Faktor Sosial Ekonomi yang Berhubungan dengan Pengalihan Kebun Karet ke Kebun Kelapa Sawit di Kecamatan Pamenang Kabupaten Merangin

Penelitian ini bertujuan 1). Untuk mengetahui faktor sosial ekonomi apa saja yang ada pada petani kebun karet yang beralih ke kebun kelapa sawit di Kecamatan Pamenang Kabupaten Merangin, 2). Untuk mengetahui hubungan faktor sosial ekonomi dengan petani kebun karet yang beralih ke kebun kelapa sawit. Penelitian ini dilaksanakan pada tanggal 20 Mei – 20 Juni 2013. Penelitian ini dilakukan didua Desa, Desa Pelakar Jaya dan Tanah Abang. Pengumpulan data penelitian ini terdiri dari data primer dan data skunder. Untuk memperoleh data yang lebih mendalam dilakukan wawancara (In-depht interview) dan observasi. Hasil penelitian menunjukkan bahwa faktor sosial ekonmi di daerah penelitian tergolong tinggi, namun dari faktor sosial ekonomi itu hanya pengetahuan berusahatani dan motif ekonomi yang mempunyai hubungan yang sangat nyata terhadap pengalihan kebun karet ke kebun kelapa sawit, sedangkan pengalaman berusahatani, jumlah tanggungan keluarga dan harapan pendapatan USAhatani tidak terdapat hubungan yang nyata terhadap pengalihan kebun karet ke kebun kelapa sawit. Pengalihan lahan perlu peran dan bimbingan penyuluh lapangan dan pemerintah agar lebih sesuai dengan yang diinginkan, petani juga perlu mempertimbangkan terlebih dahulu apakah USAhatani ini menguntungkan atau justru sebaliknya

The cellular toxicology of mitragynine, the dominant alkaloid of the narcotic-like herb, Mitragyna speciosa Korth

Mitragyna speciosa Korth (Kratom), a herb of the Rubiaceae family is indigenous to southeast Asia. The plant and its dominant alkaloid mitragynine (MIT) are narcotic/analgesic and illicit consumption is widespread in Asia; the toxicological consequences of consumption are poorly documented. We determined cytotoxicity of MIT on human cell lines and report dose and time-dependent stimulation and inhibition of proliferation. Since MIT has powerful opiate-like activity, we focussed on human neuronal SH-SY5Y cell line and found the colony forming ability of cells treated with MIT showed a dose-dependent trend for reduced survival. Studies using metabolically competent MCL-5 cells and chemical inhibitors indicated that CYP 2E1 and 2A6 were involved in the cytotoxicity. Cytotoxicity was preceded by cell cycle arrest mainly at G1 and S phase. To assess whether arrest was due to DNA damage or mutation, we examined genotoxic potential using the L5178 TK +/− mouse lymphoma assay and found that MIT was not genotoxic at the TK locus, even at doses that were highly cytotoxic. To investigate mechanisms of MIT cytotoxicity, we used flow cytometry and annexin V with 7-amino-actinomycin D staining and show apoptosis and necrotic activity. Apoptosis was further supported as MIT rapidly induced the activity of executioner caspases 3/7. However, cytotoxicity of MIT was partially reduced by inclusion of the opioid receptor antagonist naloxone, a μ and δ opioid receptor antagonist, suggesting that cytotoxicity depends in part on opioid signalling, consistent with the known toxicity of other opiates. Based on consumption of 20 leaves per day of Mitragyna speciosa, we estimated daily human exposure to MIT to be about 17 mg MIT for regular consumers, potentially giving plasma concentrations in of 10−9 to 10 −7 M. Importantly, fatalities after kratom consumption have been reported to occur in individuals with blood mitragynine concentrations of between 0.45–1.0 μM, substantially lower than the threshold of toxicity predicted from this in vitro report. Clearly the implications of these findings to humans consuming Mitragyna speciosa leaves will require further study, but individuals taking large quantities of these opiate-like materials may be at risk, especially those who have a high CYP2E1 activity, such as heavy alcohol users

Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis

T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis. We demonstrated \u201cAutophagic memory\u201d as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD4+ T cells subsets from autoimmune arthritis patients. Using RNA-sequencing, transcription factor gene regulatory network and methylation analyses we identified MYC as a key regulator of autophagic memory. We validated MYC levels using qPCR and further demonstrated that inhibiting MYC increased autophagy. The present study proposes the novel concept of autophagic memory and suggests that autophagic memory confers metabolic advantage to pathogenic T cells from arthritis and supports its resilience and long term survival. Particularly, suppression of MYC imparted the heightened autophagy levels in pathogenic T cells. These studies have a direct translational valency as they identify autophagy and its metabolic controllers as a novel therapeutic target

Potential use of friction welding for fabricating semi-biodegradable bone screws

Certain surgical interventions, such as fractures, may require implants that have a combination of external and internal parts made of inert and biodegradable biomaterials, respectively. This implant design can be fabricated using specific fabrication methods such as friction welding that are able to efficiently combine two biomaterials. This study reports the utilization of the direct friction welding technique for the fabrication of semi-biodegradable bone screws using two parent metals of low carbon steel and austenitic stainless steel 202. The welding parameters were optimized to obtain welded joints for bone screw fabrication. The mechanical properties of metals that have been welded were identified through tensile and three-point bending analyses. The corrosion test was then conducted on the welded metals through the measurement of corrosion rate, changes in pH value, morphology visualization, and element release, while the cytotoxicity effect was evaluated through a cell viability test. Screw implant materials with a diameter of up to 12.7 mm were successfully fabricated using a continuous friction drive welding machine at 4000 rpm and 24.5 MPa hydraulic pressure. The results of mechanical testing show that the tensile strength of weld joints decreased by 3.6% from low carbon steel and 20.4% from stainless steel. Fractures were observed at the welding interface after being subjected to flexural testing. The pH value of the Saline solution decreased from 7.13±0.06 to 6.73±0.06 after the welded metals were immersed for up to 8 weeks. Evaluation of the surface morphology in all welding zones at week eight samples obtained that almost all types of corrosion that occurred were uniform corrosion, except in the PZ zone where galvanic corrosion was formed. The concentrations of Cr and Ni ions (ppm level) were very low, namely 0.058 ppm for Cr and 0.199 ppm for Ni. The viability of human fibroblast cells was maintained at higher than 75% viability after the cell incubation at 1, 3, and 5 days with different parts of welded joints

TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis

Objectives The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. Methods We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. Results We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. Conclusions Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity

Cytotoxicity of extract of Malaysian Mitragyna speciosa Korth and its dominant alkaloid mitragynine

Mitragyna speciosa Korth (Kratom), a herb of the Rubiaceae family is indigenous in southeast Asia mainly in Malaysia and Thailand. It is used as an opium substitute and has been increasingly abused by drug addicts in Malaysia. Recently, the potent analgesic effect of plant extract and its dominant alkaloid mitragynine (MIT) were confirmed in vivo and in vitro. MIT acted primarily on μ- and δ-opioid receptors, suggesting that MIT or similar compounds could be promising alternatives for future pain management treatments. However the potential cytotoxicity of this plant is unknown. Therefore, the cytotoxicity of methanol-chloroform extract (MSE) and MIT on human cell lines (HepG2, HEK 293, MCL-5, cHol and SH-SY5Y cells) has been examined. MSE appeared to exhibit dose-dependant inhibition of cell proliferation in all cell lines examined, at concentration > 100 μg/ml with substantial cell death at 1000 μg/ml. SH-SY5Y was the most sensitive cell line examined. MIT showed a similar response. Clonogenicity assay was performed to assess the longer-term effects of MSE and MIT. The colony forming ability of HEK 293 and SH-SY5Y cells was inhibited in a dose-dependant manner. Involvement of metabolism in cytotoxicity was further assessed by clonogenicity assay using rat liver S9 (induced by Arochlor 1254); toxicity increased 10-fold in both cell lines. To determine if cytotoxicity was accompanied by DNA damage, the Mouse lymphoma tk gene mutation assay was used. The results were negative for both MSE and MIT. Studies on the involvement of metabolism in cytotoxicity of MSE and MIT were performed using MCL-5 and it appeared that CYP 2E1 is involved in activation of cytotoxicity. Studies with opioid antagonists were performed using SH-SY5Y cells treated with MSE and MIT. Naloxone (μ and δ receptor antagonists), naltrindole (δ receptor antagonist) and cyprodime hydrobromide (μ receptor antagonist) confirmed that MSE cytotoxicity was associated with μ and δ receptor while MIT mainly acted on μ receptor. Studies on mechanism of MSE and MIT cytotoxicity showed that cell death observed at high dose was preceded by cell cycle arrest, however MSE cell arrest was independent of p53 and p21 while MIT showed opposite result. Studies have been undertaken to examine the nature of this cell death. Morphological examinations showed that cell death induced by MSE was cell type dependant, in which SH-SY5Y cells appeared to die via apoptosis-like cell death while HEK 293 and MCL-5 cells predominantly via necrosis. Biochemical assessments confirmed that MSE induced cell death independent of p53 or caspases pathway while MIT cell death appeared to be associated with p53 and caspases pathway. The involvement of reactive oxygen species (ROS) generation in MSE and MIT mediating cell death was performed using SH-SY5Y cells. The results appeared negative for both MSE and MIT treated cells. Collectively, the findings of these studies suggest that MSE and its dominant alkaloid MIT produced cytotoxicity effects at high dose. Thus, the consumption of Mitragyna speciosa Korth leaves may pose harmful effects to users if taken at high dose and the evidence for involvement of CYP 2E1 in increasing the MSE cytotoxicity suggests that caution may be required if the leaves are to be taken with CYP 2E1 inducers.EThOS - Electronic Theses Online ServiceMinistry of Higher Education Malaysia, International Islamic University MalaysiaGBUnited Kingdo

Endophytic Bacillus species isolated from mangrove plants, and their antagonestic effects against some pathogenic bacterial strains

This study aimed to isolate bacterial endophytes with potential antimicrobial effects from five mangrove plants and to investigate the stability of the most active metabolites under different PH and temperature.Bacterial colonies were isolated from the collected plant parts. Bacterial strains with potential antagonistic interactions were subjected to idnetification by VITEK 2 system or  sequencing of the 16S rRNA. MIC values of the crude substances were determined  against Bacillus cereus, Streptococcus uberis, Escherichia coli, Klebsiella pneumonia and Salmonella typhiumurium  using the the serial dilution technique.The stability of  the most active crude extracts was examined under  different, PH (2-7)  and temperature (60 -90 °C).Twenty one of the isolated strains showed potential antagonistic effects. Of these, 16 identified as Bacillus species. Best antimicrobial effects were recorded for Bacillus tequilensis against, B. cereus and S. typhimurium  (MIC value=65 µl/m1),  S.uberis  (MIC value 78 µl/ml),  E.coli and K.pneumonia  (MIC value=125 µl/m1). Both Bacillus subtilis and Brevibacillus brevis inhibited growth of S. typhimurium with MIC value of 78 and 60 µl/m1 respectively.  The metabolites of  B.subtilis and B.tequilensis appeared to be stable under PH2-9. Product of B.subtilis showed stability under high temperature (90 °C) against S. typhimurium.The isolated endophytes possessed wide range of antimicrobial activities against the selected pathogens. Bacillus tequilensis and B.subtilis produced the most active metabolites. This is the first report on isolation of endophytic strains of B.tequilensis. The crude extracts obtained from B.tequilensis and B.subtilis in this study could be further developed as food preservatives

N-acyl homoserine lactone production by bacteria within the sponge Suberites domuncula (Olivi, 1792) (Porifera, Demospongiae)

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