Molecular and Physiological Mechanisms of Toxin Resistance in Toad-Eating Snakes

Many plants and animals are defended by toxic compounds, and circumvention of those defenses often has involved the evolution of elaborate mechanisms for tolerance or resistance of the toxins. Toads synthesize potent cardiotonic steroids known as bufadienolides (BDs) from cholesterol and store those toxins in high concentrations in their cutaneous glands. Those toxins protect toads from the majority of predators, including most snakes that readily consume other species of frogs. BDs exert their effect by inhibiting ion transport by the Na+/K+-ATPase (NKA). This ubiquitous transmembrane enzyme consists of a catalytic alpha-subunit, which carries out the enzyme\u27s functions, and a glycoprotein beta-subunit, which provides structural stability. Inhibition of the NKA causes highly elevated intracellular Ca2+ levels and results in often lethal increased cardiac contraction strength. Molecular resistance to bufadienolides in snakes is conferred by mutations in the alpha-subunit of the Na+/K+-ATPase. I have found that these mutations are more prevalent in snakes than previously suggested, and that many genetically resistant species do not feed on toads. This suggests that possession of the mutations alone does not carry substantial negative consequences, and that feeding on toads may have been an ancestral habit in some groups of snakes. I have further found evidence of tissue-specific variation in resistance to bufadienolides, and gene expression investigations revealed that the bufadienolide resistance-conferring mutations are not expressed equally among different organs. Variation in resistance among different tissues indicates that possession of the mutations does not protect all cells equally. Finally, by testing the physiological responses of resistant snakes to exposure to cardiotonic steroid, I have found that feeding on toads incurs negative consequences and that toad-specialized resistant snakes respond differently from nontoad-specialized resistant snakes. The presence of physiological consequences of toxin exposure may explain why feeding on toads has been lost in some lineages of snakes that retain resistance-conferring mutations. In summary, these findings indicate that genetic resistance of the Na+/K+-ATPase is necessary in order for snakes to survive acute toxicity of bufadienolides, but it is not sufficient to explain fully the physiological mechanisms involved in dealing with chronic exposure to the toxins

A Comparison of Adrenal in Toad-Eating and Nontoad-Eating Snakes

Toads are chemically defended by bufadienolides, a class of cardiotonic steroids lethal to most predators, including many snakes. Bufadienolides bind to Na+K +-ATPase, inhibiting their ability to transport ions. In cardiocytes, this inhibition cause arrhythmia and severely increased contraction strength, which, if prolonged, lead to death. However, several snakes are resistant to bufadienolides and consume toads with no ill effects. Adrenal glands produce hormones that are important for the maintenance of Na+K +ATPase, and may therefore play an important role in countering the negative effects of bufadienolides. Indeed, the toad-eating specialist Heterodon platirhinos has been known to possess enlarged, and sexually dimorphic, adrenal glands. I hypothesized that toadeating snakes have modified adrenal glands that play a role in the snakes\u27 resistance to bufadienolides and that sexual dimorphism in adrenal gland size is a general characteristic of bufophagous snakes. I used phylogenetically independent taxa to investigate adrenal morphology in bufophagous and non-bufophagous species. Icompared adrenal mass among species and found that the allometric relationship between adrenal mass and body size is significantly different in bufophagous and non-bufophagous snakes, and that these differences also exist between sex in bufophagous species. One bufophagous species, Natrix natrix,fell out of the pattern seen in the others, having adrenal glands more similar to nonbufophagous species. In addition to the morphological comparisons, I compared tissue proportions in histological sections of the adrenal glands but found no significant differences there

Up-regulation of CatSper genes family by selenium

<p>Abstract</p> <p>Background</p> <p>CatSper1-4 are a unique family of sperm cation channels, which are exclusively expressed in the testis and play an important role in sperm motility and male fertility. Despite their vital role in male fertility, almost nothing is known about the factors regulating their expression. Here, we investigated the effects of selenium (Se) on the expression of CatSper genes and sperm parameters in aging versus young male mice.</p> <p>Methods</p> <p>Forty 11-13 months aging male mice and forty 2-3 months young adult male mice were used. The animals were divided in two experimental groups: first group including aging males and second group comprising of young adult males, both treated with Se. The experimental groups were injected intra-peritoneally with Se (0.2 mg/kg) daily, for up to 5 weeks. Two other groups, aging and young adult mice without Se treatment were used as controls. All the animals were rapidly sacrificed by cervical dislocation on the days 21, 28, 35 and 42 after Se treatment. Subsequently, the morphology of the collected sperms was analyzed, and one of the testes from each mouse used for semi-quantitative RT-PCR. The significancy of the data was analyzed using ANOVA.</p> <p>Results and Discussion</p> <p>Our data revealed that there was a significant up-regulation of CatSper genes in the experimental groups compared to the control ones. Furthermore, the results of sperm analysis showed that the sperm parameters were improved in the aging as well as young adult male mice following Se treatment.</p> <p>Conclusion</p> <p>Se treatment in the aging subjects could up-regulate the expression of CatSper genes, and therefore results in elevation of sperm motility. Furthermore, Se treatment improved sperm parameters, especially morphology and viability rates.</p

The effect of acupuncture on pain during extracorporeal shock wave lithotripsy- a clinical trial

زمینه و هدف: سنگ شکنی برون اندامی به عنوان روشی انتخابی در درمان سنگ های ادراری شناخته شده است. اکثر بیماران حین عمل سنگ شکنی درد تجربه می کنند. طب سوزنی، روش درمانی سنتی است که یکی از کاربردهای آن تسکین درد می باشد. این مطالعه با هدف بررسی اثر درمانی طب سوزنی بر روی میزان کاهش درد حین عمل سنگ شکنی برون اندامی انجام شده است. روش بررسی: این مطالعه کارآزمایی بالینی دو سو کور، بر روی 100 بیمار مبتلا به سنگ کالیسیل کلیه که کاندید عمل سنگ شکنی برون اندامی بودند، انجام گرفت. بیماران قبل از سنگ شکنی توسط متخصص طب سوزنی ویزیت شدند و به صورت تصادفی در یکی از دو گروه طب سوزنی (50 بیمار) و شم (50 بیمار) قرار گرفتند. در گروه طب سوزنی 4 نقطه مخصوص به مدت 30 دقیقه و در گروه شم همان نقاط به صورت غیر مؤثری به مدت 30 دقیقه تحریک شدند. سپس سنگ شکنی انجام شد و شدت درد بیمار بر اساس مقیاس دیداری درد ثبت و مورد مقایسه قرار گرفت. یافته ها: در 100 بیمار ارزیابی شده میانگین میزان درد در گروه طب سوزنی حقیقی 92/0±74/2 و در گروه طب سوزنی غیر واقعی 87/0±34/4 بود (01/0>P). سایز سنگ در دو گروه با میزان درد ارتباط معنی داری داشت (05/0>P) و هرچه سایز سنگ بیشتر بود، میزان درد ناشی از سنگ شکنی نیز بیشتر می بود. سن و جنس بر روی میزان درد اثری نداشت. نتیجه گیری: استفاده از طب سوزنی در بیمارانی که تحت عمل سنگ شکنی برون اندامی قرار گرفتند، باعث کاهش شدت درد حین عمل سنگ شکنی شد؛ لذا با انجام این روش می توان تا حدود زیادی به بیماران جهت تحمل درد کمک نمود

The Effect of Different Periods of Enamel Microabrasion on the Microleakage of Class V Glass-Ionomer Restorations

Objective: Removal of enamel superficial layer during microabrasion treatments may adversely affect sealing ability of the restorative materials. The aim of this study was to measure the effect of different periods of enamel microabrasion on the microleakage of class V glass-ionomer  restorations.Methods: This in vitro experimental study was conducted on 96 Class V cavities which had been prepared on the buccal and lingual surfaces of 48 sound human premolars. After conditioning with 10% polyacrylic acid (GC, Tokyo, Japan) one half of the cavities were restored with the  conventional glass-ionomer (Fuji II GC, Tokyo, Japan) and another half with resin-modified glass- ionomer (Fuji II LC GC, Tokyo, Japan). Finishing and polishing were performed after 24 hours and the teeth incubated for 2 weeks (37°C and 100% humidity).Then the teeth were classified into eight groups (n=12). Microabrasion treatment was performed with Opulster (Ultradent product Inc, South Jordan, UT, USA) in 0(control no treatment), 60, 120 and 180 seconds. Then teeth were thermocycled between 5°C-55°C (×1000), immersed in 0.5% basic-fushin solution (24h) and sectioned longitudinally in bucco-lingual direction (n=192). Dye penetration was examined with stereomicroscope (×40). Microleakage scores were statistically analyzed by Kruskal-Wallis test while the paired comparisons were done using Mann-Whitney U test.Results: The mean microleakage scores were significantly increased following increased microabrasion times in occlusal margin in FU II (p&lt;0.009) and FU II LC (p&lt;0.02) and in gingival margin in resin-modified glass-ionomer (p&lt;0.04).Conclusion: In Fuji II restorations after microabrasion in occlusal margins, microleakage increased up to 120s but in gingival margins no significant difference were seen. In Fuji II LC restorations  after microabrasion in occlusal margin, microleakage from 60s up to 180s was significantly increased. In gingival margin with increasing the time up to 180s microleakage increased

Defence mitigation by predators of chemically defended prey integrated over the predation sequence and across biological levels with a focus on cardiotonic steroids

Predator–prey interactions have long served as models for the investigation of adaptation and fitness in natural environments. Anti-predator defences such as mimicry and camouflage provide some of the best examples of evolution. Predators, in turn, have evolved sensory systems, cognitive abilities and physiological resistance to prey defences. In contrast to prey defences which have been reviewed extensively, the evolution of predator counter-strategies has received less attention. To gain a comprehensive view of how prey defences can influence the evolution of predator counter-strategies, it is essential to investigate how and when selection can operate. In this review we evaluate how predators overcome prey defences during (i) encounter, (ii) detection, (iii) identification, (iv) approach, (v) subjugation, and (vi) consumption. We focus on prey that are protected by cardiotonic steroids (CTS)—defensive compounds that are found in a wide range of taxa, and that have a specific physiological target. In this system, coevolution is well characterized between specialist insect herbivores and their host plants but evidence for coevolution between CTS-defended prey and their predators has received less attention. Using the predation sequence framework, we organize 574 studies reporting predators overcoming CTS defences, integrate these counter-strategies across biological levels of organization, and discuss the costs and benefits of attacking CTS-defended prey. We show that distinct lineages of predators have evolved dissecting behaviour, changes in perception of risk and of taste perception, and target-site insensitivity. We draw attention to biochemical, hormonal and microbiological strategies that have yet to be investigated as predator counter-adaptations to CTS defences. We show that the predation sequence framework will be useful for organizing future studies of chemically mediated systems and coevolution

The Natural Selection Game: Incorporating Active Learning in Evolution Curricula for General Biology

Teaching evolution in high school and in entry-level college courses can be challenging due to the inherent misinformation, misunderstanding, and biases with which students approach the topic. In this setting, it is critical to both teach the basic concepts and address common student misconceptions about evolution. We present two paired activities that allow students to (1) explore the processes of natural selection in a direct and experiential way and (2) address common misconceptions in evolutionary theory. The first activity, the “Natural Selection Game,” has students simulate a bird population and experience shifts in phenotype frequency as a result of selective pressures. Following the end of the game, students discuss the outcomes and connect them to real-life examples. The second activity encourages students to actively research common misconceptions with the use of personal technology in order to distinguish between scientifically supported data and poor information online. Both activities can be incorporated in high school and university-level general biology curricula. They will allow students to connect their firsthand experiences to lecture-based instruction and, as a result, develop a stronger understanding of the mechanisms of evolution

Serum Hsp70 antigen: Early diagnosis marker in perinatal asphyxia

BACKGROUND: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. OBJECTIVES: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. PATIENTS AND METHODS: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). RESULTS: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. CONCLUSIONS: A significant difference between the serum concentrations of Hsp70 of the control and patient group was observed in this study. It is inferred serum concentrations of Hsp70 antigen may be a useful marker for the early diagnosis of that prenatal hypoxia

Axial-torsional dynamics of a drilling bit with non-uniform blade arrangement

Peer reviewedPostprin

Diagnosis and Treatment of Fasciola Infection with Endoscopic Retrograde Cholangiopancreatography (ERCP) in Ardabil, Northwest of Iran: Two Case Reports

Here we report biliary fascioliasis in two women 27 and 54 years old from Ardabil Province, Iran who presented with nausea, anorexia, weight loss, and pain between shoulder blades. Endoscopic ultrasound showed distal common bile duct strictures (CBD) and a lesion in its proximal. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and live parasites were diagnosed and successfully managed into the duodenal lumen. The clinical findings of the patient improved after the procedure. This report emphasizes that the prevalence of Fasciola in Ardabil is predictable and this infection could be simultaneously diagnosed and treated by the ERCP