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The present study aimed to investigate the problems in speaking English as a second language in the Institute of English language and literature at the University of Sindh Jamshoro. The research paradigm was qualitative, and the tool for this study was an open-ended questionnaire that was distributed among the 40 students of IELL, including both male and female students who participated in this work and had their previous education from both private and public academic sectors. The results revealed the problems occurred to the students while speaking. This research explains the problems faced by the students of IELL by dividing them into three categories. The first category is linguistic problems, including vocabulary, pronunciation, and grammar. The second category is psychological and external problems, including low motivation, anxiety, negative attitude towards the target language, and no environment for second language English. The last category is teaching methods and materials problems, including untrained teachers, traditional teaching methods, and syllabus problems. These problems are common in the ESL context due to the faulty education system. The last part of the study recommends some steps to be taken by the students, schools, and future researchers regarding speaking skills improvements.

Objective: To decide the mindfulness and competency of dental and clinical experts in offering smoking discontinuance guidance. Study Design: Cross-sectional study. Place and Duration of Study: Tertiary Care Teaching Institute, Rawalpindi Pakistan, from Oct 2019 to Feb 2020. Methodology: A pilot study carried out at 15-20 participants for questionnaire validation and reviewed by independent experts for face validity. A final questionnaire comprised of ten multiple-choice questions in addition to demographic profile. The minimum sample size required for the study was 261, where the national prevalence of smoking was 21.6%. Results: A total of 550 participants participated in the study and data were extracted from their responses. There were 335 (61.0%) males and 215 (39.0%) females in the study group, with a mean age of 32.4 ± 4.3 and the age range 25 – 44 years. Among total respondents, 380 (69%) were qualified dental and medical practitioners whereas 170(31%) were medical and dental students. Only (40%) respondents were confident in rendering cessation advice whereas (60%) were not. Only (15.5%) participants declared that they received formal training to counsel for quitting smoking. Among the total 234 (100%) males were confident in giving in advice whereas none of the females were sure enough p value

Objective This study aimed to translate to Arabic language and culturally adapt the Self-Efficacy for Managing Chronic Diseases Scale (SEMCD) and The Perceived Medical Condition Self-Management Scale (PMCSMS). Design The translation of the two scales was conducted according to the framework by Beaton et al. Then, these scales were tested in a cross-sectional correlational study with 85 Arabic-speaking participants with multimorbidities in Qatar. Psychometric tests to assess the reliability and validity of the translated scales were done. Results The internal consistency reliability (α) for the Arabic version of both PMCSMS and SEMCD scales was 0.953 and 0.949, respectively. Correlation coefficient ( r) used to assess convergent validity between the PMCSMS and the SEMCD was 0.76 (p Discussion The translated PMCSMS and SEMCD are valid and reliable scales that can be used by researchers and healthcare providers to assess levels of self-efficacy among individuals with multimorbidities. The translated scales can be employed in research or interventional programmes that aim to improve self-management or self-efficacy among individuals with multimorbidities.

This paper aimed to investigate the effect of rosmarinic acid (RA; 10, 75, 250 µmol/g protein) addition on silver carp myofibrillar protein (MP) oxidation under MetHemoglobin (MetHb) catalyzed doco...

Purpose: The purpose of this study is to investigate the relationship between entrepreneurship competencies and entrepreneurship motivation through moderating role of entrepreneurial education in the university students of (Punjab) Pakistan. This study provides a comprehensive answer to the research question of how entrepreneurship competencies and entrepreneurial education effects the entrepreneurship motivation among university students. Design/Methodology/Approach: A survey questionnaire was used to collect data from faculty of management sciences students of different departments at various campuses in (Punjab) Pakistan. Factor analysis, reliability, and regression and correlation analysis was the techniques to analyze the links between the study variables. Findings: There is a positive significant impact of entrepreneurship competencies on entrepreneurship motivation while entrepreneurship education as a moderator. Implications/Originality/Value: At the last, this paper also presents some implications, limitations and suggestions for future research.

Background: Primary healthcare nurses are pivotal to the successful uptake of immunization worldwide. Central to this, is the attitude and practice nurses may have toward vaccines during administration. It is postulated that altering knowledge towards immunization may impact both attitude and practice towards successful immunization uptake. The aim of this research was to assess nurses’ knowledge, attitude and practice after the delivery of a three-day continuing professional development program regarding administration, safe handling and delivery of vaccines. Method: This research consisted of a quantitative cross-sectional study, utilizing a self-administered survey. The survey contained questions related to immunization knowledge, attitude, and practice. Before and after attendance of an immunization program for continuing professional development, the survey was administered to nurses working in well-baby clinics, communicable diseases clinics, travel clinics and school nurses. Specific areas identified gaps in knowledge, attitude, and practice among participating nurses. Results: Results from our study suggest that attitudes and practices of participants identified a significant difference after receiving an immunization educational program that focused on administration and delivery of immunization skills. Conclusion: Continuous professional development activities such as this have shown a marked increase in the attitude and practices of nurses making it tantamount to the success of vaccine uptake. Implications for Practice: Nurses are poised to be frontline advocates for the uptake of immunization; therefore education and training needs to be provided in order for them to understand and further affect change. Keywords: Vaccine, Immunization, Knowledge, Attitude, Practice

Rose-ringed parakeet (P. krameri) is commonly found native psittacid in Pakistan. It is most popular companion bird in Pakistan. It is an unprotected species as per The Punjab Wildlife Act, 1974. The objectives of the present study were to study its population paradigm and basic nesting biology in the Gujar Khan, Punjab, Pakistan. Previously, no studies were carried out to assess its live and vacant nest cavities, nesting site, nest height, cavity position on substrate, and potential roosts in the area. Moreover, this study also assesses the potential threats and factors in this area and conservation of the parakeet. Results show that in the study area (36.77%) active and (63.22%) inactive nests were found. A total of 10 tree species were utilized to make nests. It was found Ficus bengalensis, Syzygium cumini, Morus alba, Melia azedarach and Broussonetia papyrifera as the most used tree species for nesting due to more frequencies and old ages. Parakeets make nest at 3-11 m height. The preferred nest height (42.48%) was in the range of 7-9 m, while (5.88%) least at 3-5 m height. For safety reasons they made more nests (45.09%) on the tree trunk followed by terminal (31.37%) and at fork (23.52%). Due to smaller thriving population we found only (mean=7±4) parakeets during roost counting. Severe cutting of trees, destruction of its habitat and poaching for selling in the bird market are the main causes of its population decline. Government must change its status from unprotected to protected species and should ban its dealing for pet.

The rheological behavior, assembly measurements, thermal stability, molecular conformation, and molecular interactions of myofibrillar proteins (MP) modified by transglutaminase (TGase) and epigallocatechin-3-gallate (EGCG) were investigated. Fluorescence and ultraviolet spectra showed that TGase and ECCG quenched the endogenous fluorescence of MP and improved the exposure of chromophoric and hydrophobic groups of MP caused by unraveling the tertiary structure. TGase and EGCG treatment increased the α-helix and β-turn contents and the structure became more ordered. It also increased the thermal stability of MP and the storage modulus of MP gels as reflected in the rheological and thermal properties tests. Meanwhile, changes in SDS-PAGE, FT-IR, and sulfhydryl contents showed that TGase increased the disulfide bond contents, whereas it decreased after EGCG was added, suggesting that EGCG could react with MP via non-covalent and covalent interactions. Assembly measurements illustrated that TGase increased the turbidity and particle size of MP, while TGase and EGCG treatment accelerated MP aggregation and it was associated with the increase in the EGCG concentration, which was further confirmed by SEM and AFM. This work could contribute new insights into the synergistic effect of TGase and EGCG on modifying MP and guide for its application in surimi processing.

The study aims to investigate the effects of pomegranate peel extract (PGPE) and grape seed extract (GSE) at acidic pH. Surimi-based edible films incorporated with pomegranate peel extract (PGPE) and grape seed extract (GSE) at different concentrations (2%, 4% and 6% w/w protein content) under acidic condition were characterized. In extract-containing films, elongation at break (EAB) and film solubility (FS) decreased, as well as water vapor permeability (WVP) and transparency while tensile strength (TS) (P

Furan is generally produced during thermal processing of various foods including baked, fried, and roasted food items such as cereal products, coffee, canned, and jarred prepared foods as well as in baby foods. Furan is a toxic and carcinogenic compound to humans and may be a vital hazard to infants and babies. Furan could be formed in foods through thermal degradation of carbohydrates, dissociation of amino acids, and oxidation of polyunsaturated fatty acids. The detection of furan in food products is difficult due to its high volatility and low molecular weight. Headspace solid-phase microextraction coupled with gas chromatography/mass spectrometer (GC/MS) is generally used for analysis of furan in food samples. The risk assessment of furan can be characterized using margin of exposure approach (MOE). Conventional strategies including cooking in open vessels, reheating of commercially processed foods with stirring, and physical removal using vacuum treatment have remained unsuccessful for the removal of furan due to the complex production mechanisms and possible precursors of furan. The innovative food-processing technologies such as high-pressure processing (HPP), high-pressure thermal sterilization (HPTS), and Ohmic heating have been adapted for the reduction of furan levels in baby foods. But in recent years, only HPP has gained interest due to successful reduction of furan because of its nonthermal mechanism. HPP-treated baby food products are commercially available from different food companies. This review summarizes the mechanism involved in the formation of furan in foods, its toxicity, and identification in infant foods and presents a solution for limiting its formation, occurrence, and retention using novel strategies.

Human Development Index includes health, education, pay records, and family unit structures to show the suicide rate. A biological study was carried out in individuals in the range of 15 and 49 years of age. The three indexes were developed that were education index (EI), income index (II), and HDI. From authentic information bases per capita income, poverty, and household rates were gathered. Pearson’s correlation coefficient, which is (r), is utilized to decide the strength between per capita pay, suicide rate, joblessness, poverty and depression rates. A various linear regression model was utilized to know the relationship rate between the Human Development Index (HDI) and suicide rates. Human Development Index (HDI) focuses on longevity, basic education and moderate-income. First, an educational component made up of two elements mean and expected years of schooling. Second, a life expectancy component should be estimated using a minimum value. The last element is gross national income (GNI) per capita adjusted to purchasing standards. As a major health issue, there is no global study on suicide. Suicidal rate varies between most countries with different human development index levels. The research examined that the male gender and HDI component is directly linked to increased suicide risk rates. It was the study of the Mexican state. Human Development Index (HDI) of 32 states of Mexican were low 16%, the middle 41% high 22%, and extremely high 13%. An immediate and positive relationship was found between non-family households and the suicide rate. The suicide rate adversely and significantly connected with Pearson (r = -0.350; p < 0.001). The individuals of this state, with the predominance of non-family households, had a positive relationship with the suicide rate. Because of the consequence of this investigation, it is possible to expect that the Human Development Index (HDI) expands and there is a chance of living alone and having suicidal conduct.

Collagen Type I derived from fish is mainly limited by its poor physicochemical properties for further applications. In this study, we developed epigallocatechin gallate (EGCG) cross-linked collagen hydrogels (EC hydrogels) to realize physicochemical improvements, basing on the interaction mechanism between collagen and EGCG. The integrity of collagen framework with slight secondary structure change in the presence of EGCG was confirmed. The stronger stability of collagen fibrils was proved by slower swelling ratio, declined enzymatic degradation, improved thermal analysis and mechanical test due to EGCG modification. To illustrate the potential mechanism between collagen and EGCG, molecular docking was used to identify both covalent (CN bond, between lysine of collagen and C2-ring B of EGCG) and non-covalent bonds (hydrogen bond and hydrophobic interaction) within in EC hydrogel. Taken together, this work would offer some insights into the further study about the interaction between EGCG and collagen.

Background: The current nursing workforce needs to be skilled, confident, and competent to address the rapid change in Primary Health Care services, to align with the National Vision of Qatar. This is emphasized in the Primary Health Care Strategy 2018-2023. This strategy outlines the need of having a skilled nursing workforce to administer and educate the public about the importance of immunizations. Primary Health Care nurses emanate from several nationalities and hence possess various level of knowledge and background related to immunization administration. Design and methods: To assess Primary Health Care nurses’ knowledge before and after the delivered immunization education program in Qatar. The study was part of a Sequential mixed method research study that aimed to assess the Primary Health Care nurses’ knowledge, attitude, and practice of nurses before and after the conducted training program. A self-administered survey, specifically developed for the research project was loaded in Qualtrics and sent to participants of the immunization education program before and after training. Participants were trained in two cohorts from October to December, 2018 in Qatar. For the purposes of this paper, data about the immunization knowledge was statistically analyzed using the SPSS Software version 25 and Microsoft Excel. Results: Specific areas were identified as knowledge gaps among the participants of the two cohorts. Moreover, the developed education program showed overall improvement in the participants’ knowledge. Conclusions: The study results have demonstrated that the delivered immunization education program significantly increases the participants’ knowledge about immunization in certain areas of the primary healthcare clinics they work, including vaccine safety, efficiency, and contraindications in the delivery of vaccines to the public. Significance for public health Qatar is a multinational country containing expatriates from all over the world from either developing or developed nations that are transient in their length of stay. As a result, having misconceptions related to vaccine administration can be varied, these may include such things as vaccine schedules, varying beliefs and myths related to vaccine administration as well as knowledge about each of the vaccines. For this reason, Primary Health Care nurses need to be equipped with the immunization related knowledge and skill to deliver the required education that encourages vaccine uptake to mitigate the transmission of vaccine preventable diseases.

The coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 due to its rapid and extensive spread among many countries through its very contagious nature and its high mortality among the elderly and infirm. Recently, data on the survival of SARS-CoV-2 on contact surfaces has been reported, but there is none on the survival of COVID-19 on food surfaces and packages. The potential survival and transmission of SARS-CoV-2 on/via food and packages are discussed based on data available for other respiratory viruses such as SARS-CoV and MERS-CoV. However, studies are needed to explore its transmission via food and survival on food packaging materials. The implementation of food safety management systems such as Hazard Analysis and Critical Control Points (HACCP), and Good Manufacturing Practices (GMP) are important to reduce the risk of COVID-19 infection. Cleaning, sanitation, good hygienic practices, and active packaging are also needed from farm to fork.

Enteropathogenic microorganisms like Escherichia coli cause severe intestinal problems by disrupting the gut homeostasis. The live microorganisms, when given in adequate quantities provide several beneficial effects to the host are known as probiotics. One of the pronounced benefits conferred by probiotic is to antagonize the growth of enteropathogens competing for adherence to the intestinal epithelium. Bifidobacterium is the major genera of human especially infant are intestinal microbiota. In current study, Bifidobacterium bifidum was isolated from the infant stools and probiotic potential was assessed using prescribed tolerance tests against low pH, gastric juices and bile salts. Anti-infectious activity of probiotic Bifidobacterium bifidum against enteropathogenic E. coli was checked both in vitro and in vivo using agar well diffusion assay and mice model respectively. Mice feces were evaluated for both Bifidobacterium bifidum and E. coli counts in all groups and analyzed statistically. In vitro results showed Bifidobacterium bifidum possess marked antibacterial activity against E. coli. There was significant decrease in enteropathogenic E. coli burden in the mice group fed with Bifidobacterium bifidum before and after challenge. In conclusion, the endogenous Bifidobacterium bifidum have excellent probiotic potential and can be used prophylactic and treatment option against enteropathogens.

Calcium (Ca(2+)) has emerged as a significant secondary messenger that regulates the activities of hormonal and environmental signals that are associated with biotic and abiotic stresses. Ca(2+) binding proteins typically contain a Ca(2+) binding EF-hand (a helix-loop-helix structure) motif. In this study, tomato genes encoding calmodulin-like (CML) proteins that possess EF-hand motifs and no other identifiable functional domains were analyzed. Using genome analysis and BLAST searches in database, 52 CML genes were identified in tomato. Comprehensive analyses, including evolutionary relationships, gene structures, chromosomal locations, functional annotations, and gene duplications, were performed. Distribution mapping exhibited that 52 SlCML proteins containing different intron/exon patterns were unevenly distributed among ten chromosomes. In addition, 24 SlCML proteins were predicted as segmentally duplicated. Conserved motifs, promoter cis-regulatory elements, organ-based expression patterns and expression analyses indicated the potential responsiveness of SlCML proteins to abiotic stresses and phytohormones. These results illustrate the complexity of the CML gene family and indicate a potential vital role for these molecules in tomato growth and development as Ca(2+) signal transducers.

Natural enemies of herbivores function in a multitrophic context, and their performance is directly or indirectly influenced by herbivores and their host plants. Very little is known about tritrophic interactions between host plants, pests and their parasitoids, particularly when the host plants are under any stress. Herbivores and their natural enemies’ response to plants under stress are diverse and variable. Therefore, in this study we investigated how diamondback moth, Plutella xylostella (L.), reared on water-stressed host plants (Brassica napus L. and Sinapis alba L.) influenced the development of its larval parasitoid, Diadegma insulare (Cresson). No significant differences were observed in development of P. xylostella when reared on water-stressed host plants. However, all results indicated that water stress had a strong effect on developmental parameters of D. insulare. Development of D. insulare was delayed when the parasitoid fed on P. xylostella, reared on stressed host plants. Egg to adult development of D. insulare was faster on non-stressed B. napus than non-stressed S. alba followed by stressed B. napus and S. alba. Female parasitoids were heavier on non-stressed host plants than stressed counterparts. Furthermore, the parasitoid lived significantly longer on stressed B. napus. However, body size was not affected by water treatment. Most host plant parameters measured were significantly lower for water-stressed than non-stressed treatments. Results suggest that development of this important and effective P. xylostella parasitoid was influenced by both water stress and host plant species.

Background and objective: Hamad Medical Corporation nurse leaders established nursing journal clubs in 2014 as an important strategy to involve nurses in translating research into practice and as an effort to provide patients with the highest possible standards of care. Since the implementation of journal clubs in Hamad Medical Corporation (HMC), evaluative research within HMC has not been conducted to examine the effectiveness of this strategy. The aim of this review was to increase decision makers’ knowledge about the effectiveness of journal clubs in translating knowledge into clinical practice and to provide a framework to guide the development of a survey tool that would aide in the evaluation of nursing journal clubs’ effectiveness at Hamad Medical Corporation. A literature search was conducted as an initial step top guide the development of this tool.Methods: A literature search was conducted yielded 13 studies that evaluated the effectiveness of journal clubs after removing all duplicates and applying the inclusion criteria. The Mixed Methods Appraisal Tool-version 2011 was used to evaluate the quality of the included articles. Data was analyzed and extracted from each study and assembled into a summary table.Results: Four themes related to journal clubs’ effectiveness that are important in translating knowledge into practice: encouraging discussion among healthcare professionals, enhancing critical appraisal skills, promoting evidence-based practice knowledge, and impacting clinical practice.Conclusions: This literature review provides information about the four main interrelated themes that contribute to journal clubs’ effectiveness in translating knowledge into practice. This information would be useful to nurse educators at Hamad Medical Corporation and further utilized as a backdrop to the development of a tool to evaluate Hamad Medical Corporation nurses’ perceptions of journal clubs’ effectiveness.

Summaryp27Kip1, a cyclin-dependent kinase (CDK) inhibitor, is a multi-functional protein that regulates various cellular activities. Trophoblast proliferation, migration and invasion are some of the key processes of placental development. We have recently reported that Nodal, a member of the transforming growth factor-β (TGF-β) superfamily, inhibits human trophoblast cell proliferation, migration and invasion. In the present study, we investigated the mechanism by which Nodal regulates trophoblast activities. We found that Nodal increased p27 mRNA and protein levels by enhancing their stability. Interestingly, Nodal signaling also induced nuclear export of p27 and CDK2. Cytoplasmic translocation of p27 induced by Nodal requires p27 phosphorylation at S10. In addition, Nodal enhanced the association of p27 with CDK2, CDK5 and a microtubule-destabilizing protein, stathmin, and induced stathmin phosphorylation at S25 and S38. Furthermore, Nodal increased tubulin stability as revealed by immunofluorescent staining of acetylated tubulin. Finally, silencing of p27 reversed the inhibitory effect of Nodal on trophoblast cell proliferation, migration and invasion. Taken together, our findings revealed a novel function of simultaneous p27 and CDK2 cytoplasmic mislocalization in mediating growth-factor-regulated cell proliferation, migration and invasion.

Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.

Research article

One of the fundamental goals of genetic research is to understand the pattern of heritability associated with the manifestation of various complex diseases. Elucidation of underlying genetic variation associated with common traits is one of the major challenges faced by clinical researchers. Gestational diabetes Mellitus (GDM) is multifactorial disorder of pregnancy. GDM refers to abnormal glucose tolerance that is first identified or diagnosed during pregnancy. GDM has long term impacts on the health of mother, developing fetus and child. Women and their offspring with history of GDM are at a greater risk of developing Type 2 Diabetes Mellitus (T2DM). GDM increases the risk of adverse pregnancy outcomes, including preeclampsia, birth injuries, macrosomia and neonatal hypoglycemia, respiratory distress syndrome, neonatal cardiac dysfunction and stillbirth. It is estimated that 4% of pregnancies in the United States are complicated with GDM; however, rates of GDM are significantly increasing with an overall increased prevalence of diabetes. It is reported that prevalence of GDM varies considerably among racial and ethnic groups. Genetic causes of this disease are uncovered by many recent studies. A systematic review of genetic association studies of GDM was performed by using Pubmed navigator. Key terms used were GDM, genetics, genetic variants, genome wide association studies, genetic risk factors and genetic susceptibility and loci. Functional studies of GLUT1, FOXC2, IRS1, PPARGC1 and UCP2 genes have data suggesting an influence of these genes on GDM. Genetic variants that are common in GDM and T2DM are documented in several promising studies. Genetic variants of CAPN10, MBL2, KCNJ11, ABCC8, ND1, TCF7L2, ADIPOQ and PAI1 genes are associated with the development of both GDM and T2D. However, six genes are widely studied and all of them reported to have significant association with the risk of GDM are TCF7L2, GCL, KCNJ11, CDKAL1, IGF2BP2 and MTNR1B. It is therefore, determined that some susceptibility loci are unique to GDM and can be used in future as markers for identifying women with a high risk of GDM. There is an increasing need of replication of these studies in other populations. Identification of genetic variants in specific populations will significantly contribute to our understanding of the pathogenesis of GDM and will ultimately improve our prediction of GDM and future of T2DM.

Preeclampsia is a pregnancy specific condition characterized by hypertension and proteinuria. It complicates about 10% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Interestingly, preeclampsia may have an impact on the health of the mother or infant, beyond the pregnancy. It is believed that several ligands and receptors of different families of growth factors have been involved in the development of preeclampsia. We performed a systematic search of PubMed including combination of terms such as preeclampsia, growth factors, treatment, vascular endothelial growth factor A, activin A, inhibin A, placental growth factor, transforming growth factor β-1, Nodal, placenta, trophoblast cells, biomarkers and detection. In this review we have summarized current knowledge on the role of growth factors in early detection and treatment of preeclampsia. Although these growth factors have significant roles in normal and complicated pregnancies, the current value of these growth factors as biomarkers, for the precise prediction of preeclampsia, has its limitation. Therefore, future studies need to be done to support some of the very promising and interesting data to develop affordable and widely available tests for early detection and treatment of preeclampsia.

Prolactin (PRL) is a polypeptide hormone, secreted mainly by the anterior pituitary gland. It is involved in many endocrine activities. The key functions of PRL are related to reproduction and lactation in mammals. To ascertain the presence of polymorphisms in the bovine PRL gene (bPRL), the bPRL gene was sequenced. Five mutations were identified in exonic region and eleven in associated intronic regions in 100 cattle from four Pakistani cattle breeds. Haplotype of predicted amino acid changes represent a common alteration at codon 222 from R-Arginine into K-Lysine in all four breeds. Significant statistical variations were observed in the distribution of single nucleotide polymorphism (SNP) in various cattle populations. However, on basis of present study, an association of these SNPs with milk performance traits in four Pakistani cow breeds cannot be truly replicated but at least can be effective DNA markers for some of the breeds studied. Linkage analysis between these SNPs on larger populations can be useful for the association with milk production traits. Furthermore, present study may be used for marker-assisted selection and management in cattle breeding program in local cattle breeds.

Human epithelial ovarian cancer is the most lethal female cancer. Hormones and growth factors, including the TGF-beta superfamily, have been suggested to play a role in ovarian tumorigenesis. The biological effects of TGF-beta superfamily are mediated by type I and type II serine/threonine kinase receptors and by intracellular Smad proteins. Recently, we have cloned four transcripts of human activin receptor-like kinase 7 (ALK7), a type I receptor for Nodal. In this study, we have investigated the role of Nodal and ALK7 in four ovarian cancer cell lines, OV2008, C13*, A2780-s, and A2780-cp. Overexpression of Nodal resulted in a significant decrease in the number of metabolically active cells. This effect was mimicked by a constitutively active ALK7 (ALK7-ca) but blocked by dominant negative mutants of ALK7, Smad2, or Smad3. Transient transfection of Nodal and ALK7-ca significantly decreased X-linked inhibitor of apoptosis protein (Xiap) expression, activated both caspase-3 and caspase-9, and increased apoptosis as determined by Hoechst nuclear staining and flow cytometry. In addition, Nodal and ALK7-ca also inhibited cell proliferation as measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Interestingly, the effects of Nodal and ALK7-ca were more potent in chemosensitive A2780-s cells than in its chemoresistant counterpart, A2780-cp cells. These findings demonstrate that Nodal induces apoptosis and inhibits proliferation via ALK7 and Smad2/3 and that the effect of Nodal-ALK7 on apoptosis may be mediated in part by the down-regulation of Xiap and activation of caspase-9 and caspase-3.

Nodal, a member of the transforming growth factor-beta superfamily, is known to play critical roles in early vertebrate development, but its functions in extraembryonic tissues are unclear. ALK7 is a type I receptor for Nodal. Recently, we demonstrated that Nodal mRNA and several ALK7 transcripts are expressed in human placenta throughout pregnancy (Roberts, H. J., Hu, S., Qiu, Q., Leung, P. C. K., Cannigia, I., Gruslin, A., Tsang, B., and Peng, C. (2003) Biol. Reprod. 68, 1719-1726). In this study, we determined the role of Nodal and ALK7 in trophoblast cell proliferation and apoptosis. Overexpression of Nodal in normal trophoblast cells (HTR8/SVneo) and several choriocarcinoma cell lines resulted in a significant decrease in the number of metabolically active cells. The effect of Nodal could be mimicked by constitutively active ALK7 (ALK7-ca), but was blocked by kinase-deficient ALK7. The growth inhibitory effect of Nodal was also blocked by dominant-negative Smad2/3. Overexpression of Nodal and ALK7-ca induced apoptosis in trophoblast cells as determined by Hoechst staining, flow cytometry, and caspase-3 Western blotting. In addition, Nodal and ALK7-ca decreased the number of proliferating cells as measured by bromodeoxyuridine assays. Furthermore, overexpression of Nodal or ALK7-ca increased p27 expression, but reduced the levels of Cdk2 and cyclin D(1). Taken together, this study demonstrates for the first time that Nodal, acting through ALK7 and Smad2/3, inhibits proliferation and induces apoptosis in human trophoblast cells. Our findings also suggest that the Nodal-ALK7 pathway inhibits cell proliferation by inducing G(1) cell cycle arrest and that this effect is mediated in part by the p27-cyclin E/Cdk2 pathway.