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Background Breast cancer (BC) is the most often diagnosed cancer in women globally. Cancer cells appear to rely heavily on RNA helicases. DDX43 is one of DEAD- box RNA helicase family members. But, the relationship between clinicopathological, prognostic significance in different BC subtypes and DDX43 expression remains unclear. Therefore, the purpose of this study was to assess the clinicopathological significance of DDX43 protein and mRNA expression in different BC subtypes. Materials and methods A total of 80 females newly diagnosed with BC and 20 control females that were age-matched were recruited for this study. DDX43 protein levels were measured by ELISA technique. We used a real-time polymerase chain reaction quantification (real-time PCR) to measure the levels of DDX43 mRNA expression. Levels of DDX43 protein and mRNA expression within BC patients had been compared to those of control subjects and correlated with clinicopathological data. Results The mean normalized serum levels of DDX43 protein were slightly higher in control than in both benign and malignant groups, but this result was non-significant. The mean normalized level of DDX43 mRNA expression was higher in the control than in both benign and malignant cases, although the results were not statistically significant and marginally significant, respectively. Moreover, the mean normalized level of DDX43 mRNA expression was significantly higher in benign than in malignant cases. In malignant cases, low DDX43 protein expression was linked to higher nuclear grade and invasive duct carcinoma (IDC), whereas high mRNA expression was linked to the aggressive types of breast cancer such as TNBC, higher tumor and nuclear grades. Conclusion This study explored the potential of using blood DDX43 mRNA expression or protein levels, or both in clinical settings as a marker of disease progression in human breast cancer. DDX43 mRNA expression proposes a less invasive method for discriminating benign from malignant BC.

The molecular Egyptology field started in the mid-eighties with the first publication on the ancient DNA (aDNA) analysis of an Egyptian mummy. Egypt has been a major interest for historians, archeologists, laymen as well as scientists. The aDNA research on Egyptian biological remains has been fueled by their abundance and relatively well-preserved states through artificial mummification and by the advanced analytical techniques. Early doubts of aDNA integrity within the Egyptian mummies and data authenticity were later abated with studies proving successfully authenticated aDNA retrieval. The current review tries to recapitulate the published studies presenting paleogenomic evidence of disease diagnosis and kinship establishment for the Egyptian human remains. Regarding disease diagnosis, the prevailing literature was on paleogenomic evidence of infectious diseases in the human remains. A series of reports presented evidence for the presence of tuberculosis and/or malaria. In addition, there were solitary reports of the presence of leprosy, diphtheria, bacteremia, toxoplasmosis, schistosomiasis and leishmaniasis. On the contrary, paleogenomic evidence of the presence of rare diseases was quite scarce and mentioned only in two articles. On the other hand, kinship analysis of Egyptian human remains, including that of Tutankhamen, was done using both mitochondrial DNA sequences and nuclear DNA markers, to establish family relationships in four studies. It is clear that the field of molecular Egyptology is still a largely unexplored territory. Nevertheless, the paleogenomic investigation of Egyptian remains could make significant contributions to biomedical sciences (e.g. elucidation of coevolution of human host–microbe interrelationship) as well as to evidence-based archeology.

Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients’ HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy controls. Bioinformatics was conducted involving functional annotation and pathway enrichment analyses. Results The studied microRNAs were significantly deregulated in thalassemia patients in correlation with HbF. Functional annotation and pathway enrichment analyses revealed a major role of miR-486-3p and miR-15a in HbF induction. Conclusion MiR-486-3p and miR-15a are crucial for HbF induction. Further validating studies are needed.

Carpenter syndrome 1 (CRPT1) is an acrocephalopolysyndactyly (ACPS) disorder characterized by craniosynostosis, polysyndactyly, obesity, and other malformations. It is caused by mutations in the gene RAB23. We are reporting on two patients from two unrelated consanguineous Egyptian families. Patient 1 presented with an atypical clinical presentation of Carpenter syndrome including overgrowth with advanced bone age, epileptogenic changes on electroencephalogram and autistic features. Patient 2 presented with typical clinical features suggestive of Carpenter syndrome. Therefore, Patient 1 was subjected to whole exome sequencing (WES) to find an explanation for his unusual features and Patient 2 was subjected to Sanger sequencing of the coding exons of theRAB23 gene to confirm the diagnosis. We identified a novel homozygous missense RAB23 variant (NM_001278668:c.T416C:p.Leu139Pro) in Patient 1 and a novel homozygous splicing variant (NM_016277.5:c.398+1G > A) in Patient 2. We suggest that the overgrowth with advanced bone age, electroencephalogram epileptogenic changes, and autistic features seen in Patient 1 are an expansion of the Carpenter phenotype and could be due to the novel missense RAB23 variant. Additionally, the novel identified RAB23 variants in Patient 1 and 2 broaden the spectrum of variants associated with Carpenter syndrome.

Background Asthma is a common and heterogeneous respiratory disease characterized by airway obstruction and chronic inflammation. Innate and adaptive immune system plays an important role in its pathogenesis. Vitamin D has regulatory effects on the immune system via gene expression. Its functions are mediated by the transcription factor vitamin D receptor (VDR). Our aim was to analyze VDR gene expression and vitamin D status in asthmatic children, and to evaluate the effect of vitamin D supplementation on asthma severity as well as VDR mRNA level. Methods VDR mRNA expression was measured by real-time PCR in 50 patients and 20 healthy controls. Serum vitamin D, asthma exacerbations and spirometry level were evaluated. Patients with deficiency were supplemented for two months and the level of serum Vitamin D and VDR expression level were remeasured. Results Results showed that Vitamin D level was low in all patients. VDR mRNA level significantly upregulated in patients than the control group (P = 0.01) and significantly down regulated in response to 2 months of Vit D supplementation (P Conclusion VDR expression level associated with bronchial asthma and may serve as a predictor. The present study provides some molecular evidences about vitamin D effectiveness in bronchial asthma treatment.

Bioarcheology is the study of archived human and animal remains. The term was first proposed by the British archeologist Grahame Clark to denote the investigations of animal bones from archeological sites. Since its introduction in 1972, this term has been applied to encompass additional scientific domains and has also been used for the multidisciplinary papers collected in this special issue. Agriculture's first appearance on the archeological horizon is a matter of debate. Evidence provided by multidisciplinary studies encompassing archaeobotany and zooarchaeology and the emergence of agricultural practices in the “fertile crescent” (a crescent shaped area containing fertile lands amidst semiarid regions of Western Asia, the Nile valley, and northeast Africa) in Iran add to the science of ancient agriculture (S. Riehl et al.). Egyptian archeology has been a widely accepted aspect of bioarcheology. Here a wealth of information has been collected with the applications of new techniques to ancient tissues such as X-ray analyses applied in the field to archived human bones (F. Ruhli et al.). Mandibles excavated from Qubbet el-Hawa cemetery in Aswan, Egypt, have yielded information on the food consumed by middle class people during several periods of ancient Egyptian history. The elemental analysis of the bones hinted at social and climatic changes affecting ancient populations and shows the effects of state socialism (a variant socialism in which the power of the state is employed to creating an egalitarian society through the control of production of all goods) and agricultural conditions during the 17th Dynasty in Upper Egypt (G. D. AL-Khafif and R. El-Banna). South American frozen mummies from mountain tops of the high Andes have only recently become available for bioarcheological studies. Such studies have revealed important aspects of human sacrificial practices in pre-Hispanic times. Because of the exceptional preservation of the soft tissues of these mummies due to the intense cold and ambient dryness at altitudes at which they were found, important human pathologies accompanying life under Inca rule have become accessible to modern techniques (M. C. Ceruti). The histology of soft tissues is a well-accepted diagnostic method in modern human pathology. However, its application to ancient tissues brings challenges to the standard interpretation of histological stains because of the variable preservation of specimens depending on numerous unforeseeable factors. The postmortem interval before histological study is one crucial obstacle. The longer this time the less dependable the results. Paleopathological examinations provided guidelines to the tissues likely to be best preserved and allowed the most reliable diagnoses (C. Grove et al.). Successful and cheap methods recently developed for the extraction of ancient DNA (aDNA) have led to important studies in evolution and worldwide human migrations. East Asian mitochondrial DNA (mtDNA) especially of Koreans has been used to determine single nucleotide polymorphisms in mtDNA in human bone samples from premodern Joseon tombs in Republic of Korea (C. S. Oh et al.). Archeological materials useful for the study of bioarcheology are conserved in museums throughout the world. Curators prefer the study of their collections by noninvasive methods. The desire to maintain specimens intact is shared by bioarcheologists too. Nevertheless, invasive methods such as autopsies, endoscopies, and biopsies are sometimes unavoidable for accurate diagnosis. In this setting controversies are unavoidable but scientific criteria coupled with ethical considerations are proposed which may resolve disputes (D. Moissidou et al.). Monastic inhabitants of ancient institutions provide fertile grounds for the investigations of diseases and social aspects of a particularly privileged population. Regional differences are not often revealed but when such studies are restricted to defined populations such as those in Bavaria, Germany, insights into paleopathology, nutrition, and lifestyles of a well-defined human group become apparent (A. G. Nerlich et al.). Statistical modeling has advanced science in general and bioarcheology in particular. Growth lines in archived biological materials such as teeth and hair proved valuable in providing evidence of metabolic health, physiology, and lifestyles of long dead individuals. Thus new noninvasive methods for the analyses of curated archeological specimens could avoid ethical consideration in bioarcheological investigations (C. Qualls and O. Appenzeller). Computational methods could also predict the physical appearance, mood, and clinical diagnosis such as hirsutism (excessive hair growth) also known in some individuals as Cantu syndrome (C. Qualls et al.). Recent massive sequencing of ancient DNA has transformed the study of human evolution and human history. Such studies are only now beginning in bioarcheology but important insights into modern diseases are likely to be gleaned from analyses of bioarcheological specimens.

We applied, for the first time, next-generation sequencing (NGS) technology on Egyptian mummies. Seven NGS datasets obtained from five randomly selected Third Intermediate to Graeco-Roman Egyptian mummies (806 BC–124AD) and two unearthed pre-contact Bolivian lowland skeletons were generated and characterised. The datasets were contrasted to three recently published NGS datasets obtained from cold-climate regions, i.e. the Saqqaq, the Denisova hominid and the Alpine Iceman. Analysis was done using one million reads of each newly generated or published dataset. Blastn and megablast results were analysed using MEGAN software. Distinct NGS results were replicated by specific and sensitive polymerase chain reaction (PCR) protocols in ancient DNA dedicated laboratories. Here, we provide unambiguous identification of authentic DNA in Egyptian mummies. The NGS datasets showed variable contents of endogenous DNA harboured in tissues. Three of five mummies displayed a human DNA proportion comparable to the human read count of the Saqqaq permafrost-preserved specimen. Furthermore, a metagenomic signature unique to mummies was displayed. By applying a “bacterial fingerprint”, discrimination among mummies and other remains from warm areas outside Egypt was possible. Due to the absence of an adequate environment monitoring, a bacterial bloom was identified when analysing different biopsies from the same mummies taken after a lapse of time of 1.5 years. Plant kingdom representation in all mummy datasets was unique and could be partially associated with their use in embalming materials. Finally, NGS data showed the presence of Plasmodium falciparum and Toxoplasma gondii DNA sequences, indicating malaria and toxoplasmosis in these mummies. We demonstrate that endogenous ancient DNA can be extracted from mummies and serve as a proper template for the NGS technique, thus, opening new pathways of investigation for future genome sequencing of ancient Egyptian individuals.

International audience; The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis.

Context The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th dynasties, spanned the mid-16th to the early 11th centuries BC. The late 18th dynasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, the exact relationships between some members of the royal family, and possible illnesses and causes of death have been matters of debate. Objectives To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and to search for pathological features attributable to possible murder, consanguinity, inherited disorders, and infectious diseases. Design From September 2007 to October 2009, royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project. Mummies distinct from Tutankhamun's immediate lineage served as the genetic and morphological reference. To authenticate DNA results, analytical steps were repeated and independently replicated in a second ancient DNA laboratory staffed by a separate group of personnel. Eleven royal mummies dating from circa 1410-1324 BC and suspected of being kindred of Tutankhamun and 5 royal mummies dating to an earlier period, circa 1550-1479 BC, were examined. Main Outcome Measures Microsatellite-based haplotypes in the mummies, generational segregation of alleles within possible pedigree variants, and correlation of identified diseases with individual age, archeological evidence, and the written historical record. Results Genetic fingerprinting allowed the construction of a 5-generation pedigree of Tutankhamun's immediate lineage. The KV55 mummy and KV35YL were identified as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation of malformations in Tutankhamun's family was evident. Several pathologies including Kohler disease II were diagnosed in Tutankhamun; none alone would have caused death. Genetic testing for STEVOR, AMA1, or MSP1 genes specific for Plasmodium falciparum revealed indications of malaria tropica in 4 mummies, including Tutankhamun’s. These results suggest avascular bone necrosis in conjunction with the malarial infection as the most likely cause of death in Tutankhamun. Walking impairment and malarial disease sustained by Tutankhamun is supported by the discovery of canes and an afterlife pharmacy in his tomb. Conclusion Using a multidisciplinary scientific approach, we showed the feasibility of gathering data on Pharaonic kinship and diseases and speculated about individual causes of death.