A Reexamination of Correlations of Amino Acids with Particular Secondary Structures

Using the data from Protein Data Bank the correlations of primary and secondary structures of proteins were analyzed. The correlation values of the amino acids and the eight secondary structure types were calculated, where the position of the amino acid and the position in sequence with the particular secondary structure differ at most 25. The diagrams describing these results indicate that correlations are significant at distances between −9 and 10. The results show that the substituents on Cβ or Cγ atoms of amino acid play major role in their preference for particular secondary structure at the same position in the sequence, while the polarity of amino acid has significant influence on α-helices and strands at some distance in the sequence. The diagrams corresponding to polar amino acids are noticeably asymmetric. The diagrams point out the exchangeability of residues in the proteins; the amino acids with similar diagrams have similar local folding requirements. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparison of three microscopic techniques for diagnosis of Cyclospora cayetanensis

Cyclospora cayetanensis oocysts in the feces of humans from Kathmandu, Nepal were identified on the basis of their size and other morphological characteristics. We compared the detection of C. cayetanensis oocysts in the feces using three microscopic techniques such as formalin-ether sedimentation, sucrose centrifugal floatation, and direct smear. Standard procedures were used for the formalin-ether sedimentation and the sucrose centrifugal floatation techniques using 0.5 g of feces, however, the direct smear technique was performed using 10 microl of fecal suspension (0.005 g of feces) and observed under the fluorescent microscope. Of the 403 samples examined, 21 samples were positive for oocysts by all three techniques. Therefore, in these 21 samples, the number of oocysts recovered by the three techniques were compared. The highest number of oocyst was obtained by the sucrose centrifugal floatation technique. In contrast, the formalin-ether sedimentation technique was found to be the least reliable concentration technique for the detection of Cyclospora in human feces. Surprisingly, the direct smear technique was found to be an effective and rapid technique for diagnosis of C. cayetanensis making it a technique of choice for routine epidemiological investigation of the prevalence of this infection in human populations.     

Trade‐offs between land and water requirements for large‐scale bioenergy production

Bioenergy is expected to play an important role in the future energy mix as it can substitute fossil fuels and contribute to climate change mitigation. However, large‐scale bioenergy cultivation may put substantial pressure on land and water resources. While irrigated bioenergy production can reduce the pressure on land due to higher yields, associated irrigation water requirements may lead to degradation of freshwater ecosystems and to conflicts with other potential users. In this article, we investigate the trade‐offs between land and water requirements of large‐scale bioenergy production. To this end, we adopt an exogenous demand trajectory for bioenergy from dedicated energy crops, targeted at limiting greenhouse gas emissions in the energy sector to 1100 Gt carbon dioxide equivalent until 2095. We then use the spatially explicit global land‐ and water‐use allocation model MAgPIE to project the implications of this bioenergy target for global land and water resources. We find that producing 300 EJ yr^?1 of bioenergy in 2095 from dedicated bioenergy crops is likely to double agricultural water withdrawals if no explicit water protection policies are implemented. Since current human water withdrawals are dominated by agriculture and already lead to ecosystem degradation and biodiversity loss, such a doubling will pose a severe threat to freshwater ecosystems. If irrigated bioenergy production is prohibited to prevent negative impacts of bioenergy cultivation on water resources, bioenergy land requirements for meeting a 300 EJ yr^?1 bioenergy target increase substantially (+ 41%) – mainly at the expense of pasture areas and tropical forests. Thus, avoiding negative environmental impacts of large‐scale bioenergy production will require policies that balance associated water and land requirements.     

Protoveratrines A and B increase sleep apnea index in Sprague-Dawley rats

Trbovic, Sinisa M., Miodrag Radulovacki, and David W. Carley. Protoveratrines A and B increase sleep apneaindex in Sprague-Dawley rats. J. Appl.Physiol. 83(5): 1602-1606, 1997.The action ofprotovertarines A and B, which stimulate carotid sinus baroreceptorsand vagal sensory endings in the heart as well as pulmonary bed, wereassessed on spontaneous and postsigh central sleep apneas in freelymoving Sprague-Dawley rats. During the 6-h recording period, animalswere simultaneously monitored for sleep by using electroencephalogramand electromyogram recordings, for respiration by single-chamberplethysmography, and for blood pressure and heart period by usingradiotelemetry. After administration of 0.2, 0.5, or 1 mg/kg sc ofprotoveratrines, cardiopulmonary changes lasting at least 6 h wereobserved in all three behavioral states [heart period increasedup to 23% in wakefulness, 21% in non-rapid-eye-movement (non-REM)sleep, and 20% in REM sleep; P < 0.005 for each]. At the same time, there was a substantial increase in the number of spontaneous (375% increase;P = 0.04) and postsigh (268%increase, P = 0.0002) apneas. Minuteventilation decreased by up to 24% in wakefulness, 25% in non-REM,and 35% in REM sleep (P < 0.05 foreach). We conclude that pharmacological stimulation of baroreflexespromotes apnea expression in the sleeping rat.

     

Selenium content and distribution in rat tissues irradiated with gamma rays

The effects of supplementation with selenous yeast and ionizing radiation on selenium (Se) content and distribution were evaluated in rat tissues (liver, kidney, spleen, heart, muscle, blood, front brain, hind brain, hypothalamus, pituitary, adrenal glands, testes, and hair). This study had 16 Se-supplemented (0.5 μg Se/d) and 16 placebo adult male Wistar rats. One half of the animals (eight Se-supplemented and eight placebos) were irradiated with a single dose of 4.2 Gy from a Co-60 source and sacrificed 7 d after irradiation along with nonirradiated animals and analyzed for Se content determination. The data obtained showed that selenous yeast supplementation increased Se levels in rat tissues (highest increases in hypothalamus, 161%; hind brain, 126%; spleen, 110%; and adrenal gland, 105%). Ionizing radiation induced significant changes in Se content and distribution (decrease in liver, blood, hair, femoral muscle, spleen, and hypothalamus; increase in kidney, testes, adrenal glands, and brain of placebo group). Supplementation with selenous yeast reduces changes in Se content and distribution after irradiation. It seems that the animal tissue susceptibility to oxidative damage may be correlated to their ability to retain Se in tissues.     

Empagliflozin on top of metformin treatment improves arterial function in patients with type 1 diabetes mellitus

Background

Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We explored the possible effects of empagliflozin’s effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients.

Methods

Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function [brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI)], arterial stiffness [pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness)]. For statistical analysis one-way analysis of variance with Bonferroni post-test was used.

Results

Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD [2.6-fold (P?<?0.001) vs. 1.8-fold (P?<?0.05)] and RHI [1.4-fold (P?<?0.01) vs. 1.3-fold (P?<?0.05)]. Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin [by 15.8% (P?<?0.01) and by 36.6% (P?<?0.05), respectively]. Metformin alone did not influence arterial stiffness.

Conclusion

Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies.Trial registration Clinical trial registration: NCT03639545

     

Cardiopulmonary control in sleeping Sprague-Dawley rats treated with hydralazine

Carley, David W., Sinisa M. Trbovic, Alex Bozanich, andMiodrag Radulovacki. Cardiopulmonary control in sleepingSprague-Dawley rats treated with hydralazine. J. Appl.Physiol. 83(6): 1954-1961, 1997.To test thehypothesis that hydralazine can suppress spontaneous sleep-relatedcentral apnea, respiratory pattern, blood pressure, and heart periodwere monitored in Sprague-Dawley rats. In random order and on separatedays, rats were recorded after intraperitoneal injection of1) saline or2) 2 mg/kg hydralazine. Normalizedminute ventilation(NI)declined significantly with transitions from wake tonon-rapid-eye-movement (NREM) sleep (5.1%;P = 0.01) and rapid-eye-movement (REM)sleep (4.2%; P = 0.022).Hydralazine stimulated respiration(NIincreased by 21%; P < 0.03) andeliminated the effect of state onNI. Bloodpressure decreased by 17% after hydralazine, and the correlationbetween fluctuations in mean blood pressure andNI changedfrom strongly positive during control recordings to weakly negativeafter hydralazine (P < 0.0001 foreach). Postsigh and spontaneous apneas were reduced during NREM and REMsleep after hydralazine (P < 0.05 for each). This suppression was strongly correlated with the reductionin blood pressure and with the degree of respiratory stimulation. Weconclude that mild hydralazine-induced hypotension leads to respiratory stimulation and apnea suppression.

     

Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients

Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.     

Immune evasion strategies of trypanosomes: a review

Trypanosomes are digenetic protozoans that infect domestic and wild animals, as well as humans. They cause important medical and veterinary diseases, making them a major public health concern. There are many species of trypanosomes that infect virtually all vertebrate taxa. They typically cycle between insect or leech vectors and vertebrate hosts, and they undergo biochemical and morphological changes in the process. Trypanosomes have received much attention in the last 4 decades because of the diseases they cause and their remarkable armamentarium of immune evasion mechanisms. The completed genome sequences of trypanosomes have revealed an extensive array of molecules that contribute to various immune evasion mechanisms. The different species interact uniquely with their vertebrate hosts with a wide range of evasion strategies and some of the most fascinating immune evasion mechanisms, including antigenic variation that was first described in the trypanosomes. This review focuses on the variety of strategies that these parasites have evolved to evade or modulate immunity of endothermic and ectothermic vertebrates.