How Mitochondrial DNA Can Write Pre-History: Kinship and Culture in Duero Basin (Spain) during Chalcolithic and Bronze Age

The chronological period from the beginning of the Chalcolithic Age to the end of the Bronze Age on the Iberian northern sub-plateau of the Iberic Peninsula involves interesting social and cultural phenomena, such as the appearance of the Bell Beaker and, later, the Cogotas I cultures. This work constructs a genetic characterisation of the maternal lineages of the human population that lived on the northern sub-plateau between 5000 and 3000 years ago through an analysis of mitochondrial DNA (mtDNA), a kind of genetic marker that is inherited through maternal lineages, unaltered from generation to generation. Population and cultural questions are investigated through mtDNA analyses. This study intends to shed light on the following questions. Were individuals who were buried together in multiple or collective burials biologically related through their maternal lineages? Were there distinct maternal human lineages in the same or different geographical areas if different material cultures (Bell Beaker and Cogotas I) were associated with the arrival of new human populations who established close biological relationships with the endogenous populations? Or could this be the result of the transmission of knowledge without human populations mixing? Another important question is whether the material cultures were related to the female populations. We analysed 91 individuals from 28 different archaeological sites of the Iberian northern sub-plateau from four different chrono-cultural periods (Pre-Bell Beaker, Bell Beaker, Proto-Cogotas I, and Cogotas I), from the end of the Chalcolithic Age up to the Bronze Age. There were two historical moments of new populations arriving: the first during the Pre-Bell Beaker period, associated with the K mtDNA haplogroup, and the second during the Proto-Cogotas I culture, with new lineages of the H, HVO, and T haplogroups. Neither of these new population flows were directly associated with the maximum development of the two main material cultures Bell Beaker and Cogotas I, so they must have occurred immediately beforehand, during the Pre-Bell Beaker and Proto-Cogotas I periods, respectively. However, we cannot discard an association between the populations and material cultures. Curiously, it has also been observed that there was also a tendency towards multiple burials, in which the individuals who were buried together belonged to the same maternal lineage, during these two periods of population change. This study has shed some light on the populational changes that occurred through these different periods in this specific geographical area of the northern sub-plateau of the Iberian Peninsula

Wear Behavior of a Ni/Co Bilayer Coating by Physical Vapor Deposition on AISI 1045 Steel

Coatings by physical vapor deposition (PVD) have become highly relevant due to their wide range of applications and the rapid rate of coating formation. In this work, AISI steel 1045 was coated with two layers, Ni and Co using the PVD technique. Each coating was deposited with a thickness of 1 μm. After applying the coatings, a post-treatment was applied in an AC plasma reactor using a boron nitride blank in an Ar atmosphere at a pressure of 3 Torr, 0.3 A, and 460 V at 4, 8, and 12h. The post-treatment was characterized by optical emission spectroscopy (OES) in a range of 200-1100 nm. The main species observed by OES were Ar+, N2, N2+, and B+. The coatings on 1045 steel and posttreatment were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Also, were subjected to tribological tests to analyze wear resistance, using the Pin-on-Disk technique. The coatings on steel 1045 present remarkably better wear properties than the uncoated 1045 steel, being the sample post-treated at 4h that showed a lower wear rate

Early detection of Parkinson's disease: Systematic analysis of the influence of the eyes on quantitative biomarkers in resting state electroencephalography

[EN] While resting state electroencephalography (EEG) provides relevant information on pathological changes in Parkinson's disease, most studies focus on the eyes-closed EEG biomarkers. Recent evidence has shown that both eyes-open EEG and reactivity to eyes-opening can also differentiate Parkinson's disease from healthy aging, but no consensus has been reached on a discriminatory capability benchmark. The aim of this study was to determine the resting-state EEG biomarkers suitable for real-time application that can differentiate Parkinson's patients from healthy subjects under both eyes closed and open. For this, we analysed and compared the quantitative EEG an-alyses of 13 early-stage cognitively normal Parkinson's patients with an age and sex-matched healthy group. We found that Parkinson's disease exhibited abnormal excessive theta activity in eyes-closed, which was reflected by a significantly higher relative theta power, a higher time percentage with a frequency peak in the theta band and a reduced alpha/theta ratio, while Parkinson's patients showed a significantly steeper non-oscillatory spectral slope activity than that of healthy subjects. We also found considerably less alpha and beta reactivity to eyes-opening in Parkinson's disease plus a significant moderate correlation between these EEG-biomarkers and the MDS-UPDRS score, used to assesses the clinical symptoms of Parkinson's Disease. Both EEG recordings with the eyes open and reactivity to eyes-opening provided additional information to the eyes-closed condition.We thus strongly recommend that both eyes open and closed be used in clinical practice recording protocols to promote EEG as a complementary non-invasive screening method for the early detection of Parkinson's disease, which would allow clinicians to design patient-oriented treatment and improve the patient's quality of life.This work was supported by the European Union - NextGenerationEU under the Investigo Program (INVEST/2022/67) and Polisabio (Polisabio 2021/A04). Funding for open access charge: CRUE-Universitat Politecnica de Valencia.Giménez-Aparisi, G.; Guijarro Estelles, E.; Chornet-Lurbe, A.; Ballesta-Martinez, S.; Pardo-Hernandez, M.; Ye Lin, Y. (2023). Early detection of Parkinson's disease: Systematic analysis of the influence of the eyes on quantitative biomarkers in resting state electroencephalography. Heliyon. 9(10). https://doi.org/10.1016/j.heliyon.2023.e2062591

Effect of n-3 polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers in type 2 diabetes mellitus patients

Artículo derivado de un proyecto de investigación de Suplementación con ácidos grasos poliinsaturados n-3 y vitamina D en pacientes con diabetes mellitus tipo 2Abstract: Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.CONACyT, Desarrollo Científico para atender problemas nacionales, No. 21294

Family History in the Iberian Peninsula during Chalcolithic and Bronze Age: An Interpretation through the Genetic Analysis of Plural Burials

Throughout history, it has been observed that human populations have buried the deceased members of their communities following different patterns. During the Copper Age and the Bronze Age-periods on which this study focuses-in the northern sub-plateau of the Iberian Peninsula, we identified different patterns of multiple or collective burial. This work analyzes a total of 58 individuals buried in different multiple or collective graves, to investigate whether the practice of these burials implies a family or biological link between individuals buried together. With this aim, STR markers of nuclear DNA were analyzed, as well as the hypervariable regions I and II of mitochondrial DNA, establishing both close kinship relationships and relationships through maternal lineage. We observed different burial patterns, detecting certain maternal lines preserved in some common burials maintained over time. Close family relationships were observed to a lesser extent, with some occasional exceptions. The results of the analysis formed the basis for a discussion on the concepts of family and community

Effectiveness and costs of phototest in dementia and cognitive impairment screening

<p>Abstract</p> <p>Background</p> <p>To assess and compare the effectiveness and costs of Phototest, Mini Mental State Examination (MMSE), and Memory Impairment Screen (MIS) to screen for dementia (DEM) and cognitive impairment (CI).</p> <p>Methods</p> <p>A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care (PC) centers. After undergoing all screening tests at the PC center, participants were extensively evaluated by researchers blinded to screening test results in a Cognitive-Behavioral Neurology Unit (CBNU). The gold standard diagnosis was established by consensus of expert neurologists. Effectiveness was assessed by the proportion of correct diagnoses (diagnostic accuracy [DA]) and by the kappa index of concordance between test results and gold standard diagnoses. Costs were based on public prices and hospital accounts.</p> <p>Results</p> <p>The study included 140 subjects (48 with DEM, 37 with CI without DEM, and 55 without CI). The MIS could not be applied to 23 illiterate subjects (16.4%). For DEM, the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [k = 0.31 (95% Confidence interval [95%CI], 0.19-0.43), DA = 0.60 (95%CI, 0.52-0.68)], and that of the MIS with a cutoff of 3/4 [k = 0.63 (95%CI, 0.48-0.78), DA = 0.83 (95%CI, 0.80-0.92)]. Effectiveness of the Phototest [k = 0.71 (95%CI, 0.59-0.83), DA = 0.87 (95%CI, 0.80-0.92)] was similar to that of the MIS and higher than that of the MMSE. Costs were higher with MMSE (275.9 ± 193.3€ [mean ± sd euros]) than with Phototest (208.2 ± 196.8€) or MIS (201.3 ± 193.4€), whose costs did not significantly differ. For CI, the effectiveness did not significantly differ between MIS [k = 0.59 (95%CI, 0.45-0.74), DA = 0.79 (95%CI, 0.64-0.97)] and Phototest [k = 0.58 (95%CI, 0.45-0.74), DA = 0.78 (95%CI, 0.64-0.95)] and was lowest for the MMSE [k = 0.27 (95%CI, 0.09-0.45), DA = 0.69 (95%CI, 0.56-0.84)]. Costs were higher for MMSE (393.4 ± 121.8€) than for Phototest (287.0 ± 197.4€) or MIS (300.1 ± 165.6€), whose costs did not significantly differ.</p> <p>Conclusion</p> <p>MMSE is not an effective instrument in our setting. For both DEM and CI, the Phototest and MIS are more effective and less costly, with no difference between them. However, MIS could not be applied to the appreciable percentage of our population who were illiterate.</p

Deciphering Adipose Tissue Extracellular Vesicles Protein Cargo and Its Role in Obesity

The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue (AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action

Diphenyl Urea Derivatives as Inhibitors of Transketolase: A Structure-Based Virtual Screening

Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor

Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury

BACKGROUND/AIM: Hepatic stellate cells (HSCs) express alpha-smooth muscle actin (alphaSMA) and acquire a profibrogenic phenotype upon activation by noxious stimuli. Insulin-like growth I (IGF-I) has been shown to stimulate HSCs proliferation in vitro, but it has been reported to reduce liver damage and fibrogenesis when given to cirrhotic rats. METHODS: The authors used transgenic mice (SMP8-IGF-I) expressing IGF-I under control of alphaSMA promoter to study the influence of IGF-I synthesised by activated HSCs on the recovery from liver injury. RESULTS: The transgene was expressed by HSCs from SMP8-IGF-I mice upon activation in culture and in the livers of these animals after CCl4 challenge. Twenty four hours after administration of CCl4 both transgenic and wild type mice showed similar extensive necrosis and increased levels of serum transaminases. However at 72 hours SMP8-IGF-I mice exhibited lower serum transaminases, reduced hepatic expression of alphaSMA, and improved liver morphology compared with wild type littermates. Remarkably, at this time all eight CCl4 treated wild type mice manifested histological signs of liver necrosis that was severe in six of them, while six out of eight transgenic animals had virtually no necrosis. In SMP8-IGF-I mice robust DNA synthesis occurred earlier than in wild type animals and this was associated with enhanced production of HGF and lower TGFbeta1 mRNA expression in the SMP8-IGF-I group. Moreover, Colalpha1(I) mRNA abundance at 72 hours was reduced in SMP8-IGF-I mice compared with wild type controls. CONCLUSIONS: Targeted overexpression of IGF-I by activated HSCs restricts their activation, attenuates fibrogenesis, and accelerates liver regeneration. These effects appear to be mediated in part by upregulation of HGF and downregulation of TGFbeta1. The data indicate that IGF-I can modulate the cytokine response to liver injury facilitating regeneration and reducing fibrosis

Superconducting Magnetization above the Irreversibility Line in Tl2Ba2CuO6

Piezolever torque magnetometry has been used to measure the magnetization of superconducting Tl2Ba2CuO6. Three crystals with different levels of oxygen overdoping were investigated in magnetic fields up to 10 Tesla. In all cases, the magnetization above the irreversibility line was found to depart from the behaviour M ~ ln(Hc2/H) of a simple London-like vortex liquid. In particular, for a strongly overdoped (Tc = 15K) crystal, the remnant superconducting order above the irreversibility line is characterized by a linear diamagnetic response (M ~ H) that persists well above Tc and also up to the highest field employed.Comment: RevTeX, 11 pages, 7 encapsulated PostScript figures, submitted to Physical Review