases ZIKV infection in the placenta and fetus, and results in fetal demise. The inducement of cross-reactive CD8+ T cells via peptide immunization or adoptive transfer results in decreased ZIKV infection in the placenta. Prior DENV immunity can protect against ZIKV infection during pregnancy in mice, and CD8+ T cells are sufficient for this cross-protection. This has implications for understanding the natural history of ZIKV in DENV-endemic areas and the development of optimal ZIKV vaccines.
Sensor-regulator and RNAi based bifunctional dynamic control network for engineered microbial synthesis
Authors: Yang Yaping , Lin Yuheng , Wang Jian , Wu Yifei , Zhang Ruihua , Cheng Mengyin , Shen Xiaolin , Wang Jia , Chen Zhenya , Li Chenyi , Yuan Qipeng , Yan Yajun
Published: July 2018

Writing artificial logic and dynamic function into complex cellular background to achieve desired phenotypes or improved outputs calls for the development of new genetic tools as well as their innovative use. In this study, we present a sensor-regulator and RNAi-based bifunctional dynamic control network that can provide simultaneous upregulation and downregulation of cellular metabolism for engineered biosynthesis. The promoter-regulator-mediated upregulation function and its transduced downregulation function through RNAi are systematically verified and characterized. We apply this dynamic control network to regulate the phosphoenolpyruvate metabolic node in Escherichia coli and achieve autonomous distribution of carbon flux between its native metabolism and the engineered muconic acid biosynthetic pathway. This allows muconic acid biosynthesis to reach 1.8 g L−1. This study also suggests the circumstances where dynamic control approaches are likely to take effects.
An isolable catenane consisting of two Möbius conjugated nanohoops
Authors: Fan Yang-Yang , Chen Dandan , Huang Ze-Ao , Zhu Jun , Tung Chen-Ho , Wu Li-Zhu , Cong Huan
Published: July 2018

Besides its mathematical importance, the Möbius topology (twisted, single-sided strip) is intriguing at the molecular level, as it features structural elegance and distinct properties; however, it carries synthetic challenges. Although some Möbius-type molecules have been isolated by synthetic chemists accompanied by extensive computational studies, the design, preparation, and characterization of stable Möbius-conjugated molecules remain a nontrivial task to date, let alone that of molecular Möbius strips assembling into more complex topologies. Here we report the efficient synthesis, crystal structure, and theoretical study of a catenane consisting of two fully conjugated nanohoops exhibiting Möbius topology in the solid state. This work highlights that oligoparaphenylene-derived nanohoops, a family of highly warped and synthetically challenging conjugated macrocycles, can not only serve as building blocks for interlocked supermolecular structures, but also represent a new class of compounds with isolable Möbius conformations stabilized by non-covalent interactions.
De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations
Authors: Wong Karen H. Y. , Levy-Sakin Michal , Kwok Pui-Yan
Published: July 2018

The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) “Linked-Read” technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations.
Soil bacterial networks are less stable under drought than fungal networks
Authors: de Vries Franciska T. , Griffiths Rob I. , Bailey Mark , Craig Hayley , Girlanda Mariangela , Gweon Hyun Soon , Hallin Sara , Kaisermann Aurore , Keith Aidan M. , Kretzschmar Marina , Lemanceau Philippe , Lumini Erica , Mason Kelly E. , Oliver Anna , Ostle Nick , Prosser James I. , Thion Cecile , Thomson Bruce , Bardgett Richard D.
Published: July 2018

Soil microbial communities play a crucial role in ecosystem functioning, but it is unknown how co-occurrence networks within these communities respond to disturbances such as climate extremes. This represents an important knowledge gap because changes in microbial networks could have implications for their functioning and vulnerability to future disturbances. Here, we show in grassland mesocosms that drought promotes destabilising properties in soil bacterial, but not fungal, co-occurrence networks, and that changes in bacterial communities link more strongly to soil functioning during recovery than do changes in fungal communities. Moreover, we reveal that drought has a prolonged effect on bacterial communities and their co-occurrence networks via changes in vegetation composition and resultant reductions in soil moisture. Our results provide new insight in the mechanisms through which drought alters soil microbial communities with potential long-term consequences, including future plant community composition and the ability of aboveground and belowground communities to withstand future disturbances.
Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer
Authors: Kuang Yanan , Siddiqui Bilal , Hu Jiani , Pun Matthew , Cornwell MacIntosh , Buchwalter Gilles , Hughes Melissa E. , Wagle Nikhil , Kirschmeier Paul , Jänne Pasi A. , Paweletz Cloud P. , Lin Nancy U. , Krop Ian E. , Barry William T. , Winer Eric P. , Brown Myles , Jeselsohn Rinath
Published: July 2018

ESR1 mutations were recently found to be an important mechanism of endocrine resistance in ER-positive (ER + ) metastatic breast cancer. To determine the clinicopathological features driving the emergence of the ESR1 mutations we studied plasma cfDNA and detailed clinical data collected from patients with metastatic breast cancer. Droplet Digital PCR was performed for the detection of the most common ESR1 mutations and PIK3CA mutations. Among the patients with ER + /HER2- disease, ESR1 mutations were detected in 30% of the patients. There were no associations between the pathological features of the primary disease or time to distant recurrence and the emergence of ESR1 mutations in metastatic disease. The prevalence of the ESR1 mutations was significantly associated with prior treatment with an aromatase inhibitor in the adjuvant or metastatic setting. The prevalence of the ESR1 mutations was also positively associated with prior fulvestrant treatment. Conversely, the prevalence of ESR1 mutations was lower after treatment with a CDK4/6 inhibitor. There were no significant associations between specific systemic treatments and the prevalence of PIK3CA mutations. These results support the evolution of the ESR1 mutations under the selective pressure of treatment with aromatase inhibitors in the adjuvant and metastatic settings and have important implications in the optimization of adjuvant and metastatic treatment in ER + breast cancer.
Subunit-specific NMDAR antagonism dissociates schizophrenia subtype-relevant oscillopathies associated with frontal hypofunction and hippocampal hyperfunction
Authors: Pittman-Polletta Benjamin , Hu Kun , Kocsis Bernat
Published: July 2018

NMDAR antagonism alters mesolimbic, hippocampal, and cortical function, acutely reproducing the positive, cognitive, and negative symptoms of schizophrenia. These physiological and behavioral effects may depend differentially on NMDAR subtype- and region-specific effects. The dramatic electrophysiological signatures of NMDAR blockade in rodents include potentiated high frequency oscillations (HFOs, ∼140 Hz), likely generated in mesolimbic structures, and increased HFO phase-amplitude coupling (PAC), a phenomenon related to goal-directed behavior and dopaminergic tone. This study examined the impact of subtype-specific NMDAR antagonism on HFOs and PAC. We found that positive-symptom-associated NR2A-preferring antagonism (NVP-AAM077), but not NR2B-specific antagonism (Ro25-6985) or saline control, replicated increases in HFO power seen with nonspecific antagonism (MK-801). However, PAC following NR2A-preferring antagonism was distinct from all other conditions. While θ-HFO PAC was prominent or potentiated in other conditions, NVP-AAM077 increased δ-HFO PAC and decreased θ-HFO PAC. Furthermore, active wake epochs exhibiting narrowband frontal δ oscillations, and not broadband sleep-associated δ, selectively exhibited δ-HFO coupling, while paradoxical sleep epochs having a high CA1 θ to frontal δ ratio selectively exhibited θ-HFO coupling. Our results suggest: (1) NR2A-preferring antagonism induces oscillopathies reflecting frontal hyperfunction and hippocampal hypofunction; and (2) HFO PAC indexes cortical vs. hippocampal control of mesolimbic circuits.
Developing dual herbicide tolerant transgenic rice plants for sustainable weed management
Authors: Fartyal Dhirendra , Agarwal Aakrati , James Donald , Borphukan Bhabesh , Ram Babu , Sheri Vijay , Agrawal Pawan K. , Achary V. Mohan Murali , Reddy M. K.
Published: July 2018

Herbicides are important constituents of modern integrated weed management system. However, the continuous use of a single herbicide leads to the frequent evolution of resistant weeds which further challenges their management. To overcome this situation, alternating use of multiple herbicides along with conventional weed-management practices is suitable and recommended. The development of multiple herbicide-tolerant crops is still in its infancy, and only a few crops with herbicide tolerance traits have been reported and commercialized. In this study, we developed transgenic rice plants that were tolerant to both bensulfuron methyl (BM) and glufosinate herbicides. The herbicide tolerant mutant variant of riceAHAS(Acetohydroxyacid synthase) was overexpressed along with codon optimized bacterialbargene. The developed transgenic lines showed significant tolerance to both herbicides at various stages of plant development. The selected transgenic lines displayed an increased tolerance against 100 μM BM and 30 mg/L phosphinothricin during seed germination stage. Foliar applications further confirmed the dual tolerance to 300 μM BM and 2% basta herbicides without any significant growth and yield penalties. The development of dual-herbicide-tolerant transgenic plants adds further information to the knowledge of crop herbicide tolerance for sustainable weed management in modern agricultural system.
RNA markers enable phenotypic test of antibiotic susceptibility in Neisseria gonorrhoeae after 10 minutes of ciprofloxacin exposure
Authors: Khazaei Tahmineh , Barlow Jacob T. , Schoepp Nathan G. , Ismagilov Rustem F.
Published: July 2018

Antimicrobial-resistant Neisseria gonorrhoeae is an urgent public-health threat, with continued worldwide incidents of infection and rising resistance to antimicrobials. Traditional culture-based methods for antibiotic susceptibility testing are unacceptably slow (1–2 days), resulting in the use of broad-spectrum antibiotics and the further development and spread of resistance. Critically needed is a rapid antibiotic susceptibility test (AST) that can guide treatment at the point-of-care. Rapid phenotypic approaches using quantification of DNA have been demonstrated for fast-growing organisms (e.g. E. coli) but are challenging for slower-growing pathogens such as N. gonorrhoeae. Here, we investigate the potential of RNA signatures to provide phenotypic responses to antibiotics in N. gonorrhoeae that are faster and greater in magnitude compared with DNA. Using RNA sequencing, we identified antibiotic-responsive transcripts. Significant shifts (>4-fold change) in transcript levels occurred within 5 min of antibiotic exposure. We designed assays for responsive transcripts with the highest abundances and fold changes, and validated gene expression using digital PCR. Using the top two markers (porB and rpmB) we correctly determined the antibiotic susceptibility and resistance of 49 clinical isolates after 10 min exposure to ciprofloxacin. RNA signatures are therefore promising as an approach on which to build rapid AST devices for N. gonorrhoeae at the point-of-care, which is critical for disease management, surveillance, and antibiotic stewardship efforts.
MYC-type transcription factors, MYC67 and MYC70, interact with ICE1 and negatively regulate cold tolerance in Arabidopsis
Authors: Ohta Masaru , Sato Aiko , Renhu Na , Yamamoto Tsuyoshi , Oka Nodoka , Zhu Jian-Kang , Tada Yasuomi , Suzaki Takuya , Miura Kenji
Published: July 2018

The expression of hundreds of genes is induced by low temperatures via a cold signaling pathway. ICE1, a MYC-type transcription factor, plays an important role in the induction of CBF3/DREB1A to control cold-responsive genes and cold tolerance. To elucidate other molecular factors, a yeast 2-hybrid screening was performed. Two MYC-type transcription factors, MYC67 and MYC70, were identified as ICE1-interacting proteins. The myc mutants were more tolerant to freezing temperatures than wild type. CBF3/DREB1A and other cold-responsive genes were up-regulated in the myc mutants. Overexpression of the MYC genes increased the cold sensitivity and down-regulated the expression of cold-responsive genes. The MYC proteins interacted with the cis-elements in the CBF3/DREB1A promoter, probably to interfere interaction between ICE1 and the cis-elements. Taken together, these results demonstrate that MYC67 and MYC70, ICE1 interactors, negatively regulate cold-responsive genes and cold tolerance.
Alternatively spliced variants in Atlantic cod (Gadus morhua) support response to variable salinity environment
Authors: Kijewska Agnieszka , Malachowicz Magdalena , Wenne Roman
Published: July 2018

Analysis of gill transcriptome of the Atlantic cod from the Baltic Sea demonstrated that alternatively spliced (AS) variants may be actively involved in the process of adaptation to altered salinity. Some AS variants of different genes, like phospholipase A2 group IVC (PLA2G4C), appeared only in fish exposed to altered salinity, while other isoforms of the same genes were present in all experimental groups. Novel sequence arrangements represent 89% of all AS in the Baltic cod compared to the Atlantic population. Profiles of modified pathways suggest that regulation by AS can afford specific changes of genes expressed in response to the environment. The AS variants appear to be involved in the response to stress by modifications of signalling in apoptosis pathways, an innate immunological response and pro-inflammatory process. Present results support the hypothesis that developing new AS variants could support genome complexity and reinforce the ability to fast adapt to local environments.
Holocene evolution of Portus Pisanus, the lost harbour of Pisa
Authors: Kaniewski D. , Marriner N. , Morhange C. , Vacchi M. , Sarti G. , Rossi V. , Bini M. , Pasquinucci M. , Allinne C. , Otto T. , Luce F. , Van Campo E.
Published: July 2018

The ancient harbour of Pisa, Portus Pisanus, was one of Italy’s most influential seaports for many centuries. Nonetheless, very little is known about its oldest harbour and the relationships between environmental evolution and the main stages of harbour history. The port complex that ensured Pisa’s position as an economic and maritime power progressively shifted westwards by coastal progradation, before the maritime port of Livorno was built in the late 16th century AD. The lost port is, however, described in the early 5th century AD as being “a large, naturally sheltered embayment” that hosted merchant vessels, suggesting an important maritime structure with significant artificial infrastructure to reach the city. Despite its importance, the geographical location of the harbour complex remains controversial and its environmental evolution is unclear. To fill this knowledge gap and furnish accurate palaeoenvironmental information on Portus Pisanus, we used bio- and geosciences. Based on stratigraphic data, the area’s relative sea-level history, and long-term environmental dynamics, we established that at ~200 BC, a naturally protected lagoon developed and hosted Portus Pisanus until the 5th century AD. The decline of the protected lagoon started at ~1350 AD and culminated ~1500 AD, after which time the basin was a coastal lake.
Dietary supplementation with Essential-oils-cobalt for improving growth performance, meat quality and skin cell capacity of goats
Authors: Lei Zhaomin , Zhang Ke , Li Chao , Wu Jianping , Davis Delmer , Casper David , Jiang Hui , Jiao Ting , Wang Xiaolong , Wang Jianfu
Published: July 2018

Essential oils (EO) are secondary metabolites usually made up of terpenoids and phenylpropanoids and have antimicrobial properties. However, the feeding effects of EO-Cobalt (EOC) on the performance of goats are largely unknown. Herein we investigated and reported the effects of dietary EOC (0, 52, and 91 mg daily) on fiber producing cashmere goats. We determined the resulting phenotypes including live growth, carcass weight, meat quality, and cashmere fiber traits. We show that dietary supplement of EOC significantly promoted average daily gain (P < 0.05), and significantly improved carcass weight, and meat and hair fiber quality (P < 0.05). We further conducted RNA-seq using skin and liver tissues from each group to assess the molecular mechanism conferring these phenotypic changes. A total of 191 differentially expressed genes were found in the skin tissues (0 vs 91 mg), while 1,127 DEGs were found in livers. Analyses of liver samples for differential gene action and functional prediction found that EOC stimulated physiological changes in the body’s immune system at both blood and cell levels. Our results demonstrated the potential of using EO-based feed ingredient to improve animal growth performance, meat quality and fiber quality, and further illustrated the molecular basis that contribute to phenotypes at physiological levels.
Enhancing quantum phase transitions in the critical point of Extended TC-Dicke model via Stark effect
Authors: Salah Ahmed , Abdel-Rady A. S. , Osman Abdel-Nasser A. , Hassan Samia. S. A.
Published: July 2018

A system of N two-level atoms, Tavis-Cummings Dicke (TC-Dicke) model, interacting with a one-mode electromagnetic radiation field in the presence of the Stark shifts is studied, which is expected to predict new phenomena that are not explored in the original TC-Dicke model. We obtained the potential energy surface of the system using a trial state the direct product of coherent states in each subspace. In the frame of mean-field approaches, the variational energy is evaluated as the expectation value of the Hamiltonian for this state. The order of the quantum phase transitions is determined explicitly and numerically. We estimate the ground-state energy and the macroscopic excitations in the superradiant phase. Moreover, we investigated the critical properties of the TC-Dicke model in the classical spin limit and coherent state. We observed that in the thermodynamic limit, the energy surface takes a simple form a direct description of the phase transition. Moreover, it is found that when the microwave amplitude changes the new phase transition occurs with the Stark shift. The analytical solutions and numerical results, which appear in this paper are agreement with our paper which published recently in Int. J. Mod. Phys. B when we studied the same model using a different coherent state.
Magnetic hardening of Nd-Ce-Fe-B films with high Ce concentration
Authors: Ren Hanyang , Abbas Nadeem , Liu Yang , Tang Hong , Gui Wanglin , Ding Jianzhong , Liu J. Ping , Xia Weixing , Du Juan , Zhang Jian
Published: July 2018

Partial substitution of Ce in Nd-Fe-B magnets is a feasible way to cope with the crisis of Nd and Dy in Nd-Fe-B production and reduce the cost of Nd-Fe-B magnets. In the present paper, the Nd-Ce-Fe-B films with high performance have been successfully fabricated by using an ultra-high vacuum (UHV) magnetron sputtering system. High magnetic performance with a ceorcivity of 13.3 kOe, a remanence of 11.4 kGs and a maximum energy product of 29.4 GMOe is obtained with the Ce substitution for more than 50 wt.% Nd without Dy addition. The high coercivity and (BH)max achieved in this work are much larger than those of previously reported Nd-Ce-Fe-B magnets with the same Ce concentration. The phase structure, microstructure and coercivity mechanism are analyzed. The coercivity mechanism is determined to be mainly dominated by nucleation. Based on the microstructure observation and coercivity mechanism analysis, the fine and well separated grains, smooth grain surface, small and less inhomogeneities should be responsible for the high coercivity. Our results encourage the further improvement of magnetic properties in Ce magnets including the bulk material with high Ce concentration.
MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer
Authors: Kahraman Mustafa , Röske Anne , Laufer Thomas , Fehlmann Tobias , Backes Christina , Kern Fabian , Kohlhaas Jochen , Schrörs Hannah , Saiz Anna , Zabler Cassandra , Ludwig Nicole , Fasching Peter A. , Strick Reiner , Rübner Matthias , Beckmann Matthias W. , Meese Eckart , Keller Andreas , Schrauder Michael G.
Published: July 2018

Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10−5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10−23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.
Increased moral condemnation of accidental harm in institutionalized adolescents
Authors: Baez Sandra , Herrera Eduar , García Adolfo M. , Huepe David , Santamaría-García Hernando , Ibáñez Agustín
Published: July 2018

Social deprivation, as faced by children in institutional rearing, involves socio-cognitive deficits that may persist into adolescence. In particular, two relevant domains which prove sensitive to pre-adult neurodevelopment are theory of mind (ToM) and moral judgment (a complex skill which partially depend upon ToM). However, no study has assessed moral evaluation in adolescents with a history of institutional care, let alone its relationship with ToM skills. The present study aims to bridge this gap, focusing on moral evaluation of harmful actions in institutionalized adolescents (IAs). Relative to adolescents raised with their biological families, IAs exhibited less willingness to exculpate protagonists for accidental harms, suggesting an under-reliance on information about a person’s (innocent) intentions. Moreover, such abnormalities in IAs were associated with ToM impairments. Taken together, our findings extend previous findings of delayed ToM under social deprivation, further showing that the development of moral cognition is also vulnerable to the impact of institutionalization. These results could pave the way for novel research on the role of institutional rearing in ToM and moral development during adolescence.
oxLDL inhibits differentiation and functional activity of osteoclasts via scavenger receptor-A mediated autophagy and cathepsin K secretion
Authors: Dawodu Damilola , Patecki Margret , Hegermann Jan , Dumler Inna , Haller Hermann , Kiyan Yulia
Published: July 2018

Resorptive activity of osteoclasts is important for maintaining bone homeostasis. Endogenous compounds such as oxidized low density lipoprotein (oxLDL) have been shown to disturb this activity. While some studies have investigated the effects of oxLDL on the process of osteoclastogenesis, the underlying mechanism are not fully understood. We show here that oxLDL concentrations of ~10–25 µg protein (0.43–1.0 µM MDA/mg protein) completely blocked the formation of functional osteoclasts. The underlying mechanism implies an inhibition of autophagy that in turn leads to a decreased fusion of cathepsin K (CatK)-loaded lysosomal vesicles with the ruffled border membrane. As result, a lower secretion of CatK and impaired protonation of the resorption lacunae by vacuolar-ATPase (v-ATPase) is observed in the presence of oxLDL. We demonstrate that scavenger receptor A (SR-A) mediates oxLDL effects on osteoclastogenesis and repressing this receptor partially rescued oxLDL effects. Collectively, our data provides an insight into the possible mechanism of oxLDL on osteoclastogenesis suggesting that it does not perturb the packaging of CatK and v-ATPase (V-a3) in the secretory lysosome, but inhibits the fusion of these lysosomes to the ruffled border. The relevance of our findings suggests a distinct link between oxLDL, autophagy and osteoclastogenesis.
MRGPRX2-mediated mast cell response to drugs used in
perioperative procedures and anaesthesia
Authors: Navinés-Ferrer Arnau , Serrano-Candelas Eva , Lafuente Alberto , Muñoz-Cano Rosa , Martín Margarita , Gastaminza Gabriel
Published: July 2018

The study of anaphylactoid reactions during perioperative procedures
and anaesthesia represents a diagnostic challenge for allergists, as many drugs are
administered simultaneously, and approximately half of them trigger allergic
reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor
MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this
study, we analyse the ability of certain drugs used during perioperative procedures
and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and
sera from patients who experienced an anaphylactoid reaction during the
perioperative procedure. Using a β-hexosaminidase release assay, several drugs were
seen to cause mast cell degranulation in vitro in
comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium
specifically triggered this receptor, as assessed by the release of β-hexosaminidase
in the control versus the MRGPRX2-silenced cells. The same outcome was seen when
measuring degranulation based on the percentage of CD63 expression at identical
doses. Unlike that of the healthy controls, the sera of patients who had experienced
an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability
of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a
candidate for consideration in non-IgE-mediated allergic reactions to some
perioperative drugs, reinforcing its role in mast cell responses and their
pathophysiology.
Deep brain optical coherence tomography angiography in mice: in vivo, noninvasive imaging of hippocampal formation
Authors: Park Kwan Seob , Shin Jun Geun , Qureshi Muhammad Mohsin , Chung Euiheon , Eom Tae Joong
Published: July 2018

The hippocampus is associated with memory and navigation, and the rodent hippocampus provides a useful model system for studying neurophysiology such as neural plasticity. Vascular changes at this site are closely related to brain diseases, such as Alzheimer’s disease, dementia, and epilepsy. Vascular imaging around the hippocampus in mice may help to further elucidate the mechanisms underlying these diseases. Optical coherence tomography angiography (OCTA) is an emerging technology that can provide label-free blood flow information. As the hippocampus is a deep structure in the mouse brain, direct in vivo visualisation of the vascular network using OCTA and other microscopic imaging modalities has been challenging. Imaging of blood vessels in the hippocampus has been performed using multiphoton microscopy; however, labelling with fluorescence probes is necessary when using this technique. Here, we report the use of label-free and noninvasive microvascular imaging in the hippocampal formation of mice using a 1.7-μm swept-source OCT system. The imaging results demonstrate that the proposed system can visualise blood flow at different locations of the hippocampus corresponding with deep brain areas.
Cyanobacteria-specific algicidal mechanism of bioinspired naphthoquinone derivative, NQ 2-0
Authors: Lee Heon Woo , Park Bum Soo , Joo Jae-Hyoung , Patidar Shailesh Kumar , Choi Hye Jeong , Jin EonSeon , Han Myung-Soo
Published: July 2018

To mitigate cyanobacterial blooms, the naphthoquinone derivative, NQ 2-0, which has selective algicidal activity against cyanobacteria, has been developed. However, due to a lack of information on its algicidal mechanisms, there are significant gaps in our understanding of how this substance is capable of selectively killing cyanobacteria. Here, we investigated the selective algicidal mechanisms of NQ 2-0 using target (Microcystis aeruginosa) and non-target (Cyclotella sp. and Selenastrum capricornutum) species. NQ 2-0 showed selective algicidal activity against only M. aeruginosa, and this activity was strongly light-dependent. This NQ compound has selectively reduced the oxygen evolution rate and photosystem II (PSII) efficiency of M. aeruginosa throughout blocking electron transfer from the photosynthetic electron transport system, and significantly (p ≤ 0.05) increased levels of reactive oxygen species (ROS), resulting in membrane damage through lipid peroxidation. In ultrastructural observations, thylakoid membranes were disintegrated within 12 h after NQ 2-0 treatment, and cytoplasmic vacuolation and disintegrated cellular membrane were observed at 24 h. These findings suggest that increased ROS levels following NQ 2-0 treatment may induce cell death. Interestingly, compared to non-target eukaryotic cells, M. aeruginosa showed relatively late antioxidant response to reduce the increased ROS level, this may enhance algicidal activity against this cyanobacterium.
Evidence for Host-Bacterial Co-evolution via Genome Sequence Analysis of 480 Thai Mycobacterium tuberculosis Lineage 1 Isolates
Authors: Palittapongarnpim Prasit , Ajawatanawong Pravech , Viratyosin Wasna , Smittipat Nat , Disratthakit Areeya , Mahasirimongkol Surakameth , Yanai Hideki , Yamada Norio , Nedsuwan Supalert , Imasanguan Worarat , Kantipong Pacharee , Chaiyasirinroje Boonchai , Wongyai Jiraporn , Toyo-oka Licht , Phelan Jody , Parkhill Julian , Clark Taane G. , Hibberd Martin L. , Ruengchai Wuthiwat , Palittapongarnpim Panawun , Juthayothin Tada , Tongsima Sissades , Tokunaga Katsushi
Published: July 2018

Tuberculosis presents a global health challenge. Mycobacterium tuberculosis is divided into several lineages, each with a different geographical distribution. M. tuberculosis lineage 1 (L1) is common in the high-burden areas in East Africa and Southeast Asia. Although the founder effect contributes significantly to the phylogeographic profile, co-evolution between the host and M. tuberculosis may also play a role. Here, we reported the genomic analysis of 480 L1 isolates from patients in northern Thailand. The studied bacterial population was genetically diverse, allowing the identification of a total of 18 sublineages distributed into three major clades. The majority of isolates belonged to L1.1 followed by L1.2.1 and L1.2.2. Comparison of the single nucleotide variant (SNV) phylogenetic tree and the clades defined by spoligotyping revealed some monophyletic clades representing EAI2_MNL, EAI2_NTM and EAI6_BGD1 spoligotypes. Our work demonstrates that ambiguity in spoligotype assignment could be partially resolved if the entire DR region is investigated. Using the information to map L1 diversity across Southeast Asia highlighted differences in the dominant strain-types in each individual country, despite extensive interactions between populations over time. This finding supported the hypothesis that there is co-evolution between the bacteria and the host, and have implications for tuberculosis disease control.
Systemisers are better at maths
Authors: Bressan Paola
Published: July 2018

People with superior mathematical abilities turn out to have an autism spectrum disorder more often than others do. The empathising-systemising theory proposes that this link is mediated by these individuals’ stronger tendency to systemise (detect patterns, derive rules), along with the fact that mathematics is the perfect example of a rule-based, lawful system. This account, however, requires that individuals from the general population who are more inclined to systemise be better at maths than those who are less inclined to do so. Based on the scant available evidence, this has been argued not to be the case. The data presented here show, for the first time, that systemising tendencies do predict both self-assessed maths skills (201 participants) and mathematical intelligence (151 participants), before and after controlling for nonmathematical intelligence, sex, and occupation (social sciences vs biological/physical fields). These findings support the empathising-systemising theory and the “hyper-systemising” explanation of autism.
Experimental Evidence of Amplitude Death and Phase-Flip Bifurcation between In-Phase and Anti-Phase Synchronization
Authors: Manoj Krishna , Pawar Samadhan A. , Sujith R. I.
Published: July 2018

Nonlinear phenomena emerging from the coupled behaviour of a pair of oscillators have attracted considerable research attention over the years, of which, amplitude death (AD) and phase-flip bifurcation (PFB) are two noteworthy examples. Although theoretical research has postulated the coexistence of AD and PFB upon variation of different control parameters, such an occurrence has not been reported in practical systems. Here, we provide the first experimental evidence of the coexistence of AD and PFB in a physical system, comprising of a coupled pair of candle-flame oscillators. As the strength of coupling between the oscillators is increased, we report a decrease in the span of AD region between the states of in-phase and anti-phase oscillations, leading up to a point of PFB. Understanding such a switching of phenomena between AD and PFB helps us to evade their undesirable occurrences such as AD in neuron and brain cells, oscillatory state in prey-predator systems, oscillatory spread of epidemics and so forth.
Transcriptome analysis highlights key differentially expressed genes involved in cellulose and lignin biosynthesis of sugarcane genotypes varying in fiber content
Authors: Kasirajan Lakshmi , Hoang Nam V. , Furtado Agnelo , Botha Frederik C. , Henry Robert J.
Published: July 2018

Sugarcane (Saccharum spp. hybrids) is a potential lignocellulosic feedstock for biofuel production due to its exceptional biomass accumulation ability, high convertible carbohydrate content and a favorable energy input/output ratio. Genetic modification of biofuel traits to improve biomass conversion requires an understanding of the regulation of carbohydrate and lignin biosynthesis. RNA-Seq was used to investigate the transcripts differentially expressed between the immature and mature tissues of the sugarcane genotypes varying in fiber content. Most of the differentially expressed transcripts were found to be down-regulated during stem maturation, highlighting their roles in active secondary cell-wall development in the younger tissues of both high and low fiber genotypes. Several cellulose synthase genes (including CesA2, CesA4, CesA7 and COBRA-like protein), lignin biosynthesis-related genes (ρ-coumarate 3-hydroxylase, ferulate 5-hydroxylase, cinnamyl alcohol dehydrogenase and gentiobiase) and transcription regulators for the secondary cell-wall synthesis (including LIM, MYB, PLATZ, IAA24, C2H2 and C2C2 DOF zinc finger gene families) were exclusively differentially expressed between immature and mature tissues of high fiber genotypes. These findings reveal target genes for subsequent research on the regulation of cellulose and lignin metabolism.