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Background: MicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that inhibit gene expression through either destabilization of the target mRNA or translational repression. MiRNAs recognize target sites, most commonly found in the 3′-untranslated regions of cognate mRNAs. This review aims to provide a state-of-the-art overview of the role of miRNAs in the regulation of major blood group antigens such as ABH as well as cancer-specific glycans. Summary: Besides their known roles in the control of developmental processes, proliferation, apoptosis, and carcinogenesis, miRNAs have recently been identified to play a regulatory role during erythropoiesis and blood group antigen expression. Since only little is known about the function of the red cell membrane proteins carrying blood group antigens, it is of great interest to shed light on the regulatory mechanisms of blood group gene expression. Some carrier proteins of blood group antigens are not restricted to red blood cells and are widely expressed in other bodily fluids and tissues and quite a few play a crucial role in tumor cells, as either tumor suppressors or promoters. Key Message: All available data point at a tremendous physiological as well as pathophysiological relevance of miRNAs in context of blood group regulation. Furthermore, miRNAs are involved in the regulation of pleiotropic genetic pathways such as hematopoiesis and tumorigenesis and thus have to be studied in future research on this subject. [ABSTRACT FROM AUTHOR]

Background: The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes. Methods: We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999–2018 (n = 1,591,932). We modelled birthweight trends separately in 1999–2008 and 2008–2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants. Results: Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate. Conclusions: Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999–2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies. Plain English Summary: Birthweights showed an increase followed by a decrease in several high income countries in the last 20 years, however the reasons for these changes is not well described. Thus, we aimed to investigate birthweight trends and their potential explanatory factors in Hungary between 1999 and 2018. We used registry data of all deliveries from Hungary in 1999–2018 (n = 1 591 932). Birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g until 2018. Maternal age explained approximately half of increase in the first period, while a substantial part of the decrease in the second period was explained by the presence of shorter pregnancies. The increasing birthweights in 1999–2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, its long-term consequences cannot be predicted, as the trend is mostly explained by the shorter pregnancies. [ABSTRACT FROM AUTHOR]

SDZ NIM 811 is a cyclosporin A analog that is completely devoid of immunosuppressive capacity but exhibits potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity. The mechanism of action of SDZ NIM 811 is clearly different from those of all other anti-HIV agents described so far. In cell-free assays, it is not an inhibitor of reverse transcriptase, protease, integrase, and it does not interfere with Rev or Tat function. SDZ NIM 811 does not down-regulate CD4 or inhibit fusion between infected and uninfected, CD4-expressing cells. p24 production from chronically HIV-infected cells is not impaired either. To elucidate the mode of action of SDZ NIM 811, we performed DNA PCR analysis in HIV-1 IIIB-infected MT4 cells in one cycle of virus replication. The effects of SDZ NIM 811 on the kinetics of viral DNA synthesis, appearance of two-long terminal repeat circles (2-LTR circles), and integration of DNA were studied. SDZ NIM 811 inhibited 2-LTR circle formation in a concentration-dependent manner, which is indicative of nuclear localization of preintegration complexes. Half-maximal inhibition was achieved at 0.17 microgram/ml; this concentration is close to the 50% inhibitory concentrations (0.01 to 0.2 microgram/ml) for viral growth inhibition. As expected, integration of proviral DNA into cellular DNA was also inhibited by SDZ NIM 811. Analysis of the viral particles produced by SDZ NIM 811-treated, chronically infected cells revealed amounts of capsid proteins, reverse transcriptase activity, and viral RNA comparable to those of the untreated control. However, these particles showed a dose-dependent reduction in infectivity (50% inhibitory concentration of 0.028 microgram/ml) which indicates that the assembly process is also impaired by SDZ NIM 811. Gag proteins are postulated to play a role not only in assembly but also in early steps of viral replication, e.g., nuclear localization of the preintegration complex. Recently, it was reported that HIV-1 Gag protein binds to cyclophilin A, the intracellular receptor for cyclosporin A. Interference with Gag-cyclophilin interaction may be the molecular basis for the antiviral activity of cyclosporin A and its analogs.

Cyclophilin A, a widely prevalent cellular protein, exhibits peptidyl-prolyl cis-trans isomerase activity. This protein is predominantly located in the cytosol; additionally, it can be secreted by the cells in response to inflammatory stimuli. Cyclophilin A has been identified to be a key player in many of the biological events and is therefore involved in several diseases, including vascular and inflammatory diseases, immune disorders, aging, and cancers. It represents an attractive target for therapeutic intervention with small molecule inhibitors such as cyclosporin A. Recently, a number of novel inhibitors of cyclophilin A have emerged. However, it remains elusive whether and how many cyclophilin A inhibitors function in the inflammatory diseases and cancers. In this review, we discuss current available data about cyclophilin A inhibitors, including cyclosporin A and its derivatives, quinoxaline derivatives, and peptide analogues, and outline the most recent advances in clinical trials of these agents. Inhibitors of cyclophilin A are poised to enhance our comprehension of the molecular mechanisms that underpin inflammatory diseases and cancers associated with cyclophilin A. This advancement will aid in the development of innovative pharmaceutical treatments in the future. [ABSTRACT FROM AUTHOR]

OTOF mutations are the principal causes of auditory neuropathy. There are reports on Otof‐related gene therapy in mice, but there is no preclinical research on the drug evaluations. Here, Anc80L65 and the mouse hair cell‐specific Myo15 promoter (mMyo15) are used to selectively and effectively deliver human OTOF to hair cells in mice and nonhuman primates to evaluate the efficacy and safety of OTOF gene therapy drugs. A new dual‐AAV‐OTOF‐hybrid strategy to transfer full‐length OTOF is generated, which can stably restore hearing in adult OTOFp.Q939*/Q939* mice with profound deafness, with the longest duration being at least 150 days, and the best therapeutic effect without difference in hearing from wild‐type mice. An AAV microinjection method into the cochlea of cynomolgus monkeys without hearing impairment is further established and found the OTOF can be safely and effectively driven by the mMyo15 promoter in hair cells. In addition, the therapeutic dose of AAV drugs has no impact on normal hearing and does not cause significant systemic toxicity both in mouse and nonhuman primates. In summary, this study develops a potential gene therapy strategy for DFNB9 patients in the clinic and provides complete, standardized, and systematic research data for clinical research and application. [ABSTRACT FROM AUTHOR]

Evidence-based research now allows clear separation of syphilis from other diseases in its class of treponematoses. Examination of skeletons from populations with clinically diagnosed bejel and yaws revealed bone alterations distinctive to those diseases, clearly separating them from alterations due to syphilis, transcending the limitations of current DNA and immunologic technologies. These insights allowed confident identification of the New World origin of syphilis. Absence of skeletal evidence of any treponemal disease in continental Europe before the time of Columbus excludes it as site of origin of syphilis. Treponemal disease appears to have originated in East Africa with late transmission to England, perhaps as a complication of the slave trade. The original treponemal disease apparently spread from Mrica through Asia, entering North America. Approximately 8 millennia later, it mutated to syphilis. Presence of skeletal evidence of syphilis at the site in the Dominican Republic where Columbus landed suggests the route by which it was transmitted to the Old World. [ABSTRACT FROM AUTHOR]

Plant growth is significantly impacted by abiotic stress factors including soil salinity and plants do have different mechanism to nullify the effect of these stresses. The current study is to understand the various physio-biochemical characteristics of Mexican prickly poppy (Argemone mexicana L.), a medicinally valued species belongs to poppy family under different saline conditions (0 mM, 100 mM, 200 mM and 300 mM) to investigate the mechanisms underlying salinity tolerance. The results showed that salinity caused a negative impact on number of leaves, stomatal index and chlorophyll content in plants. Decreased chlorophyll content suggests a decline in photosynthetic rate. The concentrations of stress specific amino acid proline, soluble sugar sucrose, and secondary metabolite phenol were increased in plants treated with increasing concentrations of NaCl solution. Sucrose helps to protect the isolated chloroplast from damage caused by salinity stress. The degree of bleaching seen in the leaf disc assay was an indication of the damage caused by stress. These findings indicated that higher proline, sugar, and phenol content could be the key factors, which offer advantage to Argemone under saline conditions. [ABSTRACT FROM AUTHOR]

Mass culture of immobilized cells in airlift-fermenters usually ends up with the beads accumulating in the foamy layer on the surface of the reactor fluid or, in stirred tankreactors, with partial destruction of the beads. We tried to use an airlift fermenter vessel for growing cells, immobilized in agarose beads. Instead of using the gas for driving, we mounted a slowly turning marine type impeller within the drought tube. Oxygen was supplied on occasional demands by the original sparger. This set up leads to sufficient operational characteristics of the reactor without accumulation of the beads in the foamy layer and without mechanical destruction. Different productivities of either immobilized cells or cells in free suspension culture are reported.

This article investigates the propagation of a deadly human disease, namely leprosy. At the outset, the mathematical model is transformed into a fractional-order model by introducing the Caputo differential operator of arbitrary order. A result is established, which ensures the positivity of the fractional-order epidemic model. The stability of the continuous model at different points of equilibria is investigated. The basic reproduction number, R 0 , is obtained for the leprosy model. It is observed that the leprosy system is locally asymptotically stable at both steady states when R 0 < 1 . On the other hand, the fractional-order system is globally asymptotically stable when R 0 > 1 . To find the approximate solutions for the continuous epidemic model, a non-standard numerical scheme is constructed. The main features of the non-standard scheme (such as positivity and boundedness of the numerical method) are also confirmed by applying some benchmark results. Simulations and a feasible test example are presented to discern the properties of the numerical method. Our computational results confirm both the analytical and the numerical properties of the finite-difference scheme. [ABSTRACT FROM AUTHOR]

North China and South Siberia, populated by Altaic‐ and Sino‐Tibetan‐speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroads for the initial peopling of America and western–eastern transcontinental communication. However, the population genetic structure and admixture history of northern East Asians remain poorly understood due to a lack of genome‐wide data, especially for Mongolic‐speaking people in China. We genotyped genome‐wide single nucleotide polymorphisms for 510 individuals from 38 Mongolic, Tungusic, and Sinitic‐speaking populations. We first explored the shared alleles and haplotypes within the studied groups. We then merged with 3508 published modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified genetic substructures within Altaic‐speaking populations: Western Turkic people harbored more western Eurasian‐related ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed a majority of Neolithic ARB related ancestry; Southern Mongolic people in China possessed apparent genetic influence from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians, and the latter retained the primary Neolithic YRB and ARB ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountains possessed a strong genetic affinity with Neolithic Mongolian Plateau (MP) people, supporting the hypothesis of their eastern Eurasian origin and long‐distance migration history. We also illuminated that historical pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to the southern ones. We finally found natural selection signatures in Mongolians associated with alcohol metabolism. Our results demonstrated that the Neolithic ancestral sources from the MP or ARB played an important role in spreading Altaic populations and languages. The observed multisources of genetic diversity contributed significantly to the extensive ethnolinguistic diversity in northern East Asia. [ABSTRACT FROM AUTHOR]

Background: The Le y antigen is a carbohydrate chain belonging to the ABH-Lewis blood group family. Le y has been reported to be present on red blood cells (RBCs) and granulocytes, but its distribution and function in platelets remain unknown. There are a variety of glycoproteins on platelets, which may carry the Le y antigen. This study aims to investigate the expression pattern and the function of Le y in human platelets., Study Design and Methods: Flow cytometry, Western blot, and immunofluorescence assays were performed to determine Le y expression on human platelets. ADP (1.25-10 μM) and thrombin (0.05-1 IU/mL) were used to activate platelets in the presence or absence of prostaglandin E1 (PGE1) and the Le y expression was evaluated again by flow cytometry. Blockade was performed with an anti-Le y monoclonal antibody to verify the role of this epitope in platelet function. Finally, coimmunoprecipitation was performed to identify glycoproteins associated with Le y ., Results: Le y was expressed on human platelets independent of ABO blood type. Le y expression was decreased in a dose-dependent manner after activation with either ADP or thrombin, and this effect could be partially reversed by PGE1. Anti- Le y mAb treatment increased alpha-granule release and neutralized the inhibitory effect of the anti-CD61 antibody on platelet aggregation. In addition, Le y was proven to interact and colocalize with CD61., Conclusions: These results demonstrate nondifferential expression of Le y in platelets of different ABO blood types and suggest the involvement of Le y in platelet function, possibly via interaction with CD61., (© 2020 AABB.)

Rice is an important food crop, and its production is significantly affected by salt stress under the changing climate. Soil-inhabiting microbial inoculants as well as efficient nitrogen (N) nutrition may have ameliorative effects on rice growth and yield under salt stress. However, the effects of the interaction between N application and microbial inoculants on the growth and grain yield of rice under salt stress is not yet fully understood. This study aimed to clarify whether the use of the Bacillus pumilus strain TUAT-1 biofertilizer, along with the right amount of N fertilizer, would alleviate salt stress in lowland rice production. We applied the Bacillus pumilus strain TUAT-1 as a biofertilizer in combination with different rates of N fertilizer: control (0% N), 2.64 g (NH4)2SO4 per nursery tray (100% N: the farmer-recommended amount), and 3.96 g (NH4)2SO4 per nursery tray (150% N). Salinity (100 mM of NaCl) was applied at the heading stage of rice plants in pot culture in the greenhouse, and the growth and yield components were accessed at harvest. In the nursery phase, the application of the biofertilizer TUAT-1 significantly increased seedling vigor and the root development of 21-day-old seedlings. Salinity stress at the heading stage significantly reduced chlorophyll content, panicle number, straw biomass, and grain yield; however, either the application of N alone or in combination with TUAT-1 ameliorated the salinity-related reduction in grain yield and yield component parameters. Plants receiving a high amount of N fertilizer (150% N) showed similar straw biomass and grain yield with or without TUAT-1 inoculation, regardless of saline or non-saline conditions. In both saline and control conditions, straw biomass and grain yield were higher in the plants inoculated with TUAT-1 than in those without TUAT-1. Specifically, the combined application of TUAT-1 and the farmer-recommended N level (100% N) led to an increase of 8% in straw biomass and 15% in grain yield under saline stress when compared with their respective plants without TUAT-1. Straw biomass and grain yield were similar in the (un-inoculated) plants grown under normal conditions and TUAT-1 + 100% N under salinity treatments, because TUAT-1 enhanced root development, which may promote soil nutrient uptake. Our results indicated that combined nursery application of TUAT-1 biofertilizer and 100% N fertilizer rate has the potential to boost the capacity of this bacteria to increase seedling vigor, which subsequently ameliorated the salt-induced reduction in the grain and straw yield. [ABSTRACT FROM AUTHOR]

This work is focused on the characterization of metallic finds that are part of an ancient war biga from the Tomba della Biga, using different approaches for the diagnostics and also the conservation of this important cultural heritage. The materials analyzed were brought to light in the necropolis of Canal Bianco (Adria, Italy). The samples were analyzed using Optical Reflected Light Microscopy (ORLM), Scanning Electron Microscopy (SEM) and micro-Raman Spectroscopy (µ-RS). The results highlighted the occurrence of two different alloys (Fe and Cu-Sn-bronze) showing important structural and textural variations. These results, along with µ-RS, gave details on the surface and subsurface morphology, as well as the microstructures and the chemical and mineralogical composition of the finds. In particular, µ-RS highlighted the presence of magnetite and goethite as the main mineralogical phases for Fe-samples and malachite, azurite and Cu-oxide for bronze samples. In addition, an attempt was made to trace the manufacturing process, the purity of the alloys and the degree of slagging. Results of analytical studies show corrosion products of the samples which could be evidence of metallurgical aspects. The good state of conservation due to favorable conditions in the burial environment preserved the metal finds from intense corrosion, supporting the hypothesis that the samples reached equilibrium with soil during their life in the burial environment. This proposed methodology based on the microstructure, chemistry and mineral microanalysis allows the diagnostic and evaluation of the state of conservation of metallic finds. [ABSTRACT FROM AUTHOR]

This osteobiography describes a probable disease co‐occurrence in a juvenile interred in the Erie County Poorhouse (ECPH) cemetery, Buffalo, New York. The remains were associated with a salvage excavation project at the University at Buffalo. The osteobiography details the palaeopathology of the skeletal remains of an 11‐ to 12‐year‐old child who died between 1851 and 1913 at the ECPH. The skeleton displayed lesion patterning consistent with co‐occurrence of healing scurvy, probable tuberculosis or another type of chronic bacterial infection, and possibly other metabolic disorders via co‐morbidity or co‐occurrence. In 19th‐century Buffalo, New York, a child with these pathologies, and their associated functional limitations, was likely disabled by society. This may have contributed to the child's stay in the ECPH and ultimate interment in its associated cemetery. The palaeopathology community will find the lesion manifestations insightful when attempting to diagnose co‐occurrence via skeletal remains in children. We were limited in the certainty of our diagnoses due to the pathological skeletal manifestations and preservation of the vertebral column, inability to conduct histological analyses, reburial of material in 2017, and thus no photos/radiographs of certain diagnostic items. Considerations about how age intersects with pathology can lead to insightful investigations of disability and impairment in the past. [ABSTRACT FROM AUTHOR]

Capsicum L. (tribe Capsiceae, Solanaceae) is an American genus distributed ranging from the southern United States of America to central Argentina and Brazil. The genus includes chili peppers, bell peppers, ajíes, habaneros, jalapeños, ulupicas and pimientos, well known for their economic importance around the globe. Within the Solanaceae, the genus can be recognised by its shrubby habit, actinomorphic flowers, distinctive truncate calyx with or without appendages, anthers opening by longitudinal slits, nectaries at the base of the ovary and the variously coloured and usually pungent fruits. The highest diversity of this genus is located along the northern and central Andes. Although Capsicum has been extensively studied and great advances have been made in the understanding of its taxonomy and the relationships amongst species, there is no monographic treatment of the genus as a whole. Based on morphological and molecular evidence studied from field and herbarium specimens, we present here a comprehensive taxonomic treatment for the genus, including updated information about morphology, anatomy, karyology, phylogeny and distribution. We recognise 43 species and five varieties, including C. mirum Barboza, sp. nov. from São Paulo State, Brazil and a new combination C. muticum (Sendtn.) Barboza, comb. nov.; five of these taxa are cultivated worldwide (C. annuum L. var. annuum, C. baccatum L. var. pendulum (Willd.) Eshbaugh, C. baccatum L. var. umbilicatum (Vell.) Hunz. & Barboza, C. chinense Jacq. and C. frutescens L.). Nomenclatural revision of the 265 names attributed to chili peppers resulted in 89 new lectotypifications and five new neotypifications. Identification keys and detailed descriptions, maps and illustrations for all taxa are provided. [ABSTRACT FROM AUTHOR]

Nutrient recovery from biomass streams generates novel recycling-derived fertilizers (RDFs). The effect of RDFs depends on their nutrient content and variability, which can aid or hinder their use by end-users. Detailed characterization of RDFs can help in evaluating product properties, whereas blending RDFs can optimize their nutrient ratios and reduce nutrient variability. This study assesses ammonium nitrate (AN) from stripping-scrubbing, ammonium water (AW) and concentrate (CaE) from evaporation, and two tailor-made blends (AN + CaE and AW + CaE), for their potential as nitrogen (N) fertilizers in the pot cultivation of lettuce. Parallelly, a soil incubation experiment was conducted to investigate the N release dynamics of the tested RDFs. The RDFs were compared against the commercial calcium ammonium nitrate (CAN) and an unfertilized control. AN and AW fertilization resulted in a similar crop yield and N uptake to the CAN treatment. CaE and blends exhibited poor yield and N uptake, possibly due to the sodium toxicity detected. AN and AW displayed N fertilizer replacement values above 100%, whereas CaE and blends exhibited poor results in the current experiments. The soil incubation experiment showed a positive soil priming effect in AN and AW treatment, as their N release was over 100%. Further research under uncontrolled field conditions utilizing AN and AW for diverse crop types can validate their N replacement potential. [ABSTRACT FROM AUTHOR]

During excavations carried out at the necropolis of San Genesio, taphonomic analysis permitted the detection of a small nucleus of distinctive graves dated to the sixth century and set within the wider context of autochthonous burials. This group was characterized by features such as wooden coffins and tree trunk burials, elements typical of the Germanic cultural milieu. Furthermore, anthropological analysis of the skeletal remains identified a case of Artificial Cranial Deformation (ACD), a distinctive element of Gothic ethnic groups. Individuals with ACD are extremely rare in the Italian archeological record and are related to the period in which the Gothic migrations took place. The subject, buried in a wooden casket, was a male individual with a deformed skull, polytraumatized, and most likely killed in combat, possibly during the Gothic War. This is the first Italian case of an individual with ACD, who died a certified violent death. The present study, despite the absence of traditional Germanic grave goods, has allowed to hypothesize the existence at San Genesio of an allochthonous group, a theory further supported by strontium isotope analysis. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein 4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, and the presence of Lewis y antigen modifications on HE4 in ovarian cancer cell lines has been detected in previous studies. The aim of this study was to analyze the expression of HE4 and Lewis y antigen in human ovarian cancer in order to find a correlation between them, as well as with the clinical pathological parameters of patients with ovarian cancer. Methods: Immunohistochemistry was used to detect the respective expression of these compounds in two patient groups (chemotherapy-resistant and chemotherapy-sensitive) containing a total of 95 patients. Then, a bioinformatic approach was adopted and online large sample databases (TCGA, CCLE, and GTEx; Metascape, Cytoscape) were used to explore the potential mechanisms of action of these compounds. Results: The results of this study demonstrate that high HE4 and Lewis y expression could be used as markers for chemotherapy resistance and poor prognosis in patients with ovarian cancer. These two expression events were widely correlated in various cancer tissues and are thought to act by activating the p38 mitogen-activated protein kinases (MAPK) pathway and inducing Vascular Endothelial Growth Factor A (VEGFA), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Early Growth Response 1 (EGR1), and Hypoxia-Inducible Factor 1-Alpha (HIFI1A), thereby promoting malignant biological behavior and resistance in ovarian cancer. Conclusions: These findings not only reveal the possible mechanism by which HE4 and Lewis y antigen affect ovarian cancer but also identify a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies. [ABSTRACT FROM AUTHOR]

This paper reports a new palaeopathological case of ankylosing spondylitis and a differential diagnosis performed to determine the etiology of the condition. A female skeleton from the Lori Berd archaeological cemetery. located near the city of Stepanavan (Lori Province of Armenia) is described. In this skeleton. changes in the spine, ribs. the sacrum. acetabulum. head of the femur and greater trochanter. as well as the anterior inferior iliac spine are typical of ankylosing spondylitis in advanced stage. Using osteological markers in combination with the reconstruction of the archaeological context. the burial pattern suggests that the injury the female suffered was more likely due to her physical deficiencies. [ABSTRACT FROM AUTHOR]

The La Chapelle-aux-Saints 1 skeleton of an old (>60-year-old) male Neanderthal is renowned for the advanced osteoarthritis of its spinal column and hip joint, and their implications for posture and lifestyle in these Mid- to Late Pleistocene humans. Reassessment of the pathologic lesions reveals erosions at multiple non-contiguous vertebrae and reactive bone formation extending far beyond the left hip joint, which suggests the additional diagnosis of brucellosis. This implies the earliest secure evidence of this zoonotic disease in hominin evolution. Brucellosis might have been transmitted via butchering or eating raw meat and is well compatible with the range of prey animals documented for Neanderthals. The associated infertility could have represented an important aspect of health in these late archaic humans. [ABSTRACT FROM AUTHOR]

Although cranial and dental nonmetric traits have proven to be reliable proxies for genetic data, the usefulness of infracranial nonmetric traits as phenetic markers in population affinity studies remains unclear. Our aim was to analyze infracranial and cranial nonmetric trait frequencies in the same samples in comparison with genetic data to determine the value of infracranial nonmetric traits in assessing genetic relationships among populations. We examined the frequencies of 25 cranial and 16 infracranial nonmetric traits in seven adult osteological samples from different regions of northern Eurasia (northern Russians, indigenous populations of Volga–Ural region, Buryats, and Yupik) and the data on mitochondrial DNA polymorphisms in the same ethnic groups. The biological distance between each pair of samples was estimated using the Smith's mean measure of divergence (MMD) for nonmetric traits and Cavalli–Sforza distance measure for mtDNA data. Mantel correlations were calculated between two matrices of mean measures of divergence (MMD) distances, and a multidimensional scaling (MDS) procedure was applied to each matrix. The Mantel test showed a strong correlation between the two nonmetric distance matrices. The three‐dimensional spatial representations of each matrix revealed similar patterns of intergroup differences. On both nonmetric MDS maps, the sample locations roughly reflected the geographic separation of the groups, with the exception of northern Russians, who were grouped with Volga–Ural populations. Comparison of our results with those obtained from genetic data confirmed that both sets of nonmetric traits provide reliable genetic affinities among the samples. The association of northern Russians with the Volga–Ural groups can be explained by their genetic background. Our findings show that infracranial nonmetric traits can be successfully used as phenetic markers to define a population's affinity and divergence, particularly in cases where only infracranial bones are available for study. [ABSTRACT FROM AUTHOR]

Purpose: Aging is known to play a critical role in the etiopathogenesis of several diseases. Among them, cardiovascular disorders are especially relevant since they are becoming the first cause of death in western countries. Resveratrol is a polyphenolic compound that has been shown to exert beneficial effects at different levels, including neuronal and cardiovascular protection. Those effects of resveratrol are related, at least in part, to its antioxidant and anti-inflammatory properties. In the current investigation we were interested in exploring whether the positive effects of resveratrol at cardiac level were taking place even when the supplementation started in already old animals. Methods: Old male rats were supplemented with resveratrol during 10 weeks. Using RT-PCR, we analyzed the effects of resveratrol supplementation on the expression of different genes related to inflammation, oxidative stress and apoptosis in rat heart. Results: Resveratrol reverted age-related changes in inflammatory, oxidative and apoptotic markers in the rat heart. Among others, the expression of two major inflammatory markers, INF-γ and TNF-α and two oxidative markers, heme oxygenase-1 and nitric oxide synthase, were increased with aging, and resveratrol supplementation reduced the level of some of these to those observed in the heart of young animals. Moreover, age-related changes in apoptotic markers in rat heart tend to be also reverted by resveratrol treatment. Conclusion: Our results suggest that resveratrol might exert beneficial effects as an anti-aging compound to revert age-related changes in cardiac function. [ABSTRACT FROM AUTHOR]

Mycobacteria in drinking water and in the water of swimming pools, whirlpools, hydrotherapy facilities and aquaria contribute significantly to human exposure to triggers of immune regulated chronic inflammatory and autoimmune diseases. Technological elements of water distribution systems, especially their inner surface, taps, shower heads and blind spots where sediments settle, affect the number of mycobacteria in the water. The review presents the possibilities of using analytical instruments for rapid determination of mycobacteria and for their typing as an alternative to classical culture and a method of monitoring specific nucleic acid sequences by polymerase chain reaction (PCR). Information about the use of flow cytometry (FCM), matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) spectrometry, Raman and infrared (IR) spectroscopy and biosensors are presented. [ABSTRACT FROM AUTHOR]

Summary: Background: In tertiary syphilis, Treponema pallidum triggers the formation of granulomatous nodules in various organs of the human body. Within the skeleton, predominantly in the skull and long bones, these characteristic syphilitic lesions cause typical patterns of bone damage. In this study, micro-computed tomography (µ-CT) was used to assess the microarchitecture of these osseous defects in untreated syphilitic skull bones. Material and methods: Bone structure of 30 macerated human skulls was noninvasively examined by means of µ-CT images (Viscom X8060 NDT). A total of 20 specimens showing typical morphological signs of syphilis were provided by the Collection of Anatomical Pathology of the Museum of Natural History in Vienna. They were compared to 10 macerated control skulls provided by the Division of Anatomy of the Medical University of Vienna. Results: All samples affected by syphilis showed perforating defects and increased porosity. Furthermore, we observed sclerotic reorganization and complete loss of the cortical bone in 80% of infected cases. Cortical thinning occurred in 75%. Conclusion: Our findings revealed extensive micromorphological bone destruction and a broad variability of osseous manifestations of (tertiary) syphilis. [ABSTRACT FROM AUTHOR]

Phenolic compounds in plants are essential components of human nutrition, which provide various health benefits. However, some missing links became the research in phenolic compounds structures and potential applications in a challenging work. Despite universal extraction methods with mixtures of different organic solvents are generally adopted in the analysis of phenolic compounds, a need for establish a specific procedure is still open. The great heterogeneity in food and food by-products matrices and the lack of standardized methods which combine chromatographic with spectrophotometric techniques to calculate the amount of phenolic compounds joined with the absence of specific standards hamper to accurate know the real amount of phenolic compounds. Indeed, the high complexity in nature and chemistry of phenolic compounds clearly difficult to establish a daily intake to obtain certain healthy outcomes. Hence, despite the potential of phenolic compounds to use them in cosmetic and healthy applications have been widely analyzed, some concerns must be considered. The chemical complexity, the interactions between phenolic compounds and other food components and the structural changes induced by food processing joined with the lack in the understanding of phenolic compounds metabolism and bioavailability undergo the need to conduct a comprehensive review of each factors influencing the final activity of phenolic compounds. This paper summarizes the potential of phenolic compounds for disease prevention and cosmetics production, as well as their many other uses derived from their antioxidant activity. This paper illustrates the potential of phenolic compounds for disease prevention and cosmetics production, as well as their many other uses derived from their antioxidant activity. [ABSTRACT FROM AUTHOR]

This research focuses on the Neolithic populations of Western Switzerland (5500–2200 BCE) and on establishing their paleopathological profile. This chronological period presents varying burial practices, and the aim was to be able to synthesise all information regarding the pathologies these populations exhibited, in such a way that statistical tests could be performed to determine whether geographical (site location), biological (age, sex, stature) and chronological factors played a role in lesion distribution. As a result, a methodology was devised to consider bone lesions in both a quantified and qualified manner, and able to handle individualised, multiple and commingled remains. The statistical analysis showed that pathological profiles differed depending on site location, with some exhibiting patterns that raise further questions as to the socio-economical functioning of these prehistoric societies. Biological factors also appear to play a role in lesion distribution, with immature individuals exhibiting more metabolic deregulations, whilst the adults—as expected—showed more signs of degenerative pathologies. Some chronological evolution of health is also perceivable; however, the small sample size available for some periods means these results are tentative at best. These remains, however, proved more than an accumulation of bone lesions, and the qualified data collected from them also yielded individual and collective narratives of health. Instances of infectious diseases were discovered, indicating that pathologies such as tuberculosis were a persistent presence at the time, with all the consequences this entails. [ABSTRACT FROM AUTHOR]

The ancient geographical origins of Brahmins—a prominent ethnic group in the Indian subcontinent—have remained controversial for a long time. This study employed the AMOVA (analysis of molecular variance) test to evaluate genetic affinities of this group with thirty populations of Central Asia and Europe. A domestic comparison was performed with fifty non-Brahmin groups in India. The results showed that Brahmins had genetic affinities with several foreign populations and also shared their genetic heritage with several domestic non-Brahmin groups. The study identified the deep ancient origins of Brahmins by tracing their Y-chromosome haplogroups and genetic markers on the Y-DNA phylogenetic tree. It was confirmed that the progenitors of this group emerged from at least 12 different geographic regions of the world. The study concluded that about 83% of the Brahmins in the dataset belonged to four major haplogroups, of which two emerged from Central Asia, one from the Fertile Crescent, and one was of an indigenous Indian origin. [ABSTRACT FROM AUTHOR]

Atlas occipitalization (AO) is a spinal anomaly, characterized by the fusion of the first cervical vertebra and occipital bone, with a complex etiology that can arise from congenital and environmental causes. AO has been reported in three regions of pre-Hispanic Peru in skeletal remains with artificial cranial modification (ACM), which involves the use of compression devices to permanently alter cranial shape and may have affected the fusion of the atlas and occipital bone. The aims of this study were to gain insights into AO's etiology by testing correlations between AO and ACM presence/type and geographic region as well as to characterize morphological variation associated with AO. We investigated the geographic distribution of AO and its potential relationship to ACM in a large sample of human crania from eight coastal and highland regions of pre-Hispanic Peru, held at the Smithsonian's National Museum of Natural History (n = 608, 1300–1500 CE). Eleven cases of AO were observed in three coastal regions—including two previously unreported regions—at an overall frequency of 1.8%. The frequency of AO did not differ significantly between crania with and without ACM, in general or by type, suggesting that ACM is not an etiological factor that influences AO in this sample. AO was observed at a significantly higher rate in the southern coastal region of Arequipa than in any other region. Genetic, dietary, and epidemiological conditions are evaluated as factors possibly shaping the geographic distribution of AO along the central and southern coasts of Peru. [ABSTRACT FROM AUTHOR]

Background: The Ley antigen is a carbohydrate chain belonging to the ABH-Lewis blood group family. Ley has been reported to be present on red blood cells (RBCs) and granulocytes, but its distribution and function in platelets remain unknown. There are a variety of glycoproteins on platelets, which may carry the Ley antigen. This study aims to investigate the expression pattern and the function of Ley in human platelets.Study Design and Methods: Flow cytometry, Western blot, and immunofluorescence assays were performed to determine Ley expression on human platelets. ADP (1.25-10 μM) and thrombin (0.05-1 IU/mL) were used to activate platelets in the presence or absence of prostaglandin E1 (PGE1) and the Ley expression was evaluated again by flow cytometry. Blockade was performed with an anti-Ley monoclonal antibody to verify the role of this epitope in platelet function. Finally, coimmunoprecipitation was performed to identify glycoproteins associated with Ley .Results: Ley was expressed on human platelets independent of ABO blood type. Ley expression was decreased in a dose-dependent manner after activation with either ADP or thrombin, and this effect could be partially reversed by PGE1. Anti- Ley mAb treatment increased alpha-granule release and neutralized the inhibitory effect of the anti-CD61 antibody on platelet aggregation. In addition, Ley was proven to interact and colocalize with CD61.Conclusions: These results demonstrate nondifferential expression of Ley in platelets of different ABO blood types and suggest the involvement of Ley in platelet function, possibly via interaction with CD61. [ABSTRACT FROM AUTHOR]

Background: Leprosy is an oldest chronic infectious disease known to mankind that predominantly affects the skin and peripheral nerves. Objective: To evaluate the bacteriological and morphological indices in smear positive cases. Materials and Method: Retrospective observational study was undertaken for one year duration on suspected cases of leprosy. Smears were prepared from one from each of the ear lobes by slit and scrap method and one from the site of lesion. Smears were stained with modified Ziehl-Neelsen stain and bacteriological/morphological indices were calculated. Results: Among 345 clinically suspected cases, 160 (46.38%) were multibacillary with male to female ratio 1.9:1 and most of cases from rural area of lower/middle class of third and fourth decade. All the three sites smears were positive in 112 (70%) cases. 66 (41.25%) cases had bacteriological index of 1+ while more than 1000 bacilli, on average, in 1each oil-immersion field (BI 6+) was observed in 1 (0.62%) cases. In 70 (43.75%) cases morphological index was less than 25 while in 14(8.75%) cases it was more than 50. Conclusion: Bacteriological and morphological index is one of the most important tools for diagnosis, classification, monitoring of treatment and disease severity. [ABSTRACT FROM AUTHOR]

Hypnosis and hypnotic suggestions are gradually gaining popularity within the consciousness community as established tools for the experimental manipulation of illusions of involuntariness, hallucinations and delusions. However, hypnosis is still far from being a widespread instrument; a crucial hindrance to taking it up is the amount of time needed to invest in identifying people high and low in responsiveness to suggestion. In this study, we introduced an online assessment of hypnotic response and estimated the extent to which the scores and psychometric properties of an online screening differ from an offline one. We propose that the online screening of hypnotic response is viable as it reduces the level of responsiveness only by a slight extent. The application of online screening may prompt researchers to run large-scale studies with more heterogeneous samples, which would help researchers to overcome some of the issues underlying the current replication crisis in psychology. [ABSTRACT FROM AUTHOR]

Introduction: Dental pulp with special structure has become a good reference sample in paleomicrobiology‐related blood‐borne diseases, many pathogens were detected by different methods based on the diagnosis of nucleic acids and proteins. Objectives: This review aims to propose the preparation process from ancient teeth collection to organic molecule extraction of dental pulp and summary, analyze the methods that have been applied to detect septicemic pathogens through ancient dental pulps during the past 20 years following the first detection of an ancient microbe. Methods: The papers used in this review with two main objectives were obtained from PubMed and Google scholar with combining keywords: "ancient," "dental pulp," "teeth," "anatomy," "structure," "collection," "preservation," "selection," "photography," "radiography," "contamination," "decontamination," "DNA," "protein," "extraction," "bone," "paleomicrobiology," "bacteria," "virus," "pathogen," "molecular biology," "proteomics," "PCR," "MALDI‐TOF," "LC/MS," "ELISA," "immunology," "immunochromatography," "genome," "microbiome," "metagenomics." Results: The analysis of ancient dental pulp should have a careful preparation process with many different steps to give highly accurate results, each step complies with the rules in archaeology and paleomicrobiology. After the collection of organic molecules from dental pulp, they were investigated for pathogen identification based on the analysis of DNA and protein. Actually, DNA approach takes a principal role in diagnosis while the protein approach is more and more used. A total of seven techniques was used and ten bacteria (Yersinia pestis, Bartonella quintana, Salmonella enterica serovar Typhi, Salmonella enterica serovar Paratyphi C, Mycobacterium leprae, Mycobacterium tuberculosis, Rickettsia prowazeki, Staphylococcus aureus, Borrelia recurrentis, Bartonella henselae) and one virus (Anelloviridae) were identified. Y. pestis had the most published in quantity and all methods were investigated for this pathogen, S. aureus and B. recurrentis were identified by three different methods and others only by one. The combining methods interestingly increase the positive rate with ELISA, PCR and iPCR in Yersinia pestis diagnosis. Twenty‐seven ancient genomes of Y. pestis and one ancient genome of B. recurrentis were reconstructed. Comparing to the ancient bone, ancient teeth showed more advantage in septicemic diagnosis. Beside pathogen identification, ancient pulp help to distinguish species. Conclusions: Dental pulp with specific tissue is a suitable sample for detection of the blood infection in the past through DNA and protein identification with the correct preparation process, furthermore, it helps to more understand the pathogens of historic diseases and epidemics. [ABSTRACT FROM AUTHOR]

Studies of the ancient history of infectious diseases have been facilitated greatly by development of a succession of novel analytical methods. In particular, laboratory analytical methods that are based on high‐throughput ancient deoxyribonucleic acid sequencing have received considerable attention in this respect. Even so, significant environmental caveats remain. There are many means by which microbes move through soil, often fairly readily. Thus, the depositional component of the postmortem environment, especially with respect to unshielded animal or human remains, is a fertile arena for many microbes that can contaminate archaeological specimens well after deposition and decay of soft tissues. The huge number of pathogenic and nonpathologic genera and species clearly dictate renewed interest and research into the long‐term biological activities of soil‐covered remains. In a tuberculosis context, we focus on various depositional concerns and limitations, such as contamination prior to archaeological discovery (perhaps many years prior), various means of microorganism movement in soil, the influence of these factors on differential diagnosis, and real hazards for misinterpretation of investigational results. [ABSTRACT FROM AUTHOR]

Summary: Silver(I)-assisted reduction of Blue tetrazolium chloride (3,3'-(3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)-bis(2,5-diphenyl-2H-tetrazolium) dichloride, BTC) by semicarbazide hydrochloride (SCH) was investigated in water-chloroform medium. The obtained colored products can be used for the visual detection and sensitive liquid-liquid extraction- spectrophotometric determination of Ag(I). Under the optimum conditions the calibration curve (which can be best approximated by a third-order polynomial; R2=0.9990) has two linear segments. For Ag(I) concentrations up to 0.011 g/ml, the linear regression equation had an intercept that was statistically indistinguishable from zero. The limit of detection, limit of quantitation, and molar absorptivity coefficient at λmax=573 nm were 0.6 ng/ml, 2 ng/ml and 1.2×106 l/(molcm), respectively. The regression equation of the second linear segment (0.021- 0.028 g/ml) was A = 200γ - 3.5 (R2=0.9989), where γ is the concentration in µg/ml. The relative standard deviation at the 22 ng/ml level (n = 5) was 3.8%. The effect of concomitant ions was studied, and the analysis of real samples tested the applicability of the developed procedure. [ABSTRACT FROM AUTHOR]

In this study, we aimed to develop an approach for genetic material extraction and sample preparation of ancient DNA for next generation sequencing that minimizes intra-laboratory contamination. A special module system consisting of four sterile gloveboxes connected by antechambers, which maintain a high purity atmosphere and allow conducting all stages of sample preparation in an isolated clean environment, starting with the processing of archaeological material, was developed. Furthermore, a fast and cost-effective double-stranded library preparation protocol for massive parallel sequencing was developed using non-standard modified sequencing adaptors, which enabled obtaining a library of fragments from extremely low amounts of starting degraded material. Bioinformatics data processing showed that the distribution of substitution frequencies in a subset of reads, mapped to the human reference genome, completely coincides with the pattern of postmortem modifications expected when the double-stranded library preparation method is employed. This is a strong evidence for the endogenous origin of the sequenced fragments of the human genome. Thus, the results of ancient sample and negative control sample sequencing, indicated the absence of visible contamination during sample preparation procedure. [ABSTRACT FROM AUTHOR]