Discrimination and Characterization of Two Mediterranean Species from the Laurencia Complex (Rhodomelacea) Using an NMR‐Based Metabolomic Approach

Generic and specific determination among the Laurencia complex is a challenging task. DNA barcoding combined with phenotypic investigations are mandatory for species differentiation. In this study, two morphologically different members of the Laurencia complex were investigated using untargeted ¹H‐NMR‐based metabolomics. Twenty‐one population samples were collected in order to evaluate both temporal and geographical homogeneity. Data obtained from ¹H‐NMR analysis followed by statistical analysis allowed a clear separation of all the samples into two groups. DNA mitochondrial tests confirmed this pattern and identified the two species as Laurenciella sp. and Laurencia obtusa. In addition, metabolites responsible of this discrimination were investigated directly in crude extracts by ¹³C‐NMR using an in‐house computer‐assisted method. The combination of both untargeted (¹H) and targeted (¹³C) NMR‐based metabolomic approaches proves to be a powerful and complementary approach to discriminate species from the Laurencia complex.     

Is COPD a Progressive Disease? A Long Term Bode Cohort Observation

BackgroundThe Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades.ObjectiveExplore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up.MethodsPatients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a “survival selection” bias. The proportion of patients that had a change (improvement or worsening) in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade.ResultsA total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and 11% of non survivors had an improvement of at least one GOLD grade. Seventy one percent of survivors and non-survivors remained in the same GOLD grade. Those that improved had a greater degree of airway obstruction at baseline.ConclusionsIn this selected population of COPD patients, a high proportion of patients remained in the same spirometric GOLD grade or improved in a long-term follow-up. These findings suggest that once diagnosed, COPD is usually a non-progressive disease.     

Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.     

The Essential Oil of Bupleurum fruticosum L. from Corsica: A Comprehensive Study

A detailed analysis of Bupleurum fruticosum oil was carried out by combination of GC (RI), GC/MS, and ¹³C‐NMR analyses. After fractionation by column chromatography, 34 components accounting for 97.8% of the oils were identified. The main component was β‐phellandrene (67.7%), followed by sabinene (9.3%), and limonene (5.6%). The evolution of the chemical composition according to the stages of development of the plant was investigated as well as the composition of leaf, twig, and flower oils. A solvent‐free microwave extraction (SFME) of aerial parts was carried out and the composition of the extract compared with that of the essential oil. Finally, 57 oil samples isolated from aerial parts of individual plants, collected all around Corsica, were analyzed, and the data were submitted to statistical analysis. Although the contents of the main components varied, only one group emerged, accompanied with some atypical compositions.     

The kinase activity of IL-1 receptor-associated kinase 4 is required for interleukin-1 receptor/toll-like receptor-induced TAK1-dependent NFkappaB activation

Two parallel interleukin-1 (IL-1)-mediated signaling pathways have been uncovered for IL-1R-TLR-mediated NFkappaB activation: TAK1-dependent and MEKK3-dependent pathways, respectively. The TAK1-dependent pathway leads to IKKalpha/beta phosphorylation and IKKbeta activation, resulting in classic NFkappaB activation through IkappaBalpha phosphorylation and degradation. The TAK1-independent MEKK3-dependent pathway involves IKKgamma phosphorylation and IKKalpha activation, resulting in NFkappaB activation through dissociation of phosphorylated IkappaBalpha from NFkappaB without IkappaBalpha degradation. IL-1 receptor-associated kinase 4 (IRAK4) belongs to the IRAK family of proteins and plays a critical role in IL-1R/TLR-mediated signaling. IRAK4 kinase-inactive mutant failed to mediate the IL-1R-TLR-induced TAK1-dependent NFkappaB activation pathway, but mediated IL-1-induced TAK1-independent NFkappaB activation and retained the ability to activate substantial gene expression, indicating a structural role of IRAK4 in mediating this alternative NFkappaB activation pathway. Deletion analysis of IRAK4 indicates the essential structural role of the IRAK4 death domain in receptor proximal signaling for mediating IL-1R-TLR-induced NFkappaB activation.     

Auditing sex- and gender-based medicine (SGBM) content in medical school curriculum: a student scholar model

Background

Sex- and gender-based medicine (SGBM) aims to (1) delineate and investigate sex- and gender-based differences in health, disease, and response to treatment and (2) apply that knowledge to clinical care to improve the health of both women and men. However, the integration of SGBM into medical school curricula is often haphazard and poorly defined; schools often do not know the current status of SGBM content in their curricula, even if they are committed to addressing gaps and improving SGBM delivery. Therefore, complete auditing and accounting of SGBM content in the existing medical school curriculum is necessary to determine the baseline status and prepare for successful integration of SGBM content into that curriculum.

Methods

A review of course syllabi and lecture objectives as well as a targeted data analysis of the Curriculum Management and Information Tool (CurrMIT) were completed prior to a real-time curriculum audit. Subsequently, six “student scholars,” three first-year and three second-year medical students, were recruited and trained to audit the first 2 years of the medical school curriculum for SGBM content, thus completing an audit for both of the pre-clinical years simultaneously. A qualitative analysis and a post-audit comparative analysis were completed to assess the level of SGBM instruction at our institution.

Results

The review of syllabi and the CurrMIT data analysis did not generate a meaningful catalogue of SGBM content in the curriculum; most of the content identified specifically targeted women’s or men’s health topics and not sex- or gender-based differences. The real-time student audit of the existing curriculum at Texas Tech revealed that most of the SGBM material was focused on the physiological/anatomical sex differences or gender differences in disease prevalence, with minimal coverage of sex- or gender-based differences in diagnosis, prognosis, treatment, and outcomes.

Conclusions

The real-time student scholar audit was effective in identifying SGBM content in the existing medical school curriculum that was not possible with a retrospective review of course syllabi and lecture objectives or curriculum databases such as the CurrMIT. The audit results revealed the need for improved efforts to teach SGBM topics in our school’s pre-clinical curriculum.

     

Identification and Quantitative Determination of Resin Acids from Corsican Pinus pinaster Aiton Oleoresin Using 13C‐NMR Spectroscopy

Twenty‐three resin samples have been obtained by tapping from individual Pinus pinaster adult trees grown in Corsica and submitted to acido‐basic partition. Identification and quantitative determination of resin acids has been carried out using ¹³C‐NMR spectroscopy following a method developed by our group. The main components were dehydroabietic acid (up to 37.6 %), levopimaric acid (up to 35.5 %) and abietic acid (up to 24.7 %). A lignan, pinoresinol, has been identified in some samples. Within the 23 compositions, submitted to k‐means analysis and Principal Component Analysis, two clusters have been perfectly differentiated, whose compositions were dominated by dehydroabietic acid (Group I, M=23.5 %, SD=6.3) and levopimaric acid (Group II, M=21.2 %; SD=6.2), respectively. Both compositions have been observed in the three locations of harvest.     

Non-Hebbian Learning Implementation in Light-Controlled Resistive Memory Devices

Non-Hebbian learning is often encountered in different bio-organisms. In these processes, the strength of a synapse connecting two neurons is controlled not only by the signals exchanged between the neurons, but also by an additional factor external to the synaptic structure. Here we show the implementation of non-Hebbian learning in a single solid-state resistive memory device. The output of our device is controlled not only by the applied voltages, but also by the illumination conditions under which it operates. We demonstrate that our metal/oxide/semiconductor device learns more efficiently at higher applied voltages but also when light, an external parameter, is present during the information writing steps. Conversely, memory erasing is more efficiently at higher applied voltages and in the dark. Translating neuronal activity into simple solid-state devices could provide a deeper understanding of complex brain processes and give insight into non-binary computing possibilities.