Circadian rhythm and its role in malignancy

Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer

Second Language International Postgraduate Students’ Perceptions of Assessment Feedback: An Analysis

This study seeks to investigate the attitudes, beliefs and experiences of second language (L2) international students regarding tutor written feedback and its impact upon their learning in a UK university. The present study uses qualitative interpretive research paradigm that synthesizes the academic literacies (AL) approach and critical discourse analysis (CDA) to investigate students’ perceptions of feedback on their assessed work. The AL approach positions the students’ feedback experiences as socially situated phenomena enmeshed within the wider socio-cultural context of academia. The data for this study came from two main sources: (1) semi-structured in-depth interviews with 26 students of varying nationalities and departments (2) teachers’ feedback sheets. To collect appropriate qualitative data, the participants read aloud their tutor feedback comments, which were transcribed verbatim and analysed using CDA techniques. The data were divided into various themes such as functions of feedback, helpful and unhelpful feedback, feedback and its impact on self-esteem, motivation, confidence and the power-differentials of the student-teacher relationship. The findings of the study have shown that assessment feedback is a unique form of communication which takes place within the wider socio-cultural context of a UK university. The study highlights that the process of giving and receiving feedback involves a complex interplay of self-esteem, identity, motivation, emotion and the power relations. The study also highlights that the participants have had little or no experience of receiving such feedback in their countries of origin. Therefore, the move from one academic context to a UK university turned out to be challenging for L2 international students. The study sheds light on the question of how different linguistic, educational and cultural backgrounds of L2 international student presented them challenges while coming to terms with new assessment expectations, writing requirements and academic culture of a UK university. The CDA of tutor comments on students’ assignments revealed that the amount of feedback varied from tutor to tutor. Moreover, the tone of comments indicated a lack of balance between praise, criticism and suggestions. By looking at the student perspective, the study has offered deep insights into the reasons why international students show dissatisfaction with feedback, what problems they encounter while making meaning of the feedback discourse situated in new educational and socio-cultural environment. In brief, to better understand assessment feedback as a socially situated practice, this research has addressed the questions of how the interplay of issues such as discourse, identity, power, control and social relationships mediated students’ perceptions of feedback

Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder

Parental Effects on Primary School Enrolment under Different Types of Household Headship: Evidence from Pakistan

Previous studies in Pakistan have established the number of pupil, parents, household, and community characteristics as determinants of primary school enrolment. However, treatment of the role of the household power structure in these studies is limited to the inclusion of a single dummy variable for female headship. Present study estimates separate probit regressions for different types of headships, hence allowing for an analysis of the power structure of the household and its impact on other explanatory variables. In addition to confirming the findings of previous studies, this study concludes that mother‘s headship results in greater positive influence of her own education and the economic status of the household on child‘s primary school enrolment. Father‘s headship in this regard has only limited influence. JEL Classification: C25, J16, I21 Keywords: Probit Models, School Enrolment, Gender Issue

Informativeness of St14 VNTR Polymorphic Marker in the Carrier Detection of Hemophilia A

Hemophilia A is the most common hereditary severe disorder of blood clotting. In families affected with hemophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostic strategy for carrier-ship determination in Pakistani population using an extragenic polymorphic marker for the first time. The analysis of St14 VNTR (DXS52) was carried out by polymerase chain reaction (PCR), in order to determine its informativeness in terms of heterozygosity in Pakistani population. This may be a milestone for further analysis of other polymorphic markers for carrier detection and prenatal diagnosis of hemophilia. Seventy eight blood samples (Hemophiliac = 23, Normal = 55) from 15 families were analyzed for determining informativeness of St14 VNTR in carrier detection of hemophilia A. A total of nine alleles (2400, 2100, 1750, 1690, 1630, 1570, 1390, 1300, 1220 bp) was detected in the pool of subjects. 19 out of 40 females were found to be carriers with respect to the St14 VNTR polymorphic marker. The marker was informative in 73.33% of families. The expected heterozygosity rate of the St14 VNTR was 0.86 while the observed heterozygosity was 0.7. This shows that St14 VNTR is 70% informative in our population, allowing it to be a useful marker in carrier detection, as informativeness is the direct reflection of heterozygosity of a polymorphic marker

Mutational analysis of CYP1B1 gene in Pakistani pediatric patients affected with Primary Congenital Glaucoma

Background: Glaucoma is the significant cause of blindness all over the world. Primary congenital glaucoma (PCG) reduces the vision and ultimately causes the blindness by damaging the aqueous drainage system of the eye. The purpose of the current study was to determine the pathogenic mutations in the CYP1B1 gene responsible for PCG.Methods: A total of thirty-five PCG patients were enrolled in this study. Blood samples were collected from the enrolled patients, and after DNA extraction and amplification, the coding regions of CYP1B1 were sequenced to determine the pathogenic mutations. In-silico analysis of the identified mutation was executed to study the effect of genetic variation on protein structure.Results: One mutation, c.1169 G>A has been revealed in exon 3 of the CYP1B1 gene leading to p.R390H, present in 20% of the patients enrolled. Besides, two missense sequence variants c.1294G>C (2 patients), c.1358A>G (4 patients) and a synonymous variant c.1347T>C (18 patients) has also been observed.Conclusion: Our study not only reaffirms the role of CYP1B1 mutations in PCG but also supports the use of genetic screening for molecular diagnosis and carrier identification, which will reduce the burden of disease on society. Furthermore, the in-silico analysis of the identified mutations provided an in-depth understanding of the PCG pathogenesis at the molecular level.Keywords: Primary congenital glaucoma; CYP1B1, mutation; Genetic variatio

RISK PERCEPTION OF SOCIALLY RESPONSIBLE INVESTORS IN MUSLIM COUNTRIES

From the evidence that socially responsible investment is an emerging concept in Muslim countries, we have developed a socio-demographic behavior based model. We have shown the direct effect of social factors (religion and family influence) and indirect effect of demographic factors (age, education and income) on investment choices through risk perception. Investors may be experienced in investment market but particularly in SRI investments of Muslim countries they will be new entrants. We have developed hypotheses from literature in our study regarding this concept of new entrants. In Pakistan, SRI investment is not prevailing but opportunities do exist. Pakistani firms can take the initiative by attracting SRI investments if firms develop more sophisticated CSR

Lightweight ECC Based Multifactor Authentication Protocol (LEMAP) for Device to Device Cellular Network

Device to Device (D2D) communication is a type of technology where two devices can communicate directly with each other without the need to contact Base Station or any central infrastructure. With emerging of Long Term Evaluation (LTE) and Fifth Generation (5G) technology, D2D has gained a lot of attention for communication between closely located mobile devices for offering high speed, energy efficiency, throughput, less delay, and efficient spectrum usage. D2D has changed recent wireless networks with new trends as D2D can play a vital role in sharing resources by load off the network in local areas by direct communication between devices and useful in natural disasters where BS is destroyed. D2D has revolutionized the direct communication as it is a basis for 5G network. D2D allows miniature devices like cell phone, tablets and radio devices to work as Non-Transparent Relays (NTR) where they can provide services as well as forward traffic, request services by direct communication without the need of Base Station (BS) or central network infrastructure. Multi-hop D2D can be used for peer-to-peer communication or even access to cellular networks. This concept of multihop D2D communication has introduced a number of issues and challenges that were not prevalent in traditional current cellular communication. One of the major issues in D2D is security that is required in D2D communication to transmit information securely over non secure channel. The major challenge when considering security is that current established security techniques cannot be modified as security-requiring devices are miniature with restricted processing and storage or are constrained by power and bandwidth issues. Another issue is that how devices can get secure mutual authentication for secure communication. To tackle these issues, a lightweight multifactor authentication scheme that allows multihop secure communication over open channel is designed called as Lightweight ECC based Multifactor Authentication Protocol (LEMAP) in multihop D2D communication. Formal analysis of scheme is performed using well known BAN Logic method which is used to check correctness of protocol. The formal analysis of LEMAP proves that it can mitigate replay attack, Man-in-the-Middle (MITM) attack, Rogue device attack, Denial of Service (DoS) attack, timestamp exploitation attack, impersonation attack and masquerading attack. LEMAP also achieves security requirements confidentiality, integrity, privacy, non-repudiation, secure mutual authentication and anonymity. The communication cost and computational overhead of benchmark protocols and the proposed scheme LEMAP are also calculated. The results show that LEMAP is 6%-28% percent stronger than the selected benchmark algorithms such as 2PAKEP, Chaotic based authentication and TwoFactor authentication protocol. Additionally, LEMAP provides additional security by using trust validation, double hashing, and reduced authentication overhead. Discrete logarithm analysis shows that LEMAP is more secure compared to current security algorithms or current security algos are used as attacks against LEMAP. LEMAP is a lightweight and flexible scheme which can be used in 5G as well as multihop D2D communication to provide secure communication environment. Keywords: D2D security, multihop D2D security, multi factor, light-weight security, EC

Biosynthesis of lovastatin using agro-industrial wastes as carrier substrates

Purpose: To compare fungal strains including Aspergillus flavipes GCBL-72, Aspergillus flavus GCBL-60, and Aspergillus niger GCBL-45 and determine whether solid- or liquid-state fermentation (SSF or LSF) is more appropriate for lovastatin production using various inexpensive raw materials.Methods: LSF and SSF techniques were used to produce the drug lovastatin.  High-performance liquid chromatography was performed out to quantify lovastatin production. A kinetic growth model was applied to estimate product formation at the expense of substrate utilization.Results: Aspergillus flavus GCBL-60 was a superior lovastatin-producing strain consuming wheat bran as the raw material in SSF. The optimum lovastatin production was 28.36 ± 0.76 mg/100mL at 35 °C, pH 5.5, inoculum size 2 mL, 96 h incubation time, and 60 % moisture content. Evaluation of the kinetic growth parameters for lovastatin production confirmed that product formation was improved after fermentation parameter optimization.Conclusion: Our results indicate that Aspergillus flavus GCBL-60 was best  lovastatin-producing strain and that SSF was superior to LSF for maximum  production. Careful optimization can enhance product formation.Keywords: Hypercholesterolemia, Kinetics, Optimization, Lovastatin, Solid-State Fermentation, Raw material