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1.
J Pak Med Assoc ; 73(3): 687-689, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36932784

RESUMO

Ellis-Van Creveld Syndrome (EVC) is a rare genetic disorder with autosomal recessive inheritance, caused by mutations in two genes, EVC1 and EVC2 in the 4p16 chromosome. The exact prevalence of EVC is unknown and is estimated at approximately seven per million. It affects males and females equally. It is a constellation of four findings, including chondrodysplasia, polydactyly, ectodermal dysplasia, and congenital heart defects. Our case was unique as it had left inguinal hernia, short phallus, hyperpigmented scrotum, cryptorchidism, and other defining features of this syndrome. A multidisciplinary team managed this patient with regular follow up. Only six cases have been reported in Pakistan, and only one of them was reported in a neonate. This report highlights the importance of timely and proper multidisciplinary management of such disorders for better outcomes. It will also create awareness among medical professionals and will help them to identify promptly.


Assuntos
Displasia Ectodérmica , Síndrome de Ellis-Van Creveld , Humanos , Recém-Nascido , Masculino , Síndrome de Ellis-Van Creveld/complicações , Síndrome de Ellis-Van Creveld/diagnóstico , Síndrome de Ellis-Van Creveld/genética , Mutação , Paquistão
2.
BMC Bioinformatics ; 23(1): 6, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983370

RESUMO

MOTIVATION: Protein backbone angle prediction has achieved significant accuracy improvement with the development of deep learning methods. Usually the same deep learning model is used in making prediction for all residues regardless of the categories of secondary structures they belong to. In this paper, we propose to train separate deep learning models for each category of secondary structures. Machine learning methods strive to achieve generality over the training examples and consequently loose accuracy. In this work, we explicitly exploit classification knowledge to restrict generalisation within the specific class of training examples. This is to compensate the loss of generalisation by exploiting specialisation knowledge in an informed way. RESULTS: The new method named SAP4SS obtains mean absolute error (MAE) values of 15.59, 18.87, 6.03, and 21.71 respectively for four types of backbone angles [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]. Consequently, SAP4SS significantly outperforms existing state-of-the-art methods SAP, OPUS-TASS, and SPOT-1D: the differences in MAE for all four types of angles are from 1.5 to 4.1% compared to the best known results. AVAILABILITY: SAP4SS along with its data is available from https://gitlab.com/mahnewton/sap4ss .


Assuntos
Redes Neurais de Computação , Proteínas , Aprendizado de Máquina , Estrutura Secundária de Proteína
3.
Mol Biol Rep ; 49(6): 5611-5624, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35618939

RESUMO

BACKGROUND: Salinity stress (SS) is a serious detrimental factor for crop growth and productivity and its intensity it is continuously increasing which is posing serious threat to global food security. Hydrogen peroxide (H2O2) priming has emerged as an excellent strategy to mitigate the adverse impacts of SS. However, the role of H2O2 priming in mitigating the salinity induced toxicity is not fully explored. METHODS AND RESULTS: Therefore, in this context the present study was conducted in complete randomized design (CRD) in factorial combination to determine the impact of H2O2 priming on germination, growth, physiological and biochemical traits, osmo-regulating compounds, hormonal balance and ionic homeostasis. The experiment was based on different levels of SS; control, 6 and 12 dS m-1 SS and priming treatments, control and H2O2 priming (2%). Salinity stress significantly reduced the growth, leaf water status (- 15.55%), calcium (Ca2+), potassium (K+) and magnesium (Mg2+) accumulation and increased malondialdehyde (MDA: + 29.95%), H2O2 (+ 21.48%) contents, osmo-regulating compounds (proline, soluble sugars), indole acetic acid (IAA), anti-oxidant activities (ascorbate peroxidase: APX, catalase: CAT, peroxidase: POD and ascorbic acid: AsA) and accumulation of sodium (Na+) and chloride (Cl-.). H2O2 priming effectively reduced the effects of SS on germination and growth and strengthen the anti-oxidant activities through reduced MDA (- 12.36%) and H2O2 (- 21.13%) and increasing leaf water status (16.90%), soluble protein (+ 71.32%), free amino acids (+ 26.41%), proline (+ 49.18%), soluble sugars (+ 71.02%), IAA (+ 57.59%) and gibberlic acid (GA) (+ 21.11%). Above all, H2O2 priming reduced the massive entry of noxious ions (Na+ and Cl-) while increased the entry of Ca2+, K+ and Mg2+ thus improved the plant performance under SS. CONCLUSION: In conclusion H2O2 priming was proved beneficial for improving maize growth under SS thorough enhanced anti-oxidant activities, photosynthetic pigments, leaf water status, accumulation of osmo-regulating compounds, hormonal balance and ionic homeostasis.


Assuntos
Antioxidantes , Salinidade , Antioxidantes/metabolismo , Homeostase , Peróxido de Hidrogênio/metabolismo , Potássio/metabolismo , Prolina/metabolismo , Açúcares , Água , Zea mays/metabolismo
4.
Nucleic Acids Res ; 48(D1): D204-D219, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31598718

RESUMO

We present the Small RNA Expression Atlas (SEAweb), a web application that allows for the interactive querying, visualization and analysis of known and novel small RNAs across 10 organisms. It contains sRNA and pathogen expression information for over 4200 published samples with standardized search terms and ontologies. In addition, SEAweb allows for the interactive visualization and re-analysis of 879 differential expression and 514 classification comparisons. SEAweb's user model enables sRNA researchers to compare and re-analyze user-specific and published datasets, highlighting common and distinct sRNA expression patterns. We provide evidence for SEAweb's fidelity by (i) generating a set of 591 tissue specific miRNAs across 29 tissues, (ii) finding known and novel bacterial and viral infections across diseases and (iii) determining a Parkinson's disease-specific blood biomarker signature using novel data. We believe that SEAweb's simple semantic search interface, the flexible interactive reports and the user model with rich analysis capabilities will enable researchers to better understand the potential function and diagnostic value of sRNAs or pathogens across tissues, diseases and organisms.


Assuntos
Bases de Dados de Ácidos Nucleicos , Pequeno RNA não Traduzido/metabolismo , Animais , Infecções Bacterianas/microbiologia , Bovinos , Humanos , Internet , Camundongos , Especificidade de Órgãos , Doença de Parkinson/sangue , RNA Bacteriano/metabolismo , RNA Viral/metabolismo , Ratos , Viroses/virologia
5.
Chem Soc Rev ; 50(4): 2696-2736, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33409511

RESUMO

Metal-halide hybrid perovskites have prompted the prosperity of the sustainable energy field and simultaneously demonstrated their great potential in meeting both the growing consumption of energy and the increasing social development requirements. Their inimitable features such as strong absorption ability, direct photogeneration of free carriers, long carrier diffusion lengths, ease of fabrication, and low production cost triggered the development of perovskite solar cells (PSCs) at an incredible rate, which soon reached power conversion efficiencies up to the commercialized level. During their evolution process, it has been witnessed that alkali metal cations play a pivotal role in the crystal structure as well as intrinsic properties of hybrid perovskites, thus enabling the unique positioning of the correlated doping strategy in the development history of PSCs in the past decade. Herein, we summarize the growth and progress of the state-of-the-art alkali metal cation (Cs+, Rb+, K+, Na+, Li+) doping in the field of hybrid perovskite-based photovoltaics. To start with, the accurate identification of different alkali metal-occupied locations in the perovskite crystal lattice are discussed in detail with highlighted advanced characterization methods. Beyond that, the location-dependent functions induced by alkali metal doping are intensely focused upon and comprehensively assessed, indicating their versatile and special effects on perovskites in terms of bottleneck issues such as crystallinity modulation, crystal structure stabilization, defect passivation, and ion-migration inhibition. Thereafter, we are committed to analyze their responsible working mechanisms so as to unveil the relationship between occupied locations and crucial roles for each doped cation. The systematical overview and in-depth understanding of the superiorities of such strategies together with their future challenges and prospects would further boost the advancement of perovskite-related fields.

6.
Nanotechnology ; 32(22)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33601353

RESUMO

Since the discovery of graphene and other two-dimensional (2D) materials in recent years, heterostructures composed of multilayered 2D materials have attracted immense research interest. This is mainly due to the potential prospects of the heterostructures for basic and applied applications related to the emerging technology of energy-efficient optoelectronic devices. In particular, heterostructures of graphene with 2D materials of similar structure have been proposed to open up the band gap to tune the transport properties of graphene for a variety of technological applications. In this paper, we propose a heterostructure scheme of band-gap engineering and modification of the electronic band structure of graphene via the heterostructure of graphene-boron nitride (GBN) based on first-principles calculations. For a comparative analysis of the properties of the proposed GBN heterostructure, we employ Kohn-Sham density functional theory (DFT) using local density and generalized gradient approximations within Perdew-Burke-Ernzehof parameterization. To account for weak interlayer van der Waals interactions, we employ the semi-empirical dispersion-corrected DFT scheme of Grimme, called the DFT-D2 approximation. In the vertical stacking arrangement of boron-nitride-doped graphene with hexagonal boron nitride, we predict a band-gap opening of 1.12 eV which, to our knowledge, is the largest value attained for this kind of system. The impact of interlayer spacing on the band-gap opening arising from the interlayer coupling effect is also analyzed. The band-gap enhancement supports the widely proposed promise of GBN heterostructure in design of high-performance optoelectronic devices such as field-effect transistors for potential applications.

7.
BMC Vet Res ; 17(1): 13, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413380

RESUMO

BACKGROUND: Mycobacterium avium complex (MAC) causes a chronic infectious in the birds known as avian mycobacteriosis. Almost all species of the birds are susceptible to MAC which consists of two closely related species of mycobacteria, that is, M. avium and M. intracellulare. This study aimed to determine the occurrence of Mycobacterium avium subsp. avium (MAA) in chickens and captive birds in selected states of Peninsular Malaysia. RESULTS: A 300 fecal samples were collected from village chickens (n = 100), layer chickens (n = 100) and captive birds (n = 100). Fecal samples were split into two aliquots for microbiological and molecular detection of MAA. Microbiology detection consisted of microscopy (Ziehl-Neelsen staining) and culture of samples decontaminated with 1% Cetylperidinium chloride and vancomycin, nalidixic acid and amphotericin B (VNA) antibiotic cocktail [vancomycin (VAN) 100 µg/ml, nalidixic acid (NAL) 100 µg/ml and amphotericin B (AMB) 50 µg/ml] onto Löwenstein-Jensen (L-J). Molecular detection (PCR-IS901) was performed to detect MAA DNA from the feces and PCR-16S rRNA and IS901 for identification of genus Mycobacterium and Mycobacterium avium sub species avium isolated onto L-J. All samples (296) were AFB negative smear. M. avium was isolated in 0.3% (1/296) samples by culture and detected in 2.5% (6/242) samples by PCR (IS901). Other mycobacteria were found in 1.7% (5/296) chickens. Of five isolates, two were identified as Mycobacterium terrae and M. engbaekii and remaining isolates were not sequenced. Birds positive for M. avium included White Pelican (n = 1) Black Hornbill (n = 1), Macaw (n = 2), Cockatoo (n = 2) and village chicken (n = 1). CONCLUSION: It is concluded that chickens and birds were infected with M. avium in selected areas of Peninsular Malaysia. Although, PCR is rapid, reliable and cost effective method for detection of M. avium in a subclinical stage, the culture of the avian feces should still be used as a reference test for the diagnosis of avian tuberculosis.


Assuntos
Mycobacterium/isolamento & purificação , Micobactérias não Tuberculosas/isolamento & purificação , Tuberculose Aviária/epidemiologia , Animais , Aves , Galinhas , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Malásia , Reação em Cadeia da Polimerase/veterinária , RNA Ribossômico 16S , Tuberculose Aviária/microbiologia
8.
Reprod Domest Anim ; 56(11): 1369-1376, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34370879

RESUMO

Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of estrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1 week after calving were randomly divided into three groups: without oxytocin (CON; n = 7), 10 i.u. oxytocin (LOW; n = 8), 30 i.u. oxytocin - (HIGH; n = 8) and used to record the PEI for the study period of 154 days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6 weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.


Assuntos
Estro/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ocitocina/farmacologia , Animais , Búfalos , Indústria de Laticínios/métodos , Feminino , Ovário/diagnóstico por imagem , Ocitocina/administração & dosagem , Período Pós-Parto/fisiologia , Progesterona/sangue
9.
J Antimicrob Chemother ; 75(10): 2919-2924, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32719853

RESUMO

BACKGROUND: During antifungal prophylaxis, micafungin is generally infused IV once daily over 1 h. In practice, less-frequent dosing could improve the quality of life in patients requiring long-term treatment or prophylaxis. The feasibility of this approach was assessed using humanized doses of daily or infrequent micafungin regimens. OBJECTIVES: To evaluate the effectiveness of intermittent high-dose micafungin, simulating human exposure, for prophylaxis of invasive candidiasis in a rat model of chronic Candida albicans gastrointestinal colonization and systemic dissemination. METHODS: Two weeks post-infection with an oral challenge of C. albicans, Sprague-Dawley rats were immunocompromised with a cytotoxic drug and a steroid. Rats received IV infusions of: daily vehicle control; daily subcutaneous micafungin (20 mg/kg SC); high-dose micafungin (20 mg/kg bolus SC + 80 mg/kg infusion/72 h, to simulate intermittent human dosing of 300 mg/72 h); or daily fluconazole by mouth (10 mg/kg PO). The effects of antifungal prophylaxis on faecal fungal burden and systemic C. albicans dissemination were evaluated. RESULTS: A rat model of chronic C. albicans gastrointestinal colonization and systemic dissemination was established, characterized by a sustained microbiological burden over 29 days and fungal recovery from normally sterile tissues. Using this model, intermittent high-dose micafungin (delivered via iPrecio pumps) to simulate humanized doses of 300 mg/72 h was significantly more effective than vehicle control, as effective as once-daily micafungin and similar to daily fluconazole at reducing faecal burden and preventing systemic dissemination. CONCLUSIONS: These data indicate that intermittent high-dose micafungin can be as effective as daily therapy, supporting clinical assessment in high-risk patients requiring long-term antifungal prophylaxis.


Assuntos
Candida albicans , Equinocandinas , Animais , Antifúngicos/uso terapêutico , Humanos , Lipopeptídeos , Micafungina , Qualidade de Vida , Ratos , Ratos Sprague-Dawley
10.
J Pak Med Assoc ; 70(12(A)): 2195-2198, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33475597

RESUMO

OBJECTIVE: The study objective was to identify the main foci of leprosy in Southern Punjab and identify the problems precipitating prevalence of disease. METHODS: This was a retrospective study, from 2017 to 2012. A total number of sixty-five cases (n=65) were detected during this period. Snowball sampling technique was used. Every year contact survey was carried out for new case detection and compliance of medication. Family members of patients were examined for any anaesthetic patch or nerve involvement or any deformity. Grading of the deformity, if present, was also done according to WHO criteria. Data analysis was carried out by using SPSS version 18.0. Chi square test was applied and P-value calculated. Snow ball sampling procedure was applied to study the disease burden. RESULTS: In this study, the total number of new leprosy patients detected were sixty-five; female patients were 49 (75.38%) and male patients 16 (24.6%). Prevalence of Pauci- bacillary disease was 50.77%. Maximum number of cases were reported from rural area of Southern Punjab. Main foci of disease were concentrated in tribal areas of Dera Ghazi Khan and Rajan Pur. CONCLUSIONS: Leprosy is still evidenced in tribal areas of Dera Ghazi Khan and Rajan Pur.


Assuntos
Hanseníase , Feminino , Humanos , Hanseníase/epidemiologia , Masculino , Paquistão/epidemiologia , Prevalência , Estudos Retrospectivos
11.
Angew Chem Int Ed Engl ; 59(28): 11573-11582, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32259338

RESUMO

The matching of charge transport layer and photoactive layer is critical in solar energy conversion devices, especially for planar perovskite solar cells based on the SnO2 electron-transfer layer (ETL) owing to its unmatched photogenerated electron and hole extraction rates. Graphdiyne (GDY) with multi-roles has been incorporated to maximize the matching between SnO2 and perovskite regarding electron extraction rate optimization and interface engineering towards both perovskite crystallization process and subsequent photovoltaic service duration. The GDY doped SnO2 layer has fourfold improved electron mobility due to freshly formed C-O σ bond and more facilitated band alignment. The enhanced hydrophobicity inhibits heterogeneous perovskite nucleation, contributing to a high-quality film with diminished grain boundaries and lower defect density. Also, the interfacial passivation of Pb-I anti-site defects has been demonstrated via GDY introduction.

12.
BMC Genomics ; 19(Suppl 9): 982, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999862

RESUMO

BACKGROUND: Post-translational modifications are viewed as an important mechanism for controlling protein function and are believed to be involved in multiple important diseases. However, their profiling using laboratory-based techniques remain challenging. Therefore, making the development of accurate computational methods to predict post-translational modifications is particularly important for making progress in this area of research. RESULTS: This work explores the use of four half-sphere exposure-based features for computational prediction of sumoylation sites. Unlike most of the previously proposed approaches, which focused on patterns of amino acid co-occurrence, we were able to demonstrate that protein structural based features could be sufficiently informative to achieve good predictive performance. The evaluation of our method has demonstrated high sensitivity (0.9), accuracy (0.89) and Matthew's correlation coefficient (0.78-0.79). We have compared these results to the recently released pSumo-CD method and were able to demonstrate better performance of our method on the same evaluation dataset. CONCLUSIONS: The proposed predictor HseSUMO uses half-sphere exposures of amino acids to predict sumoylation sites. It has shown promising results on a benchmark dataset when compared with the state-of-the-art method. The extracted data of this study can be accessed at https://github.com/YosvanyLopez/HseSUMO .


Assuntos
Algoritmos , Aminoácidos/química , Biologia Computacional/métodos , Proteínas/química , Proteínas/metabolismo , Sumoilação , Sítios de Ligação , Humanos , Máquina de Vetores de Suporte
13.
J Reprod Dev ; 65(1): 29-36, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30393273

RESUMO

The objective of this study was to determine if there are differences in luteal size (LS), progesterone (P4), and luteal blood flow (LBF) between pregnant and non-pregnant Bos indicus dairy cows during the first three weeks after insemination, and whether these parameters are related to each other. Lactating cows (n = 13) of mixed parity with a body weight of 430 ± 18 kg (mean ± SD), showing regular estrous cycle were used in the study. All cows were artificially inseminated and were classified as pregnant (embryonic heartbeat on day 30; n = 8) or non-pregnant (inter-estrus interval 17 to 21 days, n = 5). In order to compare the LS and LBF after artificial insemination, B-mode and color Doppler ultrasonography of ovaries were performed on days 4, 5, 6, 7 (first week), 8, 10, 12, 14, (second week), and 16, 17, 18, 19, 20, 21 (third week) in pregnant and non-pregnant cows. Results revealed that the mean LBF was consistently higher (P < 0.05) during days 7 through 21 in pregnant cows than in non-pregnant cows. The mean LS was higher (P < 0.05) on days 6 and 7, and from day 17 onwards, and the mean concentration of P4 was higher (P < 0.05) on days 19, 20, and 21 in pregnant cows. In conclusion, LBF is a more sensitive parameter than LS and P4 for detection of differences in luteal function between pregnant and non-pregnant Bos indicus dairy cows during the first three weeks after AI.


Assuntos
Bovinos/fisiologia , Corpo Lúteo/irrigação sanguínea , Inseminação Artificial/veterinária , Ultrassonografia Doppler/veterinária , Animais , Corpo Lúteo/anatomia & histologia , Corpo Lúteo/diagnóstico por imagem , Feminino , Lactação , Tamanho do Órgão , Gravidez , Progesterona/sangue
14.
BMC Bioinformatics ; 19(1): 54, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29444641

RESUMO

BACKGROUND: Small RNA molecules play important roles in many biological processes and their dysregulation or dysfunction can cause disease. The current method of choice for genome-wide sRNA expression profiling is deep sequencing. RESULTS: Here we present Oasis 2, which is a new main release of the Oasis web application for the detection, differential expression, and classification of small RNAs in deep sequencing data. Compared to its predecessor Oasis, Oasis 2 features a novel and speed-optimized sRNA detection module that supports the identification of small RNAs in any organism with higher accuracy. Next to the improved detection of small RNAs in a target organism, the software now also recognizes potential cross-species miRNAs and viral and bacterial sRNAs in infected samples. In addition, novel miRNAs can now be queried and visualized interactively, providing essential information for over 700 high-quality miRNA predictions across 14 organisms. Robust biomarker signatures can now be obtained using the novel enhanced classification module. CONCLUSIONS: Oasis 2 enables biologists and medical researchers to rapidly analyze and query small RNA deep sequencing data with improved precision, recall, and speed, in an interactive and user-friendly environment. AVAILABILITY AND IMPLEMENTATION: Oasis 2 is implemented in Java, J2EE, mysql, Python, R, PHP and JavaScript. It is freely available at https://oasis.dzne.de.


Assuntos
Pequeno RNA não Traduzido/genética , Análise de Sequência de RNA/métodos , Estatística como Assunto/métodos , Sequência de Bases , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , Software
15.
BMC Genomics ; 19(Suppl 1): 923, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29363424

RESUMO

BACKGROUND: Post-translational modification is considered an important biological mechanism with critical impact on the diversification of the proteome. Although a long list of such modifications has been studied, succinylation of lysine residues has recently attracted the interest of the scientific community. The experimental detection of succinylation sites is an expensive process, which consumes a lot of time and resources. Therefore, computational predictors of this covalent modification have emerged as a last resort to tackling lysine succinylation. RESULTS: In this paper, we propose a novel computational predictor called 'Success', which efficiently uses the structural and evolutionary information of amino acids for predicting succinylation sites. To do this, each lysine was described as a vector that combined the above information of surrounding amino acids. We then designed a support vector machine with a radial basis function kernel for discriminating between succinylated and non-succinylated residues. We finally compared the Success predictor with three state-of-the-art predictors in the literature. As a result, our proposed predictor showed a significant improvement over the compared predictors in statistical metrics, such as sensitivity (0.866), accuracy (0.838) and Matthews correlation coefficient (0.677) on a benchmark dataset. CONCLUSIONS: The proposed predictor effectively uses the structural and evolutionary information of the amino acids surrounding a lysine. The bigram feature extraction approach, while retaining the same number of features, facilitates a better description of lysines. A support vector machine with a radial basis function kernel was used to discriminate between modified and unmodified lysines. The aforementioned aspects make the Success predictor outperform three state-of-the-art predictors in succinylation detection.


Assuntos
Algoritmos , Aminoácidos/química , Evolução Molecular , Lisina/química , Processamento de Proteína Pós-Traducional , Ácido Succínico/metabolismo , Sequência de Aminoácidos , Aminoácidos/metabolismo , Biologia Computacional/métodos , Lisina/metabolismo
16.
J Antimicrob Chemother ; 72(3): 778-781, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27999015

RESUMO

Objectives: To investigate the efficacy of a potent novel antimicrobial protein of mass 6 kDa, epidermicin NI01, for eradicating the nasal burden of MRSA in a cotton rat ( Sigmodon hispidus ) model. Methods: MRSA strain ATCC 43300 was used to establish a robust colonization of cotton rat nares. This model was used to evaluate the efficacy of topical 0.04% and 0.2% epidermicin NI01, administered twice daily for 3 days consecutively, and topical 0.8% epidermicin NI01 administered once, for reducing nasal MRSA burden. Control groups remained untreated or were administered vehicle only (0.5% hydroxypropylmethylcellulose) or 2% mupirocin twice daily for 3 days. The experiment was terminated at day 5 and MRSA quantitative counts were determined. Tissues recovered from animals treated with 0.2% epidermicin twice daily for 3 days were examined for histological changes. Results: Mupirocin treatment resulted in a reduction in burden of log 10 (log R) of 2.59 cfu/nares compared with vehicle ( P < 0.0001). Epidermicin NI01 administered once at 0.8% showed excellent efficacy, resulting in a log R of 2.10 cfu/nares ( P = 0.0004), which was equivalent to mupirocin. Epidermicin NI01 administered at 0.2% or 0.04% twice daily for 3 days did not have a significant impact on the tissue burden recovered from the nares. Mild to marked histological abnormalities were noted, but these were determined to be reversible. Conclusion: A single dose of topical epidermicin NI01 was as effective as mupirocin administered twice daily for 3 days in eradication of MRSA from the nares of cotton rats. This justifies further development of epidermicin for this indication.


Assuntos
Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Bacteriocinas/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nariz/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Administração Tópica , Animais , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Carga Bacteriana/efeitos dos fármacos , Bacteriocinas/uso terapêutico , Relação Dose-Resposta a Droga , Mupirocina/uso terapêutico , Nariz/efeitos dos fármacos , Ratos , Sigmodontinae , Infecções Estafilocócicas/microbiologia
17.
Bioinformatics ; 32(6): 843-9, 2016 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-26568622

RESUMO

MOTIVATION: Solvent exposure of amino acid residues of proteins plays an important role in understanding and predicting protein structure, function and interactions. Solvent exposure can be characterized by several measures including solvent accessible surface area (ASA), residue depth (RD) and contact numbers (CN). More recently, an orientation-dependent contact number called half-sphere exposure (HSE) was introduced by separating the contacts within upper and down half spheres defined according to the Cα-Cß (HSEß) vector or neighboring Cα-Cα vectors (HSEα). HSEα calculated from protein structures was found to better describe the solvent exposure over ASA, CN and RD in many applications. Thus, a sequence-based prediction is desirable, as most proteins do not have experimentally determined structures. To our best knowledge, there is no method to predict HSEα and only one method to predict HSEß. RESULTS: This study developed a novel method for predicting both HSEα and HSEß (SPIDER-HSE) that achieved a consistent performance for 10-fold cross validation and two independent tests. The correlation coefficients between predicted and measured HSEß (0.73 for upper sphere, 0.69 for down sphere and 0.76 for contact numbers) for the independent test set of 1199 proteins are significantly higher than existing methods. Moreover, predicted HSEα has a higher correlation coefficient (0.46) to the stability change by residue mutants than predicted HSEß (0.37) and ASA (0.43). The results, together with its easy Cα-atom-based calculation, highlight the potential usefulness of predicted HSEα for protein structure prediction and refinement as well as function prediction. AVAILABILITY AND IMPLEMENTATION: The method is available at http://sparks-lab.org CONTACT: yuedong.yang@griffith.edu.au or yaoqi.zhou@griffith.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Proteínas/química , Sequência de Aminoácidos , Aminoácidos , Modelos Moleculares , Solventes
18.
Anal Biochem ; 527: 24-32, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28363440

RESUMO

Post-Translational Modification (PTM) is a biological reaction which contributes to diversify the proteome. Despite many modifications with important roles in cellular activity, lysine succinylation has recently emerged as an important PTM mark. It alters the chemical structure of lysines, leading to remarkable changes in the structure and function of proteins. In contrast to the huge amount of proteins being sequenced in the post-genome era, the experimental detection of succinylated residues remains expensive, inefficient and time-consuming. Therefore, the development of computational tools for accurately predicting succinylated lysines is an urgent necessity. To date, several approaches have been proposed but their sensitivity has been reportedly poor. In this paper, we propose an approach that utilizes structural features of amino acids to improve lysine succinylation prediction. Succinylated and non-succinylated lysines were first retrieved from 670 proteins and characteristics such as accessible surface area, backbone torsion angles and local structure conformations were incorporated. We used the k-nearest neighbors cleaning treatment for dealing with class imbalance and designed a pruned decision tree for classification. Our predictor, referred to as SucStruct (Succinylation using Structural features), proved to significantly improve performance when compared to previous predictors, with sensitivity, accuracy and Mathew's correlation coefficient equal to 0.7334-0.7946, 0.7444-0.7608 and 0.4884-0.5240, respectively.


Assuntos
Aminoácidos/metabolismo , Lisina/metabolismo , Modelos Estatísticos , Processamento de Proteína Pós-Traducional , Proteoma/metabolismo , Ácido Succínico/metabolismo , Algoritmos , Sequência de Aminoácidos , Animais , Humanos , Proteoma/genética , Roedores/genética , Roedores/metabolismo
19.
J Theor Biol ; 425: 97-102, 2017 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-28483566

RESUMO

Post-translational modification (PTM) is a covalent and enzymatic modification of proteins, which contributes to diversify the proteome. Despite many reported PTMs with essential roles in cellular functioning, lysine succinylation has emerged as a subject of particular interest. Because its experimental identification remains a costly and time-consuming process, computational predictors have been recently proposed for tackling this important issue. However, the performance of current predictors is still very limited. In this paper, we propose a new predictor called PSSM-Suc which employs evolutionary information of amino acids for predicting succinylated lysine residues. Here we described each lysine residue in terms of profile bigrams extracted from position specific scoring matrices. We compared the performance of PSSM-Suc to that of existing predictors using a widely used benchmark dataset. PSSM-Suc showed a significant improvement in performance over state-of-the-art predictors. Its sensitivity, accuracy and Matthews correlation coefficient were 0.8159, 0.8199 and 0.6396, respectively.


Assuntos
Biologia Computacional/métodos , Lisina/metabolismo , Matrizes de Pontuação de Posição Específica , Processamento de Proteína Pós-Traducional , Algoritmos , Sequência de Aminoácidos , Aminoácidos/química , Animais , Evolução Molecular , Sensibilidade e Especificidade
20.
Trop Anim Health Prod ; 49(2): 347-351, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27913974

RESUMO

The present study was designed to determine the effect of estradiol benzoate (EB) on reproductive response following a controlled internal drug release (CIDR) protocol in crossbred (Sahiwal × Friesian) dairy heifers. In the first trial, a total of 100 crossbred dairy heifers were treated with CIDR protocol for 7 days and injected with the PGF2α on day 6. After 24 h of CIDR removal, one group (EB = 50) was injected with estradiol benzoate whereas the other (control = 50) remained untreated. Estrus intensity and response were recorded visually and ovulation rate was recorded by ultrasonography. All heifers were artificially inseminated at 48 and 60 h following CIDR removal. Heifers were scanned for pregnancy within days 30-40 of artificial insemination (AI). In the second trial, two subgroups of heifers were included to observe the estrus and ovulatory events. The results of the first trial revealed that estrus response was achieved 100% in both the treatment groups. Estrus intensity (2.9 ± 0.1 vs. 2.0 ± 0.7) and ovulation rate (100 vs. 88%) differed significantly (P < 0.05) between the EB and control groups. However, a tendency for higher pregnancy per AI was observed (54 vs. 36%; P = 0.07) in EB than that in control groups. The results of the second trial revealed that a significantly (P < 0.05) shorter estrus and earlier ovulatory events were observed in EB-treated heifers. It is concluded that the incorporation of estradiol benzoate to the CIDR protocol is helpful to improve the estrus signs and enhance the ovulation and the pregnancy per AI in crossbred dairy heifers.


Assuntos
Estradiol/análogos & derivados , Sincronização do Estro/efeitos dos fármacos , Animais , Bovinos , Indústria de Laticínios , Preparações de Ação Retardada , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Gravidez , Taxa de Gravidez , Progesterona/administração & dosagem
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