The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-de-pendent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages

Angiotensin 1-7 prevents the excessive force loss resulting from 14- and 28-day denervation in mouse EDL and soleus muscle

Denervation leads to muscle atrophy, which is described as muscle mass and force loss, the latter exceeding expectation from mass loss. The objective of this study was to determine the efficiency of angiotensin (Ang) 1-7 at reducing muscle atrophy in mouse extensor digitorum longus (EDL) and soleus following 14- and 28-d denervation periods. Some denervated mice were treated with Ang 1-7 or diminazene aceturate (DIZE), an ACE2 activator, to increase Ang 1-7 levels. Ang 1-7/DIZE treatment had little effect on muscle mass loss and fiber cross-sectional area reduction. Ang 1-7 and DIZE fully prevented the loss of tetanic force normalized to cross-sectional area and accentuated the increase in twitch force in denervated muscle. However, they did not prevent the shift of the force-frequency relationship toward lower stimulation frequencies. The Ang 1-7/DIZE effects on twitch and tetanic force were completely blocked by A779, a MasR antagonist, and were not observed in MasR-/- muscles. Ang 1-7 reduced the extent of membrane depolarization, fully prevented the loss of membrane excitability, and maintained the action potential overshoot in denervated muscles. Ang 1-7 had no effect on the changes in α-actin, myosin, or MuRF-1, atrogin-1 protein content or the content of total or phosphorylated Akt, S6, and 4EPB. This is the first study that provides evidence that Ang 1-7 maintains normal muscle function in terms of maximum force and membrane excitability during 14- and 28-d periods after denervation

Detection of a new Apicomplexa group from buffaloes in Mosul city, Iraq

This study was focused on the detection of a new apicomplexan parasite (Plasmodium spp.) and its clinical and haematological effects during infection of domesticated water buffaloes (Bubalis bubalis) in Mosul city, Iraq. Although Plasmodium parasites of ungulates are diverse and distributed world-wide, no data are available in Iraq about any ungulate malaria, so the current investigation endea¬voured to bridge this gap in the existing body of knowledge. The study included 70 cases of domesti-cated water buffaloes at different ages and from both sexes that were brought to the Veterinary Teach-ing Hospital, University of Mosul, Mosul, Iraq. The animals were from different regions of Mosul in northern Iraq. Microscopic examination was carried out on blood smears to detect Plasmodium para-site. The nested PCR assay was also conducted using Plasmodium spp. cytochrome b gene (cytb) specific primers to confirm the infection. Results showed the presence of Plasmodium parasite in 24.28% (17/70) of cases. Plasmodium bubalis was detected by PCR in three cases from 11 buffaloes. Among infected buffaloes, the symptomatic cases of malaria were 64.5%, while only 35.5% were asymptomatic (occult) cases. Moreover, fever in 54% of cases, paleness of the mucous membranes in 36% of cases, and recumbences in 10% of cases were the clinical signs reported in symptomatic ma-laria cases. Anaemia and thrombocytopaenia made up the majority of the haematological abnormalities observed in malaria-infected buffaloes. This is the first report about Plasmodium bubalis in Iraqi buffaloes

Prediction of Exchange-Correlation Energy of Graphene Sheets from Reverse Degree-Based Molecular Descriptors with Applications

Over the past few years, the popularity of graphene as a potential 2D material has increased since graphene-based materials have applications in a variety of fields, including medicine, engineering, energy, and the environment. A large number of graphene sheets as well as an understanding of graphene’s structural hierarchy are critical to the development of graphene-based materials. For a variety of purposes, it is essential to understand the fundamental structural properties of graphene. Molecular descriptors were used in this study to investigate graphene sheets’ structural behaviour. Based on our findings, reverse degree-based molecular descriptors can significantly affect the exchange-correlation energy prediction. For the exchange-correlation energy of graphene sheets, a linear regression analysis was conducted using the reverse general inverse sum indeg descriptor, RGISI(p,q). From RGISI(p,q), a set of reverse topological descriptors can be obtained all at once as a special case, resulting in a model with a high correlation coefficient (R between 0.896 and 0.998). Used together, these reverse descriptors are graphed in relation to their response to graphene. Based on this study’s findings, it is possible to predict the exchange correlation energy as well as the geometric structures of graphene sheets with very little computational cost

Angiotensin 1-7 increases fiber cross sectional area and force in juvenile mouse skeletal muscle

Recent studies reported that in skeletal muscle angiotensin 1-7 (Ang 1-7), via its receptor Mas (MasR), prevents the atrophy induced by angiotensin II and by cast immobilization; it also improves muscle integrity and function in the mdx mouse, a muscular dystrophy model. The objectives of this study were to document i) the extent of the Ang 1-7's hypertrophic effect in terms of muscle mass and muscle fiber cross sectional area (CSA), ii) how Ang 1-7 affects muscle contractile function in terms of twitch and tetanic force, force-frequency relationship, and iii) whether the effect involves MasR. Wild type and MasR deficient (MasR(-/-)) mice were treated with Ang 1-7 (100 ng/kg body weight·min using an osmotic pump) for 4 or 16 weeks. Ang 1-7 significantly increased skeletal muscle/body weight ratio of soleus, tibialis and gastrocnemius, but not of EDL. It significantly increased fiber cross sectional area in the order of type I>IIA>IIB. In EDL and soleus muscles, it significantly increased twitch and tetanic force while causing a shift in the force-frequency relationship toward lower stimulation frequencies. It had no effect on fiber type composition. None of the Ang 1-7 effects observed in wild type mice were observed in MasR(-/-) muscles. It caused a transient increase in phosphorylated Akt and 4EBP proteins while having no effect on the phosphorylation of S6, MuRF-1 and atrogin-1 and a decrease in PAX7 expression in satellite cells. This is the first study demonstrating the hypertrophic effects of Ang 1-7 in normal muscle acting via its MasR

<i>Fagonia cretica</i>-Mediated Synthesis of Manganese Oxide (MnO₂) Nanomaterials Their Characterization and Evaluation of Their Bio-Catalytic and Enzyme Inhibition Potential for Maintaining Flavor and Texture in Apples

The apple is the most widely used fruit globally. Apples are more prone to fungal spoilage, which leads to browning and subsequent changes in their flavor and texture. Browning is also caused by the tyrosinase enzyme. By inhibiting tyrosinase initiation and fungal spoilage in fruits, the natural flavor and texture of fruits can be maintained. Biogenic NPs can act as antioxidants to inhibit tyrosinase and due to oxidative stress, it also catalyzes the deformation of fungal hyphae and spores. Nanotechnology is a research hotspot that has gained considerable interest due to its potential inferences in biosciences and food preservation technology. The present study aims to use biomass from the Fagonia cretica to create bio-inspired manganese oxide MnO2 NPs and to evaluate its bio-catalytic potential for antifungal anti-browning through the inhibition of tyrosinase and its antioxidant potential for preserving apple flavor and texture. The green synthesized nanoparticles were extensively analyzed using UV spectroscopy, XRD, SEM, EDX, and FTIR techniques. Moreover, the synthesized manganese oxide nanoparticles (MnO2 NPs) were evaluated for their bio-catalytic potential as anti-fungal and anti-spoiling agents. The values of antifungal activity among all the samples were 14.2 ± 86 mm, 8.9 ± 6.0 mm, 17.7 ± 1.26, and 20.7 ± 4.38 mm for Penicillium expansum, Monilinia fructigena, Penicillium chrysogenum, and Aspergillus oryzae at 200 µg/well, respectively. Moreover, the biogenic NPs were evaluated for their anti-browning potential through the inhibition of tyrosinase. MnO2 NPs have been shown to have considerable inhibitory effects on tyrosinase up to 64.8 ± 0.16 at 200 µg/mL and (27.2 ± 0.58) at 25 µg/mL. Biogenic MnO2 NPs can also act as antioxidants to inhibit tyrosinase and fungal growth by the formation of free radicals that damage the fungal hyphae and, as a result, slow down browning. The maximum DPPH free radical scavenging activity was 74.5 ± 0.39% at 200 µg/mL, and the minimum was 12.4 ± 0.27 at 25 µg/mL. The biogenic MnO2 NPs are biocompatible and play a potent role in maintaining the flavor and texture of apples

Biological Mineralization of Methyl Orange by Pseudomonas aeruginosa

Due to its recalcitrant and carcinogenic nature, the presence of methyl orange (MO) in the environment is a serious threat to human and animal life and is also toxic to plants. MO being recalcitrant cannot be effectively reclaimed from industrial effluents through physical and chemical approaches. Biological methods on the other hand have the potential to degrade such dyes because of their compatibility with nature and low chances of adverse effects on the environment. Bacteria, due to their fast growth rate and capability of surviving in extreme environments can effectively be used for this purpose. In the current research study, Pseudomonas aeruginosa was isolated and characterized using 16rRNA from textile wastewater. In the preliminary tests it was found that Pseudomonas aeruginosa has the ability to degrade and mineralize methyl orange effectively. The physicochemical conditions were then optimized, in order to get maximum degradation of MO which was achieved at 37 &deg;C, a pH of 7, a low salt concentration of 0.1 g/15 mL, a high carbon source of 0.6 g/15 mL, and 72 h experimental time. In a single set of experiments where all these optimum conditions were combined, 88.23% decolorization of the selected dye was achieved. At the end of the experimental cycle, the aliquots were homogenized and filtered. The filtrates were subjected to FTIR and GC-MS analysis where azo linkage breaking was confirmed from the FTIR spectra. The filtrates were then extracted with ethyl acetate and then passed through a silica gel column. On the basis of Rf value (TLC plates used) similar fraction were combined which were then subjected to NMR analysis. The compounds detected through GC-MS, peaks were not observed in proton and C-13 NMR. Instead, solvent and some impurity peaks were present, showing that complete mineralization of the dye had occurred due to the action of different bacterial enzymes such as azoreductase, peroxidases, and classes on MO. The prosed mechanism of complete mineralization is based on spectral data that needs to be verified by trapping the individual step products through the use of appropriate inhibitors of individual enzymes

A molecular informatics and in-vitro approach to evaluate the HMG-CoA reductase inhibitory efficacy of monoterpenes, carvacrol and geraniol

Currently, statins, the β-hydroxy-β-methyl-glutaryl-CoA reductase (HMG-R) inhibitors, are widely used to lower cholesterol, nevertheless, they have several side effects. Consequently, the present study is designed to unravel the cardioprotective role of selected natural monoterpenoids (carvacrol and geraniol) via in-vitro targeting and molecular informatics study of HMG-R. Computational molecular informatics study revealed that carvacrol and geraniol efficiently occupies the catalytic site of HMG-R with the binding affinity (ΔG) of −4.60, and −1.99 Kcal/mol, respectively, and molecular mechanical-generalized Born surface area (MM-GBSA) free binding energy was depicted as −17.05 and −29.48 Kcal/mol, respectively. Further, molecular dynamics simulation was carried out for 100 ns. Carvacrol and geraniol potentially and competitively inhibit the in-vitro HMG-R activity with an IC50 value of 78.23 ± 2.21 µM, and 72.91 ± 2.92 µM, respectively. Thus, both carvacrol and geraniol exhibited significant anti-hypercholesterolemic activity while the molecular simulation studies depicted that the GR complex showed better stability than the carvacrol complex

Apitoxin alleviates methyl mercury-induced peripheral neurotoxicity in male rats by regulating dorsal root ganglia neuronal degeneration and oxidative stress

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats

The nuclear matrix protein CIZ1 facilitates localisation of Xist RNA to the inactive X-chromosome territory

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins, and has been linked with adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells, and is retained by interaction with the RNAdependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of Xist RNA during the earliest stages of X-inactivation in embryonic stem cells, and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E-repeats of Xist. CIZ1 null mice, although viable, display fully penetrant female specific lymphoproliferative disorder. Interestingly, in MEF cells derived from CIZ1 null embryos Xist RNA localisation is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localisation is reinstated following re-expression of CIZ1. Focal localisation of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1 null animals, suggesting a possible explanation for female specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages