A comprehensive genetic characterization of bacterial motility

We have developed a powerful experimental framework that combines competitive selection and microarray-based genetic footprinting to comprehensively reveal the genetic basis of bacterial behaviors. Application of this method to Escherichia coli motility identifies 95% of the known flagellar and chemotaxis genes, and reveals three dozen novel loci that, to varying degrees and through diverse mechanisms, affect motility. To probe the network context in which these genes function, we developed a method that uncovers genome-wide epistatic interactions through comprehensive analyses of double-mutant phenotypes. This allows us to place the novel genes within the context of signaling and regulatory networks, including the Rcs phosphorelay pathway and the cyclic di-GMP second-messenger system. This unifying framework enables sensitive and comprehensive genetic characterization of complex behaviors across the microbial biosphere.     

Carnosine and Histidine Supplementation Blunt Lead-Induced Reproductive Toxicity through Antioxidative and Mitochondria-Dependent Mechanisms

Biological Trace Element Research - Lead (Pb)-induced reproductive toxicity is a well-characterized adverse effect associated with this heavy metal. It has been found that Pb exposure is associated...     

Trastuzumab-monomethyl auristatin E conjugate exhibits potent cytotoxic activity in vitro against HER2-positive human breast cancer

Targeted therapy using specific monoclonal antibodies (mAbs) conjugated to chemotherapeutic agents or toxins has become one of the top priorities in cancer therapy. Antibody–drug conjugates (ADCs) are emerging as a promising strategy for cancer-targeted therapy. In this study, trastuzumab, a humanized monoclonal anti-HER2 antibody, was reduced by dithiothreitol and conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) through a valine-citrulline peptide linker (trastuzumab-MC-Val-Cit-PABC-MMAE [trastuzumab-vcMMAE]). After conjugation, ADCs were characterized by using UV–vis, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and flow cytometry. The antitumor activity of the ADC was evaluated in breast cancer cells in vitro. In addition, ADCs were further characterized using purification by the protein A chromatography, followed by assessment using apoptosis and MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. Hydrophobic interaction chromatography was used to determine drug-to-antibody ratio species of ADCs produced. Our finding showed that approximately 5.12 drug molecules were conjugated to each mAb. H2L2, H2L, HL, H2, H, and L forms of ADCs were detected in nonreducing SDS-PAGE. The binding of trastuzumab-vcMMAE to HER2-positive cells was comparable with that of the parental mAb. The MTT assay showed that our ADCs induced significant cell death in HER2-positive cells, but not in HER2-negative cells. The ADCs produced was a mixture of species, unconjugated trastuzumab (14.147%), as well as trastuzumab conjugated with two (44.868%), four (16.886%), six (13.238%), and eight (10.861%) molecules of MMAE. These results indicated that MMAE-conjugated trastuzumab significantly increases the cytotoxic activity of trastuzumab, demonstrating high affinity, specificity, and antitumor activity in vitro. Trastuzumab-vcMMAE is an effective and selective agent for the treatment of HER2-positive breast tumors.     

Reversible permeabilization of the mitochondrial membrane promotes human cardiomyocyte differentiation from embryonic stem cells

Cell death and differentiation appear to share similar cellular features. In this study, we aimed to investigate whether differentiation and mitochondrial cell death use a common pathway. We assessed the hallmarks of apoptosis during cardiomyocyte differentiation of human embryonic stem cells and found remarkable changes in P53, reactive oxygen species, apoptotic protease-activating factor 1, poly[ADP-ribose]polymerase 1, cellular adenosine triphosphate, and mitochondrial complex I activity. Furthermore, we observed reversible mitochondrial membrane permeabilization during cardiomyocyte differentiation accompanied by reversible loss of mitochondrial membrane potential, and these changes coincided with the fluctuating patterns of cytosolic cytochrome c accumulation and subsequent caspase-9 and -3/7 activation. Moreover, the use of apoptosis inhibitors (BCL2-associated X protein [BAX] inhibitor and caspase-3/7 inhibitor) during differentiation impaired cardiomyocyte development, resulting in substantial downregulation of T, MESP1, NKX2.5, and α-MHC. Additionally, although the expression of specific differentiation markers (T, MESP1, NKX2.5, MEF2C, GATA4, and SOX17) was enhanced in doxorubicin-induced human embryonic stem cells, the stemness-specific markers (OCT4 and NANOG) showed significant downregulation. With increasing doxorubicin concentration (0.03–0.6 µM; IC₅₀ = 0.5 µM), we observed a marked increase in the expression of mesoderm and endoderm markers. In summary, we suggest that reversible mitochondrial outer membrane permeabilization promotes cardiomyocyte differentiation through an attenuated mitochondria-mediated apoptosis-like pathway.     

Impact of chrysin on the molecular mechanisms underlying diabetic complications

Diabetes mellitus is a chronic metabolic disorder, resulting in high morbidity and mortality worldwide. Neuropathy, ocular diseases, kidney diseases, and cardiovascular disease are common complications of diabetes that threats the patient’s life. Chrysin (CH), a natural flavonoid, has several pharmacological effects, including antioxidant, antiapoptotic, anti-inflammatory, and anticancer. Strong scientific documents indicated that chrysin may be effective for preventing and treating complications of diabetes in experimental models. The present study was designed to review the association between chrysin administration and diabetes complications by focusing on the possible molecular pathway. The findings indicate that chrysin has protective effects against diabetes outcomes by modulating oxidative stress, inflammation, and apoptosis in animal models. However, more clinical trial study should be done to clear the protective effects of chrysin in diabetic patients.     

Non-dipping blood pressure in the metabolic syndrome among Arabs of the Oman family study

Objective: The objective was to examine the circadian changes in blood pressure and their relation to the metabolic syndrome and its components in Omani Arabs. Research Methods and Procedures: Ambulatory blood pressure (ABPM) was recorded in 1124 subjects from 5 large, extended, consanguineous, and young Arab pedigrees. According to the International Diabetes Federation's definition, 264 subjects had the metabolic syndrome, a prevalence of 23%. Subjects were defined as non‐dippers when their nocturnal systolic blood pressure (SBP) fell by <10% from daytime SBP. Results: Non‐dippers with the metabolic syndrome were 131 of 264 (50%), compared with 265 of 860 (31%) without the metabolic syndrome. Of the non‐dippers, 99 of 131 (76%) were females and 32 of 131 (24%) were males. Daytime and nighttime SBP and DBP and nighttime pulse pressure were significantly higher in non‐dipper subjects with the metabolic syndrome. The important determinants of a non‐dipping BP in this cohort were high BMI and high serum triglycerides. Discussion: We hypothesize that obesity and nocturnal volume‐dependent hypertension may be involved in the pathophysiology of non‐dipping in the metabolic syndrome. This study showed that non‐dipping BP was common in subjects with the metabolic syndrome. Higher 24‐hour blood pressure load may add to the indices of the overall cardiovascular burden already associated with the metabolic syndrome.     

Photosynthetic Efficiency and Antioxidant Defense Potential are Key Players in Inducing Drought Tolerance in Transgenic Tobacco Plants Over-Expressing AVP1

Journal of Plant Growth Regulation - Plants have developed a number of physiological, biochemical, and molecular strategies to overcome water deficit conditions. Arabidopsis vacuolar...     

TGF-β1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways

Journal of Molecular Histology - Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal...     

AI-assisted bio-inspired algorithm for secure IoT communication networks

Cluster Computing - The Internet of Things (IoT) is made up of intelligent devices that interact with each other. It allows information to be gathered and shared by these devices. In addition, IoT...     

Remote Paraparesis due to a Traumatic Extradural Arachnoid Cyst Developing 2 Years after Brachial Plexus Root Avulsion Injury: Case Report and Review of the Literature

Traumatic extradural arachnoid cyst is a rare entity. However, late appearance of paraparesis due to formation of an extradural arachnoid cyst as a sequel of brachial plexus injury is extremely rare and the literature regarding this issue is scarce revealing only 11 cases. Herein, we report a patient with delayed progressive spastic paraparesis appearing after a multilevel brachial plexus root avulsion injury where imaging revealed formation of a large traumatic extradural arachnoid cyst at the cervicothoracic region. Furthermore, to propose that a high-energy trauma might simultaneously result in delayed formation of an extradural arachnoid cyst. However, preganglionic root avulsion injury with pseudomeningocele formation in association with extradural arachnoid cyst is not reported previously. A case of a 36-year-old man with spastic paraparesis developing 2 years after a multilevel brachial plexus root avulsion injury is presented. Root avulsion had immediately resulted in complete paralysis of the left upper limb that had not ameliorated. Imaging studies of the cervicothoracic region disclosed left-sided multilevel pseudomeningoceles and a large extradural arachnoid cyst extending from C5 to T2. After appropriate en bloc laminotomy, the cyst was excised and the causative dural tear was closed. Subsequently, three large defects of pseudomeningoceles were obliterated with artificial dural patch for the prevention of cord herniation. This was followed with laminoplasty of the corresponding levels after dural closure. The postoperative course was uneventful and paraparesis recovered steadily within 2 months. Paraparesis even years after brachial plexus injury should be regarded as a serious event that deserves extensive imaging survey for the possibility of the formation of an extradural arachnoid cyst. Careful review of the literature disclosed that the current case is the 12th case that an extradural arachnoid cyst has developed after brachial plexus injury and the first example that the pathogenic factor that might be implicated in occurrence of this rare association could be clarified with review of the MRI features. Actually, the presence of posttraumatic pseudomeningoceles in association with an arachnoid cyst in the current case is in favor of the belief that only preganglionic root injuries that are in close proximity to the spinal canal had been the cause dural tear with remote formation of extradural arachnoid cyst.