dataesr/scientific-paragraphs-categorization huggingface dataset:
Melatonin levels are believed to govern the vertebrate daily rhythm with high levels occurring at night thus providing a hormonal analog signal of environmental lighting, which can be used to optimize circadian physiology and possibly form the basis of treatment in sleeping disorders. 91, 92 In 2001, the crystal structure of 14-3-3ζ in complex with AANAT was published by the group of Dyda showing that binding to 14-3-3 activates the enzyme by significantly increasing its affinity for its substrates serotonin Crystal structures of 14-3-3 complexes with larger partner protein constructs. (A) 14-3-3ζ/AANAT (PDB ID: 1IB1),  89  (B) T14-3c/PMA2-CT52 (PDB ID: 2O98),  108  and (C) GF14c/Hd3a (PDB ID: 3AXY). 107 Upper row: surface representation of the complex. Lower row: details of the protein-protein complex interfaces.
4  interact in an asymmetric fashion with the ACD dimer of HSPB6 binding to one 14-3-3 monomer and both N-terminal domains in the phosphoaccepting grooves of 14-3-3 (PDB ID: 5LTW). 56 nd acetyl-coenzyme A. 89  In the crystal structure, two AANAT monomers (residues 18-196) bind to the central channel of a 14-3-3 dimer (Figure  4A ). In addition to the phosphorylationdependent interaction of the N-terminus of AANAT, which is accommodated in an extended conformation by the amphipathic groove of the 14-3-3 monomer, the well-structured C-terminal part of the enzyme makes extensive contacts with the inner wall of the 14-3-3 channel. T14-3c/PMA2-CT52 Complex. The plant plasma membrane H + -ATPase (PMA) generates both a chemical proton as well as an electrical gradient (membrane potential) across the plasma membrane.
5 Å. The asymmetric unit was found to contain Figure  6. Binding of peptide 1 (green sticks) to 14-3-3ζ (white cartoon). Residues from 14-3-3 important for interaction with 1 are shown as sticks. Polar interactions are depicted as black dotted lines, and hydrophobic contact surfaces from 14-3-3 are displayed as semitransparent spheres (PDB ID: 1A38). 112.
Further biophysical analyses suggested that the improved binding affinity resulting from the incorporation of the crosslink comes from the significantly decreased conformational flexibility of the macrocyclic molecule. Because all 14-3-3 binding ExoS establishes an extensive hydrophobic contact interface with 14-3-3 with its four leucine residues (Leu422, Leu423, Leu426, Leu428) binding to a hydrophobic patch (blue surface) in the 14-3-3 channel (PDB ID: 2O02). 67 (B) Structural superimposition of wild-type ExoS (orange cartoon and sticks) and the 12-carbon-linker cyclic peptide 2 (green cartoon and sticks) derived from ExoS (PDB ID: 4N84). 115 (C) The 12-carbon linker of 2 engages a semicircular, hydrophobic ring in 14-3-3 (white, semitransparent surface and blue sticks; PDB ID: 4N84). 115 (D) Further optimization of the constrained peptide derived from ExoS using an alkyne-cross-link in 3 (PDB ID: 5J31).
Targeting the 14-3-3σ/TaupS214 interface with modified peptides. (A) Wild-type TaupS214 (golden sticks) bound to 14-3-3σ (white surface and white sticks). Residues from 14-3-3σ important for binding are shown as labeled sticks; polar contacts are depicted as black dotted lines (PDB ID: 4FL5). 121 (B) Structural superimposition of wild-type TaupS214 (golden sticks) and the modified Tau-peptide 4 (green sticks, PDB ID: 4Y32) binding to 14-3-3σ (white surface). 121 (C) Structural superimposition of wild-type TaupS214 (golden sticks) and the modified Tau-peptide hybrid 5 (magenta sticks, PDB ID: 4Y5I) binding to 14-3-3σ (white surface). 121 (D) Structural superimposition of wild-type TaupS214 (golden sticks) and the modified Tau-peptide hybrid 6 (purple sticks, PDB ID: 4Y5I) binding to 14-3-3σ (white surface).
129 These primary screen hits show at least 20% reduction of the polarization emission in the assay that was set up (B) Complex structure of covalent adduct formed between 15 and 14-3-3ζ upon X-ray irradiation (PDB ID: 3RDH). 130 sing a FAM-labeled 8-mer phosphopeptide derived from HSP20 to test for full-length 14-3-3 γ isoform (247 amino acid residues) binding. Compounds belonging to the scaffold PRLX24905 (US patent 20090136561) were further analyzed by FP for their concentration-dependent activity of inhibition. Structurally related scaffolds show a range of activity from no inhibition to 50 μM IC 50 for compound 85070 (14, structure not disclosed). 129 These compounds were additionally evaluated in cell-based assays. Compound 14 was the most efficient in causing, in a dose-dependent manner, a decrease in cell stiffness, decrease in contractile force in ASM cells, and an attenuation of active force development of intact tissue ex vivo.
Their virtual docking into a high-resolution crystal structure of 14-3-3σ (PDB ID: 3P1N) and follow-up analysis led to the synthesis and cocrystallization of 11 14-3-3 inhibitors (e. g. , compound B2 (19, Figure  12 )). 138 A detailed computational analysis of the binding mode of eight of these molecules was performed by the group of Wang et al. 139  They showed that the hydrophilic residues (Arg56, Arg129, and Tyr130 of 14-3-3σ) at the bottom of the binding pocket form seven stable hydrogen bonds with the phosphate group. In addition, two residues (Leu174 and Val178) in contact with a moiety accommodating the phosphate group contribute large van der Waals energies, and residue Leu126 provides large electrostatic energies. This is in agreement with the statement that the phosphate has the strongest pharmacophoric properties.
Polar contacts are depicted as black dotted lines (PDB ID: 5F74). 158 nderstanding of the structure and function of fusicoccadiene synthase  155  will provide the necessary starting points for diverse synthetic strategies. Epibestatin, Pyrrolidone1, and Pyrazole34. In 2010, the results of the first high-throughput screening for 14-3-3 PPI stabilizers were published. 156 Out of a library of 37,000 small molecules, two compounds were found by a surface-based format monitoring the binding of GFP-14-3-3 to surface-immobilized PMA2-CT52: Epibestatin (28)  156  and Pyrrolidone1 (29)  156  (Figure  17 ). The crystal structures of these two compounds in the 14-3-3/PMA2 complexes revealed two distinctive binding pockets in the 14-3-3/PMA2 protein-protein interface. Two years later, Pyrazole34 (30) was published.
Figure3. 14-3-3 structure and binding of partner protein peptides exemplified by the 14-3-3ζ/C-Raf complex (PDB ID: 4FJ3). 61 Top: the physiological 14-3-3 dimer can accommodate two phosphorylated peptide motifs. In the case of C-Raf, two of these motifs (pSer233 and pSer259) are located in the N-terminal region of this protein kinase. When synthesized as a diphospho peptide (C-RafpS233pS259) and crystallized with 14-3-3ζ dimer, a significant proportion of the peptide does not engage an intimate contact with 14-3-3 and is thus not visible in the X-ray crystal structure (right dimer: green dotted line). Bottom: C-RafpS259 site accommodated in the groove of a 14-3-3ζ monomer.
Before taking up his current position in Eindhoven, he was a group leader at the Chemical Genomics Centre (CGC) of the Max Planck Society in Dortmund, Germany. He obtained his Ph. D. in 2003 from the University of Tubingen with Prof. Claudia Oecking. ■ ACKNOWLEDGMENTS This work was funded by The Netherlands Organization for Scientific Research (NWO) via Gravity program 024. 001. 035 and VICI grant 016. 150. 366 and by the Deutsche Forschungsgemeinschaft (DFG) via Collaborative Research Centre 1093. ■ ABBREVIATIONS USED PPI, protein-protein interaction; AANAT, arylalkylamine Nacetyltransferase; PMA, plasma membrane H + -ATPase; FT, flowering locus T; HSP, heat shock protein; ACD, α-Crystallin domain; NTD, N-terminal domain; CTE, C-terminal extension; ExoS, Exoenzyme S; NFT, neurofibrillary tangle; SMM, small molecule microarray; CML, chronic myelogenous leukemia; FP, fluorescence polarization; MDR, multidrug resistant; FT, farnesyl transferase; ERα, estrogen receptor α; CFTR, cystic fibrosis transmembrane conductance regulator; ChREBP, carbohydrate-response element-binding protein; β-HB, βhydroxybutyrate.
140 140 Figure 13. Chemical structure of molecular tweezer 20 (A) and a 3D view of the molecule conformation it adopts for protein recognition (B). (C) Binding of molecular tweezer 20 (yellow sticks) to Lys214 of 14-3-3σ (white sticks) and the electron density (blue mesh, 2F O -F C , contoured at 1. 0 σ). (D) Superimposition of the binding of molecular tweezer 20 (yellow spheres) and the ExoS peptide (416-430, purple sticks) to 14-3-3σ (white surface). (E) Molecular tweezer 20 (yellow sticks and surface) binding to Lys214 of 14-3-3σ (white cartoon and sticks) (PDB IDs: 4HQW and 4HRU). 140.
150 150 Figure 15. Semisynthetic derivatives 23, 26, and 27 stabilize the interaction between 14-3-3σ and TASK3 peptide. (A) Semisynthetic derivative 23 (purple sticks) and the C-terminus of TASK3 peptide (yellow sticks) in the binding groove of 14-3-3σ (cyan surface). (B) Electron density (red, blue, and black mesh, 2F O -F C , contoured at 1. 0 σ) around 23 (purple sticks), C-terminus of TASK3 peptide (yellow sticks), and 14-3-3σ (green sticks). (C) Comparison of 23 (purple sticks) with 26 (orange sticks) and 27 (yellow sticks) in the binding pocket formed by 14-3-3σ (cyan surface) and TASK3 peptide (yellow surface) (PDB IDs: 3SMN, 3SMM, and 3SP5). 150.
Sound generation and recordings (frequency, sound pressure and acceleration) Oysters were exposed to different pure tones in order to assess the frequencies and acoustic energy levels that induce behavioural responses. The sound stimuli were created in Cool Edit Pro (version 2. 0, Syntrillium Software Corporation, USA) using the tone generation tool (WAV format, sampling rate: 44. 1 KHz, 16-bit resolution). Each track of 180 sec pure tone included a 70 sec fade-in (a gradual increase in the level of the audio signal) and no fade-out (no gradual decrease in the level of the signal). The tracks were played with a computer connected to an amplifier (model: AA-5810, AKAI Electric Co. Ltd. , Japan) through two different underwater speakers depending on the sound stimulus: a commercial underwater loudspeaker and a laboratory-made loudspeaker.
Only the rectangular plastic plate was underwater. The sound was recorded at the level of the oysters using a broad-band hydrophone with an internal buffer amplifier (model: H2a-XLR, sensitivity -180 dB re 1 V/μPa, useful range: 10 Hz to 100 kHz, Aquarian Audio Product) linked to a voltage amplifier (Mx34c, Rolls Corporation, USA) and recording software (Wave-Lab v4. 0, Steinberg Media Technologies). In a preliminary experiment, an accelerometer (Dytran underwater accelerometer, model 3217A-10, frequency range 1-10000 Hz, sensitivity 97 mV/g from 10-1000 Hz, weight 5 grams, size 12. 7 x 12. 7 mm) with 2 amplifiers in series (1 M28 IEPE, gain x1; 1 laboratory-made amplifier, gain x 100) was used to determine oyster shell accelerations at various sound pressure levels (SPLs) and frequencies.
The laboratory protocol used here was designed to sample at 3. 3 Hz from 16 animals in a sequential order. Every 300 ms, 3 packets of information were produced: distance between valves at the electrode level, sampling time and animal number. According to the present sampling rate, at the individual level, the system performed a measurement of the opening status every 4. 8 sec. The basic principles are developed in Sow et al. [27] , and examples of application are reviewed in Andrade et al. [28]. The data were analysed according to two protocols. They were transmitted via an acquisition card (NI-USB-6009, National Instrument, Austin, TX, USA) and recorded by a computer using in-house script in LabVIEW (National Instrument). They were also processed to a DELL workstation for analysis performed automatically using both a Bash script (Unix) and mathematical code written in R.
Comparisons among frequency groups were performed by analysis of variance (ANOVA), after checking assumptions of independence, normality and homoscedasticity of the data. When the normality and the homoscedasticity were not met graphically and from ad-hoc tests, we used a Kruskall-Wallis test. If significant effects were detected, the multiple comparison tests between treatments was used to determine which groups are different with pairwise comparisons adjusted appropriately. For all statistical results, a probability of p < 0. 05 was considered significant. All data are provided as supporting Informations (S1 Database).
7%. This minimal decrease was not different from the closing amplitude observed at 300 and 600 Hz (12 ± 2% at A, a logistic regression described the relationship between the percentage of responding oysters in a group and sound frequency. For each frequency, the distribution is described by quartiles (bold line, median). B1, the measured sound pressure level, SPL, for the studied frequencies expressed in rms. B2, the measured shell accelerations at various frequencies expressed in rms. C, the relationship between the percentage of valve opening amplitude and sound frequency. At each frequency, the data distribution is described by quartiles. N = 16 oysters. D1 and D2, Principal Component Analysis describing the correlation between the percentage of responding oysters (% Rep, D1) and valve opening-amplitude decrease (VOA, D2) combined with frequency (Hz), shell acceleration (Acc) and sound pressure level (SPL).
Transcriptome resources Gene expression data were produced to aid the annotation process. Samples from 30 tissues were collected from 2 buffalo calves following humane euthanasia and stored in liquid nitrogen. RNA was prepared using a TRizol TM -based protocol (Thermofisher Scientific, Via G. B. Tiepolo, 18. I-20900 Monza MB, Italy) or RNeasy mini isolation kit (Qiagen, Venlo, the Netherlands), depending on the tissue. RNA integrity was assessed using an Agilent Technologies 2100 Bioanalyzer, and samples with an RNA Integrity Number (RIN) value greater than 8. 5 were used to prepare libraries with an mRNA-Seq sample preparation kit (Illumina Inc. San Diego, CA, USA) according to the manufacturer's protocol. Sequencing of 2 × 100 paired-ends was carried out on an Illumina HiSeq 2000. An average of 53.
Genome annotation Annotation of genes, transcripts, and proteins was done using the NCBI Eukaryotic Genome Annotation Pipeline  [12]. The NCBI pipeline operates on a RefSeq copy of the submitted assembly and produces RefSeq transcript and protein models, which are tracked with NCBI Gene IDs. Prior to annotation, the genome was first masked for repeats using WindowMasker  [13]. Transcripts, RNA-Seq reads, and proteins that were publicly available in NCBI archival databases as of November 2013 were aligned with the masked assembly using splice-aware global alignment tools Splign  [14]  and ProSplign  [15]. The evidence used as input for this annotation run included 3004 buffalo transcripts present in Genbank or EST records, 737 buffalo Genbank protein sequences, 35 660 human known RefSeq proteins (with   [16].
Partial putative models were then extended by Gnomon, using an HMM-based algorithm from GenScan (GenScan, RRID:SCR 012902)  [17]  to gain start or stop codons or fill small internal gaps. In some cases, Gnomon also introduced sequence insertions or deletions (In-Dels) in the models to retain the supported reading frame at genomic InDel locations. The frame-shift corrected models were annotated with a title prefix "PREDICTED: LOW QUALITY PRO-TEIN. " In addition, a small number of models was predicted ab initio by Gnomon. The final set of models selected from the Gnomon set excluded ab initio predictions with no strong hit to UniProtKB/SwissProt or to eukaryotic proteins in the nr database, predictions with high homology to transposable or retro-transposable elements and poorly supported predictions conflicting with better-supported models annotated on the opposite strand.
In addition, for genes with multiple alternative variants, the model selected had to be supported in its entirety by a single long alignment (e. g. , a full-length mRNA) or by RNA-Seq reads from a single sample. Protein naming was based on human orthologs, or lacking that, on best protein similarity; human orthologs were identified based on shared best Swiss-Prot alignments for the human Ref-Seq protein and the buffalo protein model, as well as considerations of local conservation of synteny  [18]. The gene "type" categorization (e. g. , protein-coding, pseudogene, non-coding RNA locus) was determined based on observed open reading frame lengths, statistical coding propensity, protein alignments, and protein orthology to human orthologs. The final RefSeq annotation contains a total of 21 711 protein-coding genes (Table  3 ) and is collectively called Bubalus bubalis Annotation Release 100, which is available in the NCBI Nucleotide, Protein, and Gene resources database  [10].
Sequence repeats Repeats in the buffalo genome assembly were identified using the RepeatMasker suite (RepeatMasker, RRID:SCR 012954)  [20]. Scanning the buffalo genome assembly for cattle repeats as defined in the Repbase database  [21]  identified more than 3. 8 million repetitive elements (Table  S1 ). The majority of these repeated elements belong to the short interspersed elements (SINE > 2 million) and long interspersed elements (LINE > 1. 1 million) families. In total, more than 1. 2 giga base pairs (Gbp) of the buffalo genome assembly belong to repetitive elements, corresponding to 43. 69% of the whole assembly.
All genomes in the table were annotated by NCBI, and the average genome size is approximately 2. 8 Gbp. The total number of annotated proteins in buffalo is most similar to cattle (21 295), followed by goat  (20 755) , sheep (20 645), and then pig, the latter of which has more annotated protein coding genes (24 205). The number of partial coding sequence (CDS) is an indication of the quality of the genome annotation; the smaller the number of partial CDS, the better the annotation. The recently published goat genome  [17]  was assembled using the latest sequencing technologies and hence has high annotation quality, with only 455 partial CDS. Surprisingly, the buffalo genome assembly described here has fewer partial CDS than cattle and pig (see Table  4 ), considering that it was assembled using a combination of data from older 454 and Illumina short reads.
Despite the economic importance of spider mites (Acari: Tetranychidae), data on their biodiversity are scarce in some regions of Europe, such as Balkan Peninsula and particularly in Serbia. In this country, according to the Spider Mites Web database, only 17 spider mite species belonging to seven genera have been reported. This study provides a review of the Serbian literature dealing with spider mite species recorded in Serbia and presents results of a four-year faunistic survey in which spider mites were collected on cultivated plants and native vegetation throughout the country. In the survey, a total of 23 species were recorded, including six species new to Serbian acarofauna: Bryobia praetiosa, Eotetranychus aceri, E. fraxini, E. pruni, Panonychus citri and Tetranychus evansi. Together with previously reported data, it raises the number of known spider mite species in Serbia to 36.
Introduction Spider mites (Acari: Tetranychidae) represent the most important pest mites with 1305 valid species and 3808 host plant records according to the Spider Mites Web database  (Migeon and Dorkeld, 2017). This family includes species belonging to the most important mite pests of agricultural crops and ornamentals worldwide  (Bolland et al. , 1988; Zhang, 2003; Hoy, 2011). Despite the economic importance of spider mites, data on their biodiversity are scarce in some regions of Europe, such as Balkan Peninsula. In Serbia, which is located in the center of Balkans, 17 spider mite species belonging to six genera have been reported, according to the Spider Mites Web database  (Migeon and Dorkeld, 2017). In Balkan countries located to the west and south of Serbia, 7 species have been reported from Slovenia  (Bohinc and Trdan, 2013) ; in Bulgaria and Romania, located in the eastern part of Balkans, 8 and 12 species have been reported, respectively.
Mites were recovered from plant samples in two different ways: i) one by one, directly from field samples using a paint brush; ii) in the laboratory, mites were extracted from leave samples following the soaking-washing-filtering method  (Boller, 1984). All the specimens were temporarily preserved in 70% ethyl alcohol and then cleared in lactic acid (50%) for 24-48 hours and mounted in Hoyer's medium  (Krantz and Walter 2009). Mites were examined using a Leica DMLB II phase contrast microscope and for some specimens, when needed, measurements were performed using the imaging software Perfect Image ® (Clara Vision) coupled with ProgRes ® Capture Pro 2. 6 software for image acquisition. Identification of mites at the genus level was performed using the key to the spider mites genera of the world  (Bolland et al.
The others were mostly oligophagous species of minor economic importance, found on ornamental and shade trees (for details see Table  1 ). Diapausing individuals of B. graminum were found in fallen cones of Douglas-fir (Pseudotsuga menziesii (Mirb. ) Franco). A total of 58 plant species from 26 families were recorded as hosts of 17 spider mite species in the survey. Mladenović et al. (2013)  and  Mladenović (2014)  provided faunistic data on tetranychids collected mostly on wild fruit trees and shrubs in forest habitats. They found 12 species new to Serbian acarofauna (Table  1 ) and 14 new plant species and three new families were recorded as hosts of tetranychids in Serbia. Stojnić et al. (2014)  studied spider mites diversity on cultivated and wild apple trees in Serbia and reported two wild apple species as new hosts of A.
Acknowledgements This research was funded by the  Ministry of Education, Science and Technological Development of the Republic of Serbia  (grant  TR31043 ). The authors are very grateful to  Professor Carlos H. W. Flechtmann  for his valuable suggestions and help in preparation of the manuscript. We are also very grateful to  Maria Navajas  for providing us lab accommodation for the biggest part of this research, and to  Philipp Chetverikov  who provide us translations of some important manuscripts.
, 2014). A third, atlas-based AC method is currently being developed  (Koesters et al. , 2016; Paulus et al. , 2015). To further improve the quantitative accuracy, a number of methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. The template/atlas-based methods create a pseudo-CT image by co-registering database-subjects to a patient's MR image. The atlas or template can be based on pairs of CT and dual UTE  (Delso et al. , 2014b; Roy et al. , 2014) , CT and anatomical MRI (Dixon, T1, and/or T2-weighted sequences)  (Anazodo et al. , 2014; Andreasen et al. , 2015; Burgos et al. , 2014; Izquierdo-Garcia et al. , 2014; Merida et al. , 2015; Schreibmann et al. , 2010; Sekine et al. , 2016a; Torrado-Carvajal et al.
Patients Data sets were obtained retrospectively from two different centers; Rigshospitalet, University Hospital Copenhagen, Denmark, and Washington University, St. Louis, United States of America. The Rigshospitalet data were comprised from data sets from the complete cohort of patients referred for a clinical FDG PET/MRI brain examination, either in neuro-oncology or dementia, as well as the complete cohort of subjects having undergone PiB PET/MRI examinations. These cohorts included healthy subjects and patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), or clinical dementia. In total, 210 subjects with FDG PET/MRI scans (5 healthy volunteers, 4 neuro-oncological patients, 201 MCI, AD or clinical dementia patients) and 51 subjects scanned with PiB (1 healthy volunteer, 50 MCI, AD or clinical dementia patients) were consecutively selected between November 2013 and April 2015.