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Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. Identification of genetic variants that pose risks to MS is of high interest since they contribute largely to disease pathogenesis. A rich body of literature associated these risks with variants of HLA genes located mostly on the short arm of chromosome 6 (6p21). These genetic variations may result in alteration in protein function and are associated, therefore, with disease phenotype and therapy outcome. Although the HLA region has been routinely known to have the strongest correlation with MS, other genes found within and outside HLA locus are considered risk factors for MS. The objective of this review is to shed light on the non-HLA genes implicated with multiple sclerosis. Due to the interplay between the polygenetic and environmental factors, along with their differential contribution and genetic heterogeneity among populations, it is extremely challenging to determine the contribution of the non-HLA genes to the outcome and onset of MS disease. We conclude that a better assemblage of genetic factors involved in MS can have a critical impact on the establishment of a genetic map of MS that allows proper investigation at the expression and functional levels.

The preservation of pure fungal cultures is considered as an important part of applied and industrial microbiology applications. In this study, we are focusing on filamentous fungi preservation as these species are very useful in industrial applications such as wastewater treatment, biofuel production etc. We are presenting an evaluation of three methods to maintain and preserve filamentous fungi: refrigeration on filter paper, refrigeration with glycerol and cryopreservation with DMSO. The three methods were tested on the pure cultures of Aspergillus versicolor and Aspergillus niger. The three methods were successful where the viability measured by colony forming unit CFU counts was confirmed. We suggest that for the short-term preservation of filamentous fungi, the filter paper method could be preferred as it is very simple, quick and effective.

Targeting cell cycle and inducing DNA damage by activating cell death pathways are considered as effective therapeutic strategy for combating breast cancer progression. Many of the naturally known small molecules target these signaling pathways and are effective against resistant and/or aggressive types of breast cancers. Here, we investigated the effect of catechol, a naturally occurring plant compound, for its specificity and chemotherapeutic efficacies in breast cancer (MCF-7 and MDA-MB-231) cells. Catechol treatment showed concentration-dependent cytotoxicity and antiproliferative growth in both MCF-7 and MDA-MB-231 cells while sparing minimal effects on noncancerous (F-180 and HK2) cells. Catechol modulated differential DNA damage effects by activating ATM/ATR pathways and showed enhanced γ-H2AX expression, as an indicator for DNA double-stranded breaks. MCF-7 cells showed G1 cell cycle arrest by regulating p21-mediated cyclin E/Cdk2 inhibition. Furthermore, activation of p53 triggered a caspase-mediated cell death mechanism by inhibiting regulatory proteins such as DNMT1, p-BRCA1, MCL-1, and PDCD6 with an increased Bax/Bcl-2 ratio. Overall, our results showed that catechol possesses favorable safety profile for noncancerous cells while specifically targeting multiple signaling cascades to inhibit proliferation in breast cancer cells.

Antibiotic resistance (AR) is a significant threat to the health of many worldwide. The emergence of AR has become the main source of morbidity and mortality from infections that would otherwise have been treatable. AR is mainly caused by the inappropriate use of antibiotics. In the United Arab Emirates (UAE), bacterial resistance to antibiotics is escalating due to: a) practice of self-medication with antibiotics among the residents of the UAE; b) the easy procurement of antibiotics from local pharmacies without prescription; and c) expatriates’ importation of antibiotics from their home country. The present study focused on the usage of antibiotics among the population of Ras Al Khaimah. This study surveyed 306 residents of Ras Al Khaimah to understand their knowledge, awareness, attitude, practices, and perceptions on antibiotics usage. The major pharmacies in Ras Al Khaimah were also surveyed to identify whether the policies on dispensing antibiotics are followed. Of the 306 respondents, %49 have practiced self-medication using antibiotics at least once. The study also finds that pharmacies dispense antibiotics without prescription due to customer demand for antibiotics, lack of patients’ time, patients’ needs, lack of medical insurance, and money concerns. In conclusion, this study provides insight into the level of AR awareness and usage among the Ras Al Khaimah population and emphasizes the need to implement best practices at the grassroots level to overcome the crisis.

Siglecs are widely expressed on leukocytes and bind to ubiquitously presented glycans containing sialic acids (sialoglycans). Most Siglecs carry an immunoreceptor tyrosine-based inhibition motif (ITIM) and elicit an inhibitory intracellular signal upon ligand binding. A few Siglec receptors can, however, recruit an immunoreceptor tyrosine-based activation motif (ITAM)-containing factors, which activate cells. The role of hypersialylation (the enhanced expression of sialolglycans) - in cancer progression has recently been explored. Mechanistic studies have shown that hypersialylation on cancer cells can engage inhibitory Siglecs on the surface of innate immune cells and induce immunosuppression. These recent studies strongly suggest that the Siglec-sialic acid axis can act as a potential target for cancer immunotherapy. Moreover, the use of new tools and techniques are facilitating these studies. In this review we summarise techniques used to study Siglecs, including different mouse models, monoclonal antibodies, Siglec fusion proteins and sialoglycan arrays. Furthermore, we discuss the recent major developments in the study of Siglecs in cancer immunosuppression, tools and techniques used in targeting the Siglec-sialic acid axis and the possibility of clinical intervention.

Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anti-cancer therapy. Many anti-cancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with adenosine triphosphate binding cassette efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anti-cancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.

Siglecs (Sialic acid-binding immunoglobulin-type lectins) are a I-type lectin that typically binds sialic acid. Siglecs are predominantly expressed in immune cells and generate activating or inhibitory signals. They are also shown to be expressed on the surface of cells in the nervous system and have been shown to play central roles in neuroinflammation. There has been a plethora of reviews outlining the studies pertaining to Siglecs in immune cells. However, this review aims to compile the articles on the role of Siglecs in brain function and neurological disorders. In humans, the most abundant Siglecs are CD33 (Siglec-3), Siglec-4 (myelin-associated glycoprotein/MAG), and Siglec-11, Whereas in mice the most abundant are Siglec-1 (sialoadhesin), Siglec-2 (CD22), Siglec-E, Siglec-F, and Siglec-H. This review is divided into three parts. Firstly, we discuss the general biological aspects of Siglecs that are expressed in nervous tissue. Secondly, we discuss about the role of Siglecs in brain function and molecular mechanism for their function. Finally, we collate the available information on Siglecs and neurological disorders. It is intriguing to study this family of proteins in neurological disorders because they carry immunoinhibitory and immunoactivating motifs that can be vital in neuroinflammation.

By analyzing the abundant microorganisms in the naturally occurring mangroves of Ras Al Khaimah in the United Arab Emirates (UAE), this policy paper discusses the feasibility of a future where the emirate invests in biofuels sourced from its mangroves as opposed to using conventional methods of fuel production and usage, which can have negative impacts on the environment and economy. It explores the successes and challenges of each phase of biofuel technology innovation, so that the previous trials and errors can help decision makers critically assess the potentials of utilizing biofuels in current technology as well as in future projects. This paper finds that currently it is possible to use the existing mangroves as a source of fungi for biofuel production, but more investment is needed to support industrial-level production. It concludes with policy recommendations for supporting future research, implementing long-term energy solutions that address the UAE’s environmental and economic concerns, and encouraging future leaders and innovators to think local in addressing global problems.

Ancient DNA (aDNA) refers to the genetic material found in dead paleontological and archeological samples. Being subject to various types of stressors, it undergoes different hydrolytic and oxidative post mortem modifications that result in the formation of DNA lesions. These lesions are found to either block the DNA polymerase during replication or induce nucleotide misincorporations. Besides, aDNA samples occur in minimal quantities; which represents an additional obstacle that researchers have to overcome in order to study aDNA. The earliest major efforts included the use of molecular cloning and polymerase chain reaction (PCR) to amplify aDNA sequences. These techniques were later found to be associated with a number of false results and unauthentic findings. There have been numerous attempts to eliminate the shortcomings of PCR and improve the quality of aDNA through avoiding contamination, repairing lesions, using translesion polymerases, etc. However, the majority of these have failed to yield accurate and specific results. Surface- enhanced resonance Raman scattering (SERRS), on the other hand, starts in the right foot by introducing a sensitive non- enzymatic approach for the specific detection of single- and double-stranded DNA. The ability of this method to evade DNA degradation is particularly important for not only studying aDNA, but also analyzing DNA refractory to PCR amplification in processed products.

Mitochondria are unique organelles carrying their own genetic material, independent from that in the nucleus. This review will discuss the nature of mitochondrial DNA (mtDNA) and its levels in the cell, which are the key elements to consider when trying to achieve molecular identification in ancient and degraded samples. mtDNA sequence analysis has been appropriately validated and is a consistent molecular target for the examination of biological evidence encountered in forensic cases—and profiling, in certain conditions—especially for burnt bodies and degraded samples of all types. Exceptional cases and samples will be discussed in this review, such as mtDNA from leather in Beethoven’s grand piano, mtDNA in mummies, and solving famous historical criminal cases. In addition, this review will be discussing the use of ancient mtDNA to understand past human diet, to trace historical civilizations and ancient trade routes, and to uncover geographical domestication origins and lineage relationships. In each topic, we will present the power of mtDNA and how, in many cases, no nuclear DNA was left, leaving mitochondrial DNA analysis as a powerful alternative. Exploring this powerful tool further will be extremely useful to modern science and researchers, due to its capabilities in providing us with previously unattainable knowledge.

Great ancient composers have endured many obstacles and constraints which are very difficult to understand unless we perform the restoration process of ancient music. Species identification in leather used during manufacturing is the key step to start such a restoration process in order to produce a facsimile of a museum piano. Our study reveals the species identification in the leather covering the hammer head in a piano created by Erard in 1802. This is the last existing piano similar to the piano that Beethoven used with its leather preserved in its original state. The leather sample was not present in a homogeneous piece, yet combined with glue. Using a DNA extraction method that avoids PCR inhibitors; we discovered that sheep and cattle are the origin of the combination. To identify the species in the leather, we focused on the amounts of mitochondrial DNA in both leather and glue and results have led us to the conclusion that the leather used to cover the hammer head in this piano was made of cattle hide.

The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction - based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage.

We have developed a fully enzyme-free SERRS hybridization assay for specific detection of double-stranded DNA sequences. Although all DNA detection methods ranging from PCR to high-throughput sequencing rely on enzymes, this method is unique for being totally non-enzymatic. The efficiency of enzymatic processes is affected by alterations, modifications, and/or quality of DNA. For instance, a limitation of most DNA polymerases is their inability to process DNA damaged by blocking lesions. As a result, enzymatic amplification and sequencing of degraded DNA often fail. In this study we succeeded in detecting and quantifying, within a mixture, relative amounts of closely related double-stranded DNA sequences from Rupicapra rupicapra (chamois) and Capra hircus (goat). The non-enzymatic SERRS assay presented here is the corner stone of a promising approach to overcome the failure of DNA polymerase when DNA is too degraded or when the concentration of polymerase inhibitors is too high. It is the first time double-stranded DNA has been detected with a truly non-enzymatic SERRS-based method. This non-enzymatic, inexpensive, rapid assay is therefore a breakthrough in nucleic acid detection.

International audience; In this study, we have applied Surface Enhanced Resonance Raman Scattering (SERRS) technology to the specific detection of DNA. We present an innovative SERRS sandwich-hybridization assay that allows specific DNA detection without any enzymatic amplification, such as is the case with Polymerase Chain Reaction (PCR). In some substrates, such as ancient or processed remains, enzymatic amplification fails due to DNA alteration (degradation, chemical modification) or to the presence of inhibitors. Consequently, the development of a non-enzymatic method, allowing specific DNA detection, could avoid long, expensive and inconclusive amplification trials. Here, we report the proof of concept of a SERRS sandwich-hybridization assay that leads to the detection of a specific chamois DNA. This SERRS assay reveals its potential as a nonenzymatic alternative technology to DNA amplification methods (particularly the PCR method) with several applications for species detection. As the amount and type of damage highly depend on the preservation conditions, the present SERRS assay would enlarge the range of samples suitable for DNA analysis and ultimately would provide exciting new opportunities for the investigation of ancient DNA in the fields of evolutionary biology and molecular ecology, and of altered DNA in food frauds detection and forensics.

Gene therapy is the use of genes to heal diseases at the genetic level. It involves insertion, correction or inactivation of specific genes in organisms suffering from genetic disorders. Ever since it was introduced as a hypothesis in the 1960s, gene therapy has gone on to become a medical wonder that promises relief from the likes of Parkinson ’ s disease and multiple sclerosis. Today, the technique is used to manipulate the genome of not only somatic cells but also the germline cells of early embryos and gametes with a vast range of viral and non-viral vectors. The diseases targeted by gene therapy are among the deadliest on the planet: they are categorized into cancers, genetic deficiencies and autoimmune diseases. On the one hand, gene therapy is deemed by some to be an ethically and technically problematic technology because of its cost, its treatment of human dignity and its questionable accuracy and safety. In contrast to what its opponents say, the pro-gene therapy arguments support the technique by highlighting its remarkable efficiency, long-term cost-effectiveness and ability to cure unique diseases, among others.