South American Archaeological Isotopic Database, a regional-scale multi-isotope data compendium for research.

The South American Archaeological Isotopic Database (SAAID) is a comprehensive open-access resource that aggregates all available bioarchaeological stable and radiogenic isotope measurements, encompassing data from human individuals, animals, and plants across South America. Resulting from a collaborative effort of scholars who work with stable isotopes in this region, SAAID contains 53,781 isotopic measurements across 24,507 entries from individuals/specimens spanning over 12,000 years. SAAID includes valuable contextual information on archaeological samples and respective sites, such as chronology, geographical region, biome, and spatial coordinates, biological details like estimated sex and age for human individuals, and taxonomic description for fauna and flora. SAAID is hosted at the PACHAMAMA community within the Pandora data platform and the CORA repository to facilitate easy access. Because of its rich data structure, SAAID is particularly well-suited for conducting spatiotemporal meta-analyses. It serves as a valuable tool for addressing a variety of research topics, including the spread, adoption, and consumption intensification of food items, paleo-environmental reconstruction, as well as the exploration of mobility patterns across extensive geographic regions.

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia.

Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

Outbreak report of SARS-CoV-2 infection by airborne transmission: Epidemiologic and molecular evidence / Reporte de un brote de infección por SARS-CoV-2 por transmisión aérea: evidencia epidemiológica y molecular

Introduction: It has been shown that the transmission of SARS-CoV-2 occurs mainly by air, and the risk of infection is greater in closed spaces. Objective: To describe the epidemiology, virology and molecular characterization of a COVID-19 outbreak at a closed vaccination point during the third wave of SARS-CoV-2 in Colombia. Materials and methods: Diagnostic tests, interviews, sampling, cell cultures and viral sequencing were carried out, the latter being molecular characterization and lineage identification. Results: Seven workers were positive for SARS-CoV-2; among these, 3 samples were analyzed, plus an additional sample belonging to the mother of the presumed index case; all samples were identified with lineage B.1.625, with a maximum of 2 nucleotides difference between them. Conclusions: Variant B.1.625 was identified as the cause of the COVID-19 outbreak, and a co-worker was also identified as the index case. Unexpectedly, attending a vaccination day became a risk factor for acquiring the infection.

Introducción. Se ha demostrado que la transmisión de SARS-CoV-2 se produce principalmente por vía aérea y el riesgo de infección es mayor en espacios cerrados con alta concentración de personas; este último factor se presentó en algunos de los puestos de vacunación de la ciudad de Medellín. Objetivo. Describir la epidemiología, virología y caracterización molecular de un brote de COVID-19 en un punto de vacunación cerrado durante la tercera ola de SARS-CoV-2 en Colombia. Materiales y métodos. Se realizaron test diagnósticos, entrevistas, toma de muestras, aislamiento viral y secuenciación genómica. Con esta última, se hizo la caracterización molecular y se identificó el linaje. Resultados. Siete trabajadores fueron positivos para SARS-CoV-2, y de estos, tres muestras fueron secuenciadas, más una muestra adicional perteneciente a la madre del presunto caso índice. Todas las muestras fueron identificadas con el linaje B.1.625, con un máximo de dos nucleótidos de diferencia entre ellas. Conclusiones. Se identificó la variante B.1.625 como la causante del brote de COVID-19, y también un compañero de trabajo fue identificado como el caso índice. De forma imprevista, asistir a una jornada de vacunación se convirtió en un factor de riesgo para adquirir la infección.

Mitochondrial interactome quantitation reveals structural changes in metabolic machinery in the failing murine heart.

Advancements in cross-linking mass spectrometry (XL-MS) bridge the gap between purified systems and native tissue environments, allowing the detection of protein structural interactions in their native state. Here we use isobaric quantitative protein interaction reporter technology (iqPIR) to compare the mitochondria protein interactomes in healthy and hypertrophic murine hearts, 4 weeks post-transaortic constriction. The failing heart interactome includes 588 statistically significant cross-linked peptide pairs altered in the disease condition. We observed an increase in the assembly of ketone oxidation oligomers corresponding to an increase in ketone metabolic utilization; remodeling of NDUA4 interaction in Complex IV, likely contributing to impaired mitochondria respiration; and conformational enrichment of ADP/ATP carrier ADT1, which is non-functional for ADP/ATP translocation but likely possesses non-selective conductivity. Our application of quantitative cross-linking technology in cardiac tissue provides molecular-level insights into the complex mitochondria remodeling in heart failure while bringing forth new hypotheses for pathological mechanisms.

Solid and papillary neoplasm of the pancreas (SPNP): a case report.

Background: Solid and papillary neoplasm of the pancreas (SPNP) is a rare pancreatic tumor, well known for its predilection for young women and large volume. The tumor has a favorable prognosis and differentiating it from other pancreatic tumors with aggressive behavior is necessary. Case Description: We present the case of a 34-year-old female without relevant background. She presented with abdominal pain and by fine needle biopsy was diagnosed as ductal carcinoma. During the evaluation, an abdominal ultrasound revealed a pancreatic growth that was "bulky, solid, with irregular margins, in homogeneously hypoechoic, with anechoic areas of necrosis, located lateral to the tail of the pancreas and medial to the upper pole of the left kidney and the lower splenic pole". The patient was admitted, and surgery was performed. At the laparotomy, a tumor of 15 cm in diameter was detected. The tumor was located in the tail of the pancreas, was well encapsulated, and of solid consistency. Caudal pancreatectomy with a splenectomy was carried out. The final pathology diagnosis was a SPNP. Conclusions: In the presence of a large abdominal mass of pancreatic relevance, even in older women, the possibility of having an SPNP should always be evaluated. Given the low malignancy potential of this tumor and the excellent prognosis with radical surgical treatment, the preoperative diagnosis should always be particularly accurate. Surgical resection is recommended as the treatment of choice.

Electrochemical and CD-spectroelectrochemical studies of the interaction between BSA and the complex [Cu(Bztpen)]2+, (Bztpen = (N-benzyl-N, N', N'-tris (pyridin-2-ylmethyl) ethylenediamine).

In this work we report the electrochemical, spectroscopical and spectro-electrochemical studies of a model complex [CuΙΙ(Bztpen)]2+, (Bztpen = (N-benzyl-N,N',N'-tris(pyridin-2-ylmethyl)ethylenediamine) in order to propose a methodology to evaluate the interaction of potential metal based anticancer agents during electron transfer processes, with transport proteins such as Bovine Serum Albumin (BSA). It was possible to establish a reversible electron transfer [CuΙΙ(Bztpen)]2+ +1e â†’ [CuΙ(Bztpen)]+ and a weak interaction energy between BSA and [CuΙΙ(Bztpen)] and [CuΙ(Bztpen)] species, with no adsorption of protein over the electrode surface. Circular Dichroism (CD) Spectroelectrochemistry, not reported before, reveals no significant changes in BSA structure during the electron transfer [CuΙΙ(Bztpen)]2+ + 1e â†’ [CuΙ(Bztpen)]+. CD experiments at variable temperature for BSA denaturalization in the absence and in the presence of [CuΙΙ(Bztpen)]2+, shown no change in thermodynamic parameters due to low interaction between the transport protein and copper complex.

Comparative Analysis of the Chloroplast Genomes of Quercus × morehus and the Presumptive Parents Q. wislizeni and Q. kelloggii (Fagaceae) from California.

Here, we present the complete chloroplast genomes of Quercus × morehus, Q. wislizeni, and Q. kelloggii from California. The genomes are 161,119 to 161,130 bp and encode 132 genes. Quercus × morehus and Q. wislizeni are identical in sequence but differ from Q. kelloggii by three indels and eight SNPs.

Rapid Weight Loss of Up to Five Percent of the Body Mass in Less Than 7 Days Does Not Affect Physical Performance in Official Olympic Combat Athletes With Weight Classes: A Systematic Review With Meta-Analysis.

Given the relevance of the effects that weight loss can generate on the physical performance in athletes, this study performed a systematic review with meta-analysis of the published literature on rapid weight loss (RWL) and examined its impact on the physical performance in Official Olympic combat sports athletes. The "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" (PRISMA) guidelines were followed to ensure an ethical and complete reporting of the findings. PubMed, SPORT Discus, and EBSCO were the electronic databases explored for article retrieval and selection. The following string was applied: "RWL" OR "weight loss" OR "weight reduction" AND "judo" OR "wrestling" or "taekwondo" or "boxing" AND "performance." Based on the quality analysis, conducted according to the "Tool for the assessment of study quality and reporting in exercise training studies" (TESTEX), ten articles achieved a score >6 points. The meta-analysis showed a significant difference in pre- vs. post-weight loss (p = 0.003) and no effects in pre- vs. post-power and strength performance analysis (p > 0.05 for both results). Based on our systematic review and meta-analysis of the literature, RWL up to ≤5% of the body mass in less than 7 days does not influence performance outcomes in Official Olympic combat athletes with weight classes, considering the strength and power measures.

Upregulation of mitochondrial ATPase inhibitory factor 1 (ATPIF1) mediates increased glycolysis in mouse hearts.

In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for the switch are poorly understood. We found that inhibitory factor 1 of the mitochondrial FoF1-ATP synthase (ATPIF1), a protein known to inhibit ATP hydrolysis by the reverse function of ATP synthase during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced by pressure overload, myocardial infarction, or α-adrenergic stimulation. Chemical cross-linking mass spectrometry analysis of hearts hypertrophied by pressure overload suggested that increased expression of ATPIF1 promoted the formation of FoF1-ATP synthase nonproductive tetramer. Using ATPIF1 gain- and loss-of-function cell models, we demonstrated that stalled electron flow due to impaired ATP synthase activity triggered mitochondrial ROS generation, which stabilized HIF1α, leading to transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the metabolic switch and protected against the pathological remodeling during chronic stress. These results uncover a function of ATPIF1 in nonischemic hearts, which gives FoF1-ATP synthase a critical role in metabolic rewiring during the pathological remodeling of the heart.

Differential Proteome and Interactome Analysis Reveal the Basis of Pleiotropy Associated With the Histidine Methyltransferase Hpm1p.

The methylation of histidine is a post-translational modification whose function is poorly understood. Methyltransferase histidine protein methyltransferase 1 (Hpm1p) monomethylates H243 in the ribosomal protein Rpl3p and represents the only known histidine methyltransferase in Saccharomyces cerevisiae. Interestingly, the hpm1 deletion strain is highly pleiotropic, with many extraribosomal phenotypes including improved growth rates in alternative carbon sources. Here, we investigate how the loss of histidine methyltransferase Hpm1p results in diverse phenotypes, through use of targeted mass spectrometry (MS), growth assays, quantitative proteomics, and differential crosslinking MS. We confirmed the localization and stoichiometry of the H243 methylation site, found unreported sensitivities of Δhpm1 yeast to nonribosomal stressors, and identified differentially abundant proteins upon hpm1 knockout with clear links to the coordination of sugar metabolism. We adapted the emerging technique of quantitative large-scale stable isotope labeling of amino acids in cell culture crosslinking MS for yeast, which resulted in the identification of 1267 unique in vivo lysine-lysine crosslinks. By reproducibly monitoring over 350 of these in WT and Δhpm1, we detected changes to protein structure or protein-protein interactions in the ribosome, membrane proteins, chromatin, and mitochondria. Importantly, these occurred independently of changes in protein abundance and could explain a number of phenotypes of Δhpm1, not addressed by expression analysis. Further to this, some phenotypes were predicted solely from changes in protein structure or interactions and could be validated by orthogonal techniques. Taken together, these studies reveal a broad role for Hpm1p in yeast and illustrate how crosslinking MS will be an essential tool for understanding complex phenotypes.

Improved Interpretation of Protein Conformational Differences and Ligand Occupancy in Large-Scale Cross-Link Data.

Chemical cross-linking of proteins in complex samples, cells, or even tissues is emerging to provide unique structural information on proteins and complexes that exist within native or nativelike environments. The public database XLinkDB automatically maps cross-links to available structures based on sequence homology. Structures most likely to reflect protein conformations in the cross-linked sample are routinely identified by having cross-linked residues separated by Euclidean distances within the maximum span of the applied cross-linker. Solvent accessible surface distance (SASD), which considers the accessibility of the cross-linked residues and the path connecting them, is a better predictor of consistency than the Euclidean distance. However, SASDs of structures are not publicly available, and their calculation is computationally intensive. Here, we describe in XLinkDB version 4.0 the automatic calculation of SASDs using Jwalk for all cross-links mapped to structures, both with and without regard to ligands, and derive empirical maximum SASD spans for BDP-NHP and DSSO cross-linkers of 51 and 43 Å, respectively. We document ligands proximal to cross-links in structures and demonstrate how SASDs can be used to help infer sample protein conformations and ligand occupancy, highlighting cross-links sensitive to ADP binding in mitochondria isolated from HEK293 cells.

Self-Assembled Monolayer of Monomercaptoundecahydro-closo-dodecaborate on a Polycrystalline Gold Surface.

In this work, we present an electrochemical study of the boron cage monomercaptoundecahydro-closo-dodecaborate [B12H11SH]2- in solution and in a self-assembled monolayer over a polycrystalline gold electrode. Cyclic voltammetry of the anion [B12H11SH]2- in solution showed a shift in the peak potentials related to the redox processes of gold hydroxides, which evidences the interaction between the boron cage and the gold surface. For an Au electrode modified with the anion [B12H11SH]2-, cyclic voltammetry response of the probe Fe(CN)63-/Fe(CN)64- showed a ΔEp value typical for a surface modification. Electrochemical impedance spectroscopy presented Rtc and Cdl values related to the formation of a self-assembled monolayer (SAM). A comparison of electrochemical responses of a modified electrode with thioglycolic acid (TGA) reveals that the boron cage [B12H11SH]2- diminishes the actives sites over the Au surface due to the steric effects. Differential capacitance measurements for bare gold electrode and those modified with [B12H11SH]2- and (TGA), indicate that bulky thiols enhance charge accumulation at the electrode-solution interface. In addition to electrochemical experiments, DFT calculations and surface plasmon resonance measurements (SPR) were carried out to obtain quantum chemical descriptors and to evaluate the molecular length and the dielectric constant of the Boron cage. From SPR experiments, the adsorption kinetics of [B12H11SH]2- were studied. The data fit for a Langmuir kinetic equation, typical for the formation of a monolayer.

[Integrated Care Protocol: Prevention, diagnosis and treatment of diabetes mellitus 2]. / Protocolo de Atención Integral: prevención, diagnóstico y tratamiento de diabetes mellitus 2.

Background: Type 2 diabetes mellitus (DM2) represents one of the ten non- transmissible chronic diseases that constitute the main causes of death and disability in Mexico. It is the leading cause of disability and the second cause of death. The IMSS serves 4.2 million people living with this disease. Objective: Establish lines of action that allow standardizing the substantive activities to be carried out by the multidisciplinary health team, promoting healthy lifestyles, establishing timely diagnoses, providing adequate and intensified care and treatments, preventing complications, and providing comprehensive care and of quality for the benefit of the beneficiaries. Material and methods: The process of development of the Integrated Care Protocols consisted of: 1) Prioritization of the health problem, 2) Conformation of an interdisciplinary work group, 3) Development of content and systematic search for information 4) Analysis, review and discussion of interventions, 5) Review and validation by regulatory areas, 6) Dissemination and implementation. Conclusions: Promotion and prevention actions must be carried out at all levels and by all health personnel, likewise, the incorporation of new treatments for DM2 in the IMSS, requires the homologation of the criteria in risk stratification, diagnosis, profile risk of hypoglycemia and adverse effects to limit the complications of the disease and reduce the burden of disease (disability and premature death).

Introducción: la diabetes mellitus tipo 2 (DM2) es una de las diez enfermedades crónicas no transmisibles que constituyen las principales causas de muerte y discapacidad en México, es la principal causa de invalidez y la segunda de muerte. El Instituto Mexicano del Seguro Social (IMSS) atiende a 4.2 millones personas que viven con esta enfermedad. Objetivo: establecer líneas de acción que permitan homologar las actividades sustantivas que debe llevar a cabo el equipo multidisciplinario de salud, promoviendo estilos de vida saludables, estableciendo diagnósticos oportunos, otorgando atención y tratamientos adecuados e intensificados, previniendo complicaciones y brindando atención integral y de calidad para el beneficio de los derechohabientes. Material y métodos: el proceso de desarrollo de los Protocolos de Atención Integral consistió en: 1) Priorización del problema de salud; 2) Conformación de grupo de trabajo interdisciplinario; 3) Desarrollo del contenido y búsqueda sistemática de información; 4) Análisis, revisión y discusión de las intervenciones; 5) Revisión y validación por las áreas normativas, y 6) Difusión e implementación. Conclusiones: las acciones de promoción y prevención deben realizarse en todos los niveles y por parte de todo el personal de salud; asimismo, la incorporación de nuevos tratamientos para DM2 en el IMSS requiere de la homologación de los criterios en estratificación de riesgo, diagnóstico, perfil riesgo de hipoglucemia y efectos adversos, con el objetivo de limitar las complicaciones de la enfermedad y disminuir la carga de enfermedad (discapacidad y muerte prematura).

[Integrated Care Protocol: Chronic complications of diabetes mellitus 2]. / Protocolo de Atención Integral: complicaciones crónicas de diabetes mellitus 2.

BACKGROUND: According to the International Diabetes Federation, 18% of Mexican adults live with diabetes and it is expected that by 2030 it will occupy the seventh place in the world in number of cases. In the population covered by the Mexican Institute of Social Security, diabetes is the second cause of mortality, years lost due to premature death, years lived with disability and years of healthy life lost, placing it as one of the costliest diseases. OBJECTIVE: Address in a timely and integrated manner chronic complications of type 2 diabetes mellitus, by implementing coordinated actions by multidisciplinary health team in the 3 levels of care. MATERIAL AND METHODS: The process of developing the Integrated Care Protocols consisted of: 1) Prioritization of the health problem, 2) Formation of an interdisciplinary working group, 3) Development of content and systematic search for information 4) Analysis, review and discussion of interventions, 5) Review and validation by regulatory areas, 6) Dissemination and implementation. CONCLUSIONS: Adequate glycemic control, blood pressure, lipids and a healthy lifestyle are the key to delaying the presence of micro and macrovascular complications of DM2. However, the progression of the disease will eventually be inevitable, it will confront the health personnel and the patient with some of the complications. In this sense, timely detection and treatment to delay them becomes the main function of the health worker.

INTRODUCCIÓN: de acuerdo con la Federación Internacional de Diabetes, en México el 18% de los adultos viven con diabetes, y se espera que para el 2030 ocupe el séptimo lugar mundial en número de casos. En la población cubierta por el Instituto Mexicano del Seguro Social, la diabetes es la segunda causa de mortalidad, así como de años perdidos por muerte prematura, de años vividos con discapacidad y de años de vida saludable perdidos, colocándola como una de las enfermedades más costosas. OBJETIVO: atender de manera oportuna e integral las complicaciones crónicas de la diabetes mellitus tipo 2 (DM2), mediante la implementación articulada de las acciones a cargo de equipo multidisciplinario de salud en los tres niveles de atención. MATERIAL Y MÉTODOS: el proceso de desarrollo de los Protocolos de Atención Integral consistió en: 1) Priorización del problema de salud, 2) Conformación de grupo de trabajo interdisciplinario, 3) Desarrollo del contenido y búsqueda sistemática de información 4) Análisis, revisión y discusión de las intervenciones, 5) Revisión y validación por las áreas normativas y 6) Difusión e implementación. CONCLUSIONES: el adecuado control glucémico, del presión arterial y lípidos, así como un estilo de vida saludable son la clave para retrasar la presencia de complicaciones micro y macrovasculares de la DM2. Sin embargo, la progresión de la enfermedad eventualmente será inevitable, enfrentará al personal de salud y al paciente a alguna de las complicaciones. En este sentido, la detección oportuna y el tratamiento para retrasarlas se convierte en la principal función del trabajador de la salud.

Multiplexed Isobaric Quantitative Cross-Linking Reveals Drug-Induced Interactome Changes in Breast Cancer Cells.

The study of protein structures and interactions is critical to understand their function. Chemical cross-linking of proteins with mass spectrometry (XL-MS) is a rapidly developing structural biology technique able to provide valuable insight into protein conformations and interactions, even as they exist within their native cellular environment. Quantitative analysis of cross-links can reveal protein conformational and interaction changes that occur as a result of altered biological states, environmental conditions, or pharmacological perturbations. Our laboratory recently developed an isobaric quantitative protein interaction reporter (iqPIR) cross-linking strategy for comparative interactome studies. This strategy relies on isotope encoded chemical cross-linkers that have the same molecular mass yet produce unique and specific isotope signatures upon fragmentation in the mass spectrometer which can be used for quantitative analysis of cross-linked peptides. The initial set of iqPIR molecules allowed for binary comparisons. Here, we describe the in vivo application of an extended set of six iqPIR reagents (6-plex iqPIR), allowing multiplexed quantitative interactome analysis of up to six biological samples in a single LC-MS acquisition. Multiplexed iqPIR is demonstrated on MCF-7 breast cancer cells treated with five different Hsp90 inhibitors revealing large scale protein conformational and interaction changes specific to the molecular class of the inhibitors.

[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Kinetics of myelin breakdown products: A labeling study in patients with progressive multiple sclerosis.

The majority of disease modifying therapies for multiple sclerosis (MS) reduce inflammation, but do no't target remyelination. Development of remyelinating therapies will benefit from a method to quantify myelin kinetics in patients with MS. We labeled myelin in vivo with deuterium, and modeled kinetics of myelin breakdown products ß-galactosylceramide (ß-GalC) and N-Octadecanoyl-sulfatide (NO-Sulf). Five patients with MS received 120 ml 70% D2 O daily for 70 days and were compared with six healthy subjects who previously received the same procedure. Mass spectrometry and compartmental modeling were used to quantify the turnover rate of ß-GalC and NO-Sulf in cerebrospinal fluid (CSF). Turnover rate constants of the fractions of ß-GalC and NO-Sulf with non-negligible turnover were 0.00186 and 0.00714, respectively, in both healthy subjects and patients with MS. The turnover half-life of ß-GalC and NO-Sulf was calculated as 373 days and 96.5 days, respectively. The effect of MS on the NO-Sulf (49.4% lower fraction with non-negligible turnover) was more pronounced compared to the effect on ß-GalC turnover (18.3% lower fraction with non-negligible turnover). Kinetics of myelin breakdown products in the CSF are different in patients with MS compared with healthy subjects. This may be caused by slower myelin production in these patients, by a higher level of degradation of a more stable component of myelin, or, most likely, by a combination of these two processes. Labeling myelin breakdown products is a useful method that can be used to quantify myelin turnover in patients with progressive MS and can therefore be used in proof-of-concept studies with remyelination therapies.

Applications and advancements of FT-ICR-MS for interactome studies.

The set of all intra- and intermolecular interactions, collectively known as the interactome, is currently an unmet challenge for any analytical method, but if measured, could provide unparalleled insight on molecular function in living systems. Developments and applications of chemical cross-linking and high-performance mass spectrometry technologies are beginning to reveal details on how proteins interact in cells and how protein conformations and interactions inside cells change with phenotype or during drug treatment or other perturbations. A major contributor to these advances is Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) technology and its implementation with accurate mass measurements on cross-linked peptide-pair precursor and fragment ions to enable improved identification methods. However, these applications place increased demands on mass spectrometer performance in terms of high-resolution spectral acquisition rates for on-line MSn experiments. Moreover, FT-ICR-MS also offers unique opportunities to develop and implement parallel ICR cells for multiplexed signal acquisition and the potential to greatly advance accurate mass acquisition rates for interactome studies. This review highlights our efforts to exploit accurate mass FT-ICR-MS technologies with chemical cross-linking and developments being pursued to realize parallel MS array capabilities that will further advance visualization of the interactome.

In-Cell Labeling and Mass Spectrometry for Systems-Level Structural Biology.

Biological systems have evolved to utilize proteins to accomplish nearly all functional roles needed to sustain life. A majority of biological functions occur within the crowded environment inside cells and subcellular compartments where proteins exist in a densely packed complex network of protein-protein interactions. The structural biology field has experienced a renaissance with recent advances in crystallography, NMR, and CryoEM that now produce stunning models of large and complex structures previously unimaginable. Nevertheless, measurements of such structural detail within cellular environments remain elusive. This review will highlight how advances in mass spectrometry, chemical labeling, and informatics capabilities are merging to provide structural insights on proteins, complexes, and networks that exist inside cells. Because of the molecular detection specificity provided by mass spectrometry and proteomics, these approaches provide systems-level information that not only benefits from conventional structural analysis, but also is highly complementary. Although far from comprehensive in their current form, these approaches are currently providing systems structural biology information that can uniquely reveal how conformations and interactions involving many proteins change inside cells with perturbations such as disease, drug treatment, or phenotypic differences. With continued advancements and more widespread adaptation, systems structural biology based on in-cell labeling and mass spectrometry will provide an even greater wealth of structural knowledge.

Evaluation of methane production from the anaerobic co-digestion of manure of guinea pig with lignocellulosic Andean residues.

The objective of this research was to evaluate anaerobic co-digestion of guinea pig manure (GP) with Andean agricultural residues such as amaranth (AM), quinoa (QU) and wheat (TR) in batch biodigesters under mesophilic conditions (37 0C) for 40 days. As microbial inoculum, sewage treatment sludge was used in two inoculum/substrate ratios (ISR of 1 and 2). In terms of methane production, the best results occurred in treatments containing AM and QU as co-substrate and an ISR of 2. Thus, the highest methane production yield in the GP:AM biodigesters (25:75) and GP:QU (25:75) with 341.86 mlCH4/g VS added and 341.05 mlCH4/g VS added, respectively. On the other hand, the results showed that methane production with an ISR of 2 generated higher yields for guinea pig waste and the methane fraction of the biogas generated was in a range from 57 to 69%. Methane production kinetics from these raw materials was studied using five kinetic models: modified Gompertz, logistic equation, transfer, cone and Richards. The cone model adjusted best to the experimental values ​​with those observed with r2 of 0.999 and RMSE of 1.16 mlCH4/g VS added. Finally, the highest biodegradability (experimental yield/theoretical yield) was obtained in the GP-AM biodigesters (25:75) with 67.92%.