bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin
Authors: Hu J. , Worrall L. J. , Hong C. , Vuckovic M. , Atkinson C. E. , Caveney N. , Yu Z. , Strynadka N. C. J. 
Published: September 2018

AbstractThe bacterial type III secretion system, or injectisome, is a syringe shaped nanomachine essential for the virulence of many disease causing Gram-negative bacteria. At the core of the injectisome structure is the needle complex, a continuous channel formed by the highly oligomerized inner and outer membrane hollow rings and a polymerized helical needle filament which spans through and projects into the infected host cell. Here we present the near-atomic resolution structure of a needle complex from the prototypical Salmonella Typhimurium SPI-1 type III secretion system, with local masking protocols allowing for model building and refinement of the major membrane spanning components of the needle complex base in addition to an isolated needle filament. This work provides significant insight into injectisome structure and assembly and importantly captures the molecular basis for substrate induced gating in the giant outer membrane secretin portal family.
Human augmentation of ecosystems: objectives for food production and science by 2045
Authors: Funabashi Masatoshi 
Published: September 2018

AbstractCurrent food production systems require fundamental reformation in the face of population growth, climate change, and degradation of health and the environment. Over the course of human history, every agricultural system that has emerged has featured some sort of trade-off between productivity and environmental load. These trade-offs are causing the planet to exceed the boundaries of its biogeochemical cycles and are triggering an unprecedented extinction rate of wild species, thus pushing global ecosystems to the brink of collapse. In this era, characterized as it is by human activity that can profoundly influence climate and the environment (i.e., the Anthropocene epoch), tipping points can be either negative or positive. While a negative tipping point can produce sudden, rapid, and irreversible deterioration of social and environmental systems, a positive tipping point can produce improved health and sustainable social-ecological systems. The key to promoting positive global tipping points is a thorough understanding of human activity and life history on an evolutionary scale, along with the comprehensive integration of science and technology to produce intelligent policies and practices of food production, particularly in the developing world (See Supplementary Material 1 summary for policymakers). Simply increasing the efficiency and scale of monoculture-intensive agriculture is unlikely to drive social-ecological change in a positive and sustainable direction. A new solution to the health-diet-environment trilemma must be developed to achieve a net positive impact on biodiversity through the anthropogenic augmentation of ecosystems based on the ecological foundation of genetic, metabolic, and ecosystem health. This paper discusses the fundamental requirements for sustainable food production on the molecular, physiological, and ecological scales, including evolutionary and geological insights, in an attempt to identify the global conditions needed for the primary food production to ensure we survive this century. Particular emphasis is placed on how to make extensive use of this planet’s genetic resources without irretrievably losing them.
Architecture-Guided Fluid Flow Directs Renal Biomineralization
Authors: Ho Sunita P. , Chen Ling , Allen Frances I. , Hsi Ryan S. , Shimotake Alex R. , Wiener Scott V. , Kang Misun , Minor Andrew M. , Stoller Marshall L. 
Published: September 2018

AbstractNephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the medullo-papillary complex (MPC) known as Randall’s plaque (RP). Contextualizing proximally observed biominerals within the MPC has led us to postulate a mechanobiological switch that can trigger interstitial biomineralization at the MPC tip, remote from the intratubular biominerals. Micro X-ray computed tomography scans of human MPCs correlated with transmission and scanning electron micrographs, and X-ray energy dispersive spectrometry demonstrated novel findings about anatomically-specific biominerals. An abundance of proximal intratubular biominerals were associated with emergence of distal interstitial RP. The fundamental architecture of the MPC and mineral densities at the proximal and distal locations of the MPC differed markedly. A predominance of plate-like minerals or radially oriented plate-like crystallites within spheroidal minerals in the proximal intratubular locations, and core-shell type crystallites within spheroidal minerals in distal interstitial locations were observed. Based on the MPC anatomic location of structure-specific biominerals, a biological switch within the mineral-free zone occurring between the proximal and distal locations is postulated. The “on” and “off” switch is dependent on changes in the pressure differential resulting from changes in tubule diameters; the “Venturi effect” changes the “circumferential strain” and culminates in interstitial crystal deposits in the distal tubule wall in response to proximal tubular obstruction. These distal interstitial mineralizations can emerge into the collecting system of the kidney linking nephrocalcinosis with nephrolithiasis.
Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma
Authors: Araujo L. F. , Siena A. D. D. , Plaça J. R. , Brotto D. B. , Barros I. I. , Muys B. R. , Biagi C. A. O. , Peronni K. C. , Sousa J. F. , Molfetta G. A. , West L. C. , West A. P. , Leopoldino A. M. , Espreafico E. M. , Silva W. A. 
Published: September 2018

AbstractMitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on energetic metabolism and pro-tumorigenic nuclear gene expression changes. We report a positive correlation between mtDNA copy number, glucose consumption, and ATP production in melanoma cell lines. Gene expression analysis reveals a down-regulation of glycolytic enzymes in cell lines and an up-regulation of amino acid metabolism enzymes in melanoma tumors, suggesting that TFAM may shift melanoma fuel utilization from glycolysis towards amino acid metabolism, especially glutamine. Indeed, proliferation assays reveal that TFAM-down melanoma cell lines display a growth arrest in glutamine-free media, emphasizing that these cells rely more on glutamine metabolism than glycolysis. Finally, our data indicate that TFAM correlates to VEGF expression and may contribute to tumorigenesis by triggering a more invasive gene expression signature. Our findings contribute to the understanding of how TFAM affects melanoma cell metabolism, and they provide new insight into the mechanisms by which TFAM and mtDNA copy number influence melanoma tumorigenesis.
Misfolded SOD1 pathology in sporadic Amyotrophic Lateral Sclerosis
Authors: Paré Bastien , Lehmann Manuela , Beaudin Marie , Nordström Ulrika , Saikali Stephan , Julien Jean-Pierre , Gilthorpe Jonathan D. , Marklund Stefan L. , Cashman Neil R. , Andersen Peter M. , Forsberg Karin , Dupré Nicolas , Gould Peter , Brännström Thomas , Gros-Louis François 
Published: September 2018

AbstractAggregation of mutant superoxide dismutase 1 (SOD1) is a pathological hallmark of a subset of familial ALS patients. However, the possible role of misfolded wild type SOD1 in human ALS is highly debated. To ascertain whether or not misfolded SOD1 is a common pathological feature in non-SOD1ALS, we performed a blinded histological and biochemical analysis ofpost mortembrain and spinal cord tissues from 19 sporadic ALS, compared with aSOD1A4V patient as well as Alzheimer’s disease (AD) and non-neurological controls. Multiple conformation- or misfolded-specific antibodies for human SOD1 were compared. These were generated independently by different research groups and were compared using standardized conditions. Five different misSOD1 staining patterns were found consistently in tissue sections from SALS cases and the SOD1 A4V patient, but were essentially absent in AD and non-neurological controls. We have established clear experimental protocols and provide specific guidelines for working, with conformational/misfolded SOD1-specific antibodies. Adherence to these guidelines will aid in the comparison of the results of future studies and better interpretation of staining patterns. This blinded, standardized and unbiased approach provides further support for a possible pathological role of misSOD1 in SALS.
Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread
Authors: Kim Deok-Ho , Ewald Andrew J. , Park JinSeok , Kshitiz  , Kwak Moonkyu , Gray Ryan S. , Su Chia-Yi , Seo Jayhyun , An Steven S. , Levchenko Andre 
Published: September 2018

AbstractThe root cause of cancer mortality and morbidity is the metastatic spread of the primary tumor, but underlying mechanisms remain elusive. Here we investigate biomechanical interactions that may accompany invasive spread of melanoma cells. We find that metastatic cells can exert considerable traction forces and modify local collagen organization within a 3D matrix. When this re-organization is mimicked using a nano-fabricated model of aligned extracellular matrix fibers, metastatic cells, including less invasive melanoma cells, were in turn induced to align, elongate and migrate, guided by the local ridge orientations. Strikingly, we found that this aligned migration of melanoma cells was accompanied by long-range regulation of cytoskeletal remodeling that show anisotropic stiffening in the direction of fiber orientation suggestive of a positive feedback between ECM fiber alignment and forces exerted by cancer cells. Taken together, our findings suggest that the invasive spread of cancer cells can be defined by complex interplay with the surrounding matrix, during which they both modify the matrix and use the matrix alignment as a persistent migration cue, leading to more extensive and rapid invasive spread.
Bandgap reduction of photocatalytic TiO2 nanotube by Cu doping
Authors: Gharaei S. Khajoei , Abbasnejad M. , Maezono Ryo 
Published: September 2018

AbstractWe performed the electronic structure calculations of Cu-doped TiO2 nanotubes by using density functional theory aided by the Hubbard correction (DFT + U). Relative positions of the sub-bands due to the dopants in the band diagram are examined to see if they are properly located within the redox interval. The doping is found to tune the material to be a possible candidate for the photocatalyst by making the bandgap accommodated within the visible and infrared range of the solar spectrum. Among several possibilities of the dopant positions, we found that only the case with the dopant located at the center of nanotube seems preventing from electron-hole recombinations to achieve desired photocatalytic activity with n-type behavior.
Saccadic inhibition interrupts ongoing oculomotor activity to enable the rapid deployment of alternate movement plans
Authors: Salinas Emilio , Stanford Terrence R. 
Published: September 2018

AbstractDiverse psychophysical and neurophysiological results show that oculomotor networks are continuously active, such that plans for making the next eye movement are always ongoing. So, when new visual information arrives unexpectedly, how are those plans affected? At what point can the new information start guiding an eye movement, and how? Here, based on modeling and simulation results, we make two observations that are relevant to these questions. First, we note that many experiments, including those investigating the phenomenon known as “saccadic inhibition”, are consistent with the idea that sudden-onset stimuli briefly interrupt the gradual rise in neural activity associated with the preparation of an impending saccade. And second, we show that this stimulus-driven interruption is functionally adaptive, but only if perception is fast. In that case, putting on hold an ongoing saccade plan toward location A allows the oculomotor system to initiate a concurrent, alternative plan toward location B (where a stimulus just appeared), deliberate (briefly) on the priority of each target, and determine which plan should continue. Based on physiological data, we estimate that the advantage of this strategy, relative to one in which any plan once initiated must be completed, is of several tens of milliseconds per saccade.
Mechanical loading, an important factor in the evaluation of ion release from bone augmentation materials
Authors: MacDonald Kathleen , Boyd Daniel 
Published: September 2018

AbstractThe controlled release of therapeutic inorganic ions from biomaterials is an emerging area of international research. One of the foci for this research is the development of materials, which spatially and temporally modulate therapeutic release, via controlled degradation in the intended physiological environment. Crucially however, our understanding of the release kinetics for such systems remains limited, particularly with respect to the influence of physiological loading. Consequently, this study was designed to investigate the effect of dynamic mechanical loading on a composite material intended to stabilize, reinforce and strengthen vertebral bodies. The composite material contains a borate glass engineered to release strontium as a therapeutic inorganic ion at clinically relevant levels over extended time periods. It was observed that both cyclic (6 MPa 2 Hz) and static (4.3 MPa) compressive loading significantly increased the release of strontium ions in comparison to the static unloaded case. The observed alterations in ion release kinetics suggest that the mechanical loading of the implantation environment should be considered when evaluating the ion release kinetics.
Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis
Authors: Odermatt Nina T. , Sala Claudia , Benjak Andrej , Cole Stewart T. 
Published: September 2018

AbstractTight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, the role of a fourth, the mycobacterial integration host factor (mIHF), remains elusive. Here, we report a multidisciplinary functional analysis that exploits a conditional mIHF mutant. Gene silencing was bactericidal and resulted in elongated cells devoid of septa, with only one nucleoid. ChIP-sequencing identified 153 broad peaks distributed around the chromosome, which were often situated upstream of transcriptional start sites where EspR also bound. RNA-sequencing showed expression of 209 genes to be heavily affected upon mIHF depletion, including those for many tRNAs, DNA synthesis and virulence pathways. Consistent with NAP function, mIHF acts as a global regulator by directly and indirectly controlling genes required for pathogenesis and for housekeeping functions.
Mechanistic insights into the host-microbe interaction and pathogen exclusion mediated by the Mucus-binding protein of Lactobacillus plantarum
Authors: Singh Kumar Siddharth , Kumar Sudarshan , Mohanty Ashok Kumar , Grover Sunita , Kaushik Jai Kumar 
Published: September 2018

AbstractSurface adhesins of pathogens and probiotics strains are implicated in mediating the binding of microbes to host. Mucus-binding protein (Mub) is unique to gut inhabiting lactic acid bacteria; however, the precise role of Mub proteins or its structural domains in host-microbial interaction is not well understood. Last two domains (Mubs5s6) of the six mucus-binding domains arranged in tandem at the C-terminus of the Lp_1643 protein of Lactobacillus plantarum was expressed in E. coli. Mubs5s6 showed binding with the rat intestinal mucus, pig gastric mucins and human intestinal tissues. Preincubation of Mubs5s6 with the Caco-2 and HT-29 cell lines inhibited the binding of pathogenic enterotoxigenic E. coli cells to the enterocytes by 68% and 81%, respectively. Pull-down assay suggested Mubs5s6 binding to the host mucosa components like cytokeratins, Hsp90 and Laminin. Mubs5s6 was predicted to possess calcium and glucose binding sites. Binding of Mubs5s6 with these ligands was also experimentally observed. These ligands are known to be associated with pathogenesis suggesting Mub might negotiate pathogens in multiple ways. To study the feasibility of Mubs5s6 delivery in the gut, it was encapsulated in chitosan-sodium tripolyphosphate microspheres with an efficiency of 65% and release up to 85% in near neutral pH zone over a period of 20 hours. Our results show that Mub plays an important role in the host-microbial cross-talk and possesses the potential for pathogen exclusion to a greater extent than mediated by L. plantarum cells. The functional and technological characteristics of Mubs5s6 make it suitable for breaking the host-pathogen interaction.
Lagrangian-like Volume Tracking Paradigm for Mass, Momentum and Energy of Nearshore Tsunamis and Damping Mechanism
Authors: Kim Dae-Hong , Son Sangyoung 
Published: September 2018

AbstractThere is a gap between model- or theory-based research outputs, which suggest that the runup and amplification of nonbreaking waves generally increase as the sea bottom slopes decrease, and field observations, which indicate that tsunami damage has been rarely reported in places with vast continental shelfs. To resolve this contradiction, we propose a Lagrangian-like volume tracking paradigm to describe the energy, mass, and momentum of travelling nearshore tsunamis and apply the paradigm to analyse the tsunami damping mechanism at typical geophysical scales. The results support the following conclusions: (i) The suggested paradigm is consistent with field observations; continental shelfs with long and mild slopes can effectively diminish tsunami impacts. (ii) Potential energy becomes significant due to the energy transformation process on steeply sloped bathymetries. (iii) On mild-sloped bathymetries, tsunami potential and kinetic energies are conserved until breaking occurs. After breaking, undular bores attenuate tsunami energies effectively. (iv) For extended continental shelf bathymetries, more of the tsunami mass is reflected offshore.
Signaling network between the dysregulated expression of microRNAs and mRNAs in propofol-induced developmental neurotoxicity in mice
Authors: Jiang Congshan , Logan Sarah , Yan Yasheng , Inagaki Yasuyoshi , Arzua Thiago , Ma Peizhong , Lu Shemin , Bosnjak Zeljko J. , Bai Xiaowen 
Published: September 2018

AbstractMounting evidence has demonstrated that general anesthetics could induce acute neuroapoptosis in developing animals followed by long-term cognitive dysfunction, with the mechanisms remaining largely unknown. The aim of this study was to investigate the effect of the intravenous anesthetic propofol on the profiles of microRNAs (miRNAs) and messenger RNAs (mRNAs), and their interactive signaling networks in the developing mouse hippocampus. Postnatal day 7 (P7) mice were exposed to propofol for 3 hours. Hippocampi were harvested from both P7 (3 hours after exposure) and P60 mice for the analysis of the expression of 726 miRNAs and 24,881 mRNAs, and apoptosis. Long-term memory ability of P60 mice was analyzed using the Morris Water Maze. Propofol induced acute apoptosis in the hippocampus, and impaired memory function of mice. There were 100 altered mRNAs and 18 dysregulated miRNAs in the propofol-treated hippocampi compared with the intralipid-treated control tissues on P7. Bioinformatics analysis of these abnormally expressed genes on P7 indicated that 34 dysregulated miRNA-mRNA target pairs were related to pathological neurological and developmental disorder processes such as cell viability, cell morphology and migration, neural stem cell proliferation and neurogenesis, oligodendrocyte myelination, reactive oxygen species, and calcium signaling. Neonatal propofol exposure also resulted in the abnormal expression of 49 mRNAs and 4 miRNAs in P60 mouse hippocampi. Specifically, bioinformatics analysis indicates that among these dysregulated mRNAs and miRNAs, there were 2 dysregulated miRNA-mRNA targets pairs (Fam46a/miR-363-3p and Rgs3/miR-363-3p) that might be related to the effect of propofol on long-term cognitive function. Collectively, our novel investigation indicates that acute and long-term dysregulated miRNA-mRNA signaling networks potentially participate in propofol-induced developmental neurotoxicity.
Meningococcus serogroup C clonal complex ST-10217 outbreak in Zamfara State, Northern Nigeria
Authors: Kwambana-Adams Brenda A. , Amaza Rahab C. , Okoi Catherine , Rabiu Murtala , Worwui Archibald , Foster-Nyarko Ebenezer , Ebruke Bernard , Sesay Abdul K. , Senghore Madikay , Umar Abdullahi S. , Usman Rabi , Atiku Adamu , Abdullahi Garba , Buhari Yahaya , Sani Rabiu , Bako Husaini U. , Abdullahi Bashir , Yarima Alliyu I. , Sikiru Badaru , Moses Aderinola Olaolu , Popoola Michael O. , Ekeng Eme , Olayinka Adebola , Mba Nwando , Kankia Adamu , Mamadu Ibrahim N. , Okudo Ifeanyi , Stephen Mary , Ronveaux Olivier , Busuttil Jason , Mwenda Jason M. , Abdulaziz Mohammed , Gummi Sulaiman A. , Adedeji Adebayo , Bita Andre , Omar Linda , Djingarey Mamoudou Harouna , Alemu Wondimagegnehu , D’Alessandro Umberto , Ihekweazu Chikwe , Antonio Martin 
Published: September 2018

AbstractAfter the successful roll out of MenAfriVac, Nigeria has experienced sequential meningitis outbreaks attributed to meningococcus serogroup C (NmC). Zamfara State in North-western Nigeria recently was at the epicentre of the largest NmC outbreak in the 21st Century with 7,140 suspected meningitis cases and 553 deaths reported between December 2016 and May 2017. The overall attack rate was 155 per 100,000 population and children 5–14 years accounted for 47% (3,369/7,140) of suspected cases. The case fatality rate (CFR) among children 5–9 years was 10%, double that reported among adults ≥ 30 years (5%). NmC and pneumococcus accounted for 94% (172/184) and 5% (9/184) of the laboratory-confirmed cases, respectively. The sequenced NmC belonged to the ST-10217 clonal complex (CC). All serotyped pneumococci were PCV10 serotypes. The emergence of NmC ST-10217 CC outbreaks threatens the public health gains made by MenAfriVac, which calls for an urgent strategic action against meningitis outbreaks.