Miracle-dz/UniFAR-FTUs huggingface dataset:
Alfalfa and Relatives: Evolution and Classification of Medicago . By E. Small. Wallingford, UK: CABI (2011), pp. 727, £110.00. ISBN 978-1-84593-750-8.

This massive publication in two volumes presents a total of 137 contributions made to a conference in Tanzania in 2007, which brought together a large, international group of scientists to discuss agricultural innovations that might lead to an African “Green Revolution”. The presentations have been organised according to four sections: 1. Constraints and opportunities for the African Green Revolution (11 papers). 2. Potential and feasibility of use of external input and improved soil and crop management to achieve the African Green Revolution (74 papers). 3. Limitations to access and adoption of innovations by poor farmers (27 papers). 4. Innovation approaches and their scaling up/out in Africa (25 papers). Almost half the number of papers deals with aspects of soil fertility and crop nutrition, often emphasizing integrated methods that combine mineral fertilisers with applications of organic materials, crop rotations and/or intercropping. Much less attention is paid to the crucial aspects of land and water management/conservation and soil health. Only a few papers deal with the socio-economic and policy issues/environments that are widely known to be most constraining to African agricultural development. Some attention is paid to market access and extension/rural communication, yet the roles, needs and views of family (smallholder) farming, supposedly the major target group, are largely missing. The overall emphasis is quite strongly on external inputs (seeds and mineral fertilisers) and external assessments by (research) experts, while the views of the major actors concerned, i.e. smallholder farmers, remain seriously underexposed. It is rather unfortunate that following an avalanche of information and a barrage of ‘silver bullet’ innovations, the book finishes abruptly with a contribution on agroforestry. Instead, one would have liked to see a coherent synthesis and critical analysis about how Africa’s huge agricultural potential is to be exploited effectively and sustainably in the future, and this above all to the benefit of local communities. A final concern is whether or not the high price of the book (€349) will make it rather inaccessible for African scientists and certainly students.
Perfusion Method for Assaying Microbial Activities in Sediments: Applicability to Studies of N2 Fixation by C2H2 Reduction

A perfusion method for assaying nitrogenase activity (acetylene reduction) in marine sediments was developed. The method was used to assay sediment cores from Spartina alterniflora (salt marsh), Zostera marina (sea grass), and Thalassia testudinum (sea grass) communities, and the results were compared with those of conventional sealed-flask assays. Rates of ethylene production increased progressively with time in the perfusion assays, reaching plateau values of 2 to 3 nmol � g of dry sediment−1 � h−1 by 10 to 20 h. Depletion of interstitial NH4+ was implicated in this stimulation of nitrogenase activity. Initial acetylene reduction rates determined by the perfusion assay of cores from the Spartina community ranged from 0.15 to 0.60 nmol of C2H4 � g of dry sediment−1 � h−1. These rates were similar to those for sediments assayed in sealed flasks without seawater when determined over linear periods of C2H4 production. Initial values obtained by using the perfusion method were 0.66 nmol of C2H4 � g of dry sediment−1 � h−1 for sediments from Zostera communities and 0.70 nmol of C2H4 � g of dry sediment−1 � h−1 for sediments from Thalassia communities. In all cases, rates determined by simultaneous slurry assays were lower than those determined by the perfusion method.
Natural products: biosynthesis, antimicrobial properties and protein targets

i Acknowledgments . iii Declaration . v Abbreviations . xv Chapter 1: General Introduction to Natural Products . 1 PART I: Biosynthesis of Antibacterial Natural Products . 1 1.1 Why study Natural Products? 1 1.1.1 Pathways and Products . 1 1.1.2 Antibacterial Resistance . 2 1.1.2.1 Burkholderia cepacia complex (Bcc) . 3 1.2 Tambjamines . 4 1.2.1 Chemical and Biological Properties . 4 1.2. 2 Biosynthesis . 6 1.3 The α-Oxoamine Synthases . 10 1.3. 1 Role in Natural Products Biosynthesis . 10 1.3. 2 Members of the AOS Family . 13 1.3. 3 PLP-Dependent Mechanism . 17 1.4 Acyl Carrier Proteins . 20 1.4. 1 Role in Natural Products Biosynthesis . 20 1.4. 2 Type I and II ACPs . 21 1.4. 3 ACP-Enzyme Complexes . 24 Part II: Antibacterial Properties of Plant Natural Products . 29 1.5 Plant Natural Products . 29 1.5. 1 Back to Our Roots . 29 1.5. 2 Flavonoids . 30
Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis

Background Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P=0.006) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P=0.002) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P=0.0005). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.
Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.
Adherence to Isoniazid Preventive Therapy among Under-Five Children in Contact with Adult Bacteriologically Confirmed Pulmonary Tuberculosis Patients: A Mixed-Method Study

Background The World Health Organization recommends that all children below the age of five who have household contact with an infectious tuberculosis case should receive isoniazid preventive treatment for at least six months after the active tuberculosis disease has been ruled out. This research aims to determine the adherence of children, eligible for isoniazid preventive treatment, to the treatment who had contact with pulmonary tuberculosis patients. Methods A mixed study design was used to prospectively assess the adherence to IPT among children under the age of 5 in contact with pulmonary TB patients through the quantitative study design and barriers of adherence in view of health care professionals and the family of children through a descriptive qualitative study. The study was conducted from July 2019 to December 2019 in Addis Ababa. Data were collected by a structured datasheet from the selected health center registration book. Data were entered into Epi Data software and analyzed by using SPSS version 20. Descriptive statistical methods were used to summarize the sociodemographic characteristics of the study participants. Result The ratio of the total number of pulmonary tuberculosis index cases recruited into the study to the number of child contacts aged less than 5 years was 1 : 1.32. The total isoniazid preventive treatment uptake in this study was 75.2%; one-fifth (21.3%) of the children who started IPT did not complete the full course of six-month isoniazid preventive treatment. Except for HIV not to be tested (P < 0.001), there was no significant association of the listed risk factors in default to complete the full six months of preventive treatment. Conclusion Enrolment of eligible children for isoniazid preventive treatment in the urban city Addis Ababa was still below the target of the World Health Organization End tuberculosis strategy by 2030. The treatment adherence rate also needs a great deal of effort to achieve the strategy. Child default after the first visit indicates a lack of understanding about the benefit and safety of preventive therapy in young children among families of TB patients, and awareness-creating efforts by health extension workers will help to improve the outcomes.
Antigen physiochemical properties allosterically effect the IgG Fc-region and Fc neonatal receptor affinity

ABSTRACT The neonatal Fc receptor (FcRn) is a key membrane protein that plays an integral role in serum immunoglobulin (IgG) recycling, which extends the half-life of antibody. In addition, FcRn is known to traffic antigen-bound immunoglobulins (Ag-IgGs), and to interact with immune complexes to facilitate the antigen cross-presentation of peptides derived from the immune complexes in antigen-presenting cells (APCs). Studies on the IgG-FcRn molecular interactions have primarily focused on the Fc region, and only recently have shown the potential impact of the antigen-binding fragment physiochemical properties on FcRn binding. However, the effect of the antigen physiochemical properties on IgG structure as it relates to Ag-IgG-FcRn binding is not well understood. Here we used an IgG-peptide antigen complex as a model system to investigate the structural effects of the antigen’s physiochemical properties on the IgG structure, and the subsequent effects of Ag-IgG-FcRn interactions. We used hydroxyl radical footprinting–mass spectrometry to investigate the structural impact on an IgG upon antigen binding, and observed that the physicochemical properties of the antigen differentially induce conformational changes in the IgG FcRn binding region. The extent of these structural changes directly correlates to the magnitude of the affinity differences between the Ag-IgG complexes and FcRn. Moreover, the antigen’s physicochemical properties differentially induce structural differences within the Ag-IgG-FcRn ternary complex. We also provide electron microscopy data that shows corroborating Fab-FcRn interactions, and confirms the hypothesis of potential 2:1 FcRn:IgG binding stoichiometry. These data demonstrate antigen-induced Fc structural rearrangements affect both the affinity toward FcRn and the trimeric antigen-IgG-FcRn complex, providing novel molecular insights in the first steps toward understanding interactions of FcRn-containing large(r)-sized immune complex.
Repurposing of Drugs for Antibacterial Activities on Selected ESKAPE Bacteria Staphylococcus aureus and Pseudomonas aeruginosa

Increasing cases of multidrug-resistant pathogens have evolved into a global health crisis. ESKAPE group of bacteria are associated with antibiotic resistance, and infections caused by these pathogens result in high mortality and morbidity. However, de novo synthesis of antibiotics is expensive and time-consuming since the development of a new drug has to go through several clinical trials. Repurposing of old drugs for the treatment of antimicrobial resistant pathogens has been explored as an alternative strategy in the field of antimicrobial drug discovery. Ten non-antimicrobial compounds were screened for antibacterial activity on two ESKAPE organisms, Staphylococcus aureus and Pseudomonas aeruginosa. The drugs used in this study were amodiaquine an antimalarial drug, probenecid used to prevent gout, ibuprofen a painkiller, 2-amino-5-chlorobenzaxazole used as a tool for assessing hepatic cytochrome P450 activity in rodents, ellargic acid an antioxidant, quercetin an antioxidant and anti-inflammatory drug, N–N diacryloylpiperazine used to crosslink polyacrylamide gel in 2D-protein electrophoresis, epicatechin an antioxidant and antiviral drug, curcumin an anticancer drug, and quinine an antimalarial drug. Antibacterial susceptibility tests were carried out for the 10 compounds. Curcumin exhibited the most potent antimicrobial activity against both bacteria, with MICs of 50 μg/ml and 100 μg/ml for P. aeruginosa and S. aureus, respectively. Ellargic acid was found to have an MIC of 100 μg/ml against S. aureus. Curcumin caused protein and nucleic acid leakage from the bacterial cell membrane in both bacterial species. When curcumin was combined with ciprofloxacin, it was found to enhance the antibacterial effects of ciprofloxacin. The combination with ciprofloxacin reduced the MIC for ciprofloxacin from 0.5 μg/ml to 0.0625 μg/ml on P. aeruginosa and 0.25 μg/ml to 0.0625 μg/ml on S. aureus. The results obtained show that curcumin has antibacterial activity against S. aureus and P. aeruginosa and may enhance the antibacterial activity of ciprofloxacin.
Beyond cardiovascular medicine: potential future uses of icosapent ethyl

Abstract The REDUCE-IT trial demonstrated that icosapent ethyl, an ethyl ester of eicosapentaenoic acid (EPA), reduced cardiovascular events in an at-risk population by a substantial degree. While the cardiovascular protective properties of this compound are now proven, several other potential uses are being actively explored in clinical studies. These areas of investigation include cancer, inflammatory bowel disease, infections, Alzheimer’s disease, dementia, and depression. The next decade promises to deepen our understanding of the beneficial effects that EPA may offer beyond cardiovascular risk reduction.
Explicating anti-amyloidogenic role of curcumin and piperine via amyloid beta (Aβ) explicit pathway: recovery and reversal paradigm effects

Previously, we reported the synergistic effects of curcumin and piperine in cell cultures as potential anti-cholinesterase and anti-amyloidogenic agents. Due to limited findings on the enrolment of these compounds on epigenetic events in AD, we aimed at elucidating the expression profiles of Aβ42-induced SH-SY5Y cells using microarray profiling. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and high-throughput microarray profiling was performed on the extracted RNA. This was then compared to curcumin and piperine used singularly at 49.11 µM and 25 µM, respectively. Our results demonstrated that in the curcumin treated group, from the top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ −2), there were five upregulated and three downregulated genes involved in the amyloidogenic pathway. While from top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p < 0.05; fold change ≥ 2 or ≤ − 2) in the piperine treated group, there were four upregulated and three downregulated genes involved in the same pathway, whereas there were five upregulated and two downregulated genes involved (p < 0.05; fold change ≥ 2 or ≤ − 2) in the curcumin-piperine combined group. Four genes namely GABARAPL1, CTSB, RAB5 and AK5 were expressed significantly in all groups. Other genes such as ITPR1, GSK3B, PPP3CC, ERN1, APH1A, CYCS and CALM2 were novel putative genes that are involved in the pathogenesis of AD. We revealed that curcumin and piperine have displayed their actions against Aβ via the modulation of various mechanistic pathways. Alterations in expression profiles of genes in the neuronal cell model may explain Aβ pathology post-treatment and provide new insights for remedial approaches of a combined treatment using curcumin and piperine.
Electroacupuncture Pretreatment Elicits Tolerance to Cerebral Ischemia/Reperfusion through Inhibition of the GluN2B/m-Calpain/p38 MAPK Proapoptotic Pathway

Background As one of the first steps in the pathology of cerebral ischemia, glutamate-induced excitotoxicity progresses too fast to be the target of postischemic intervention. However, ischemic preconditioning including electroacupuncture (EA) might elicit cerebral ischemic tolerance through ameliorating excitotoxicity. Objective To investigate whether EA pretreatment based on TCM theory could elicit cerebral tolerance against ischemia/reperfusion (I/R) injury, and explore its potential excitotoxicity inhibition mechanism from regulating proapoptotic pathway of the NMDA subtype of glutamate receptor (GluN2B). Methods The experimental procedure included 5 consecutive days of pretreatment stage and the subsequent modeling stage for one day. All rats were evenly randomized into three groups: sham MCAO/R, MCAO/R, and EA+MCAO/R. During pretreatment procedure, only rats in the EA+MCAO/R group received EA intervention on GV20, SP6, and PC6 once a day for 5 days. Model preparation for MCAO/R or sham MCAO/R started 2 hours after the last pretreatment. 24 hours after model preparation, the Garcia neurobehavioral scoring criteria was used for the evaluation of neurological deficits, TTC for the measurement of infarct volume, TUNEL staining for determination of neural cell apoptosis at hippocampal CA1 area, and WB and double immunofluorescence staining for expression and the cellular localization of GluN2B and m-calpain and p38 MAPK. Results This EA pretreatment regime could improve neurofunction, decrease cerebral infarction volume, and reduce neuronal apoptosis 24 hours after cerebral I/R injury. And EA pretreatment might inhibit the excessive activation of GluN2B receptor, the GluN2B downstream proapoptotic mediator m-calpain, and the phosphorylation of its transcription factor p38 MAPK in the hippocampal neurons after cerebral I/R injury. Conclusion The EA regime might induce tolerance against I/R injury partially through the regulation of the proapoptotic GluN2B/m-calpain/p38 MAPK pathway of glutamate.
Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma

As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in various cancers, including HCC. However, the underlying molecular mechanism has not been well-characterized. Here, evaluation on a tissue-array panel and bioinformatics analysis revealed that Rictor is highly expressed in HCC tissues. Moreover, increased Rictor expression predicts poor survival of HCC patients. Rictor knockdown significantly suppressed cell migration and actin polymerization, thereby leading to decreased nuclear accumulation of MKL1 and subsequent inactivation of SRF/MKL1-dependent gene transcription, i.e. Arp3 and c-Fos. Mechanistically, we identified ABLIM1 as a previously unknown phosphorylation target of Rictor. Rictor interacts with ABLIM1 and regulates its serine phosphorylation in HCC cells. We generated ABLIM1 knockout cell lines of HCC, in which dominant negative mutations of Ser 214 and Ser 431 residues inhibited the ABLIM1-mediated actin polymerization and the MKL1 signaling pathway. Overall, ABLIM1 phosphorylation induced by Rictor plays an important role in controlling actin polymerization in HCC cells.
HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome

Human papillomavirus (HPV) is a DNA virus that causes sexually transmitted infections. The HPV oncoprotein E7 plays a critical role in the regulation of host immunity to promote the immune escape of HPV and the occurrence of cervical cancer or genital warts. Pyroptosis, a highly inflammatory form of programmed cell death, can be induced by inflammasomes and acts as a defense against pathogenic infection. However, whether HPV E7 can regulate cell pyroptosis to evade immune surveillance has not been determined. In this study, we found that HPV E7 could inhibit cell pyroptosis induced by transfection with dsDNA. The activation of the inflammasome, and the production of IL-18 and IL-1β were also restrained by HPV E7. Mass spectrometry and immunoprecipitation showed that HPV E7 interacted with IFI16 and TRIM21. We also discovered that HPV E7 recruited the E3 ligase TRIM21 to ubiquitinate and degrade the IFI16 inflammasome, leading to the inhibition of cell pyroptosis and self-escape from immune surveillance. Thus, our study reveals an important immune escape mechanism in HPV infection and may provide targets for the development of a novel immunotherapeutic strategy to effectively restore antiviral immunity.
The journey of omega-3 fatty acids in cardiovascular medicine

Abstract In subjects with cardiovascular risk factors or in patients in need of secondary prevention, hypertriglyceridemia is a well-defined risk factor for adverse cardiac events. Drugs containing n-3 polyunsaturated fatty acids (n-3 PUFAs) are approved for treatment of hypertriglyceridemia. In 1999, a cardioprotective effect in post infarct patients was suggested by a large multicentre study, the GISSI prevention trial. The hypothesized mechanism of action was an antiarrhythmic action leading to reduction of the sudden death. However, such a cardioprotective effect of n-3 PUFAs has not been straightforward like for other cardiovascular drugs such as aspirin, statins or ACE inhibitors. On the contrary, it has been a long journey with several ups and downs. Recently, the European Medicines Agency (EMA) has not confirmed the risk benefit of low dose of n-3 PUFA in preventing outcomes after a myocardial infarction. Since the EMA decision, the use of a high dose (4g daily) of pure and stable EPA in a multicentre, international trial, the REDUCE-IT study showed a clear cardiovascular event reduction which was not confirmed in another trial, the STRENGTH study, which utilized 4g daily of an EPA+DHA mixture. It follows that the OMEGA-3 fatty acid story seems to be endless and the last word on cardiovascular benefits cannot be pronounced. We report a brief narrative of an entire journey from the beginning to nowadays.