bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions
Authors: Grebeňová Dana , Holoubek Aleš , Röselová Pavla , Obr Adam , Brodská Barbora , Kuželová Kateřina 
Published: November 2019

AbstractP21-activated kinases (PAK) are key effectors of the small GTPases Rac1 and Cdc42, as well as of Src family kinases. In particular, PAK1 has several well-documented roles, both kinase-dependent and kinase-independent, in cancer-related processes, such as cell proliferation, adhesion, and migration. However, PAK1 properties and functions have not been attributed to individual PAK1 isoforms: besides the full-length kinase (PAK1-full), a splicing variant lacking the exon 15 (PAK1Δ15) is annotated in protein databases. In addition, it is not clear if PAK1 and PAK2 are functionally overlapping. Using fluorescently tagged forms of human PAK1-full, PAK1Δ15, and PAK2, we analyzed their intracellular localization and mutual interactions. Effects of PAK inhibition (IPA-3, FRAX597) or depletion (siRNA) on cell-surface adhesion were monitored by real-time microimpedance measurement. Both PAK1Δ15 and PAK2, but not PAK1-full, were enriched in focal adhesions, indicating that the C-terminus might be important for PAK intracellular localization. Using coimmunoprecipitation, we documented direct interactions among the studied PAK group I members: PAK1 and PAK2 form homodimers, but all possible heterocomplexes were also detected. Interaction of PAK1Δ15 or PAK2 with PAK1-full was associated with extensive PAK1Δ15/PAK2 cleavage. The impedance measurements indicate, that PAK2 depletion slows down cell attachment to a surface, and that PAK1-full is involved in cell spreading. Altogether, our data suggest a complex interplay among different PAK group I members, which have non-redundant functions.
Integrative genetic map of repetitive DNA in the sole Solea senegalensis genome shows a Rex transposon located in a proto-sex chromosome
Authors: García Emilio , Cross Ismael , Portela-Bens Silvia , Rodríguez María E. , García-Angulo Aglaya , Molina Belén , Cuadrado Angeles , Liehr Thomas , Rebordinos Laureana 
Published: November 2019

AbstractRepetitive sequences play an essential role in the structural and functional evolution of the genome, particularly in the sexual chromosomes. The Senegalese sole (Solea senegalensis) is a valuable flatfish in aquaculture albeit few studies have addressed the mapping and characterization of repetitive DNA families. Here we analyzed the Simple Sequence Repeats (SSRs) and Transposable elements (TEs) content from fifty-seven BAC clones (spanning 7.9 Mb) of this species, located in chromosomes by multiple fluorescence in situ hybridization (m-BAC-FISH) technique. The SSR analysis revealed an average density of 675.1 loci per Mb and a high abundance (59.69%) of dinucleotide coverage was observed, being ‘AC’ the most abundant. An SSR-FISH analysis using eleven probes was also carried out and seven of the 11 probes yielded positive signals. ‘AC’ probes were present as large clusters in almost all chromosomes, supporting the bioinformatic analysis. Regarding TEs, DNA transposons (Class II) were the most abundant. In Class I, LINE elements were the most abundant and the hAT family was the most represented in Class II. Rex/Babar subfamily, observed in two BAC clones mapping to chromosome pair 1, showed the longest match. This chromosome pair has been recently reported as a putative sexual proto-chromosome in this species, highlighting the possible role of the Rex element in the evolution of this chromosome. In the Rex1 phylogenetic tree, the Senegalese sole Rex1 retrotransposon could be associated with one of the four major ancient lineages in fish genomes, in which it is included O. latipes.
Transcriptional Activation of Arabidopsis Zygotes Is Required for Initial Cell Divisions
Authors: Kao Ping , Nodine Michael D. 
Published: November 2019

AbstractCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is physiologically required in zygotes and early embryos. Our results indicate that zygotic genome activation occurs soon after fertilization and is required for the initial zygotic divisions in Arabidopsis.
Fabrication and characterization of AlN-based flexible piezoelectric pressure sensor integrated into an implantable artificial pancreas
Authors: Signore M. A. , Rescio G. , De Pascali C. , Iacovacci V. , Dario P. , Leone A. , Quaranta F. , Taurino A. , Siciliano P. , Francioso L. 
Published: November 2019

AbstractThis study reports on the fabrication and characterization of an event detection subsystem composed of a flexible piezoelectric pressure sensor and the electronic interface to be integrated into an implantable artificial pancreas (IAP) for diabetic patients. The developed sensor is made of an AlN layer, sandwiched between two Ti electrodes, sputtered on Kapton substrate, with a preferential orientation along c-axis which guarantees the best piezoelectric response. The IAP is made of an intestinal wall-interfaced refilling module, able to dock an ingestible insulin capsule. A linearly actuated needle punches the duodenum tissue and then the PDMS capsule to transfer the insulin to an implanted reservoir. The device is located at the connection of the needle with the linear actuator to reliably detect the occurred punching of the insulin-filled capsule. Finite Element Analysis (FEA) simulations were performed to evaluate the piezoelectric charge generated for increasing loads in the range of interest, applied on both the sensor full-area and footprint area of the Hamilton needle used for the capsule punching. The sensor-interface circuit was simulated to estimate the output voltage that can be obtained in real operating conditions. The characterization results confirmed a high device sensitivity during the punching, in the low forces (0–4 N) and low actuator speed (2–3 mm/s) ranges of interest, meeting the requirement of the research objective. The choice of a piezoelectric pressure sensor is particularly strategic in the medical field due to the request of self-powered implantable devices which do not need any external power source to output a signal and harvest energy from natural sources around the patient.
In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia
Authors: Ku Nam Su , Lee Su-Hyung , Lim Young- soun , Choi Heun , Ahn Jin Young , Jeong Su Jin , Shin Sung Jae , Choi Jun Yong , Choi Young Hwa , Yeom Joon-Sup , Yong Dongeun , Song Young Goo , Kim June Myung 
Published: November 2019

AbstractUnfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.
Photo-ID and telemetry highlight a global whale shark hotspot in Palawan, Philippines
Authors: Araujo Gonzalo , Agustines Ariana , Tracey Brian , Snow Sally , Labaja Jessica , Ponzo Alessandro 
Published: November 2019

AbstractThe Philippines is home to the second largest known population of whale sharks in the world. The species is listed as endangered due to continued population declines in the Indo-Pacific. Knowledge about the connectivity within Southeast Asia remains poor, and thus international management is difficult. Here, we employed pop-up archival tags, data mining and dedicated effort to understand an aggregation of whale sharks at Honda Bay, Palawan, Philippines, and its role in the species' conservation. Between Apr and Oct 2018, we conducted 159 surveys identifying 117 individual whale sharks through their unique spot patterns (96.5% male, mean 4.5 m). A further 66 individual whale sharks were identified from local operators, and data mined on social media platforms. The satellite telemetry data showed that the whale sharks moved broadly, with one individual moving to Sabah, Malaysia, before returning to the site <1 year later. Similarly, another tagged whale shark returned to the site at a similar periodicity after reaching the Malay-Filipino border. One individual whale shark first identified in East Kalimantan, Indonesia by a citizen scientist was resighted in Honda Bay ~3.5 years later. Honda Bay is a globally important site for the endangered whale shark with connectivity to two neighbouring countries, highlighting the need for international cooperation to manage the species.
Divergence in social traits in Trinidadian guppies selectively bred for high and low leadership in a cooperative context
Authors: Dimitriadou S. , Croft D. P. , Darden S. K. 
Published: November 2019

AbstractIn many animal species, individuals with certain morphological, physiological, or behavioural traits may have a disproportionately large role in determining group behaviour. While most empirical studies of leadership have focused on behaviour of individuals exploring new environments or foraging, little is known about leading behaviour in other ecological contexts. Here, we use a selective breeding design in the Trinidadian guppy (Poecilia reticulata) to quantify the heritability of leadership in a cooperative context, and determine the behavioural traits associated with it. Firstly we found that phenotypic selection for high and low leadership (HL and LL, respectively) over three filial generations resulted in pronounced differences in leadership tendency with a moderate degree of heritability. In our assay of other social traits, LL males were more aggressive and sampled their social environment less than HL males, but HL and LL females did not differ in either aggressiveness or sociability. Traits such as boldness and exploratory tendency did not diverge between the two lines. Leading behaviour was thus associated with social traits in males, but not females; suggesting that there may be sex-specific mechanisms driving the emergence of leadership in this context. We discuss our findings in the context of the evolution of cooperation.
A Four Month Randomized Controlled Trial on the Efficacy of Once-daily Fenofibrate Monotherapy in Persons with Spinal Cord Injury
Authors: La Fountaine Michael F. , Cirnigliaro Christopher M. , Hobson Joshua C. , Lombard Alexander T. , Specht Adam F. , Dyson-Hudson Trevor A. , Kirshblum Steven C. , Bauman William A. 
Published: November 2019

AbstractAn open-label, randomized clinical trial of once-daily fenofibrate monotherapy administered for 2- (Mo2) and 4- (Mo4) months using modified intervention thresholds for triglyceride (TG) was performed in persons with chronic spinal cord injury (SCI). Fenofibrate (145 mg tablet) was self-administered daily in 10 persons with SCI for 4 months with monthly blood testing to quantify the lipoprotein profile (e.g., serum TG, LDL-C, and HDL-C concentrations). Eight SCI participants were control subjects. In comparison to the control group, the treatment group at Mo2 had a 40% (±12%; p < 0.05) reduction in serum TG concentration, a 28% (±21%; p < 0.05) increase in HDL-C and 14% (±20%; p < 0.05) decline in LDL-C. In the same comparison at Mo4, the treatment group maintained a 40% (±20%; p < 0.05) reduction in serum TG concentration, had an 18% in reduction in LDL-C (±12%; p < 0.05) and a 23% (±23%; p < 0.05) increase in HDL-C. Fenofibrate monotherapy for Mo2 and Mo4 initiated in persons with SCI resulted in a robust and favorable change in the serum lipoprotein profile and ratios, suggesting reduced risk for cardiovascular disease.
Role of opioid receptors in modulation of P2X receptor-mediated cardiac sympathoexcitatory reflex response
Authors: Fu Liang-Wu , Tjen-A-Looi Stephanie C. , Barvarz Sherwin , Guo Zhi-Ling , Malik Shaista 
Published: November 2019

AbstractMyocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents’ activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X2/3and P2X3receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X2/3and P2X3, but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.
Colibacter massiliensis gen. nov. sp. nov., a novel Gram-stain-positive anaerobic diplococcal bacterium, isolated from the human left colon
Authors: Anani Hussein , Abdallah Rita Abou , Khoder May , Fontanini Anthony , Mailhe Morgane , Ricaboni Davide , Raoult Didier , Fournier Pierre-Edouard 
Published: November 2019

AbstractThe gut microbiota is considered to play a key role in human health. As a consequence, deciphering its microbial diversity is mandatory. A polyphasic taxonogenomic strategy based on the combination of phenotypic and genomic analyses was used to characterize a new bacterium, strain Marseille-P2911. This strain was isolated from a left colon sample of a 60-year old man who underwent a colonoscopy for an etiological investigation of iron-deficiency anemia in Marseille, France. On the basis of 16S rRNA sequence comparison, the closest phylogenetic neighbor was Anaeroglobus geminatus (94.59% 16S rRNA gene sequence similarity) within the family Veillonellaceae. Cells were anaerobic, Gram-stain-positive, non-spore-forming, catalase/oxidase negative cocci grouped in pairs. The bacterium was able to grow at 37 °C after 2 days of incubation. Strain Marseille-P2911 exhibited a genome size of 1,715,864-bp with a 50.2% G + C content, and digital DNA-DNA hybridization (dDDH) and OrthoANI values with A. geminatus of only 19.1 ± 4.5% and 74.42%, respectively. The latter value being lower than the threshold for genus delineation (80.5%), we propose the creation of the new genus Colibacter gen. nov., with strain Marseille-P2911T (=DSM 103304 = CSUR P2911) being the type strain of the new species Colibacter massiliensis gen. nov., sp. nov.
Area of residual tumor (ART) can predict prognosis after post neoadjuvant therapy resection for pancreatic ductal adenocarcinoma
Authors: Okubo Satoshi , Kojima Motohiro , Matsuda Yoko , Hioki Masayoshi , Shimizu Yasuhiro , Toyama Hirochika , Morinaga Soichiro , Gotohda Naoto , Uesaka Katsuhiko , Ishii Genichiro , Mino-Kenudson Mari , Takahashi Shinichiro 
Published: November 2019

AbstractAn increasing number of patients with pancreatic ductal adenocarcinoma (PDAC) have undergone resection after neoadjuvant therapy (NAT). We have reported Area of Residual Tumor (ART) as a useful pathological assessment method to predict patient outcomes after post NAT resection in various cancer types. The aim of this study was to assess the prognostic performance of ART in PDAC resected after NAT. Sixty-three patients with PDAC after post NAT resection were analyzed. The viable residual tumor area was outlined and the measurement of ART was performed using morphometric software. The results were compared with those of the College of American Pathologist (CAP) regression grading. Of 63 cases, 39 (62%) patients received chemoradiation therapy and 24 (38%) received chemotherapy only. The median value of ART was 163 mm2. Large ART with 220 mm2 as the cut-off was significantly associated with lymphatic invasion, vascular invasion and perineural invasion, while CAP regression grading was not associated with any clinicopathological features. By multivariate analysis, large ART (≥220 mm2) was an independent predictor of shorter relapse free survival. Together with our previous reports, an ART-based pathological assessment may become a useful method to predict patient outcomes after post NAT resection across various cancer types.
Male mice lacking ADAMTS-16 are fertile but exhibit testes of reduced weight
Authors: Livermore Catherine , Warr Nick , Chalon Nicolas , Siggers Pam , Mianné Joffrey , Codner Gemma , Teboul Lydia , Wells Sara , Greenfield Andy 
Published: November 2019

AbstractAdamts16 encodes a disintegrin-like and metalloproteinase with thrombospondin motifs, 16, a member of a family of multi-domain, zinc-binding proteinases. ADAMTS-16 is implicated in a number of pathological conditions, including hypertension, cancer and osteoarthritis. A large number of observations, including a recent report of human ADAMTS16 variants in cases of 46,XY disorders/differences of sex development (DSD), also implicate this gene in human testis determination. We used CRISPR/Cas9 genome editing to generate a loss-of-function allele in the mouse in order to examine whether ADAMTS-16 functions in mouse testis determination or testicular function. Male mice lacking Adamts16 on the C57BL/6N background undergo normal testis determination in the fetal period. However, adult homozygotes have an average testis weight that is around 10% lower than age-matched controls. Cohorts of mutant males tested at 3-months and 6-months of age were fertile. We conclude that ADAMTS-16 is not required for testis determination or male fertility in mice. We discuss these phenotypic data and their significance for our understanding of ADAMTS-16 function.
Demography, heritability and genetic correlation of feline hip dysplasia and response to selection in a health screening programme
Authors: Low Matthew , Eksell Per , Högström Kjell , Olsson Ulrika , Audell Lars , Ohlsson Åsa 
Published: November 2019

AbstractFeline hip dysplasia (FHD) is a debilitating condition affecting the hip joints of millions of domestic cats worldwide. Despite this, little is known about FHD except that it is relatively common in the large breed Maine Coon. We used 20 years of data from 5038 pedigree-registered Maine Coon cats in a radiographic health screening programme for FHD to determine, for the first time, its heritability, genetic correlation to body mass and response to selection. FHD prevalence was 37.4%, with no sex predilection; however, FHD severity increased with age and body mass. Heritability of the radiographic categories used to classify FHD severity was 0.36 (95%CI: 0.30–0.43). The severity of FHD symptoms was also genetically correlated with body mass (0.285), suggesting that selection for a large body type in this breed concurrently selects for FHD. Support for this was found by following generational responses to selective breeding against FHD. Not only did selective breeding successfully reduce the severity of FHD symptoms in descendants, but these cats were also smaller than their ancestors (−33g per generation). This study highlights the value of breeding programmes against FHD and cautions against breed standards that actively encourage large bodied cats.
Short tryptophan- and arginine-rich peptide shows efficacy against clinical methicillin-resistant Staphylococcus aureus strains isolated from skin and soft tissue infections
Authors: Bacalum Mihaela , Dragulescu Elena-Carmina , Necula George , Codita Irina , Radu Mihai 
Published: November 2019

AbstractIn recent years methicillin-resistant Staphylococcus aureus has posed a challenge in treating skin and soft tissue infections. Finding new antimicrobial agents has therefore become imperative. We evaluated the in vitro antimicrobial activity of a synthetic peptide, P6, against multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. The P6 antimicrobial effect was evaluated in vitro by determining MIC/MBC, the ratio of live/dead cells and the effects induced at membrane level. The therapeutic efficiency was determined against human skin cells. P6 inhibited growth for all strains between 8 and 16 mg/L and killed all bacterial strains at 16 mg/L. The therapeutic potential was found to be 30 and 15 in the presence of BSA. We showed that P6 localizes at membrane level, where it acts slowly, by depolarizing it and affecting its integrity. P6 can be considered a good candidate for use as an antimicrobial agent in topical applications.
Curvature increases permeability of the plasma membrane for ions, water and the anti-cancer drugs cisplatin and gemcitabine
Authors: Yesylevskyy Semen , Rivel Timothée , Ramseyer Christophe 
Published: November 2019

AbstractIn this work the permeability of a model asymmetric plasma membrane, for ions, water and the anti-cancer drugs cisplatin and gemcitabine is studied by means of all-atom molecular dynamics simulations. It is shown for the first time that permeability of the highly curved membrane increases from one to three orders of magnitude upon membrane bending depending on the compound and the sign of curvature. Our results suggest that the membrane curvature could be an important factor of drug translocation through the membrane.