Article Neuropeptide receptors as potential antiepileptic drug targets: focus on the ghrelin axis Jeanelle Portelli Pages: 4 - 7 Read Abstract | View full article |
PDF Abstract: Epilepsy is a very serious neurological disorder which is often underrepresented. Around 50 million indi- viduals worldwide have active epilepsy with recurrent seizures and in spite of the medical advances over the years, 30% of these patients remain as drug resistant (Pati and Alexopoulos, 2010). Even after several years of research, there is still a lack of good understanding on the pathophysiology of seizure disorders (Perucca, 2011). Investigators in this eld believe that there is a great need for novel antiepileptic drugs (AEDs) that act differently than the drugs available on the market. The majority of AEDs act by blocking sodium chan- nels (phenytoin, carbamazepine) or by the augment of GABAergic transmission (phenobarbital, valproic acid). A newer generation of AEDs has expanded therapeutic options, however these are not superior to the older drugs (Hitiris and Brodie, 2006). Patients with mesial temporal lobe epilepsy (mTLE) are among the most pharmacoresistant to these medications (Pati and Alex- opoulos, 2010).
Article Agreeing to disagree: Constant non-alignment of speech gestures in dialogue Holger Mitterer Pages: 8 - 14 Read Abstract | View full article |
PDF Abstract: Numerous studies suggest that interlocutors in a dialogue align with each other in terms of their articulatory gestures. It is often suggested that this, rst, is the consequence of an automatic tendency for imitation and, second, this fosters mutual understanding. Making use of online archives of media, it was tested whether alignment is hence inevitable. The focus was on the pronunciation of the German word ist (Engl., 'is'). The standard pronunciation is [ist], but speakers with a Swabian accent produce [i R t], acoustically re ected in the fricative spectra. We measured the spectra of fricatives in ist from interviewers while interviewing either a prominent German politician using the Swabian variant or an interviewee using the standard variant. Results showed neither an overall in uence of the interviewees' pronunciation on the fricative realization by the interviewer nor a tendency to align over time for interviewer-interviewee pairs with different pronunciations. This shows that phonetic alignment in conversation is a more complex process than most current theories seem to suggest. Moreover, failure to align may not impede mutual understanding.
Article Pharmacogenetics: the science of predictive clinical pharmacology Anthony G. Fenech, Godfrey Grech Pages: 15 - 32 Read Abstract | View full article |
PDF Abstract: The study of pharmacogenetics has expanded from what were initially casual family-based clinical drug response observations, to a fully- edged science with direct therapeutic applications, all within a time-span of less than 60 years. A wide spectrum of polymorphisms, located within several genes, are now recognised to in uence the pharmacokinetics and pharmacodynamics of the majority of drugs within our therapeutic armamentarium. This information forms the basis for the new development of pharmacogenetic genotyping tests, which can be used to predict the therapeutic and/or adverse effects of a specic drug in a particular patient. Pharmacogenetic-guided, patient targeted therapy has now become the developing ful- crum of personalized medicine, as it provides the best means to optimize benet/risk ratio in pharmacological management.
Article The Optimism Bias: A cognitive neuroscience perspective Claude J. Bajada Pages: 33 - 37 Read Abstract | View full article |
PDF Abstract: The optimism bias is a well-established psychological phenomenon. Its study has implications that are far reaching in elds as diverse as mental health and economic theory. With the emerging eld of cognitive neuroscience and the advent of advanced neu- roimaging techniques, it has been possible to investigate the neural basis of the optimism bias and to understand in which neurological conditions this natural bias fails. This review rst denes the optimism bias, discusses its implications and reviews the literature that investigates its neural basis. Finally some potential pitfalls in experimental design are discussed.
Article Skin Grafts: Local quest for viable alternatives to autologous grafts using silk and acellular dermal matrices Yanika Gialanzè, Angela A. Xuereb, Pierre Schembri-Wismayer Pages: 38 - 42 Read Abstract | View full article |
PDF Abstract: The gold standard with regards to skin transplantation is the use of the patient's own skin ob- tained from a healthy donor site. Such grafts can be either full thickness skin or more commonly nowadays, split thickness skin. Various materials, having either natural and or synthetic origins, have been used in the engineering of skin substitutes to-date and these grafts are then confronted against autologous skin grafts. If proven to be successful, such matrices could be utilised in clinical applications such as in the treatment of burn wounds and in cases of skin ulcers amongst others. In this study the primary cells used, keratinocytes and broblast, were obtained from donor skin and cultured. Scaolds of xenogenic (raw silk) as well as of allogenic (acellular dermal matrices) origins were obtained via low-cost methods and seeded using the broblasts and keratinocytes so as to determine which gave the closest mimic to skin grafts. Out of the matrices assessed, the raw silk matrix al- lowed the best colonisation with skin cells in our hands. The ADM matrice also showed some cell colonisation, but will need further experimentation.
Article The Structure of Protein Molecules: In Celebration of the International Year of Crystallography, 2014 Gary Hunter, Marita Vella, Rosalin Bonetta, Diane Farrugia, Therese Hunter Pages: 43 - 48 Read Abstract | View full article |
PDF Abstract: Many people, including laymen, are aware of the double helical nature of the DNA molecule. A few may actually realise that it was the technique of X-ray crystallography that was the key to solving this struc- ture. Even fewer will understand the uses and applica- tions of crystallography to the most diverse of biological materials; proteins. In this review we discuss the appli- cation of a number of methodologies required to progress from a cloned gene to protein expression and purica- tion, crystallisation conditions and eventually to X-ray structure determination. We provide our own experi- ence in the eld as examples of the procedures required. Protein crystallographers worldwide are contributing to our understanding of how enzymes work, how our im- mune system defends us against viruses and are using structural information to design novel pharmaceutical reagents.
Article A first record of Chara vulgaris var. papillata Wallroth. Ex A. Braun (Charales) in the Maltese Islands (Central Mediterranean) Jonathan Henwood Pages: 49 - 51 Read Abstract | View full article |
PDF Abstract: The Maltese list of characeans includes Chara vulgaris of which the most commonly occurring variant is C. vulgaris var. longibracteata. A less common variant, C. vulgaris var. papillata, has been recorded for the rst time locally in mats of Chara vulgaris examined from il-Qattara pool and Qawra (Dwejra, Gozo).
Article Phospho-Akt expression is high in a subset of Triple Negative Breast Cancer Patients Nigel Borg, Shawn Baldacchino, Christian Saliba, Sharon Falzon, James De Gaetano, Christian Scerri, Godfrey Grech Pages: 52 - 60 Read Abstract | View full article |
PDF Abstract: The most commonly used biomarkers to predict the response of breast cancer patients to ther- apy are oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specic therapies such as anti-oestrogen therapy in the event of ER and PgR positivity, and trastuzumab, a monoclonal antibody, in the case of HER2 positive patients. Patients who are negative for all these three biomarkers, the so-called triple negatives, however, derive little benet from such therapies. The PI3K/Akt pathway is activated in triple negative breast cancer cases, providing a possible target for therapy. The activation of Akt was investigated in Maltese triple negative breast cancer cases using an antibody detecting Akt phosphorylated at serine 473 (anti-Akt pS473). The study showed that 26% of triple negative breast cancer patients had an elevated level of Akt (pS473). Furthermore, FTY720, a pharmacological activator of the phosphatase PP2A, was shown to block Akt activation at a concentration of 1mM, in HCC1937 cells subjected to insulin-like growth factor 1 (IGF-1). Our data dened a subset of triple negative breast cancer patients based on high activity of AKT (pS473). This subset would be eligible for treatment using therapies which target the PI3K/Akt pathway, such as kinase inhibitors or phosphatase activators. In support of this, the BRCA1 mutant cells (HCC1937) were sensitive to the PP2a activator, FTY720. This suggests that FTY720 is a potential drug for use in adjuvant therapy in breast cancer cases having a high Akt (pS473).
Article Does the absolute HbA1c improve the genotype-phenotype association in Type 2 Diabetes? Alexandra Fiott, Pace N, R. Galdies, J. Vassallo, A.E. Felice Pages: 61 - 65 Read Abstract | View full article |
PDF Abstract: HbA1c is a measure of the mean blood glucose levels for the prior 90 - 120 days, the mean life- time of red blood cells. However, factors that in uence the erythrocyte turnover or the biochemical structure of haemoglobin (Hb) might complicate the interpretation of results. With a frequency of haemoglobinopathies of around 5% in the Maltese population, an alternative biomarker should be considered. The aim of this study was to determine whether the absolute HbA1c could improve the genotype-phenotype association in Type 2 Diabetes Mellitus (T2DM) and whether it could thus be an alternative measure. Ion-exchange high performance liquid chromatogra- phy (HPLC) and polymerase chain reaction (PCR) were used to genotype and phenotype ve different groups of subjects: haematologically normal adult con- trols, anaemics (Hb<10g/dL), B-thalassaemics, normal pregnant women and type 2 diabetics (controlling their diabetes either by diet alone, or using metformin for up to six months). The single nucleotide polymorphisms (SNPs) selected were in the ADRB2, LEP, FABP2, TCF7L2, MIF, IL6 and UCP1 genes. Statistical analysis showed that the absolute HbA1c did not improve the genotype-phenotype association, as it showed the same trends as the relative HbA1c. The difference between the HbF and HbA1c is due to the homogenous distribution of HbA1c among erythrocytes, unlike HbF. In vitro glycation showed that Hb Beta- Valletta, found in 1.8% of Maltese adults, does not in uence glycation and thus the HbA1c is not in uenced by this variant in heterozygotes/ homozygotes.
Article Control of globin gene expression by Kruppel-like Factors Laura Grech, Joseph Borg Pages: 66 - 77 Read Abstract | View full article |
PDF Abstract: Kruppel-like factors (KLFs) are a family of seventeen proteins designated KLF1 to KLF17. KLFs are transcriptional factors that bind GC-rich sequences such as CACCC elements. The DNA binds to KLFs via three carboxyl-terminal Cys-2/His-2 zinc ngers. KLFs control cell differentiation and embryonic development. They are also implicated in a number of cellular functions such as erythropoiesis, proliferation and tissue development. This review will focus primar- ily on KLFs that are involved in haemoglobin control. These include KLF1, KLF2, KLF3, KLF8 and KLF10. The connection between human KLF1 and elevated foetal haemoglobin was rst identied in a study done by (Borg et al., 2011) on a large Maltese family with Hereditary Persistence of Foetal Haemoglobin (HPFH) where a nonsense mutation in the Erythroid Kruppel-Like Factor 1 gene (KLF1) was identied as the main cause of HPFH. KLF2 is a positive regulator of mouse and human embryonic B-globin genes and it overlaps with KLF1 in embryonic erythropoiesis. KLF3 and KLF8 expression is driven by KLF1 while together KLF3 and KLF8 participate in the silencing of embyronic globin expression during development. KLF10 expression was also shown to be associated with high foetal haemoglobin levels in Bthalassaemia patients undergoing hydroxyurea treatment.
Article Performance evaluation of Wied Dalam (WDD) seismic station in Malta Matthew R. Agius, Sebastiano D'Amico, Pauline Galea, Francesco Panzera Pages: 78 - 86 Read Abstract | View full article |
PDF Abstract: The continual operation of a permanent seismograph, now exceeding a couple of decades in some cases, naturally involves changes of hardware and soft- ware over time. Nonetheless, the long-term, consistent performance of the seismic station, and the good quality of its data, is very important for national seismic stud- ies investigating the local seismicity, and also important for the international seismological community research- ing regional tectonics and deep Earth structures. Here we investigate the data availability and quality of the currently only seismic station on Malta (WDD) since its installation in 1995, and establish spectral patterns in the seismic data that may be in uenced by diurnal vari- ations, seasonal weather changes, and/or site-specic settings. The results are important for the future de- ployment of permanent seismic stations on the Maltese islands, and for the analysis of local seismic hazard and ground motion studies.
Article The male to female ratio at birth Victor Grech, Julian Mamo Pages: 87 - 101 Read Abstract | View full article |
PDF Abstract: The factors that in uence the male to female ratio at birth are legion. Males are usually born in excess and stress decreases the ratio while wellbeing and good health tends to increase it. This paper reviews the multitudes of factors that have been implicated as affecting this ratio, from historical times to date.
Article COST Action Chemistry Conference on Supramolecular Chemistry in Water David C. Magri Pages: 102 - 102 View full article |