Highly fluorescent aryl-cyclopentadienyl ligands and their tetra-nuclear mixed metallic potassium–dysprosium clusters

Two alkyl substituted triaryl-cyclopentadienyl ligands [4,4′-(4-phenylcyclopenta-1,3-diene-1,2-diyl)bis(methylbenzene) (1) and 4,4′,4′′-(cyclopenta-1,3-diene-1,2,4-triyl)tris(methylbenzene) (2)] have been synthesized via cross-aldol condensation followed by Zn-dust mediated cyclization and acid catalyzed dehydration reactions. The fluorescence properties of 1 and 2 have been studied in solution and solid state. The ligands exhibited aggregation-induced emission enhancement (AIEE) in THF/water solution. 1 and 2 have been found to be significantly more fluorescent in the solid state than in their respective solutions. This phenomenon can be attributed to the strong intermolecular CH⋯π interactions present in 1 and 2 which leads to the tight packing of molecules in their solid-state. Both 1, 2 and their corresponding anions have been studied by theoretical calculations. Ligands 1 and 2 have been shown to react with anhydrous DyCl₃ in the presence of potassium metal at high temperature to afford two fluorescent chloride-bridged tetra-nuclear mixed potassium–dysprosium metallocenes [(Me₂Cp)₄Dy₂^IIICl₄K₂]·3.5(C₇H₈) (5) and [(Me₃Cp)₄Dy₂^IIICl₄K₂]·3(C₇H₈) (6), respectively in good yields.

Alkyl substituted triaryl-cyclopentadienyl ligands with aggregation-induced emission enhancement (AIEE) properties and their applications in the syntheses of novel chloride bridged tetra-nuclear mixed potassium–dysprosium metallocenes.     

Optimized and Validated Stability Indicating RP-HPLC Method for Estimation of Nadolol

Pharmaceutical Chemistry Journal - A stability indicating RP-HPLC method for the determination of nadolol was developed and validated using Enable C18 (250 mm × 4.6 mm, 5 μm) column with...     

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

Diabetes mellitus (DM) is a gradually rising metabolic disease which is currently affecting millions of people worldwide. Diabetes is associated with various complications like nephropathy, neuropathy, retinopathy, diabetic foot, cognitive impairment, and many more. Evidence suggests that cognitive dysfunction is a rising complication of diabetes which adversely affects the brain of patients suffering from diabetes. Age-related memory impairment is a complication having its major effect on people suffering from diabetes and Alzheimer's. Patients suffering from diabetes are at two times higher risk of developing cognitive dysfunction as compared with normal individuals. Multiple factors which are involved in diabetes related complications are found to play a role in the development of neurodegeneration in Alzheimer's. The problem of insulin deficiency and insulin resistance is well reported in diabetes but there are many studies which suggest dysregulation of insulin levels as a reason behind the development of Alzheimer's. As the link between diabetes and Alzheimer disease (AD) is deepening, there is a need to understand the plausible tie-ins between the two. Emerging role of major factors like insulin imbalance, advanced glycation end products and micro-RNA's involved in diabetes and Alzheimer's have been discussed here. This review helps in understanding the plausible mechanism underlying the pathophysiology of amyloid beta (Aβ) plaque formation and tau hyperphosphorylation as well provides information about studies carried out in this area of research. The final thought is to enhance the scientific knowledge on this correlation and develop future therapeutics to treat the same.     

De Novo Belatacept in a Human Immunodeficiency Virus–Positive Kidney Transplant Recipient

Benefits of belatacept‐based immunosuppressive regimens in human immunodeficiency virus (HIV)–positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new‐onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV‐positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV‐positive renal transplant recipient.     

Extensive cross-reactive neutralizing antibody response in Indian patients with limited genetic diversity of HIV-1

Genome sequence analysis of HIV-1 subtype C viruses from India shows monophyletic lineage and relatively limited genetic diversity. To understand its immunological implication, cross-reactivity of neutralizing antibody response was investigated. In primary screening, neutralizing antibody response to single heterologous primary HIV-1 subtype C isolate was assessed in plasma samples from 235 HIV-1 infected, anti-retroviral treatment naive individuals from Pune, India. Plasma samples that showed > or =90% neutralization and two randomly selected plasma samples that showed 50-60% neutralization were tested against a panel of primary HIV-1 subtype C isolates obtained from epidemiologically unlinked individuals from India. The neutralizing antibody response showed extensive cross-neutralization, suggesting presence of shared neutralization determinants among circulating HIV-1 subtype C viruses in India.     

A channelized Hotelling observer study of lesion detection in SPECT MAP reconstruction using anatomical priors

In emission tomography, anatomical side information, in the form of organ and lesion boundaries, derived from intra-patient coregistered CT or MR scans can be incorporated into the reconstruction. Our interest is in exploring the efficacy of such side information for lesion detectability. To assess detectability we used the SNR of a channelized Hotelling observer and a signal-known exactly/background-known exactly detection task. In simulation studies, we incorporated anatomical side information into a SPECT MAP (maximum a posteriori) reconstruction by smoothing within but not across organ or lesion boundaries. A non-anatomical prior was applied by uniform smoothing across the entire image. We investigated whether the use of anatomical priors with organ boundaries alone or with perfect lesion boundaries alone would change lesion detectability relative to the case of a prior with no anatomical information. Furthermore, we investigated whether any such detectability changes for the organ-boundary case would be a function of the distance of the lesion to the organ boundary. We also investigated whether any detectability changes for the lesion-boundary case would be a function of the degree of proximity, i.e. a difference in the radius of the true functional lesion and the radius of the anatomical lesion boundary. Our results showed almost no detectability difference with versus without organ boundaries at any lesion-to-organ boundary distance. Our results also showed no difference in lesion detectability with and without lesion boundaries, and no variation of lesion detectability with degree of proximity.     

Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice

Obesity is characterized by hyperinsulinemia, hyperleptinemia, and an increase in islet volume. While the mechanisms that hasten the onset of diabetes in obese individuals are not known, it is possible that the adipose-derived hormone leptin plays a role. In addition to its central actions, leptin exerts biological effects by acting in peripheral tissues including the endocrine pancreas. To explore the impact of disrupting leptin signaling in the pancreas on beta cell growth and/or function, we created pancreas-specific leptin receptor (ObR) KOs using mice expressing Cre recombinase under the control of the pancreatic and duodenal homeobox 1 (Pdx1) promoter. The KOs exhibited improved glucose tolerance due to enhanced early-phase insulin secretion, and a greater beta cell mass secondary to increased beta cell size and enhanced expression and phosphorylation of p70S6K. Similar effects on p70S6K were observed in MIN6 beta cells with knockdown of the ObR gene, suggesting crosstalk between leptin and insulin signaling pathways. Surprisingly, challenging the KOs with a high-fat diet led to attenuated acute insulin secretory response to glucose, poor compensatory islet growth, and glucose intolerance. Together, these data provide direct genetic evidence, from a unique mouse model lacking ObRs only in the pancreas, for a critical role for leptin signaling in islet biology and suggest that altered leptin action in islets is one factor that contributes to obesity-associated diabetes.