Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant

Background Heterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia. Objective To identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity. Methods Whole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed. Results A homozygous c. 133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119-130 cm, mean similar to -6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140-162 cm, mean similar to -2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia. Conclusions This first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.Peer reviewe

Ochrobactrum, bacillus and Enterobacter isolates of Hot Water Spring Augment the Growth of Zea Mays Seedlings

Hot springs situated at high altitudes is a kind of remarkable ecosystem for the exploration of microbial flora. It was hypothesized that hot springs can harbor bacteria with plant growth-promoting and exopolysaccharides (EPS) producing ability that can favour the growth of plants. For the investigation of this hypothesis, seven EPS producing bacterial isolates were isolated from a water sample of hot water spring of Tattapani, Azad Kashmir and characterized morphologically and biochemically. Three out of seven isolates (BE1, BN1 and BN3) showed significant production of EPS (14-15 mg / 100 ml). Growth kinetics study revealed that optimum EPS production was attained at pH 9, with fructose as a carbon source and peptone as a nitrogen source. Inoculation of these isolates caused augmentation in seed germination (27-38 %), shoot length (27-35 %), seedling length (10-14 %), number of roots (12-25 %) of Zea mays (variety-MMRI yellow) seedlings and significant rise in auxin (28-51 %) and soluble protein content (50-68 %) as compared to non-inoculated treatment. Alcian blue staining unveiled the good colonization potential of these isolates on inoculated roots. Bacterial isolates were identified as Ochrobactrum intermedium (BE1), Bacillus pumilus (BN1) and Enterobacter cloacae (BN3), respectively through 16S rRNA analysis. Bacterial strain BN3 showed promising results for plant growth promotion along with EPS production. Fourier-transform infrared (FTIR) spectroscopy of EPS produced by strain BN3 revealed the complex composition of EPS. We concluded that hot springs can be the possible home for EPS producing bacteria with plant growth promotion capability

Daily Living Functioning, Social Engagement and Wellness of Older Adults

Aim: The present study aim to investigate the contributing role of daily living functioning and social engagement in enhancing wellness and various dimensions of wellness in older adults. Method: A correlational research was designed. Socio-demographic data was collected. Lawton Instrumental Activities of Daily Living, Lubben Social Network Scale, and Perceived Wellness Survey were administered on a sample of 112 participants, including 56 men and 56 women. Results: A correlation analysis found positive correlations between daily living functioning, social engagement and wellness of older adults. The results of regression analysis concluded that both the daily living functioning and social engagement predicted wellness and domains of wellness as well. Conclusion: The obtained results indicate that older adults who are self-reliant lead a more satisfied life in old age and demonstrate to be more adjusted to the effects of aging

Interspecific isozyme variability in Porcellanid crabs (Crustacea: Decapoda: Anomura) from the coastal waters of Pakistan

Polyacrylamide gel electrophoresis was used to investigate the interspecific isozyme variability among three species of Porcellanid crabs: Petrolisthes ornatus, P. rufescens and P. boscii from the coastal waters of Karachi, Pakistan. Seven enzyme systems and the general protein (non-specific) were examined for genetic variations. Among the three species; Nei's heterozygosity for overall loci was observed (0.067), whereas Shannon’s information Index (I) for genetic variations based on the heterozygosity was (0.055) in three species of Genus Petrolisthes. Species were differentiated from each other as Nei’s genetic distance ranged in between 0.0093- 0.0314. The genetic relationship among the three species of genus Petrolisthes similar from those inferred from morphological features

Re-description of Lupocyclus philippinensis (Crustacea: Decapoda: Brachyura: Portunidae) Semper in Nauck, 1880 from the coastal waters of Karachi, Pakistan

A specimen of the Lupocyclus philippinensis Semper in Nauck, 1880 commonly known as scissor swimming crab, was recently found in by catch of shrimp trawling and included as part of continuous taxonomic studies on crabs found in the coastal waters of Pakistan. The discovery is significant because it found after a long time. Redescription of L. philippinensis following the discovery of a female caught at Karachi fish harbor, Pakistan by Leene and Buitendijk (1952)

Tidal induced variation in the distribution, abundance and diversity of mesozooplankton along the Karachi coast, Pakistan

Temporal variations in biomass, abundance, diversity and species composition of mesozooplankton in relation to the tidal state were studied. Mesozooplankton sampling was carried out twice at the ebb and flood tides at fixed stations closed to Phitti creek (P) and Manora channel (M) near the Karachi coast during February 1999. The average percent abundance of mesozooplankton was high at ebb tide i.e., 66% and 63% whereas, low on flood tide i.e.,34% and 37%, at both stations respectively. However, there were no differences in species composition with tidal fluctuations at both sites. The mesozooplankton community was typically composed of 22 groups, out of which copepod was the most abundant group (comprising % of the total zooplankton) at both sites. During the flood tide high diversity 0.11 ± 0.021 was observed in Phitti creek, but no difference was observed at Manora channel. The species richness was high (2.30 ± 0.01273 and 2.38 ± 0.502) in the Manora channel at both ebb and flood tides, respectively, whereas the dominance values were high at Phitti creek. Complete randomized design ANOVA showed that there was no significant difference in abundance of mesozooplankton between stations and tides nested in stations, but the difference was significant for the diversity and equitability. On the short temporal scale the tidal cycle additionally determines changes in the zooplankton composition

Novel variants in natriuretic peptide receptor 2 in unrelated patients with acromesomelic dysplasia type Maroteaux

Acromesomelic dysplasia are a heterogeneous group of disorders with variable spectrum and severity of skeletal anomalies in the affected individuals. Acromesomelic dysplasia type Maroteaux (AMDM) is characterized by extreme shortening of the forelimbs and disproportionate short stature. Several homozygous inactivating mutations in NPR2 have been identified in different AMDM patients. We report five novel variants in affected individuals in four different families. These include two nonsense and three missense variants. This study broadens the genotypic spectrum of NPR2 mutations in individuals with AMDM and also describes the intra- and inter-familial phenotypic variability due to NPR2 variants.Peer reviewe

ESBL determination and antibacterial drug resistance pattern of Klebsiella Pneumoniae amongst patients at PIMS Islamabad

Background: A number of life threatening infections due to various bacterial pathogens are major cause  of death in Pakistan. In a situation like the other developing countries, there is a general increase in the  drug resistance due to the irrational use of the antibiotics. The present study was carried out to evaluate the prevalence and development of resistance in Klebsiella pneumoniae against commonly used antibiotics.Methods and Materials: A total of 200 samples from different wards of the hospitals were received by the pathology laboratory of Pakistan Institute of Medical Sciences, Islamabad, which comprised of urine  65, blood 50 and other miscellaneous samples from various sources. Klebsiella pneumoniae was isolated and characterized using morphological, cultural, and biochemical methods and were further confirmed by using commercially available API 20E kit. The isolates were subjected to culture sensitivity test using  Kirby Bauer disc diffusion method.Results: The organism was found to be the most prevalent Gram-negative bacilli. K. pneumoniae showed  highest resistance against coamoxiclav and cephalosporins.Conclusion: The study revealed that ESBL producing strains were resistant to most of the beta-lactam antibiotics. This trend therefore has become a significant problem and can be controlled with continued surveillance or monitoring for rationally improved antibiotics usage, in order to prevent the drug resistance and re-emergence of infection.Key words: Klebsiella pneumoniae, ESBL (Extended-spectrum beta-lactamase), API (Analytical Profile Index

Effect of alcohol chain length on the optimum conditions for lipase-catalysed synthesis of adipate esters

Immobilized Candida antarctica lipase B, Novozym® 435, was used in the esterification of adipic acid and alcohols with different chain lengths (C1–C18). Optimum conditions for the synthesis of adipate esters were obtained using response surface methodology (RSM) with respect to important reaction parameters including time, temperature, substrate molar ratio and amount of enzyme. Alcohol chain length specificity of the enzyme in the synthesis of adipate esters was also determined. Minimum reaction time (215 min) for achieving maximum ester yield was obtained for butyl alcohol. Methanol required an increased time (358 min) and enzyme amount (10.2%, w/w) for attaining maximum yield. The maximum required temperature and time of 65°C and 523 min, respectively, were obtained for the synthesis of dioctadecyl adipate. The results demonstrate that alcohol chain length is a determining parameter in optimization of the lipase-catalyzed synthesis of adipate esters. Reactions under optimized conditions yielded a high percentage of esterification (>97%). The optimum conditions can be used to scale up the process

Application of artificial neural network for yield prediction of lipase-catalyzed synthesis of dioctyl adipate

In this study, an artificial neural network (ANN) trained by backpropagation algorithm, Levenberg–Marquadart, was applied to predict the yield of enzymatic synthesis of dioctyl adipate. Immobilized Candida antarctica lipase B was used as a biocatalyst for the reaction. Temperature, time, amount of enzyme, and substrate molar ratio were the four input variables. After evaluating various ANN configurations, the best network was composed of seven hidden nodes using a hyperbolic tangent sigmoid transfer function. The correlation coefficient (R 2) and mean absolute error (MAE) values between the actual and predicted responses were determined as 0.9998 and 0.0966 for training set and 0.9241 and 1.9439 for validating dataset. A simulation test with a testing dataset showed that the MAE was low and R 2 was close to 1. These results imply the good generalization of the developed model and its capability to predict the reaction yield. Comparison of the performance of radial basis network with the developed models showed that radial basis function was more accurate but its performance was poor when tested with unseen data. In further part of the study, the feed forward back propagation model was used for prediction of the ester yield within the given range of the main parameters