An X‐linked Myh11‐CreERT2 mouse line resulting from Y to X chromosome‐translocation of the Cre allele

The Myh11‐CreER^T2 mouse line (Cre⁺) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y^Cre+), which excluded its application in female mice. Our group established a Cre⁺ colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X‐linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X^Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y^Cre+ mice. This mosaicism, however, diminished in homozygous X^Cre+/X^Cre+ mice. In a model of aortic aneurysm induced by a SMC‐specific Tgfbr1 deletion, the homozygous X^Cre+/X^Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X^Cre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X‐inactivation. The homozygous X^Cre+/X^Cre+ mice produce uniform Cre activity in arterial SMCs.     

Therapeutic effects of Typha elephantina leave’s extract against paracetamol induced renal injury in rabbits

Present study focuses on ameliorative potential of Typha elephantina leave’s aqueous (TE.AQ) extract against Paracetamol (PCM) induced toxicity in rabbits. We fed the male rabbits with 300 mg PCM in alone and in combination with TE.AQ at different doses i.e. (100, 200 and 300 mg/kg body weight) or silymarin (100 mg/kg) daily for 21 days. PCM in alone significantly (P < 0.5) increased serum urea, uric acid, creatinine, total protein, albumin, globulin and blood urea nitrogen. Serum sodium, potassium and magnesium level were high. The glutathione, radical scavenging activity and Thiobarbituric acid reactive substances were significantly reduced. Treatment with TE.AQ at dose rate 300 mg/kg body weight and Silymarin significantly ameliorated all the parameters when compared with PCM administered group. The 100 and 200 mg of TE.AQ showed no significant effects. The histopathological examination confirmed the therapeutic potential of TE.AQ. These results established the presence of natural antioxidants in Typha elephantina leaves.     

In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.     

Differential abundance of IGF1, bile acids,and the genes involved in their signaling in the dominant follicle microenvironment of lactating cows and nulliparous heifers

It is well documented that incidence of fertility problems is high in lactating cows but not in heifers of the same genetic merit. Understanding the metabolic and molecular differences between fertile heifers and relatively infertile lactating cows will help us understand the pathogenesis of infertility in dairy cows. Follicular waves in lactating cows (30–50 days in milk; n = 12) and heifers (n = 10) were synchronized by ultrasound-guided follicle ablation. Follicular fluid and granulosa cells of the dominant follicle were collected by ultrasound-guided aspiration along with blood sampling on Day 6 after synchronization. Dominant and subordinate follicles were larger in lactating cows than in heifers. Metabolic stress in lactating cows was evidenced by lower glucose and higher ß-hydroxy butyric acid compared with heifers. Insulin-like growth factor 1 signaling was reduced in the dominant follicle in lactating cows through reduced insulin-like growth factor 1 concentrations in plasma and follicular fluid of the dominant follicle, and reduced expression of pregnancy-associated plasma protein A (PAPPA) in their granulosa cells. We also found increased levels of total bile acids in the follicular fluid of the dominant follicle of lactating cows compared with heifers. Granulosa cells of the dominant follicle had higher expression of SLC10A2 and GPBAR1 (bile acid transporter and receptor, respectively) in lactating cows. These novel data are indicative of increased bile acid signaling within the dominant follicles of lactating cows compared with heifers. Overall, we demonstrate in the present study the metabolic, endocrine, and molecular differences within the microenvironment of the dominant follicles in lactating cows and heifers. These differences in follicular microenvironment may contribute toward abnormal ovarian function in lactating dairy cows.     

Bottom‐up effects mediated by an organic soil amendment on the cabbage aphid pests Myzus persicae and Brevicoryne brassicae

Earthworm‐produced compost or vermicompost has been shown to increase resistance of plants to a variety of insect pests, but it is still unclear whether this resistance is dose dependent and whether the mechanisms responsible are the same for insect species with differing feeding habits and preferences. Therefore, we tested the effects of plants grown in various vermicompost concentrations (0, 20, 40, and 60%) on the preference and performance of generalist, Myzus persicae L., and specialist, Brevicoryne brassicae L. (both Hemiptera: Aphididae), aphid pests. Preference was evaluated with leaf disk (apterous) and whole plant (alate) choice assays. After 24 h of feeding, there was no significant negative effect on the feeding preference noted for apterae of either species of any of the treatments tested. To the contrary, apterae B. brassicae showed a significant preference for vermicompost treatments over control leaf disks. Alate M. persicae preferred alighting on control plants over vermicompost‐grown plants, but B. brassicae showed no preference toward any of the treatments tested. Both aphid species deposited significantly more nymphs on control plants than on those grown in 20% vermicompost. Furthermore, plants grown in soil amended with 20% vermicompost significantly suppressed mass accumulation, as well as numbers of adults and nymphs of both aphid species compared to controls. These data clearly show that vermicompost soil amendments can significantly influence pest aphid preference and performance on plants and that these effects are not dose dependent, but rather species and morph dependent.     

A new role for heme, facilitating release of iron from the bacterioferritin iron biomineral

Bacterioferritin (BFR) from Escherichia coli is a member of the ferritin family of iron storage proteins and has the capacity to store very large amounts of iron as an Fe(3+) mineral inside its central cavity. The ability of organisms to tap into their cellular stores in times of iron deprivation requires that iron must be released from ferritin mineral stores. Currently, relatively little is known about the mechanisms by which this occurs, particularly in prokaryotic ferritins. Here we show that the bis-Met-coordinated heme groups of E. coli BFR, which are not found in other members of the ferritin family, play an important role in iron release from the BFR iron biomineral: kinetic iron release experiments revealed that the transfer of electrons into the internal cavity is the rate-limiting step of the release reaction and that the rate and extent of iron release were significantly increased in the presence of heme. Despite previous reports that a high affinity Fe(2+) chelator is required for iron release, we show that a large proportion of BFR core iron is released in the absence of such a chelator and further that chelators are not passive participants in iron release reactions. Finally, we show that the catalytic ferroxidase center, which is central to the mechanism of mineralization, is not involved in iron release; thus, core mineralization and release processes utilize distinct pathways.     

Electrostatic solitary structures in a magnetized nonextensive plasma with q-distributed electrons

A rigorous theoretical investigation has been made of obliquely propagating electrostatic solitary structures in a magnetized plasma, taking into account the effect of nonextensive electrons. By employing the reductive perturbation method, the basic characteristics of obliquely propagating ion-acoustic (IA) solitary waves (SWs) in a cold magnetized electron-ion plasma (consisting of inertial ions and noninertial q-distributed electrons) have been addressed. The Korteweg-de Vries equation is derived and its numerical solution is obtained. It has been shown that the effects of electron nonextensivity and external magnetic field significantly modify the natures of the small but finite-amplitude IA SWs. The present analysis may be useful to understand and demonstrate the dynamical properties of IA SWs in different astrophysical and cosmological scenarios (viz. stellar polytropes, hadronic matter, quark-gluon plasma, protoneutron stars, dark-matter halos, etc.).     

CaMKII-Induced Shift in Modal Gating Explains L-Type Ca Current Facilitation: A Modeling Study

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) plays an important role in L-type Ca²⁺ channel (LCC) facilitation: the Ca²⁺-dependent augmentation of Ca²⁺ current (I_CaL) exhibited during rapid repeated depolarization. Multiple mechanisms may underlie facilitation, including an increased rate of recovery from Ca²⁺-dependent inactivation and a shift in modal gating distribution from mode 1, the dominant mode of LCC gating, to mode 2, a mode in which openings are prolonged. We hypothesized that the primary mechanism underlying facilitation is the shift in modal gating distribution resulting from CaMKII-mediated LCC phosphorylation. We developed a stochastic model describing the dynamic interactions among CaMKII, LCCs, and phosphatases as a function of dyadic Ca²⁺ and calmodulin levels, and we incorporated it into an integrative model of the canine ventricular myocyte. The model reproduces behaviors at physiologic protein levels and allows for dynamic transition between modes, depending on the LCC phosphorylation state. Simulations showed that a CaMKII-dependent shift in LCC distribution toward mode 2 accounted for the I_CaL positive staircase. Moreover, simulations demonstrated that experimentally observed changes in LCC inactivation and recovery kinetics may arise from modal gating shifts, rather than from changes in intrinsic inactivation properties. The model therefore serves as a powerful tool for interpreting I_CaL experiments.     

Antibacterial evaluation of silver nanoparticles synthesized from lychee peel: individual versus antibiotic conjugated effects

This paper describes the extracellular synthesis of silver nanoparticles from waste part of lychee fruit (peel) and their conjugation with selected antibiotics (amoxicillin, cefixim, and streptomycin). FTIR studies revealed the reduction of metallic silver and stabilization of silver nanoparticles and their conjugates due to the presence of CO (carboxyl), OH (hydroxyl) and CH (alkanes) groups. The size of conjugated nanoparticles varied ranging from 3 to 10 nm as shown by XRD. TEM image revealed the spherical shape of biosynthesized silver nanoparticles. Conjugates of amoxicillin and cefixim showed highest antibacterial activity (147.43 and 107.95%, respectively) against Gram-negative bacteria i.e. Alcaligenes faecalis in comparison with their control counterparts. The highest reduction in MIC was noted against Gram-positive strains i.e. Enterococcus faecium (75%) and Microbacterium oxydans (75%) for amoxicillin conjugates. Anova two factor followed by two-tailed t test showed non-significant results both in case of cell leakage and protein estimation between nanoparticles and conjugates of amoxicillin, cefixime and streptomycin. In case of MDA release, non-significant difference among the test samples against the selected strains. Our study found green-synthesized silver nanoparticles as effective antibacterial bullet against both Gram positive and Gram negative bacteria, but they showed a more promising effect on conjugation with selected antibiotics against Gram negative type.