Biochemical Signatures Research Articles

Clinical and neuropathological differences between Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies - current issues and future directions.

Lewy body diseases share clinical, pathological, genetic and biochemical signatures, and are regarded as a highly heterogeneous group of neurodegenerative disorders. Inclusive of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), controversy still exists as to whether they should be considered as separate disease entities or as part of the same disease continuum. Here we discuss emerging knowledge relating to both clinical, and neuropathological differences and consider current biomarker strategies as we try to improve our diagnostic capabilities and design of disease modifying therapeutics for this group of debilitating neurodegenerative disorders. This article is part of the Special Issue "Synuclein".

Label-free Identification of Antibody-mediated Rejection in Cardiac Allograft Biopsies Using Infrared Spectroscopic Imaging.

Antibody-mediated rejection (AMR) in cardiac allograft recipients remains less well-understood than acute cellular rejection, is associated with worse outcomes, and portends a greater risk of developing chronic allograft vasculopathy. Diffuse immunohistochemical C4d staining of capillary endothelia in formalin-fixed, paraffin-embedded right ventricular endomyocardial biopsies is diagnostic of immunopathologic AMR but serves more as a late-stage marker. Infrared (IR) spectroscopy may be a useful tool in earlier detection of rejection. We performed mid-IR spectroscopy to identify a unique biochemical signature for AMR. A total of 30 posttransplant formalin-fixed paraffin-embedded right ventricular tissue biopsies (14 positive for C4d and 16 negative for C4d) and 14 native heart biopsies were sectioned for IR analysis. Infrared images of entire sections were acquired and regions of interest from cardiomyocytes were identified. Extracted spectra were averaged across many pixels within each region of interest. Principal component analysis coupled with linear discriminant analysis and predictive classifiers were applied to the data. Comparison of averaged mid-IR spectra revealed unique features among C4d-positive, C4d-negative, and native heart biopsies. Principal component analysis coupled with linear discriminant analysis and classification models demonstrated that spectral features from the mid-IR fingerprint region of these 3 groups permitted accurate automated classification into each group. In cardiac allograft biopsies with immunopathologic AMR, IR spectroscopy reveals a biochemical signature unique to AMR compared with that of nonrejecting cardiac allografts and native hearts. Future study will focus on the predictive capabilities of this IR signature.

Blood Pressure Regulation Using Electroacupuncture in Middle‐Aged Hypertensive Women Associated With Mitochondrial Beta‐Oxidation

Acupuncture at specific acupoints reduces elevated blood pressure. We have shown that 8‐week electroacupuncture (EA) at P5‐6 and St36‐37 decreases blood pressure in men (38–75 year) with mild to moderate hypertension (HTN) more effectively (70% responsiveness, ≥ −6 mmHg). In contrast, the majority (64%) of middle‐aged hypertensive women were not responsive to this treatment. We decided to add acupoints that target the endocrine system as well (LI4, CV3‐4, SP 6, LV3, K3). However, the underlying mechanisms of how acupuncture lowers blood pressure remain unclear. Metabolomics provides a powerful method to assess the biochemical signature involved in cellular processes that are involved in human health and disease. By using untargeted metabolomics, therefore, we aimed to identify metabolic biomarkers and assess pathways involved in sympathoinhibitory EA and endocrine‐sympathoinhibitory EA treatment lowering blood pressure in middle‐aged perimenopausal females with mild to moderate HTN. Twenty four enrolled women ages 45 to 70 year with hypertension were randomly assigned to sympathoinhibitory EA treatment (P5‐6+St36‐37, n=10) or endocrine‐sympathoinhibitory EA treatment (P6‐LI4+St36‐Sp6+CV3‐4+Li3‐K3, n=14). Participants were not on antihypertensive medications and hormonal therapy. The blood pressure lowering responsiveness (≥ −6 mmHg) to endocrine‐sympathoinhibitory EA was 80% while only 33% of the subjects treated with sympathoinhibitory EA lowered their blood pressures. Peak systolic blood pressure (SBP) during 24 hours dropped from 169±4.1 to 157±3.3 mmHg (P=0.002) while averaged 24‐hour SBP dropped from 138±2.3 to 131±2.3 mmHg (P=0.001) in 14 subjects treated with endocrine‐sympathoinhibitory EA. The averaged 24‐hour mean blood pressure (MBP) and peak MBP decreased respectively with P values of 0.002 and 0.025 in the 14 subjects. On the other hand, 8‐week course of sympathoinhibitory EA treatment did not decrease SBP, MBP, peak SBP, and peak MAP in 10 other subjects, consistent with our prior study. Concurrently, metabolomics analysis indicated that the plasma acylcarnitines (short (P=0.03) and medium chain fatty acids (P=.008)) were reduced significantly in 14 subjects following 8‐week endocrine‐sympathoinhibitory EA treatment in contrast to sympathoinhibitory EA. Previous studies have shown that arterial stiffness and hypertension are associated with higher acylcarnitine levels which indicate higher beta‐oxidation associated with mitochondrial dysfunction. Endocrine‐sympathoinhibition EA enhances blood pressure lowering responsiveness in middle‐aged hypertensive women likely through decreasing acylcarnitine production, reflecting lower beta‐oxidation at the mitochondrial level.Support or Funding InformationAdolph Coors FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Isolation of Microorganisms from Fermenting Parkia biglobosa in Kuje Market, Abuja

Lactic acid bacteria constitute one of the most abundant groups of microorganisms in most fermented food products across Nigeria. The biochemical signatures of these species make the ideal catalysts for a range of processing events with the food industry. This study was undertaken to isolate and screen for lactic acid bacteria strains obtainable from fermented Parkia biglobosa seeds purchased at a rural seed market in Abuja. Data obtained revealed that seven morphologically distinct bacteria isolates were obtained using antifungal induced (0.3 mg/ml Fluconazole) yeast extract, malt extract, peptone, glucose, agar media. The seven bacterial isolates were given the designations TEA, TEB, TEC, TED, TEF, TEJ, and TEL respectively. The obtained all but two isolates (TEB and TEL) were all capable of fermenting fructose, glucose, lactose, sucrose and trehalose as the sole carbon source in the broth. Morphological examination revealed that the isolates obtained were non-spore forming gram positive colonies ranging from creamy to white, clear, cocci and rod-shaped, smooth textured and flat elevation with transparent opacity. Their Growth measurements were determined by measuring the optical density of the cells in broth using spectrophotometer at 600nm over a 96 hour incubatory period in nutrient broth at 37oC. Isolate TEC displayed the highest overall growth pattern over the 24 hour period via optical density readout 1.85, 2.40, 2.65, 2.80. All isolates except TEB were negative for catalase and citrate, thereby suggesting that TEB was a specie of the Citrobacter family. All isolates tested negative for coagulase, indole and motility tests. Suggestions from the data obtained lean towards the use and suitability of the isolated bacteria as ideal cultures for commercial fermentation.

Synthetic cells protect DNA circuits

Molecular computer systems relying on DNA can already solve math problems, play games like tic-tac-toe, and detect the biochemical signatures of disease. Now researchers have used artificial cells to host DNA-based circuits, allowing them to operate in messy biological environments (Nat. Nanotechnol. 2019, DOI: 10.1038/s41565-019-0399-9). It’s a step on the way to using DNA computers as rapid diagnostic devices, or even to control systems that deliver therapeutic drugs inside patients, says Tom F. A. de Greef at Eindhoven University of Technology, part of the team behind the work. The team combined proteins and polymers to form artificial “protocells” roughly 10–60 μm wide and loaded them with molecular complexes that can function as signal-processing components such as logic gates. The gate complexes contain two different DNA strands and a fluorescent tag. Whereas conventional electronics receive signals from incoming electrons and send their own electronic signals, the protocells use DNA. An incoming

Thermal Effects on Biochemical Signatures of UHT, Pasteurized and Domestically Boiled Buffalo Milk Detected by Synchronous Fluorescence Spectroscopy.

Thermal treatment of milk is performed to limit bacterial growth and make it safe for human consumption. To increase the shelf life of milk, either ultrahigh temperature (UHT) or pasteurization techniques are employed that destroy the microorganisms. In this study, the synchronous front face fluorescence spectroscopy was employed for comparative study of raw, UHT treated, pasteurized and conventionally boiled milk at 93°C (domestic boiling). Principal Component analysis clearly showed distinct clustering of UHT milk due to formation of Maillard reaction products. Fluorescence emission peak at 410nm showed irreversible change in peak intensity attributed to conformational changes in protein due to UHT treatment while pasteurization and domestic boiling showed reversible changes when milk was cooled down to 10°C. Furthermore, fluorescence emission peaks at 410nm previously assigned to vitamin A has also been discussed.

Synchrotron infrared spectral regions as signatures for foodborne bacterial typing

Fourier-transform infrared (FTIR) spectroscopy has emerged as a viable alternative to biochemical and molecular biology techniques for bacterial typing with advantages such as short analysis time, low cost and laboratorial simplicity. In this study, synchrotron radiation-based FTIR (SR-FTIR) spectroscopy with higher spectral quality was successfully applied to type 16 foodborne pathogenic bacterial strains. Combined with principal component analysis (PCA) and hierarchical cluster analysis (HCA), we found that the specific spectral region 1300–1000 cm−1, which reflects the information of phosphate compounds and polysaccharides, can be used as the signature region to cluster the strains into groups similar with genetic taxonomic method. These findings demonstrated that FTIR spectra combined with HCA have a great potential in quickly typing bacteria depending on their biochemical signatures.

Massive Tandem Proliferation of ELIPs Supports Convergent Evolution of Desiccation Tolerance across Land Plants.

Desiccation tolerance was a critical adaptation for the colonization of land by early nonvascular plants. Resurrection plants have maintained or rewired these ancestral protective mechanisms, and desiccation-tolerant species are dispersed across the land plant phylogeny. Although common physiological, biochemical, and molecular signatures are observed across resurrection plant lineages, features underlying the recurrent evolution of desiccation tolerance are unknown. Here we used a comparative approach to identify patterns of genome evolution and gene duplication associated with desiccation tolerance. We identified a single gene family with dramatic expansion in all sequenced resurrection plant genomes and no expansion in desiccation-sensitive species. This gene family of early light-induced proteins (ELIPs) expanded in resurrection plants convergent through repeated tandem gene duplication. ELIPs are universally highly expressed during desiccation in all surveyed resurrection plants and may play a role in protecting against photooxidative damage of the photosynthetic apparatus during prolonged dehydration. Photosynthesis is particularly sensitive to dehydration, and the increased abundance of ELIPs may help facilitate the rapid recovery observed for most resurrection plants. Together, these observations support convergent evolution of desiccation tolerance in land plants through tandem gene duplication.

The Evolution of Sexual Fluids in Gymnosperms From Pollination Drops to Nectar.

A current synthesis of data from modern and fossil plants paints a new picture of sexual fluids, including nectar, as a foundational component of gymnosperm reproductive evolution. We review the morpho-anatomical adaptations, their accompanying secretions, and the functional compounds involved. We discuss two types of secretions: (1) those involved in fertilization fluids produced by gametophytes and archegonia of zooidogamous gymnosperms, i.e., Ginkgo and cycads, and (2) those involved in pollen capture mechanisms (PCMs), i.e., pollination drops. Fertilization fluids provide both liquid in which sperm swim, as well as chemotactic signals that direct sperm to the egg. Such fertilization fluids were probably found among many extinct plants such as ancient cycads and others with swimming sperm, but were subsequently lost upon the evolution of siphonogamy (direct delivery of sperm to the egg by pollen tubes), as found in modern gnetophytes, conifers, and Pinaceae. Pollination drops are discussed in terms of three major types of PCMs and the unique combinations of morphological and biochemical adaptations that define each. These include their amino acids, sugars, calcium, phosphate and proteins. The evolution of PCMs is also discussed with reference to fossil taxa. The plesiomorphic state of extant gymnosperms is a sugar-containing pollination drop functioning as a pollen capture surface, and an in ovulo pollen germination medium. Additionally, these drops are involved in ovule defense, and provide nectar for pollinators. Pollination drops in anemophilous groups have low sugar concentrations that are too low to provide insects with a reward. Instead, they appear to be optimized for defense and microgametophyte development. In insect-pollinated modern Gnetales a variety of tissues produce sexual fluids that bear the biochemical signature of nectar. Complete absence of fluid secretions is restricted to a few, poorly studied modern conifers, and is presumably derived. Aspects of pollination drop dynamics, e.g., regulation of secretion and retraction, are reviewed. Lastly, we discuss pollination drops’ control of pollen germination. Large gaps in our current knowledge include the composition of fertilization fluids, the pollination drops of Podocarpaceae, and the overall hydrodynamics of sexual fluids in general.

Biochemical signatures of acclimation by Chlamydomonas reinhardtii to different ionic stresses

Green microalgae can acclimate over short timescales to changing environmental conditions; however, it is unclear how acclimation, or phenotypic adaptation, alters the organism's metabolism and whether there are conserved responses to different stresses. Following six weeks of exposure, Chlamydomonas reinhardtii could tolerate 100 mM Na+, 100 μM Cu2+, and 35 mM PO43− and partially tolerate 25 mM NH4+, 150 mM Na+ and 150 μM Cu2+. Acclimation was coincident with increased growth rate and reduced cellular accumulation of reactive oxygen species (ROS), which was indicative of enhanced ROS scavenging. Fourier transform infrared (FT-IR) spectroscopy demonstrated distinct metabolic fingerprints of acclimated cells for each stress condition in comparison to non-acclimated cells and to non-stressed cells. Carbon allocation varied in response to stress but also following acclimation. In particular, Na+ stress increased intracellular neutral lipid content but this response was significantly reduced in acclimated cells, while carbohydrate content was enhanced in cells acclimated to excess Cu2+. Acclimation of C. reinhardtii to Na+ allowed enhanced tolerance of multiple stresses simultaneously, while the other acclimated cell lines did not display any advantage. While acclimation of C. reinhardtii to different ionic stresses elicits distinct metabolic signatures within the cells, enhanced ROS detoxification appears to be a conserved acclimation response.

Constitutive Phosphorylation of CYLD Promotes ATLL Survival By Inhibiting RIPK1-Dependent Cell Death

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T lymphocytes associated with a chronic infection by human T-cell lymphotropic virus type-1 (HTLV-1). Multistep oncogenic process induced by HTLV-1 relies on the viral transactivator protein Tax interaction with pathways important in cell survival. Prognosis of the more aggressive subtypes of ATLL is abysmal and new treatment options are urgently needed.The TNFR1 pathway is one of the best characterized pathways determining cellular fate. TNF binding to its receptor induces a survival response in a vast majority of cells. This signal can however also trigger a death response if one of its cell death checkpoints is disrupted. Since these checkpoints act by antagonizing the cell death machinery, it is presumed that they can be used by malignant cells to avoid cell death. An early checkpoint within the TNFR1 pathway is centered around RIPK1, which has a somewhat bipolar role by inducing either cell survival or cell death. These diametrically opposite endpoints are determined by the state of lysine 63 (K63) poly-ubiquitination of the RIPK1. When RIPK1 is K63-ubiquitinated, a pro-survival signal is generated, while deubiquitination leads to death signal. CYLD, an enzyme that removes K63-linked ubiquitin chains from RIPK1, is crucial regulator as it converts RIPK1 into a death-signaling molecule.CYLD was initially identified as a tumor suppressor in rare hereditary tumors such as cylindromatosis. Its role in hematologic malignancies is less clear. Our data shows that CYLD tumor suppressor activity can instead be inactivated by phosphorylation, which inhibits its catalytic activity. We found CYLD to be constitutively phosphorylated in ATLL cell line models (MT4 and C1866) as well as primary samples from patients with ATLL. This was accompanied by an increase in the phosphorylation of TBK1/IKKɛ and IKKɑ/β, upstream kinases for CYLD. Additionally, we demonstrated that Tax by itself is sufficient to induce CYLD phosphorylation by transfection of a Tax-encoding plasmid into HEK293 cells.We subsequently examined the effect of IKK inhibitors MRT67307 and TPCA on CYLD phosphorylation. Both inhibitors were potent in reducing CYLD phosphorylation individually and more potently in combination. This effect was followed by induction of cell death, mediated by both apoptosis (blocked by zVAD-FMK) and necroptosis (blocked by necrostatin-1). Next, we transfected MT4 cells with a kinase-inactive TBK1-K38A mutant. MT4 cells stably transfected with TBK1-K38A exhibited reduced CYLD phosphorylation and a significantly slower growth rate compared to cells transfected with a control gene.Knockdown of CYLD in MT4 cells reduced the level of cell death induced by IKK inhibitors. Furthermore, both apoptosis and necroptosis were diminished in CYLD-deficient cells treated with the IKK inhibitors. Association of RIPK1 with the FADD-containing death-inducing signaling complex (DISC), which is a biochemical signature of the RIPK1 switch to become a death-inducing molecule, was enhanced by IKK inhibitors and was dependent on CYLD. Finally, we show that IKK inhibitors reduced RIPK1 ubiquitination in control knockdown MT4 cells. More strikingly, RIPK1 ubiquitination was basally elevated in CYLD-deficient MT4 cells where it remained elevated upon IKK blockade. We conclude that in ATLL cells, TAX induces phosphorylation of CYLD to keep it inactive in order to prevent RIPK1 from inducing cell death. This process of tumor suppressor inactivation could be targeted as a therapeutic option in ATLL. DisclosuresNo relevant conflicts of interest to declare.

Trophic relationships of deep-sea benthic invertebrates on a continental margin in the NW Atlantic inferred by stable isotope, elemental, and fatty acid composition

As deep-sea benthic ecosystems of continental margins provide numerous functions and services to humans, a better understanding of these key habitats and their communities is needed to help predict climate-driven shifts and support conservation efforts. Here stable isotope (δ13C and δ15N), elemental (%C, %N, and molar C:N), and fatty acid (FA) composition of 50 different deep-sea species, belonging to 7 major taxa, were analyzed in order to characterize their diet and trophic position, and to study the fate of energy and essential nutrients in the food web. In addition, relationships between depth and biochemical signatures (δ13C, δ15N, %C, %N, C:Nmol, and FAs) were also investigated. In this regard, %C, oleic acid (18:1ω9), and arachidonic acid (ARA, 20:4ω6) increased with depth. While the increase of %C was likely due to the preferential assimilation of the more nutritious N along the gradient, that of 18:1ω9 was presumed to reflect the need for longer-term energy reserves in deeper organisms, and that of ARA to indicate a higher reliance on the benthic trophic pathway at greater depth. Analyses also revealed that the focal deep-sea invertebrates occupied three trophic levels, whereas the weak correlation between δ13C and δ15N indicated that two or more trophic pathways were represented. Several feeding modes were also recognized within the assemblage. The lowest trophic positions were occupied by sponges most likely feeding on bacteria. Intermediate positions were mainly occupied by suspension feeders (e.g. sea anemones, corals), detritivores (e.g. the sea urchin Phormosoma placenta), and predators on small infaunal animals (e.g. the sea star Leptychaster arcticus). Conversely, predator/scavengers (e.g. various sea stars, gastropods, polychaete worms) occupied the highest trophic positions, together with sponges that were determined to be either carnivorous (e.g. Iophon piceum), or to feed on 15N- and 13C-enriched organic matter. Energetic compounds (i.e. 20:1ω11(13), 20:1ω9, and 22:1ω7) and essential nutrients (i.e. ARA) increased in proportion across the trophic levels of this food web, emphasizing the importance of certain dietary FAs for optimal organism health, and the key role of benthic communities in carbon cycling.

Raman spectroscopic detection of high-grade cervical cytology: Using morphologically normal appearing cells

This study aims to detect high grade squamous intraepithelial cells (HSIL) by investigating HSIL associated biochemical changes in morphologically normal appearing intermediate and superficial cells using Raman spectroscopy. Raman spectra (n = 755) were measured from intermediate and superficial cells from negative cytology ThinPrep specimens (n = 18) and from morphologically normal appearing intermediate and superficial cells from HSIL cytology ThinPrep specimens (n = 17). The Raman data was subjected to multivariate algorithms including the standard principal component analysis (PCA)-linear discriminant analysis (LDA) and partial least squares discriminant analysis (PLS-DA) together with random subsets cross-validation for discriminating negative cytology from HSIL. The PCA-LDA method yielded sensitivities of 74.9%, 72.8%, and 75.6% and specificities of 89.9%, 81.9%, and 84.5%, for HSIL diagnosis based on the dataset obtained from intermediate, superficial and mixed intermediate/superficial cells, respectively. The PLS-DA method provided improved sensitivities of 95.5%, 95.2% and 96.1% and specificities of 92.7%, 94.7% and 93.5% compared to the PCA-LDA method. The results demonstrate that the biochemical signatures of morphologically normal appearing cells can be used to discriminate between negative and HSIL cytology. In addition, it was found that mixed intermediate and superficial cells could be used for HSIL diagnosis as the biochemical differences between negative and HSIL cytology were greater than the biochemical differences between intermediate and superficial cell types.

Non-vesicular Lipid Transport Machinery in Entamoeba histolytica.

Eukaryotic cells are organized into separate membrane-bound compartments that have specialized biochemical signature and function. Maintenance and regulation of distinct identity of each compartment is governed by the uneven distribution and intra-cellular movement of two essential biomolecules, lipids, and proteins. Non-vesicular lipid transport mediated by lipid transfer proteins plays a pivotal role in intra-cellular lipid trafficking and homeostasis whereas vesicular transport plays a central role in protein trafficking. Comparative study of lipid transport machinery in protist helps to better understand the pathogenesis and parasitism, and provides insight into eukaryotic evolution. Amebiasis, which is caused by Entamoeba histolytica, is one of the major enteric infections in humans, resulting in 40–100 thousand deaths annually. This protist has undergone remarkable alterations in the content and function of its sub-cellular compartments as well represented by its unique diversification of mitochondrion-related organelle, mitosome. We conducted domain-based search on AmoebaDB coupled with bioinformatics analyses and identified 22 potential lipid transfer protein homologs in E. histolytica, which are grouped into several sub-classes. Such in silico analyses have demonstrated the existence of well-organized lipid transport machinery in this parasite. We summarized and discussed the conservation and unique features of the whole repertoire of lipid transport proteins in E. histolytica.

ATR- FTIR spectroscopy application as a tool to derive biochemical signature differences in blood and human semen due to pollution. (Preliminary data). EcoFoodFertility Project

The latest Difficult Airway Society (DAS) guidelines recommend that all anaesthesiologists should to be trained in the performing of a surgical cricothyrotomy (CtQ). The aim of this study was to analyse the learning results of a CtQ workshop by assessing the success rate and time to perform CtQ on a porcine tracheal model.A workshop was designed in which each student completed a questionnaire with demographic data and theoretical knowledge about surgical approaches of airway. During the following hour, a review was presented theoretical aspects of CtQ. The model was shown and a CtQ was performed using a classical technique. Afterwards, in groups of 3–4 students with an instructor, each one of the students performed 6 CtQ. A record was made on whether the ventilation was correct, the time to perform CtQ, and the ease of performing the CtQ by the students and instructors. Finally, students completed a questionnaire on the theoretical aspects. Students and instructors performed a workshop debriefing. A statistical analysis was performed, considering a p-value < 0.05 as statistically significant.A total of 8 workshop sessions were held with a total of 91 students. At first attempt, 86% of students performed a CtQ with successful ventilation, and 92% at the sixth attempt (p < 0.0001). Time taken was 163 [107–211] s at first attempt, and 70 [55–85] s at the sixth (p < 0.0001). At the end of workshop, students had improved their theoretical knowledge (p < 0.0001) and perception of the ease of the technique.Workshop performance improved theoretical knowledge and competence in surgical cricothyrotomy.Las últimas guías de la Difficult Airway Society recomiendan que todos los anestesiólogos deberían estar entrenados para la realización de una cricotiroidotomía quirúrgica (CtQ). El objetivo de este estudio es analizar los resultados de aprendizaje de un taller de CtQ mediante la evaluación de la tasa de éxito y el tiempo necesario para realizarla en un modelo de tráquea porcina.Diseñamos un taller en el que cada alumno respondía un cuestionario con datos demográficos y conocimientos teóricos sobre el abordaje quirúrgico de la vía aérea. Durante la hora siguiente se revisaron aspectos teóricos. Se mostró el modelo y realizamos una CtQ siguiendo la técnica clásica. Después, en grupos de 3-4 alumnos con un instructor, los alumnos realizaron 6 CtQ cada uno. Registramos si la ventilación era correcta, el tiempo necesario para realizarla y la facilidad de realización evaluada por alumno e instructor. Finalmente, los alumnos respondieron un cuestionario de aspectos teóricos. Realizamos un análisis estadístico, considerando estadísticamente significativo un valor de p < 0,05.Llevamos a cabo 8 ediciones del taller, con 91 alumnos. Consiguieron hacer la CtQ y ventilar correctamente el 86% en el primer intento y el 92% en el sexto (p < 0,0001). El tiempo necesario para hacer una CtQ pasó de 163 [107-211] a 70 [55-85] segundos (p < 0,0001). Al final del taller los alumnos habían mejorado sus conocimientos teóricos (p < 0,0001) y la percepción de facilidad de la técnica.El taller realizado mejora los conocimientos teóricos y la competencia en la realización de una CtQ.

Abstract B047: Biochemical parameters of prostate cancer patients in Nigeria

Abstract The screening of biochemical parameters of cancer patients and their development into reliable and specific diagnostic and prognostic biomarkers has been reported in several studies. The biochemical signature of prostate cancer patients in Nigeria may vary from others and can serve as important leads in discovery of new biomarkers for the disease. This will ultimately provide more information on the specific causes and prognosis of the disease as well as improve its diagnosis and management. This study examined some biochemical parameters including alanine transaminase (ALT), alkaline phosphatase (ALP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TRIG), reduced glutathione (GSH), lipid peroxidation and peroxidase (POD) in the plasma of prostate cancer patients and controls. The data obtained indicate that there were no significant differences in the ALT, LDL, HDL, and POD while ALP and TRIG were significantly increased. Also, there was a significant reduction in GSH. This indicates the possible implication of ALP, TRIG, and GSH in prostate cancer disease in Nigeria and their potential to be further developed into diagnostic and prognostic biomarkers. Citation Format: Emeka Iweala, Solomon Rotimi, Faith Kanu, Chidiebere Ogo. Biochemical parameters of prostate cancer patients in Nigeria [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B047.

Solution fibre spinning technique for the fabrication of tuneable decellularised matrix-laden fibres and fibrous micromembranes

Recreating tissue-specific microenvironments of the extracellular matrix (ECM) in vitro is of broad interest for the fields of tissue engineering and organ-on-a-chip. Here, we present biofunctional ECM protein fibres and suspended membranes, with tuneable biochemical, mechanical and topographical properties. This soft and entirely biologic membrane scaffold, formed by micro-nano-fibres using low voltage electrospinning, displays three unique characteristics for potential cell culture applications: high-content of key ECM proteins, single-layered mesh membrane, and flexibility for in situ integration into a range of device setups. Extracellular matrix (ECM) powder derived from urinary bladder, was used to fabricate the ECM-laden fibres and membranes. The highest ECM concentration in the dry protein fibre was 50 wt%, with the rest consisting of gelatin. Key ECM proteins, including collagen IV, laminin, and fibronectin, were shown to be preserved post the biofabrication process. The single fibre tensile Young’s modulus can be tuned for over two orders of magnitude between ∼600 kPa and 50 MPa depending on the ECM content. Combining the fibre mesh printing with 3D printed or microfabricated structures, culture devices were constructed for endothelial layer formation, and a trans-membrane co-culture formed by glomerular cell types of podocytes and glomerular endothelial cells, demonstrating feasibility of the membrane culture. Our cell culture observation points to the importance of membrane mechanical property and re-modelling ability as a factor for soft membrane-based cell cultures. The ECM-laden fibres and membranes presented here would see potential applications in in vitro assays, and tailoring structure and biological functions of tissue engineering scaffolds. Statement of SignificanceRecreating tissue-specific microenvironments of the extracellular matrix (ECM) is of broad interest for the fields of tissue engineering and organ-on-a-chip. Both the biochemical and biophysical signatures of the engineered ECM interplay to affect cell response. Currently, there are limited biomaterials processing methods which allow to design ECM membrane properties flexibly and rapidly. Solvents and additives used in many existing processes also induced unwanted ECM protein degradation and toxic residues. This paper presents a solution fibre spinning technique, where careful selection of the solution combination led to well-preserved ECM proteins with tuneable composition. This technique also provides a highly versatile approach to fabricate ECM fibres and membranes, leading to designable fibre Young’s modulus for over two orders of magnitude.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies.Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

Biochemical diversity evaluation in chickpea accessions employing mini-core collection.

The seeds of chickpea provide an exceptional source of dietary proteins and is one of the important legumes in both developed and developing countries over the world. The available germplasm of cultivated chickpea is deficient in desired biochemical signatures. To identify new sources of variations for breeding, reduced subsets of germplasm such as mini-core collection can be explored as an effective resource. In the present investigation, mini-core collections consisting of 215 accessions of chickpea were extensively evaluated for tapping biochemical diversity. Analysis included ten biochemical parameters comprising total protein, total free amino acids, phytic acid, tannin, total phenolics, total flavonoids, lectin, DPPH radical scavenging activity, in vitro digestibility of protein and starch. The spectrum of diversity was documented for total protein (4.60-33.90%), total free amino acids (0.092-9.33mg/g), phytic acid (0.009-4.06mg/g), tannin (0.232-189.63mg/g), total phenolics (0.15-0.81mg/g), total flavonoids (0.04-1.57mg/g), lectin (0.07-330.32 HU/mg), DPPH radical scavenging activity (26.74-49.11%), in vitro protein digestibility (59.45-76.22%) and in vitro starch digestibility (45.63-298.39mg of maltose/g). The principal component analysis revealed association of chickpea higher protein content to the lower level of total phenolics and flavonoid contents. The dendrogram obtained by unweighted pair group method using arithmetic average cluster analysis grouped the chickpea accessions into two major clusters. This is the first comprehensive report on biochemical diversity analysed in the mini-core chickpea accessions. The ultimate purpose of conducting such studies was to deliver information on nutritional characteristics for effective breeding programmes. Depending on the objectives of the breeding aforesaid accessions could be employed as a parent.

Biosignature hide and seek.

A new model predicts locations on the surface of radiation-blasted Europa, the ocean moon of Jupiter, where biochemical signatures of life emergent from the subsurface ocean might survive long enough for detection on the moon's changing surface.