Sustainability challenges of hydropower and its implication on Ethiopia’s economy

Ethiopia has the potential to be 100% renewable. Its renewables are capable to solve its energy poverty and energy shortage in East Africa. The country’s climate resilient green economy strategy considers energy as key enabler for vibrant economy. The objective of this paper is to identify key challenges of the energy sector by studying 12 years of electricity generation data, 2012 to 2023, and to analyze the sector’s performance with a special emphasis on hydropower. In this study, both quantitative and qualitative methods were employed to draw performances indicators. The quantitative results showed that the country achieved 30% of its energy development plan with a deteriorating performance from 94% to 40%. This performance works for hydropower too, which dominants the electricity development and supply. The declining performance comes from government’s monopoly in the sector, financial deficit due to ongoing internal crises and technical unavailability of power plants. This performance has greatly influenced expansion of industries, access to electricity, unemployment, and other economic activities. The authors advise the government, stakeholders, and development partners to consider the recommendations given in this paper to boost the energy sector development and keep the country in healthy economic pace by all measures

Systems biology of ferroptosis: A modeling approach.

Ferroptosis is a recently discovered form of iron-dependent regulated cell death (RCD) that occurs via peroxidation of phospholipids containing polyunsaturated fatty acid (PUFA) moieties. Activating this form of cell death is an emerging strategy in cancer treatment. Because multiple pathways and molecular species contribute to the ferroptotic process, predicting which tumors will be sensitive to ferroptosis is a challenge. We thus develop a mathematical model of several critical pathways to ferroptosis in order to perform a systems-level analysis of the process. We show that sensitivity to ferroptosis depends on the activity of multiple upstream cascades, including PUFA incorporation into the phospholipid membrane, and the balance between levels of pro-oxidant factors (reactive oxygen species, lipoxogynases) and antioxidant factors (GPX4). We perform a systems-level analysis of ferroptosis sensitivity as an outcome of five input variables (ACSL4, SCD1, ferroportin, transferrin receptor, and p53) and organize the resulting simulations into \u27high\u27 and \u27low\u27 ferroptosis sensitivity groups. We make a novel prediction corresponding to the combinatorial requirements of ferroptosis sensitivity to SCD1 and ACSL4 activity. To validate our prediction, we model the ferroptotic response of an ovarian cancer stem cell line following single- and double-knockdown of SCD1 and ACSL4. We find that the experimental outcomes are consistent with our simulated predictions. This work suggests that a systems-level approach is beneficial for understanding the complex combined effects of ferroptotic input, and in predicting cancer susceptibility to ferroptosis

Cytoprotective Effect of Ferritin H in Renal Ischemia Reperfusion Injury.

Oxidative stress is a major contributor to kidney injury following ischemia reperfusion. Ferritin, a highly conserved iron-binding protein, is a key protein in the maintenance of cellular iron homeostasis and protection from oxidative stress. Ferritin mitigates oxidant stress by sequestering iron and preventing its participation in reactions that generate reactive oxygen species. Ferritin is composed of two subunit types, ferritin H and ferritin L. Using an in vivo model that enables conditional tissue-specific doxycycline-inducible expression of ferritin H in the mouse kidney, we tested the hypothesis that an increased level of H-rich ferritin is renoprotective in ischemic acute renal failure. Prior to induction of ischemia, doxycycline increased ferritin H in the kidneys of the transgenic mice nearly 6.5-fold. Following reperfusion for 24 hours, induction of neutrophil gelatinous-associated lipocalin (NGAL, a urine marker of renal dysfunction) was reduced in the ferritin H overexpressers compared to controls. Histopathologic examination following ischemia reperfusion revealed that ferritin H overexpression increased intact nuclei in renal tubules, reduced the frequency of tubular profiles with luminal cast materials, and reduced activated caspase-3 in the kidney. In addition, generation of 4-hydroxy 2-nonenal protein adducts, a measurement of oxidant stress, was decreased in ischemia-reperfused kidneys of ferritin H overexpressers. These studies demonstrate that ferritin H can inhibit apoptotic cell death, enhance tubular epithelial viability, and preserve renal function by limiting oxidative stress following ischemia reperfusion injury

Ferritin blocks inhibitory effects of two-chain high molecular weight kininogen (HKa) on adhesion and survival signaling in endothelial cells.

Angiogenesis is tightly regulated through complex crosstalk between pro- and anti-angiogenic signals. High molecular weight kininogen (HK) is an endogenous protein that is proteolytically cleaved in plasma and on endothelial cell surfaces to HKa, an anti-angiogenic protein. Ferritin binds to HKa and blocks its anti-angiogenic activity. Here, we explore mechanisms underlying the cytoprotective effect of ferritin in endothelial cells exposed to HKa. We observe that ferritin promotes adhesion and survival of HKa-treated cells and restores key survival and adhesion signaling pathways mediated by Erk, Akt, FAK and paxillin. We further elucidate structural motifs of both HKa and ferritin that are required for effects on endothelial cells. We identify an histidine-glycine-lysine (HGK) -rich antiproliferative region within domain 5 of HK as the target of ferritin, and demonstrate that both ferritin subunits of the H and L type regulate HKa activity. We further demonstrate that ferritin reduces binding of HKa to endothelial cells and restores the association of uPAR with α5β1 integrin. We propose that ferritin blocks the anti-angiogenic activity of HKa by reducing binding of HKa to UPAR and interfering with anti-adhesive and anti-proliferative signaling of HKa

Chimeric and Pseudotyped Parvoviruses Minimize the Contamination of Recombinant Stocks with Replication-Competent Viruses and Identify a DNA Sequence That Restricts Parvovirus H-1 in Mouse Cells

Recent studies demonstrated the ability of the recombinant autonomous parvoviruses MVMp (fibrotropic variant of the minute virus of mice) and H-1 to transduce therapeutic genes in tumor cells. However, recombinant vector stocks are contaminated by replication-competent viruses (RCVs) generated during the production procedure. To reduce the levels of RCVs, chimeric recombinant vector genomes were designed by replacing the right-hand region of H-1 virus DNA with that of the closely related MVMp virus DNA and conversely. Recombinant H-1 and MVMp virus pseudotypes were also produced with this aim. In both cases, the levels of RCVs contaminating the virus stocks were considerably reduced (virus was not detected in pseudotyped virus stocks, even after two amplification steps), while the yields of vector viruses produced were not affected. H-1 virus could be distinguished from MVMp virus by its restriction in mouse cells at an early stage of infection prior to detectable viral DNA replication and gene expression. The analysis of the composite viruses showed that this restriction could be assigned to a specific genomic determinant(s). Unlike MVMp virus, H-1 virus capsids were found to be a major determinant of the greater permissiveness of various human cell lines for this virus

Histopathologic examination of kidney sections reveals changes consistent with ischemia-reperfusion injury.

<p>Mice were subjected to 45 min renal ischemia to the right kidney and then allowed to recover for 24 hr. The contralateral left kidney was sham treated. Periodic acid-Schiff (PAS) stained kidney sections are shown in panels A-D]. Note the degree of loss of brush border and tubular sloughing in the cortical kidney (arrows) following ischemia-reperfusion injury is greater in the Control (A.) compared to the LAPFerH (C.) mouse. Normal tubular morphology is observed in the sham kidneys of both Control (B.) and LAPFerH animals (D.)</p

Effect of ferritin H overexpression on urinary NGAL in mice subjected to ischemia-reperfusion injury.

<p>Mice were subjected to 45 min ischemia to the right kidney, and then allowed to recover for 24 hr. Urinary NGAL levels were measured prior to ischemia and after 24 hr reperfusion in control mice (n = 9) and ferritin H overexpressing (LAPFerH) mice (n = 9). Data are shown as means ± SD. Urinary NGAL following 24 hr-reperfusion was significantly higher in the Control mice compared to the LAPFerH mice (P ≤ 0.015).</p

38 Daily vs. Intermittent Iron Therapy in Moderate Iron Deficient Pregnant Patients: A Randomized Non-inferiority Trial

Objective: Evaluate the hematological response of pregnant women to iron therapy in daily vs. intermittent treatment groups & evaluate gastrointestinal side effects & adherence to therapy. Study Design: A pragmatic non-blinded randomized controlled non-inferiority trial performed at two medical sites. Pregnant women undergoing routine prenatal labs at 26-29 weeks gestation were approached about the study. Exclusion criteria were: diagnosed iron deficiency anemia \u3c 26 weeks, already on iron supplementation, had a condition known to affect iron metabolism. Enrolled patients were randomized to supplemental iron daily or intermittently (every other day). The primary outcome was change in hemoglobin (Hgb) after treatment, with the non-inferiority margin set at 1 Standard Deviation (SD) ( 0.5 g/dL Hgb). Secondary outcomes were: differences in other hematological indices (hematocrit, mean corpuscular volume, serums transferrin receptor molecule, hepcidin, ferritin, calculated body iron store), gastrointestinal side effects & adherence. We assumed a mean increase of Hgb was 1 g/dL in the daily group. A 0.5 g/dL or more mean Hgb difference between groups was considered clinically significant. With a two sided, two-sample t-test, to achieve a power of 90%, α of 0.05, 23 patients per group were needed. Results: One hundred seventy-nine women were screened & 58 met study criteria, 29 were randomized to daily & 29 to intermittent iron groups. Twenty-two patients were analyzed in the daily group & 24 patients were analyzed in the intermittent group. Baseline characteristics were not different between groups (p \u3e.05). Intermittent iron therapy was non-inferior to daily therapy, with a mean SD difference of 0.27 g/dL (95% CI: -0.33 to 0.89) (Figure). Changes in other hematological indices were not significant (Table). Women in the daily group had more nausea compared to intermittent group (p = 0.040). Women in the intermittent group were not more adherent with therapy (p=0.244). Conclusion: Intermittent iron therapy is non-inferior to daily iron therapy and is associated with less nausea but not increased adherence

Ferritin inhibits binding of HKa to HUVECs.

<p><b>A–E.</b> HUVEC cells were treated with 50 nM Alexa-Fluor 488 labeled HKa ±100 nM unlabeled spleen ferritin or BSA for one hour at 37°C. Cells were analyzed on FACSCaliber using CellQuest Pro Software. <b>F.</b> Means and standard deviation of 3 independent experiments.</p

Ferritin reverses the anti-adhesive properties of HKa.

<p>Cells were incubated with HKa (50 nM) alone, HKa (50 nM) plus ferritin (100 nM), or ferritin (100 nM) alone and allowed to adhere on vitronectin-coated coverslips in the presence of 20 ng/ml bFGF and 10 µM ZnCl₂ for two hours. <b>A.</b> Adherent cells were fixed and stained with crystal violet and visualized by microscopy; <b>B.</b> Adherent cells per 10× field were counted; shown are means and standard deviation of 3 experiments with * p<0.001 and ** p<0.0001. <b>C.</b> Adherent cells were lysed and analyzed by western blotting. <b>D.</b> Phosphorylation of signaling molecules was quantified by densitometry. Data is expressed as percent phosphorylated/total protein; shown are means and standard deviation of three independent experiments; *p<0.02; **p<0.003.</p