Identification of an Allene Warhead That Selectively Targets a Histidine Residue in the Oxidoreductase Enzyme DsbA.

Small molecules that covalently modify proteins typically contain an electrophile that selectively reacts with nucleophilic residues in a protein target, such as cysteine, serine, and threonine. Targeting other amino acids is an emerging strategy in covalent probe design. This study reports the discovery and characterization of the covalent reaction between a novel allene warhead and a histidine residue in the active site of the bacterial thiol-disulfide oxidoreductase enzyme DsbA (DsbA).

Multiplexed Native Mass Spectrometry Determination of Ligand Selectivity for Fatty Acid-Binding Proteins.

Although multiple approaches for characterizing protein-ligand interactions are available in target-based drug discovery, their throughput for determining selectivity is quite limited. Herein, we describe the application of native mass spectrometry for rapid, multiplexed screening of the selectivity of eight small-molecule ligands for five fatty acid-binding protein isoforms. Using high-resolution mass spectrometry, we were able to identify and quantify up to 20 different protein species in a single spectrum.

Characterization and treatment of tunneling wastewater using natural and chemical coagulants.

Particles are a concern regarding tunneling wastewater, but gaps remain in understanding metal(loid)s content and coagulation efficiency. In this research, characterization of the wastewaters before and after treatment was investigated by chemical analysis and various techniques for particle characterization. Then, laboratory work was conducted to evaluate effectiveness of sedimentation and use of coagulants to remove particles and particle-associated contaminants.

Management of mung bean leaf spot disease caused by Phoma herbarum through Penicillium janczewskii metabolites mediated by MAPK signaling cascade.

Vigna radiata L., an imperative legume crop of Pakistan, faces hordes of damage due to fungi; infecting host tissues by the appressorium. The use of natural compounds is an innovative concern to manage mung-bean fungal diseases.

TcpA from the Clostridium perfringens plasmid pCW3 is more closely related to the DNA translocase FtsK than to coupling proteins.

Conjugative DNA transfer is a major factor in the dissemination of antibiotic resistance and virulence genes. In the Gram-positive pathogen Clostridium perfringens, the majority of conjugative plasmids share the conserved tcp locus that governs the assembly of the transfer system. Here, we describe multiple structures of the coupling protein TcpA, an essential ATPase that is suggested to provide the mechanical force to propel the DNA through the transfer apparatus.

Training Deep Neural Networks with Novel Metaheuristic Algorithms for Fatigue Crack Growth Prediction in Aluminum Aircraft Alloys.

Fatigue cracks are a major defect in metal alloys, and specifically, their study poses defect evaluation challenges in aluminum aircraft alloys. Existing inline inspection tools exhibit measurement uncertainties. The physical-based methods for crack growth prediction utilize stress analysis models and the crack growth model governed by Paris' law.

, a stem rot disease in potato: Characterization, distribution and management.

Potato ( L.) is one of the most important crops in maintaining global food security. Plant stand and yield are affected by production technology, climate, soil type, and biotic factors such as insects and diseases.

Outcome Of Short And Long Duration Steroid Therapy In Childhood Nephrotic Syndrome In Terms Of Frequency Of Relapse Rate.

Background: Nephrotic syndrome is a clinical syndrome defined by massive proteinuria (greater than 40 mg/m2/hour) responsible for hypoalbuminemia (less than 30 g/L) resulting in oedema and hyperlipidaemia. Objective of the study was to compare the frequency of relapse rate with short and long duration steroid therapy in Nephrotic syndrome. It was a Quasiexperimental control group design, conducted at the Department of Paediatric Nephrology, The Children's Hospital and Institute of Child Health, Lahore.

GC-MS analysis & antifungal activity of Datura metel L. against Rhizoctonia solani Kuhn.

The current study was designed to evaluate the antifungal properties of Datura metel L. against Rizoctonia solani Kuhn. To achieve this objective, six concentrations of leaves & stem methanol extract of D.

Characterization and Evaluation of Hydrothermal Liquefaction Char from Alkali Lignin in Subcritical Temperatures.

An evaluation of hydrothermal liquefaction (HTL) char is investigated in this work. Morphological studies, N adsorption behavior, FTIR analysis, thermal behavior, and elemental composition are studied. The HTL char yield showed an increase with higher operating temperatures.

9-Acridinemethanamine and Acridine-9-Carboxaldehyde as Potential Fluorescence Lifetime pH Indicators.

A significant challenge concerning the development of fluorescence lifetime (FL) based pH sensors is the paucity of fluorophores with sufficiently large FL variation with pH. Acridine is amongst the indicators with highest fluoresce lifetime responses to pH, with a change in lifetime of about 13 ns within a pH range of 5-8. Here we examine the two acridine derivatives, 9-acridinemethanamine (9-AMA) and acridine-9-carbaldehyde (9-ACA) in terms of their FL pH sensitivity and pH sensing range.

Molecular Diagnosis and Identification of Genetic Variants Underlying Distal Renal Tubular Acidosis in Pakistani Patients Using Whole Exome Sequencing.

Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder characterized by an impaired urinary acidification process in distal nephrons that results in the production of alkaline urine. Loss of function variants in any of the three genes, , , or , which all play a role in normal acidification of urine by kidneys, may lead to dRTA. This study was designed to identify genetic variants underlying dRTA in Pakistani patients using whole exome sequencing, followed by confirmatory Sanger sequencing.

A Broad-Range Fluorescence Lifetime pH Sensing Material Based on a Single Organic Fluorophore.

A general drawback for optical based pH sensors is that their response is typically limited to within 2-3 pH units centered around the pK of the indicator. Fluorescence lifetime (FL) is a particularly compelling basis for highly stable pH sensors since this is an intrinsic property of the indicator molecule. Here we demonstrate that it is possible to broaden the sensing range of FL based sensors significantly by placing the indicator in a support material where the indicator's chemical environment itself changes with pH.

Analysis of Antagonistic Potential of Secondary Metabolites and Organic Fractions of Trichoderma Species against Alternaria Alternata.

Role of Trichoderma species is well documented as antagonists as well as plant growth enhancers. Presently, the fungicidal potential of three Trichoderma species namely, T. koningii (FCBP769) , T.

Pillars or Pancakes? Self-Cleaning Surfaces without Coating.

Surfaces that stay clean when immersed in water are important for an enormous range of applications from ships and buildings to marine, medical, and other equipment. Up until now the main strategy for designing self-cleaning surfaces has been to combine hydrophilic/hydrophobic coatings with a high aspect ratio structuring (typically micron scale pillars) to trap a (semi)static water/air layer for drag and adhesion reduction. However, such coating and structuring can distort optical properties and get damaged in harsh environments, and contamination, i.

Molecular Study of Nephronophthisis in 7 Unrelated Pakistani Families.

Nephronophthisis is an autosomal recessive cystic kidney disease characterized by tubular interstitial infiltration, periglomerular fibrosis, and cysts, and is the most frequent genetic cause of end-stage renal disease in children. Nephronophthisis is pleiotropic as almost all the causative genes are involved in primary cilium and centrosome function which are found in almost all human cells. Genetic heterogeneity in nephronophthisis makes the molecular and genetic diagnosis somewhat difficult.

TACROLIMUS DRUG LEVEL AND RESPONSE TO TREATMENT IN IDIOPATHIC CHILDHOOD STEROID RESISTANT NEPHROTIC SYNDROME.

Background: The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS.

HISTOPATHOLOGICAL PATTERNS IN PAEDIATRIC IDIOPATHIC STEROID RESISTANT NEPHROTIC SYNDROME.

Background: Steroid-resistant nephrotic syndrome (SRNS) is a common problem but difficult to treat for pediatric nephrologists. Due to paucity of studies done in few centres in southern Pakistan regarding the histopathological aspects in paediatric patients with SRNS, this study was conducted to determine the histopathological spectrum in children with SRNS at our centre.

Methods: This descriptive study has been conducted at the Nephrology department, The Children's Hospital Lahore from February 2014 to January 2015.

COMPLICATIONS AND SAFETY OF POST PERCUTANEOUS RENAL BIOPSY IN PAEDIATRIC PATIENTS.

Background: Renal biopsy is gold standard in diagnosis of various renal diseases. Though it is safe yet it requires adequate patient evaluation, preparation and monitoring after the procedure.

Methods: This descriptive case series was conducted in the Paediatric Nephrology Department, The Children's Hospital Lahore over a period of one year.

High-affinity nitrate/nitrite transporters NrtA and NrtB of Aspergillus nidulans exhibit high specificity and different inhibitor sensitivity.

The NrtA and NrtB nitrate transporters are paralogous members of the major facilitator superfamily in Aspergillus nidulans. The availability of loss-of-function mutations allowed individual investigation of the specificity and inhibitor sensitivity of both NrtA and NrtB. In this study, growth response tests were carried out at a growth-limiting concentration of nitrate (1 mM) as the sole nitrogen source, in the presence of a number of potential nitrate analogues at various concentrations, to evaluate their effect on nitrate transport.

Self-assembly of ferromagnetic organic-inorganic perovskite-like films.

Perovskite-based organic-inorganic hybrids hold great potential as active layers in electronics or optoelectronics or as components of biosensors. However, many of these applications require thin films grown with good control over structure and thickness--a major challenge that needs to be addressed. The work presented here is an effort towards this goal and concerns the layer-by-layer deposition at ambient conditions of ferromagnetic organic-inorganic hybrids consisting of alternating CuCl4-octahedra and organic layers.

Alanine scanning mutagenesis of a high-affinity nitrate transporter highlights the requirement for glycine and asparagine residues in the two nitrate signature motifs.

Common to all of the nitrate nitrite porter family are two conserved motifs in transmembrane helices 5 and 11 termed NS (nitrate signature) 1 and NS2. Although perfectly conserved substrate-interacting arginine residues have been described in transmembrane helices 2 and 8, the role of NSs has not been investigated. In the present study, a combination of structural modelling of NrtA (nitrate transporter from Aspergillus nidulans) with alanine scanning mutagenesis of residues within and around the NSs has been used to shed light on the probable role of conserved residues in the NSs.

Mutation in the tight-junction gene claudin 19 (CLDN19) and familial hypomagnesemia, hypercalciuria, nephrocalcinosis (FHHNC) and severe ocular disease.

Background/aims: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare renal tubular disorder complicated by progressive renal failure during childhood or adolescence. Recently, causative mutations in the CLDN19 gene have been identified in FHHNC patients presenting with severe ocular involvement. The aim of the study was to investigate the molecular genetic defect underlying FHHNC in a consanguineous Pakistani family.

A rare case of Gitelman's syndrome with hypophosphatemia.

Gitelman's syndrome is a hereditary disorder occurring due to loss of functional mutations of the gene encoding the distal convoluted tubule sodium chloride cotransporter (NCCT) and is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. This case reports an adolescent girl presenting with episodes of carpopedal spasms and difficulty in walking with laboratory tests suggestive of Gitelman's syndrome along with hypophosphatemia.