Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer’s mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid patholog

Upregulation of Trem2 expression occurs exclusively on microglial contact with plaques

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia touching plaques, neighboring plaques, and far from plaques in 18-month-old APPNLF/NLF knock-in mice with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H. We report that, in AppNLF/NLF mice, expression of 35/55 PIGs, is exclusively upregulated in microglia that are touching plaques. In 7 PIGs including Trem2 this upregulation is prevented by the Trem2R47H/R47H mutation. Unlike in young mice, knockin of the Trem2R47H/R47H mutation does not significantly decrease the Trem2 expression but decreases protein levels by 20% in the absence of plaques. On plaques, despite the mutation preventing increased gene expression, TREM2 protein levels increased by 1.6-fold (compared to 3-fold with Trem2WT/WT) and microglial density increased 20-fold compared to 30-fold. Hence microglia must touch plaques before Trem2 gene expression is increased but small changes in protein expression can increase microglia density without a change in gene expression

Production of Biodiesel from Waste Vegetable Oil via KM Micromixer

The production of biodiesel from waste vegetable oils through its pretreatment followed by transesterification process in presence of methanol was investigated using a KM micromixer reactor. The parameters affecting biodiesel production process such as alcohol to oil molar ratio, catalyst concentration, the presence of tetrahydrofuran (THF) as a cosolvent, and the volumetric flow rates of inlet fluids were optimized. The properties of the produced biodiesel were compared with its parent waste oil through different characterization techniques. The presence of methyl ester groups at the produced biodiesel was confirmed using both the gas chromatography-mass spectrometry (GC-MS) and the infrared spectroscopy (FT-IR). Moreover, the thermal analysis of the produced biodiesel and the comparable waste oil indicated that the product after the transesterification process began to vaporize at 120°C which makes it lighter than its parent oil which started to vaporize at around 300°C. The maximum biodiesel production yield of 97% was recorded using 12 : 1 methanol to oil molar ratio in presence of both 1% NaOH and THF/methanol volume ratio 0.3 at 60 mL/h flow rate

Predictive Factors of Positive Circumferential and Longitudinal Margins in Early T3 Colorectal Cancer Resection

Background. Malignant involvement of circumferential resection margin (CRM) and longitudinal resection margin (LRM) after surgical resection of colorectal cancer (CRC) are associated with higher rates of recurrence and development of distant metastasis. This can influence the overall patient’s prognosis. The aim of the current study was to identify pathological factors as predictors for the involvement of resection margins in early T3 CRC. Patients and Methods. Fifty patients radiologically diagnosed to have cT3a/b (CRC) were included in the study. After resection, the pathological examination was performed to identify patients with positive CRM and/or LRM. Relations between the different pathological parameters and the CMR and LRM involvements were assessed. Results. Positive CRM was present in 17 cases (34%), while positive LRM was found in 6 cases (12%). The involvement of both margins was significantly associated with rectal tumors and tumors with infiltrative gross appearance, grade III, deeper invasion, and positive lymph node metastases. Also, there was a significant association between both margins’ positivity and other pathological parameters as signet ring carcinoma, tumor budding, perineural and vascular invasion, high microvessel density (MVD), and sinusoidal vascular pattern, while the presence of necrosis and infiltrative advancing tumor front was significantly associated with CRM involvement only. The depth of tumor invasion and signet ring carcinoma were identified as independent predictor factors for positive CRM and LRM, respectively. Conclusion. Preoperative identification of these pathological parameters can be a guide to tailor the management plan accordingly

Physiological and biochemical responses of thyme plants to some antioxidants

Orabi SA, Talaat IM, Balbaa LK. 2014. Physiological and biochemical responses of thyme plants to some antioxidants. Nusantara Bioscience 6: 118-125. Two pot experiments were conducted to investigate the effect of tryptophan, nicotinamide and α-tocopherol (each at 50 and 100 mg/L) on plant growth, essential oil yield and its main constituents. All treatments significantly promoted plant height, and increased fresh and dry mass (g/plant) of thyme (Thymus vulgaris L.). The treatment with 100 mg/L nicotinamide showed increasing in total potassium mainly in the first cut. Total soluble sugars, oil percentage and oil yield and protein recorded increments with tryptophan treatments. Treatment of Thymus plants with 100 mg/L nicotinamide observed the highest percentage of thymol (67.61%). Oxygenated compounds recorded the highest value with 50 mg/L α-tocopherol treatment, while the maximum non-oxygenated ones resulted from the application of 100 mg/L nicotinamide. All treatments under study significantly affected the activity of oxidoreductase enzymes (POX and PPO). Nicotinamide at the concentration of 100 mg/L recorded the highest increments in APX and GR and the lowest values in oxidoreductase enzyme activities added to the lowest values of lipid peroxidation to enhance the best protection of thyme plants

Comparative study of the efficacy of pulsed electromagnetic field and low level laser therapy on mitogen-activated protein kinases

Mitogen-Activated Protein Kinases (MAPKs) consist of three major signaling members: extracellular signal-regulated kinase (ERK), p38 and C-JUN N-terminal kinase (JNK). We investigated physiological effects of Pulsed Electromagnetic Field Therapy (PEMFT) and Low Level Laser Therapy (LLLT) on human body, adopting the expression level of mitogen-activated protein kinases as an indicator via assessment of the activation levels of three major families of MAPKS, ERK, p38 and JNK in the peripheral lymphocytes of patients before and after the therapies. Assessment for the expression levels of MAPKs families' were done, in the peripheral lymphocytes of patients recently have appendectomy, using flow cytometric analysis of multiple signaling pathways, pre and post LLLT and PEMFT application (twice daily for 6 successive days) on the appendectomy wound. There were non-significant differences in the expression levels of MAPKs families' pre- therapies application. But there were significant increase in the ERK expression levels post application of LLLT compared to its pre application (p<0.01). Also, there was significant increase in the ERK, p38 and C-Jun N terminal expression level values post application of PEMFT compared to its pre application expression levels (p<0.01 for each). The present study demonstrates that PEMFT has a powerful healing effect more than LLLT as it increase the activation of ERK, P38 and C-Jun-N Terminal while LLLT only increase the activation of ERK. LLLT has more potent pain decreasing effect than PEMFT as it does not activate P38 pathway like PEMFT