Early Neolithic Wine of Georgia in the South Caucasus

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics from sites in Georgia in the South Caucasus region, dating to the early Neolithic period (ca. 6,000–5,000 BC), provide the earliest biomolecular archaeological evidence for grape wine and viniculture from the Near East, at ca. 6,000–5,800 BC. The chemical findings are corroborated by climatic and environmental reconstruction, together with archaeobotanical evidence, including grape pollen, starch, and epidermal remains associated with a jar of similar type and date. The very large-capacity jars, some of the earliest pottery made in the Near East, probably served as combination fermentation, aging, and serving vessels. They are the most numerous pottery type at many sites comprising the so-called “Shulaveri-Shomutepe Culture” of the Neolithic period, which extends into western Azerbaijan and northern Armenia. The discovery of early sixth millennium BC grape wine in this region is crucial to the later history of wine in Europe and the rest of the world

Practice and Lived Experience of Menstrual Exiles (Chhaupadi) among Adolescent Girls in Far Western Nepal. December 2018

Background: Menstrual exile, also known as Chhaupadi, is a tradition of “untouchability” in far-western Nepal. Forbidden from touching other people and objects, women and girls are required to live away from the community, typically in a livestock shed, during menstruation. We assessed the lived experiences of Chhaupadi among Nepalese adolescent girls in the far-western Achham district of Nepal, observed the safety and sanitation of their living spaces during Chhaupadi, and assessed the perceptions of local adult stakeholders towards the practice of Chhaupadi. Methods: We collected data from 107 adolescent girls using a self-administered survey in two local schools in Achham. We also conducted a focus group discussion with seven girls, held key informant interviews, and observed the girls’ living spaces during Chhaupadi, using a checklist. Descriptive statistics of the quantitative survey and thematic analyses of qualitative interviews are presented. Results: The majority of the girls (n = 77, 72%) practiced exile, or Chhaupadi, during their menstruation, including 3 (4%) exiled to traditional Chhau sheds, 63 (82%) to livestock sheds, and 11 (14%) to courtyards outside their home. The remaining girls (n = 30, 28%) stayed inside the house, yet practiced some form of menstrual taboos. Of the 77 observed living spaces where the girls stayed during exile, only 30% (n = 23) had a toilet facility. Most exiled girls (97.4%) were restricted from eating dairy products. Participants reported having various psychological problems, including lonliness and difficulty sleeping while practicing Chhaupadi. Three of the girls were physically abused; nine were bitten by a snake. Notably high proportions of the living spaces lacked ventilation/windows (n = 20, 26%), electricity (n = 29, 38%), toilets (n = 54, 70%) and a warm blanket and mattress for sleeping (n = 29, 38%). Our qualitative findings supported our quantitative results. Conclusions: Chhaupadi has been condemned by human rights organizations. While the government has banned the practice, implementation on the ban is proceeding slowly, especially in far-western Nepal. Thus, as a temporary measure, public health professionals must work towards promoting the health and safety of Nepalese women and girls still practicing Chhaupadi

Nitrogen Heterocycles Form Peptide Nucleic Acid Precursors in Complex Prebiotic Mixtures

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth

Exploring the Fate of Nitrogen Heterocycles in Complex Prebiotic Mixtures

A long standing question in the field of prebiotic chemistry is the origin of the genetic macromolecules DNA and RNA. DNA and RNA have very complex structures with repeating subunits of nucleotides, which are composed of nucleobases (nitrogen heterocycles) connected to sugar-phosphate. Due to the instability of some nucleobases (e.g. cytosine), difficulty of synthesis and instability of D-ribose, and the likely scarcity of polyphosphates necessary for the modern nucleotides, alternative nucleotides have been proposed for constructing the first genetic material. Thus, we have begun to investigate the chemistry of nitrogen heterocycles in plausible, complex prebiotic mixtures in an effort to identify robust reactions and potential alternative nucleotides. We have taken a complex prebiotic mixture produced by a spark discharge acting on a gas mixture of N2, CO2, CH4, and H2, and reacted it with four nitrogen heterocycles: uracil, 5-hydroxymethyluracil, guanine, and isoxanthopterin (2-amino-4,7-dihydroxypteridine). The products of the reaction between the spark mixture and each nitrogen heterocycle were characterized by liquid chromatography coupled to UV spectroscopy and Orbitrap mass spectrometry. We found that the reaction between the spark mixtUl'e and isoxanthopterin formed one major product, which was a cyanide adduct. 5-hydroxymethyluracil also reacted with the spark mixture to form a cyanide adduct, uracil-5-acetonitrile, which has been synthesized previously by reacting HCN with S-hydroxymethyluracil. Unlike isoxanthopterin, the chromatogram of the 5-hydroxymethyluracil reaction was much more complex with multiple products including spark-modified dimers. Additionally, we observed that HMU readily self-polymerizes in solution to a variety of oligomers consistent with those suggested by Cleaves. Guanine and uracil, the biological nucleobases, did not react with the spark mixture, even at high temperature (100 C). This suggests that there are alternative nucleobases which are more reactive under prebiotic conditions and may have been involved in producing precursor nucleotides

Development of Biomarkers Based on Diet-Dependent Metabolic Serotypes: Concerns and Approaches for Cohort and Gender Issues in Serum Metabolome Studies

This is the publisher's version, also available electronically from: http://online.liebertpub.com/doi/pdfplus/10.1089/omi.2004.8.209Mathematical models that reflect the effects of dietary restriction (DR) on the sera metabolome may have utility in understanding the mechanisms of DR and in applying this knowledge to human epidemiological studies. Previous studies demonstrated both the feasibility of identifying biomarkers through metabolome analysis and the validity of our approach in independent cohorts of 6-month-oId male and female ad libitum fed or DR rats. Cross-cohort studies showed that cohort-specific effects distorted the dataset The present study extends these observations across the entire sample set, thereby validating our markers independently of specific cohorts. Metabolites originally identified in males were examined in females and vice-versa. DR's effect on the metabolom e is partially gender-specific and is modulated by environmental factors. DR reduces inter-gender differences in the metabolome. Univariate statistical methods showed that 56/93 metabolites in the female samples and 39/93 metabolites in the male samples were significantly altered (using our previous cut-off criteria of p ^ 0.2) by DR. The metabolites modulated by DR present a wide spectrum of concentration, redox reactivity and hydrophilicity, suggesting that our serotype is broadly representative of the metabolome and that DR has broad effects on the metabolome. These studies, coupled with those in the preceding and following reports, also highlight the utility for consideration of the metabolome as a network of metabolites using appropriate data analysis approaches. The inter-cohort and inter-gender differences addressed herein suggest potential cautions, and potential approaches, for identification of multivariate biomarker profiles that reflect changes in physiological status, such as a metabolism that predisposes to increased risk of neoplasia

Nutritional Assessment of Community-Dwelling Older Adults in Rural Nepal

Demographic transition in Nepal, like in many developing countries, has resulted in a burgeoning elderly population whose health status is not currently monitored. One pillar of health is adequate nutrition. Yet, little is known about the nutritional health status of the elderly in Nepal. The financial, material, and personnel limitations in Nepal’s health delivery services necessitate health screening instruments that require minimal clinical staff and resources. To our knowledge, no such nutritional assessment tool has been validated in Nepal. Therefore, our aims are two-fold: To assess the nutritional status of the elderly population in one typical Nepali village, Okharpauwa, in Nuwakot District, Nepal; and concurrently, to validate the Mini Nutritional Assessment (MNA) tool...(See full text for complete abstract

Development of Biomarkers Based on Diet-Dependent Metabolic Serotypes: Practical Issues in Development of Expert System-Based Classification Models in Metabolomic Studies

This is the publisher's official version, also available electronically from: http://online.liebertpub.com/doi/pdfplus/10.1089/omi.2004.8.197Dietary restriction (DR)-induced changes in the serum metabolome may be biomarkers for physiological status (e.g., relative risk of developing age-related diseases such as cancer). Megavariate analysis (unsupervised hierarchical cluster analysis IHCAJ; principal components analysis [PCAJ) of serum metabolites reproducibly distinguish DR from ad libitum fed rats. Component-based approaches (i.e., PCA) consistently perform as well as or better than distance-based metrics (i.e., HCA). We therefore tested the following: (A) Do identified subsets of serum metabolites contain sufficient information to construct mathematical models of class membership (i.e., expert systems)? (B) Do component-based metrics out-perform distance-based metrics? Testing was conducted using KNN (k-nearest neighbors, supervised HCA) and SIMCA (soft independent modeling of class analogy, supervised PCA). Models were built with single cohorts, combined cohorts or mixed samples from previously studied cohorts as training sets. Both algorithms over-fit models based on single cohort training sets. KNN models had >85% accuracy within training/test sets, but were unstable (i.e., values of k could not be accurately set in advance). SIMCA models had 100% accuracy within all training sets, 89% accuracy in test sets, did not appear to over-fit mixed cohort training sets, and did not require post-hoc modeling adjustments. These data indicate that (i) previously defined metabolites are robust enough to construct classification models (expert systems) with SIMCA that can predict unknowns by dietary category; (ii) component-based analyses outperformed distance-based metrics; (iii) use of over-fitting controls is essential; and (iv) subtle inter-cohort variability may be a critical issue for high data density biomarker studies that lack state markers

Development of Biomarkers Based on Diet-Dependent Metabolic Serotypes: Characteristics of Component-Based Models of Metabolic Serotypes

This is the publisher's version, also available electronically from: http://online.liebertpub.com/doi/pdfplus/10.1089/omi.2004Our research seeks to identify a scrum profile, or serotype, that reflects the systemic physiologic modifications resultant from dietary restriction (DR), in part such that this knowledge can be applied for biomarker studies. Direct comparison suggests that component-based classification algorithms consistently out-perform distance-based metrics for studies of nutritional modulation of metabolic serotype, but are subject to over-fitting concerns. Intercohort differences in the sera metabolome could partially obscure the effects of DR. Further analysis now shows that implementation of component-based approaches (also called projection methods) optimized for class separation and controlled for over-fitting have >97% accuracy for distinguishing sera from control or DR rats. DR's effect on the metabolome is shown to be robust across cohorts, but differs in males and females (although some metabolites are affected in both). We demonstrate the utility of projection-based methods for both sample and variable diagnostics, including identification of critical metabolites and samples that are atypical with respect to both class and variable models. Inclusion of non-statistically different variables enhances classification models. Variables that contribute to these models are sharply dependent on mathematical processing techniques; some variables that do not contribute under one paradigm arc powerful under alternative mathematical paradigms. In practical terms, this information may find purpose in other endeavors, such as mechanistic studies of DR. Application of these approaches confirms the utility of megavariate data analysis techniques for optimal generation of biomarkers based on nutritional modulation of physiological processes

Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth

Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We lso report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth