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Increased incidence and severity of fatal Newcastle Disease Virus (NDV) in commercial and domestic poultry has been reported from across Pakistan. The present study was carried out to evaluate the efficacy of various live NDV vaccines (Gallivac, Intervet and Ceva) by adapting different vaccination schemes in broilers. Antigenic count of each vaccine and its generated antibody were determined by Haeamagglutination and Haemagglutination inhibition tests respectively. Two different NDV vaccination schemes were tested in such a way that one group had received three vaccines in different time periods whereas, the other after priming at 0 day, was followed by a single booster dose. For this purpose, healthy broilers were divided into four groups A, B, C, and D. On zero day of vaccination, there was no detectable anti NDV-HI titer for all vaccines (Gallivac=2, Intervet=2 & Ceva=2). In first vaccination scheme, detectable anti NDV-HI titer was observed on 16th day of vaccination (Gallivac=3.8, Intervet=4.2 & Ceva=3.6). All vaccines showed protective anti NDV-HI titer on 32nd day, post vaccination (Gallivac=5.8, Intervet=6.2, Ceva=5.8). In second vaccination scheme, detectable anti NDV-HI titer was achieved on 16th day of post vaccination (Gallivac=3.8, Intervet=4.2 & Ceva=3.6). While on 32nd day vaccination, all vaccines showed protective anti NDV-HI titer (Gallivac=5.4, Intervet=5.6 & Ceva=5.2). It is concluded that the two-dose vaccination program, with interval of 12 days, is much effective than the 3-dose vaccination scheme. However, in broilers, anti-NDV antibody titer was induced by all three types of vaccines manufactured by various companies. Keywords: Newcastle disease virus, Humoral Response, Haemagglutination inhibition test, Vaccine schedule

The role of Alternaria sp on seed vigor of rapeseed, Brassica napus, was investigated. Seed samples were collected from rapeseed growing regions of Sindh province. The samples were processed for fungal recovery using blotter paper and agar plate methods. Both methods produced a number of parasitic and saprophytic fungi. Among the recovered fungi, Alternaria sp was predominant with 16% average infection. Similarly, effect of seed treatment with Topsin M. was examined in this experiment. It improved seed health significantly over inoculated seeds. The treated seeds showed greater germination (16.15%) with 83.69% more healthy seedling in comparison with inoculated seeds. Root and shoot systems were significantly improved in seedlings from treated seed compared to those from inoculated seeds. The results of this study suggest grading seed samples to reduce seed impurities and seed treatment (particularly with Topsin M) to eliminate seed borne pathogen, especially Alternaria from rapeseed to enhance production by the growers. Key words: Seed health, seed borne fungi, Alternaria, seed treatment.

In this experimental approach, we explored the structures, morphologies, phototoxicities, and antibacterial activities of undoped and Mn-doped ceria nanocomposite materials, MnxCe1−xO2. The MnxCe1−xO2 nanocomposites were synthesized by employing a soft chemical route. Our prime focus was on the influence of different factors, both physical and chemical, i.e., the concentration of manganese in the product, size of the nanocomposite, drug dose, and incubation time, on the bacterial strains. Different bacterial strains were selected as experimental biological models of the antibacterial activity of the manganese-doped cerium oxide nanocomposite. In addition to the photodynamic response, the adenocarcinoma cell line (MCF-7) was also studied. Based on cell viability losses and bacterial inhibition analyses, the precise mechanisms of apoptosis or necrosis of 5-ALA/PpIX-exposed MCF-7 cells under 630 nm red lights and under dark conditions were elucidated. It was observed that the undoped nanocomposites had lower cytotoxicities and inhibitions compared with those of the doped nanocomposites towards pathogens. The antibacterial activity and effectiveness for photodynamic therapy were enhanced in the presence of the manganese-doped ceria nanocomposite, which could be attributed to the correlation of the maximum reactive oxygen species generation for targeted toxicity and maximum antioxidant property in bacteria growth inhibition. The optimized cell viability dose and doping concentration will be beneficial for treating cancer and bacterial infections in the future.

BACKGROUND Wound injury is a critical issue in hair restoration. The shape and size of blades cause varying degree of tissue trauma. AIMS To check (mathematically) the tissue trauma (injury) caused by different shapes of the blades at varying angles. PATIENTS/METHODS The trigonometric theories were applied to each shape and angles to calculate the surface area (correlating with the tissue injury). These shapes included rectangular blade, 30°-angled blades, 60°-angled blade, 30°-sapphire blade, and 60°-sapphire blade. The surface areas were calculated at 90°, 45°, 30°, and 15° insertion angles. RESULTS The 30°-sapphire blade caused the least injury followed by 30°-angled blade. The rectangular blade had the largest surface area and hence will produce the maximum amount of tissue injury. The blade at 90° produced maximum injury whereas the blade entering at 15°, produced lowest amount of tissue injury. The blade in sagittal direction caused less injury as compared to the blade in coronal direction. CONCLUSION The 30°-sapphire blade caused the least tissue injury whereas the rectangular blade caused maximum injury. The amount of tissue injury decreases as the angle of insertion decreases and vice versa.

Inactivated oil based avian influenza vaccines are being used to confront viral outbreaks but seem to be ineffective due to the shorter life span of broiler birds. In such situations immunostimulating agents may play a vital role to overcome the problem. The current study was designed to investigate the co-stimulatory effect of levamisole on humoral response of chicken against inactivated oil based influenza vaccines in broiler birds. The efficacy of levamisole (LMS) hydrochloride, a standard immune modulator was evaluated on one hundred broilers in association with inactivated adjuvanted avian influenza vaccines. Avian influenza susceptible broilers were divided into nine groups, each having ten birds. The birds in groups G1, G2, G3, G5, G6 and G7 were offered 30 , 20 and 15mg kg-1 bwt levamisole for four consecutive days after being vaccinated with oil and gel based inactivated influenza vaccines respectively; birds in group G9 were kept as control. Whereas, birds in Group G4 were kept as oil base vaccinated control and Group G8 were kept as gel base vaccinated control without levamisole medication. Blood samples were obtained from wing vein on 14th, 28th and 36th days post vaccination. Anti-influenza antibody response was measured using haemagglutination inhibition (HI) technique. Data analyzed by one way ANOVA and DMR test showed that levamisole in both regimens had appreciable effect on antibody titers (p

Avian viral problems have been consistently reported in commercial poultry of Pakistan causing heavy economic losses to the poultry farmers. Authentic idenfication and confirmation of the causative agent is always been question mark for the selection of vaccinal strain in this regard. Current study was therefore undertaken to optimize the virus neutralization test for the serological survey of vaccinated poultry particularly for avian influenza virus’s subtypes and Newcastle disease virus. Various physiochemical factors such as concentration of antigen and antibody, Incubation temperature and incubation period for in vitro and in-vivo reaction of antigen and antibody were optimized in chicken embryonated eggs. Serum samples were obtained from vaccinated breeder birds of five commercial poultry breeder companies and subjected for VNT using different concentration of three antigen and their respective homologous antibodies under optimized conditions. AIV H9 (EID50-1×109.0/ml) and NDV (EID50-1×108.2/ml) having biological titer of 10-7 /50ul HA units were neutralize with 10-2/50ul HIU of antibody and incubated at 37°C for 30 minutes was injected subsequently into 10 day old chicken embryo followed by incubation at 37°C for 38 hours showed ≥90% neutralizing specificity. Furthermore, sera obtained from five AIV-H9, AIV-H5 and NDV exposed commercial poultry farms revealed that Big bird broiler, Big bird breeders and A&S chicks are 100% sensitive and specific whereas, Gateway chicks and Waqas poultry breeders showed 100% homology for AIV-H5 virus but do not confers similarity with prevailing AIV-H9 and NDV field strains. Therefore, high sensitivity, reproducibility and specificity VNT, it could be a tool for indirect detection of homology between vaccinal strain and wild virus antigen using known antisera. Particularly, for those organisms possess natural ability to mutate in the adverse climatic conditions. Keywords: Virus neutralization test, Avian Influenza Virus, Newcastle Disease Virus, Sensitivity, Specificity

This study is the first report on the epidemiological status of house dust mite (HDM) allergy in Pothwar, Pakistan. Allergy data of 2087 symptomatic patients were obtained, of whom 1706 (81.7%) patients were skin-prick-test positive for HDM allergens. This percentage was significantly higher than for pollen and food allergens. In the results of this study Dermatophagoides farinae (61%) and D. pteronyssinus (29%) were the predominant species in the study area. Besides these pyroglyphids, predatory Cheyletus sp. (10%) and an oribatid mite sp. (1%) were also observed. Random and patients' houses showed 87.4 and 87.1% positive mite infestation, respectively. Mean (± SEM) D. farinae counts per g of dust in random samples was 235.4 ± 7.93 compared to 274.7 ± 10.78 from patients' homes. Mean D. pteronyssinus counts from random houses compared to patients' houses were 115.0 ± 4.57 and 124.6 ± 5.76, respectively. Mite counts depicted seasonal variation, with peaks during monsoon season. ELISA results of dust samples demonstrated that of the dust samples with > 10 µg/g of dust, the threshold value described as a risk factor for developing asthma, 57.6% had Der f1 and 20% Der p1 allergen load. Mean Der f1 burden was significantly higher than Der p1, with maximum levels during monsoon and autumn seasons. This research established a better awareness about the epidemiological status of HDM allergy and prevalence of allergy causing HDM species in Pakistan.

High-throughput technologies, such as synthetic biology and genomics have paved new paths for discovery and utility of medicinally beneficial plants. Bioactive molecules isolated from different plants have significantly higher biological activities. The present study was done to analyze antibacterial potential of some medicinal plants against multi drug resistant (MDR) pathogens and anticancer effect against MCF-7 cell line. Methanolic and ethanolic extracts were tested for their antibacterial activity by disc diffusion method against six MDR bacterial strains and for cytotoxicity evaluation by MTT assay. Ethanolic extracts of the three tested plants exhibited growth inhibitory effect against Klebsiella pneumonia, Serratia marcescens and Methicillin-resistant S. aureus. Pseudomonas aeruginosa was more resistant to all extracts as its growth was least inhibited by the extracts of all tested plants. Ethanol extract of Foeniculum vulgare exhibited significant inhibition of cancer cells proliferation. Methanol extract of Justicia adhatoda also showed considerable inhibition of cancer cells. Future studies must converge on detailed investigation of modes of action of extracts of tested plants.

The dental restorations by the usage of implants have been one of the most favourable treatment. However, the existing dense dental implant causes overloading towards the human bone that triggers ‘stress shielding effect’ and also implant loosening. This paper focused on the development of highly porous Ti-6Al-4V dental implant by metal injection molding with palm stearin binder system with an addition of sodium chloride as space holder which has been established in the fabrication of porous Ti-6Al-4V. The evaluated compositions consist of the powder volume fraction of 63vol% and 65vol%. SEM analysis shows that highly porous Ti-6Al-4V dental implant were obtained. The average density is 3.325g/cm3 for 63vol% sample and 3.915g/cm3 for 65vol% sample. While for the Vickers hardness are 113.68HV and 162.8HV for 63vol% and 65vol% respectively.

The silver oxide nanoparticles (AgO(2) ‐NPs) were synthesised using silver foil as a new precursor in wet chemical method. X‐ray diffraction analysis shows crystallographic structures of AgO(2) ‐NPs with crystallite size of 35.54 nm well‐matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical‐shaped nanoparticles. Energy dispersive X‐ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra‐red analysis confirmed the formation of AgO(2) ‐NPs with the presence of Ag‐O‐Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO(2) ‐NPs. This study also described the effect of AgO(2) ‐NPs having synergistic activity with β lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli). Among isolated strains of E. coli, 60.0% were found to be ESBL producer. The synergistic activities of AgO(2) ‐NPs with ceftriaxone suggest that these combinations are effective against MDR‐ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR‐ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO(2) ‐NPs synergistic effect can be used as an efficient approach to combat uro‐pathogenic infections.

Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead to interindividual variability in warfarin dose requirement. The characterization of genotype frequency distribution is required in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common VKORC1 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations. Single blood sample was collected after informed consent. Genomic DNA was extracted and genotype analysis for VKORC1 1173C>T and VKORC1-1639G>A polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. A number of samples were also analyzed by direct DNA sequencing for validation of results. Data were analyzed using SPSS version 20. Genotype frequency distributions of VKORC1 1173C>T and VKORC1-1639G>A were found to be different from other populations. Both of these polymorphisms did not demonstrate significant effect on warfarin dose requirement. Although Cytochrome P450 2C9 (CYP2C9) and VKORC1 polymorphisms together attributed only 3.8% variability in warfarin dose but it was statistically significant ( p value = .004). It is concluded that there is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome. At the same time, no effect on warfarin dose variation explained by VKORC1 polymorphisms and small variability explained by studied genotypes stresses the need for exploration of more genetic and nongenetic factors in Pakistani population.

Double-stranded breaks (DSBs) are cytotoxic DNA lesions caused by oxygen radicals, ionizing radiation, and radiomimetic chemicals. Increasing understanding of DNA damage signaling has provided an ever-expanding list of modulators reported to orchestrate DNA damage repair and ataxia telangiectasia mutated (ATM) is the master regulator and main transducer of the DSB response. Increasingly, it is being realized that DNA damage response is a synchronized and branched network that functionalizes different molecular cascades to activate special checkpoints, thus temporarily arresting progression of the cell cycle while damage is being assessed and processed. It is noteworthy that both nutrigenetics and nutrigenomics have revolutionized the field of molecular biology and rapidly accumulating experimental evidence has started to shed light on biological activities of a wide range of phytochemicals reported to modulate cell cycle, DNA repair, cell growth, differentiation and apoptosis as evidenced by cell-based studies. In this review, we have attempted to provide an overview of DNA damage signaling, how ATM signaling regulates tumor necrosis factors-related apoptosis inducing ligand (TRAIL)-induced intracellular network. We also illuminate on how resveratrol, epigallocatechin gallate, curcumin, jaceosidin, cucurbitacin, apigenin, genistein, and others trigger activation of ATM in different cancer cells as well as agents for ATM inactivation. Understanding the interplay of TRAIL-induced intracellular signaling and ATM modulation of downstream effectors is very important. This holds particularly for a reconceptualization of the apparently paradoxical roles and therapeutically targetable for enhancing the response to DNA damage-inducing therapy.

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.

Reinforced concrete beam has been among major applications in construction nowadays. However, the application of nickel titanium alloy as a replacement for steel rebar in reinforced concrete beam is a new approach nowadays despite of their ability to undergo large deformations and return to their undeformed shape by removal of stresses. In this paper, the response of simply supported reinforced concrete (RC) beams with smart rebars, control beam subjected to static load has been numerically studied, and highlighted, using finite element method (FEM) where the material employed in this study is the superelastic shape memory alloys (SESMA). The SESMA is a unique alloy that has the ability to undergo large deformations and return to their undeformed shape by removal of stresses. The size of the analysed beam is 125 mm × 270 mm × 2800 mm with 2 numbers of 12 mm diameter bars as main reinforcement for compression and 12 numbers of 12 as tension or hanger bars while 6 mm diameter at 100 mm c/c used as shear reinforcement bars respectively. The concrete was modelled using solid 65 element (in ANSYS) and rebars were modelled using beam 188 elements (in ANSYS). The result for reinforced concrete with nickel titanium alloy rebar is compared with the result obtained for reinforced concrete beam with steel rebar in term of flexural behavior, load displacement relationship, crack behaviour and failure modes for various loading conditions starting from 10kN to 100kN using 3D FE modelling in ANSYS v 15. The response and result obtained from the 3D finite element analysis used in this study is load-displacement curves, residual displacements, Von-Misses, strain and stiffness are suitable for the corresponding result showed a satisfactory performance in the structural analysis. Resultant displacement, Von-Mises stress and maximum strain were influenced by the factors of the material properties, load increments and the mesh size. Nickel titanium alloy was superior to the conventional steel at limiting residual displacements and crack formation in the concrete beams and this ability makes this smart structure special to maintain their serviceability even after a strong earthquake for seismic mitigation.

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

Hydroxyapatite (HAp) is a kind of bioceramic based material that has been used extensively in many medical applications. Owing to nearly similar mineral contents to natural bone, the material has been accepted as an implant in order to improve the osteointegration with the bone tissue. In this work, an alternative processing route from waste materials, namely clamshell in producing HAp powder is presented. The effects of processing temperatures, ranging from 750°C to 950°C and pH values, ranging from 6.5 to 8.5 on the synthesized HAp prepared via chemical precipitation method were investigated. From the XRD, FTIR and EDX results, it was observed that the lowest pH value of 6.5 with the temperature of 850°C is the optimum parameters to synthesize HAp.

Hepatitis C virus is one of the major health problems worldwide. It affects mainly the liver but several extrahepatic manifestations are also accounted. Chronic hepatitis C patients are at an increased risk of developing hepatic steatosis, which share many clinical features with the metabolic syndrome. Hepatic steatosis has also been associated with elevated levels of markers of inflammation such as homocysteine, identified as hyperhomocysteinemia (HHC). HHC due to Methylenetetrahydrofolate Reductase (MTHFR) gene, in particular the C677T polymorphism, was recently associated with coronary heart diseases (CHD) in chronic hepatitis C (CHC) patients. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver metabolism. Deficiencies of micronutrients (folate, vitamin B 6 and possibly vitamin B 12) along with mild hyperhomocysteinemia, perhaps, act synergistically with other classical risk factors to further increase the risk of CHD. Clinical data indicate that HHC is associated with an increased incidence of CHD as well as with the severity of the disease in CHC patients. In conclusion, HHC might be a potential aetiological factor of CHD in CHC patients. The aim of this review is to investigate the progression of coronary heart diseases in chronic hepatitis C patients and correlate with levels of homocysteine in concurrence to genetic defects and nutrient deficiencies. However, future studies need to clarify the mechanistic role of HHC in CHD and CHC as a useful paradigm with most interesting therapeutic implications.

Pollen and mold allergies are highly problematic in Islamabad. This study was conducted to investigate the type and concentration of airborne pollens/molds causing allergic diseases in susceptible individuals. A volumetric spore trap (Burkard) was placed at the height of 11 m and ran continuously for 3 years. Once a week, the collecting drum was prepared by affixing Melinex tape with a double sided adhesive that was coated with a thin layer of silicone grease. Every Sunday at 9:00 AM the drum was replaced by another drum and the pollen/mold spores were removed and permanently mounted on slides. Using a microscope, the trapped particles were identified and recorded as counts per cubic meter of air per hour. From these data, the pollen and mold calendars were constructed and expressed as counts per cubic meter of air per day. Skin prick tests were performed on more than 1000 patients attending the Pakistan Allergy, Asthma & Clinical Immunology Centre of Islamabad. The results indicated that there were 2 main pollen plants that contributed to seasonal allergies. These were Broussonetia papyrifera and Cannabis sativa during the March/April season and the July/September season, respectively. Although mold spores were continuously detected throughout the year, the most prominent mold was undetected mold and unconfirmed mold species similar to Stachybotrys species, which was high from July to September/October. Two additional molds contributing to allergic reactions were Pithomyces species and Cladosporium species, which were active during January and April, with the latter also being detected between October and November. These results may prove beneficial to both patients and physicians in planning a therapeutic protocol for avoidance and amelioration. Keywords: pollen and mold calendar, aerobiology, Islamabad, Burkard spore trap, Broussonetia papyrifera, Cannabis sativa, skin prick test, SPT, asthma, allergic rhinitis

Fowl cholera (FC) is one of the respiratory syndromes of commercial layer, breeder and broiler farms in Pakistan. The disease is mainly controlled by vaccination. In the present study, effect of “in process quality control” factors such as amount of immunogen, chemical nature of adjuvant, fractions of bacterial culture and its storage on potency of the vaccine was investigated. Immunogen amount (1011CFU/ml) induced serum anti-Pasteurella multocida ELISA (anti-PM-ELISA) antibody titer in the vaccinated birds on 32 days post vaccination that was significantly higher (P

Research over the years has gradually and sequentially highlighted contributory role of hypothalamic- based kisspeptin-signaling axis as a major positive modulator of the neuroendocrinological reproductive axis in mammals. However, a series of landmark studies provided convincing evidence of role of this signaling in regulation of cancer development and progression. It is becoming progressively more understandable that loss or reduction of KISS1 expression in different human cancers correlates inversely with progression of tumor, metastasizing potential and survival. In this review we have attempted to provide an overview highlight of the most recent updates addressing metastasis- suppressing role of KISS1. We also summarize interplay of microRNA and KISS1 in cancer. The miRNA regulation of different genes is a rapidly expanding area of research however, the community lacks a deep understanding of miRNA regulation of KISS1. Recently, emerging laboratory findings have shown that KISS1 is transcriptionally controlled by TCF21 that is in turn regulated by miR-21. Therefore, there is an urgent need for further study of how miRNA directly or indirectly influences KISS1 at the posttranscriptional level. There is also a lack of evidence regarding natural agents that mediate upregulation or downregulation of KISS1. Increasing the knowledge of the KISS1/KISS1R signaling axis will be helpful in achieving personalized medicine.

Cone-rod retinal dystrophy (CORD) characteristically leads to early impairment of vision due to the simultaneous involvement of both cone and rod photoreceptor cells. Several loci/genes have been identified for CORD, including the cone-rod dystrophy (CORD8) locus [OMIM#605549] identified for a Pakistani family. All members of this family underwent detailed clinical re-examination to determine the nature of the dystrophy. All affected individuals suffered from bilateral CORD8 with an autosomal recessive mode of inheritance. The CORD8 locus, mapped on chromosome 1q12-q24, consisted of a very large critical disease region of 21 cM. Analysis with more recently available microsatellite markers within the reported region showed heterozygosity with some of the new markers, and the crossovers lead to a refinement of the disease region from 21 to 11.53 cM. Mutation screening has excluded some of the candidate genes in the region. The disease phenotype of this family could be due to a mutation in a novel gene located within the refined CORD8 locus.

Data obtained through high-throughput technologies have gradually revealed that a unique stratified epithelial architecture of human skin along with the antioxidant-response pathways provided vital defensive mechanisms against UV radiation. However, it is noteworthy that skin is a major target for toxic insult by UV radiations that can alter its structure and function. Substantial fraction of information has been added into the existing pool of knowledge related to natural products mediated biological effects in UV exposed skin cells. Accumulating evidence has started to shed light on the potential of these bioactive ingredients as protective natural products in cosmetics against UV photodamage by exerting biological effects mainly through wide ranging intracellular signalling cascades of oxidative stress and modulation of miRNAs. In this review, we have summarized recently emerging scientific evidences addressing underlying mechanisms of UV induced oxidative stress and deregulation of signalling cascades and how natural products can be used tactfully to protect against UV induced harmful effects.

Background: Oculodentodigital syndrome (ODD; OMIM #164200) is a rare autosomal dominant disorder with pleiotropic effects. It is caused by mutation in gap junction protein α 1 (GJA1) gene which encodes connexion 43. ODD is characterised by symptoms i.e. craniofacial, neurologic, limb, ocular abnormalities, syndactyly type III of the hands, phalangeal abnormalities, diffuse skeletal dysplasia, enamel dysplasia, and hypotrichosis. Objectives: To study the Molecular Genetics of Oculodentodigital syndrome. Patients/materials and methods: Our current study includes a Pakistani family affected with ODD. Clinical evaluation revealed that this family shows typical form of ODD with Syndactyly type III. Mutations in GJA1 have been reported in ODD and also in syndactyly type III. In this study we sequenced the coding exons of GJA1 gene in affected and normal individuals of the family for mutation detection. Results: Direct sequencing of the affected individuals showed a mutation at the nucleotide position 389 T>C. This mutation changed the codon 130 from Isoleucine to Threonine. Normal family members did not show this mutation. Conclusion: Our study showed no gross neurological upset with I130T mutation in GJA1 gene. This may present novel phenotypic outcome with the I130T. The study will help in better understanding of pathophysiology of oculodentodigital syndrome and type III syndactyly. (J Dermatol Case Rep. 2012; 6(2): 43-48)

Allergic diseases are fairly common in all parts of the world and involve all ethnic groups with bronchial asthma, allergic rhinitis, conjunctivitis and eczema being the commonest manifestations. Despite our efforts, their incidence is on an escalating path. The use of herbal remedies and standardized extracts for treatment of allergy and other diseases has been gaining momentum in recent years. The qualitative and quantitative determination of phyto-chemicals and assessment of the anti-allergic and anti-inflammatory activities using aqueous and organic extracts of different plant parts (root, stem and leaves) of Mentha arvensis in animals showed that all parts of M. arvensis (specifically, leaves) are rich source of secondary phytoconstituents, which impart their therapeutic effects against allergic andinflammatory diseases. These results support the claim about the use of this herb in folk medicines. Key words: Anti-allergic, anti-inflammatory activity, medicinal plants, Mentha arvensis,Pakistan.

Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by ocular abnormalities (myopia and retinal detachment) and occipital encephalocele. The syndrome is clinically and genetically heterogeneous (KNO1, KNO2). Previously germline mutations in COL18A1 (21q22.3) were detected in some families, but in other kindreds linkage to COL18A1 was excluded. We ascertained a large consanguineous family with high myopia, vitreoretinal degeneration and occipital scalp defect with autosomal recessive mode of inheritance. Due to the overlapping clinical presentation of this family with Knobloch syndrome we propose this phenotype as a type III variant of KS (KNO3). A genome wide linkage study using microsatellite markers at 10-20 cM interval revealed linkage to 17q11.2 with a maximum LOD scores 3.40 (theta = 0.00) for markers D17S1307 and D17S1166. Fine mapping defined a 2.67 cM disease region between D17S1307 and D17S798. Mutation analysis of three candidate genes (UNC119, MYO1D, and RAB11FIP4) within the disease region did not identify any disease-associated mutation in affected individuals.

It is becoming increasingly understood that tumor cells may have different mutations and dependencies on diverse intracellular signaling cascades for survival or metastatic potential. Overexpression of oncogenes, inactivation of tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and loss of apoptotic cell death are some of the mechanisms that have been widely investigated in molecular oncology. We partition this multicomponent review into the most recent evidence on the anticancer activity of fungal substances obtained from in vitro and xenografted models, and these fungal substances modulate expression of oncogenic and tumor suppressor miRNAs. There are some outstanding questions regarding fungus-derived chemical-induced modulation of intracellular signaling networks in different cancer cell lines and preclinical models. Certain hints have emerged, emphasizing mechanisms via which apoptosis can be restored in TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from these emerging areas of research will enable us to potentially identify natural agents with notable anticancer activity and minimal off-target effects. Integration of experimentally verified evidence obtained from cancer cell line gene expression with large-scale functional screening results and pharmacological sensitivity data will be helpful in identification of therapeutics with substantial efficacy. New tools and technologies will further deepen our understanding of the signaling networks that underlie the development of cancer, metastasis, and resistance to different therapeutics at both a personal and systems-wide level.

Overweight and obesity are highly associated with multiple co-morbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. The essential role of the renin–angiotensin system (RAS) in controlling blood pressure has well been established. Genes encoding components of the RAS have been proposed as candidate genes that determine genetic predisposition to hypertension and the risk of developing cardiovascular complications. The role of these genes in obesity is not well understood. Several studies have showed their association with obesity in animal models.