A New Paradigm for KIM-PTP Drug Discovery: Identification of Allosteric Sites with Potential for Selective Inhibition Using Virtual Screening and LEI Analysis

The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases. We have used VSpipe, a virtual screening pipeline, to identify a ligand cluster distribution that is unique to this subfamily of PTPs. Several clusters map onto KIM-PTP specific sequence motifs in contrast to the cluster distribution obtained for PTP1B, a classic PTP that mapped to general PTP motifs. Importantly, the ligand clusters coincide with previously reported functional and substrate binding sites in KIM-PTPs. Assessment of the KIM-PTP specific clusters, using ligand efficiency index (LEI) plots generated by the VSpipe, ascertained that the binders in these clusters reside in a more drug-like chemical–biological space than those at the active site. LEI analysis showed differences between clusters across all KIM-PTPs, highlighting a distinct and specific profile for each phosphatase. The most druggable cluster sites are unexplored allosteric functional sites unique to each target. Exploiting these sites may facilitate the delivery of inhibitors with improved drug-like properties, with selectivity amongst the KIM-PTPs and over other classical PTPs.

Estimating and evaluating the rice cluster distribution uniformity with UAV-based images

The uniformity of the rice cluster distribution in the field affects population quality and the precise management of pesticides and fertilizers. However, there is no appropriate technical system for estimating and evaluating the uniformity at present. For that reason, a method based on unmanned aerial vehicle (UAV images) is proposed to estimate and evaluate the uniformity in this present study. This method includes rice cluster recognition and location determination based on the RGB color characteristics of the seedlings of aerial images, region segmentation considering the rice clusters based on Voronoi Diagram, and uniformity index definition for evaluating the rice cluster distribution based on the variation coefficient. The results indicate the rice cluster recognition attains a high precision, with the precision, accuracy, recall, and F1-score of rice cluster recognition reaching > 95%, 97%, 97%, 95%, and 96%, respectively. The rice cluster location error is small and obeys the gamma (3.00, 0.54) distribution (mean error, 1.62 cm). The uniformity index is reasonable for evaluating the rice cluster distribution verified via simulation. As a whole process, the estimating method is sufficiently high accuracy with relative error less than 0.01% over the manual labeling method. Therefore, this method based on UAV images is feasible, convenient, technologically advanced, inexpensive, and highly precision for the estimation and evaluation of the rice cluster distribution uniformity. However, the evaluation application indicates that there is much room for improvement in terms of the uniformity of mechanized paddy field transplanting in South China.

A Multi-Elements Isotope Approach to Assess the Geographic Provenance of Manila Clams (Ruditapes philippinarum) via Recombining Appropriate Elements

The increasing global consumption of seafood has led to increased trade among nations, accompanied by mislabeling and fraudulent practices that have rendered authentication crucial. The multi-isotope ratio analysis is considered as applicable tool for evaluating geographical authentications but requires information and experience to select target elements such as isotopes, through a distinction method based on differences in habitat and physiology due to origin. The present study examined recombination conditions of multi-elements that facilitated geographically distinct classifications of the clams to sort out appropriate elements. Briefly, linear discriminant analysis (LDA) analysis was performed according to several combinations of five stable isotopes (carbon (δ13C), nitrogen (δ15N), oxygen (δ18O), hydrogen (δD), and sulfur (δ34S)) and two radiogenic elements (strontium (87Sr/86Sr) and neodymium (143Nd/144Nd)), and the geographical classification results of the Manila clam Ruditapes philippinarum from Democratic People’s Republic of Korea (DPR Korea), Korea and China were compared. In conclusion, linear discriminant analysis (LDA) with at least four elements (C, N, O, and S) including S revealed a remarkable cluster distribution of the clams. These findings expanded the application of systematic multi-elements analyses, including stable and radiogenic isotopes, to trace the origins of R. philippinarum collected from the Korea, China, and DPR Korea.

LOCALIZATION OF MITOCHONDRIA IN DONOR OOCYTES OBTAINED FROM COW OVARIES POST MORTEM

Проведен сравнительный морфофункциональный мониторинг популяции донорских ооцитов, выделенных из яичников коров post mortem на разных стадиях овариального цикла, с учетом статуса хроматина и интрацитоплазматической локализации митохондрий ооцит-кумулюсных комплексов. Анализу подвергались ооциты, полученные из антральных фолликулов (Ø 2—6 мм), окруженные не менее, чем 5—6 слоями клеток кумулюса. Показано, что 45% и 50% ооцитов, выделенных из яичников на стадии фолликулярного роста и развитого жёлтого тела, соответственно, имеют периферическую локализацию митохондрий в ооплазме. Доля созревших ооцитов с периферической и равномерной локализацией митохондрий на момент аспирации их из яичников составила 88 и 85% соответственно, а уровень созревших ооцитов в группе с кластерным типом локализации достиг лишь 66%. В группе ооцитов с кластерной локализацией митохондрий отмечен высокий уровень ооцитов с дегенерированным хроматином после 24 ч культивирования (90%) по сравнению с группами с периферической и равномерной локализацией митохондрий (2 и 41% соответственно, P < 0,001). Ооциты с периферической локализацией митохондрий характеризовались гомогенной ооплазмой (58%). Гаметы с кластерным распределением митохондрий в основном имели гетерогенную ооплазму (52%), а клетки с равномерным распределением — гомо- и гетерогенную ооплазму (29 и 36% соответственно). A comparative monitoring of the population of cow donor oocytes isolated from ovaries at different stages of the ovarian cycle was carried out, the chromatin status and the intracytoplasmic localization of mitochondria of oocyte-cumulus complexes were evaluated. Oocytes obtained from antral follicles (Ø 2-6 mm) were analyzed. Gametes were cultured at a temperature of 38.5°C, in an atmosphere with 5% CO2, 90% humidity for 24 hours in T-199 medium supplemented with 10% fetal bovine serum, 106 granulosa cells/ml, 50 ng/ml bovine prolactin. Mitochondria were visualized with using of vital dye rhodamine 123, the chromatin status was assessed by Tarkowski`s cytogenetic method. It was demonstrated that 45% and 50% of oocytes isolated from the ovaries in the stage of follicular growth and developed corpus luteum had a peripheral localization of mitochondria in ooplasm. The proportion of mature oocytes with the peripheral and spread localizations of mitochondria were 88% and 85%, respectively, while the maturation rate of oocytes with the mitochondrial clusters reached only 66%. Among oocytes with cluster distribution of mitochondria a high percent of cells with signs of chromatin degeneration after 24 h culture was noted (90%) compared with groups of oocutes with peripheral and spread distribution (2% and 41%, respectively, P<0,001). Oocytes with the peripheral localization of mitochondria were characterised by homogeneous ooplasm (58%). Gametes with the clusters mostly had a heterogeneous ooplasm (52%), and cells with the spread distribution – homo- and heterogeneous ooplasm (29% and 36%, respectively).

ANALISIS STRUKTUR KOMUNITAS KEPITING DI KAWASAN MANGROVE STASIUN KELAUTAN UNIVERSITAS RIAU KELURAHAN PURNAMA KOTA DUMAI PROVINSI RIAU

This research was conducted in January 2019 in the mangrove area of Purnama Village, Dumai City, Riau Province. The purpose of this study was to determine the crab community structure which includes the type, abundance, crab distribution patterns, species diversity (H '), species uniformity (E), and species dominance (C) crabs. The method used in this study is a survey method. There are three observation stations with each of the three transects at each station, on each transect line there is a square plot with a size of 5x5 m2. Crab sampling is done quantitatively and qualitatively. Based on the results of the study it was found that the species of crabs identified at the area of the research were Sesarma reticulatum, S. guttatum, Uca dussumieri, U. rosea, U. vocans, Cardisoma carnifex, and Clistocoeloma merguinse. Furthermore, the abundance of crabs obtained is between 1560-2040 Ind / Ha with cluster distribution patterns. The average value of species diversity (H ') indicates moderate diversity, uniformity (E) indicates high species uniformity, and species dominance value (C) indicates no dominating species.This research was conducted in January 2019 in the mangrove area of Purnama Village, Dumai City, Riau Province. The purpose of this study was to determine the crab community structure which includes the type, abundance, crab distribution patterns, species diversity (H '), species uniformity (E), and species dominance (C) crabs. The method used in this study is a survey method. There are three observation stations with each of the three transects at each station, on each transect line there is a square plot with a size of 5x5 m2. Crab sampling is done quantitatively and qualitatively. Based on the results of the study it was found that the species of crabs identified at the area of the research were Sesarma reticulatum, S. guttatum, Uca dussumieri, U. rosea, U. vocans, Cardisoma carnifex, and Clistocoeloma merguinse. Furthermore, the abundance of crabs obtained is between 1560-2040 Ind / Ha with cluster distribution patterns. The average value of species diversity (H ') indicates moderate diversity, uniformity (E) indicates high species uniformity, and species dominance value (C) indicates no dominating species.

Distribusi Kasus Demam Berdarah Dengue dan Habitat Perkembangbiakan Nyamuk Aedes aegypti serta Indeks Pupa pada Daerah Endemis dan Non Endemis di Kabupaten Sumba Timur, Nusa Tenggara Timur

Dengue Hemorrhagic Fever (DHF) in Indonesia has spread in 34 provinces and 463 districts/cities. The Incidence Rate (IR) of DHF in East Sumba Regency in 2016 was 28.84 and 2017 increased to 55.28/100,000 population. The descriptive research was to describe the pattern of the spread of DHF cases and the habitat for the proliferation of DHF vectors and index pupae in the DHF endemic and non-endemic areas.The results showed that the Nearest Neighbor Ratio value in endemic areas was 0.292003 and in non-endemic areas was 0.718375. Moreover, the house pupae index was 53.3% and 41.0%, respectively The number of pupae/houses in endemic areas was 16.9 pupae/house, and in non-endemic areas was 11.9 pupae per house. The average pupae in each container in endemic areas were 3.6 pupae/container and sporadic areas were 2.2 pupae/container. The pupae/person value in endemic areas was 3.5 pupae/person and non-endemic areas was 2.2 pupae/person. The study concluded that there was a spatial relationship between DHF cases and DHF vector habitat with cluster distribution patterns. The number of pupae per house and pupae per person is still above the threshold value for DHF transmission in both endemic and non endemic areas. Keywords: DHF, endemicity, habitat, pupae index, East Sumba Abstrak DBD di Indonesia telah menyebar di 34 provinsi dan 463 kabupaten/Kota. Incidence Rate (IR) DBD pada tahun 2015 sebesar 89,37/100.000 penduduk dan menurun pada tahun 2016 menjadi 78,85/100.000 penduduk. Incidence Rate (IR) DBD di Kabupaten Sumba Timur tahun 2016 sebesar 28,84 dan 2017 meningkat menjadi 55,28/100.000 penduduk. Tujuan penelitian deskriptif ini adalah untuk menggambarkan pola penyebaran kasus DBD dan habitat perkembangbiakan vektor DBD serta pupa indeks di daerah endemis dan non endemis DBD, Kabupaten Sumba Timur, NTT. Hasil penelitian menunjukkan nilai Nearest Neighbour Ratio daerah endemis sebesar 0,292003, dan pada daerah non endemis sebesar 0,718375. House pupae index pada daerah endemis sebesar 53,3 % dan daerah non endemis 41,0%. Jumlah pupae/rumah pada daerah endemis lebih besar yaitu 16,9 pupae/rumah dan daerah non endemis sebanyak 11,9 pupae per rumah. Rata-rata pupae pada setiap container pada daerah endemis sebanyak 3,6 pupae/container dan daerah sporadis sebesar 2,2 pupae/container. Nilai pupae/person pada daerah endemis sebesar 3,5 pupae/person dan daerah non endemis 2,2 pupae/person. Kesimpulan penelitian yaitu terdapat hubungan spasial antara kasus DBD dan habitat vektor DBD dengan pola penyebaran cluster. Jumlah pupa per rumah dan pupa per orang masih di atas nilai ambang batas penularan DBD baik pada daerah endemis maupun non endemis. Kata kunci: DBD endemisitas, habitat, pupa indeks, Sumba Timur

Penggunaan Matlab dan Python dalam Klasterisasi Data

Organizations need to dig through the data clustering process, both past data and data from the internet. Sometimes the data has to be re-clustered to match the actual conditions. Therefore, it is necessary to prepare clustering support equipment. In this study the K-Means method was chosen for comparing two technical computational languages, i.e. Matlab and Python which are currently in great demand by researchers and can be used by organizations for a clustering process. This study showed both Matlab and Python have enough libraries (libraries) and toolboxes to help users in data clastering as well as graphics presentation. The test results show that the two programming languages are capable of carrying out the clustering process with two clusters; cluster 1 with a center point at coordinates (1.24, 1.34) and cluster 2 with a center point at coordinates (3.1, 3.07) and are presented by a cluster distribution plot. Keywords: Clusterization, K-Means, Matlab, Python. Abstrak Organisasi perlu menggali data lewat proses klasterisasi data, baik data lampau maupun data dari internet. Terkadang data harus dilakukan klasterisasi ulang untuk mencocokan dengan kondisi yang sebenarnya. Oleh karena itu perlu dipersiapkan peralatan pendukung klasterisasi. Dalam penelitian ini metode K-Means dipilih untuk membandingkan dua bahasa komputasi teknis yaitu Matlab dan Python yang sekarang ini banyak diminati para peneliti yang dan dapat digunakan oleh organisasi yang membutuhkan proses klasterisasi. Hasil dari penelitian ini menunjukan baik Matlab maupun Python memiliki cukup pustaka (library) dan toolbox dalam membantu pengguna mengklasterisasi data, mempresentasikan grafik. Hasil pengujian menunjukan kedua Bahasa pemrograman mampu menjalankan proses klasterisasi berupa klaster 1 yang memiliki titik pusat yang berada pada koordinat (1.24, 1.34) dan klaster 2 dengan titik pusat yang berada pada koordinat (3.1, 3.07) disertai dengan plot sebaran klasternya. Kata kunci: Klasterisasi, K-Means, Matlab, Python.

An Evaluation and Region Division Method for Ecosystem Service Supply and Demand Based on Land Use and POI Data

Mastering the regional spatial differences of ecosystem service supply and ecosystem service demand is of great significance to scientifically planning the development and utilization of national land and maintaining healthy development of ecosystems. Based on the relationship analysis of ecosystem service supply and ecosystem service demand, this study explored the regional ecosystem service supply by ecosystem service value based on grid data and constructed an ecosystem service demand evaluation model that integrated the construction land ecosystem service demand equivalent for static aspects and the point of interest (POI) kernel density estimation for dynamic aspects on the basis of land use and POI data. In the end, it put forward a region division method for ecosystem service supply and ecosystem service demand and conducted an empirical analysis of Haidian District, Beijing. The following results were concluded: (1) the ecosystem service value of different grids in Haidian District was between RMB (Chinese monetary unit, Yuan) 0 and RMB 2.4787 million. In terms of spatial distribution, the ecosystem service supply took on an obvious trend of gradual decrease from the northwest to the southeast, with major ecosystem service supply coming from the northwest. (2) The construction land ecosystem service demand equivalent of Haidian District was characterized by a multicenter cluster: the high equivalent area was in the southeast, while the equivalent of the northwest was relatively low. POI kernel density estimation demonstrated cluster distribution, with a high kernel density estimation in the southeast, a lower kernel density estimation in the central part, and the lowest kernel density estimation in the northwest. The ecosystem service demand index also showed cluster distribution: high index in the southeast, low index in the northwest, and prominent sudden changes from the central part to the south. (3) The bivariate local spatial autocorrelation cluster diagram method was used to divide five types of ecosystem service supply and ecosystem service demand, namely non-significant correlation region, high ecosystem service supply and high ecosystem service demand region, high ecosystem service supply and low ecosystem service demand region, low ecosystem service supply and high ecosystem service demand region, low ecosystem service supply and low ecosystem service demand region. Grids with the highest ratio belonged to the non-significant correlation region; the distribution of low ecosystem service supply and high ecosystem service demand region had the greatest concentration, mainly in the southeast; the grids of high ecosystem service supply and low ecosystem service demand region were mainly present in the northwest and in a continuous way; the grids of low ecosystem service supply and low ecosystem service demand region, and high ecosystem service supply and high ecosystem service demand region were extremely few, with sporadic distribution in the central part. The research results could provide a basis for the adjustment and fine management of regional land use structure.