Estrogen as a Multi-Active Neuroprotective Agent in Traumatic Injuries

In the past decade, research has demonstrated that estrogens role in physiology and development is far more complicated than previously assumed. Among these discoveries, there has been an increased recognition of the impact estrogen has in neurodevelopment, central nervous system physiology, and neuropathophysiology. These observations have led many researchers to consider using estrogen pharmacotherapeutically, at physiologic or supraphysiologic doses, for a variety of injury and toxicity models. In this short review, the effects of estrogen as an anti-apoptotic agent, as an anti-oxidant, and as an anti-inflammatory agent are discussed. Finally, the possibility of using estrogen as a neuroprotectant in neurotrauma is addressed.Special issue dedicated to Dr. Lawrence F. Eng.     

Site-independently integrated transgenes in the elite restorer rice line Minghui 63 allow removal of a selectable marker from the gene of interest by self-segregation

In this study, we have demonstrated that two independent loci are involved in the integration of the insecticidal protein gene cryIAb/cryIAc and selectable marker gene hph in the recipient genome of the elite Chinese CMS restorer line Minghui 63. We have also documented the structural organization of these transgenes in each locus by restriction enzyme digestion and Southern blot analysis. The independent locus integration of different transgenes allowed us to remove the selectable marker gene hph from the gene of interest simply by self-segregation. Not having the selectable marker gene will enhance the commercial value of our transgenic line TT51-1, which showed a consistently high level of resistance against repeated infestations of yellow stem borers and natural outbreaks of leaf-folders, without a reduction in yield potential.     

SLEB3 in systemic lupus erythematosus (SLE) is strongly related to SLE families ascertained through neuropsychiatric manifestations

Seizures and psychosis are neuropsychiatric (NP) manifestations of a large number of systemic lupus erythematosus (SLE) patients. Since NP manifestations were part of the SLE phenotype for some, but not all SLE affecteds, we hypothesized that those SLE patient families with NP manifestations might be more genetically homogeneous at loci important to NP-related SLE, and hence have increased power to detect linkage. We identified 23 families of European-American (EA) origin and 20 families of African-American (AA) origin, in which at least one SLE patient in each family was diagnosed with the presence of NP manifestations. A total of 318 microsatellite markers at an average marker density of 11 cM were genotyped. Uncertainty of the genetic model led us to perform the initial genome scan by a multipoint non-parametric allele sharing linkage method. Once the evidence of linkage was suggestive, we then performed parametric model-based linkage by maximizing the relevant parameters to define a parsimonious genetic model. We found the maximum multipoint parametric LOD score was 5.19 and the non-parametric linkage score (Zlr) was 3.12 ( P=9x10(-4)) for EA NP pedigrees at 4p16, previously identified as SLEB3. The segregation behavior of this linked locus suggests a dominant mode of inheritance with an almost 100% homogeneous genetic effect in these pedigrees. The results demonstrated a significant increase of LOD score to detect SLEB3 when the families were further ascertained through NP, compared with the analysis of all EA SLE families together.     

Quercetin and Sodium Butyrate Synergistically Increase Apoptosis in Rat C6 and Human T98G Glioblastoma Cells Through Inhibition of Autophagy

Neurochemical Research - This study investigated the efficacy of quercetin (QCT) in combination with sodium butyrate (NaB) in enhancing apoptosis in rat C6 and human T98G glioblastoma cells though...     

Microwave-assisted synthesis of imidazoles: reaction of p-toluenesulfonylmethyl isocyanide and polymer-bound imines

A convenient method for the synthesis of 1,5-disubstituted imidazoles has been developed on a polymeric support using base-promoted 1,3-dipolar cycloaddition reaction of p-toluenesulfonylmethyl isocyanide (TOSMIC) with immobilized imines under microwave irradiation. The immobilized imines were synthesized by the reaction of various primary benzyl amines with 4-formyl-3-methoxyphenoxymethyl polystyrene in the presence of trimethyl orthoformate at room temperature. Cleavage from the polymeric support using trifluoroacetic acid gave the desired 1,5-disubstituted imidazoles with excellent yield and high purity.     

Glucocorticoid effects on gastric peroxidase activity

The peroxidase activity in rat gastric mucosa is inhibited after administration of glucocorticoids. The synthetic steroid dexamethasone is more potent than the naturally occurring steroids, such as cortisone or corticosterone. Almost complete inhibition of the enzyme occurs after 24 h with a single dose of 100 μg dexamethasone/120 g body weight. Other mitochondrial enzyme activities, like monoamine oxidase, succinic dehydrogenase and Mg²⁺-ATPase, remain unaltered under the same experimental condition. Submaxillary peroxidase and thyroid peroxidase activity are not inhibited by dexamethasone. Gastric peroxidase activity is increased 200–250% on the 6th day after adrenalectomy. This effect is blocked by the administration of dexamethasone. In fact, the enzyme becomes more sensitive to dexamethasone after adrenalectomy, since it is inhibited by more than 90% at the dose of 25 μg/120 g body weight. The inhibition by dexamethasone in normal animals is reversible. The enzyme is also inhibited after the administration of a single dose of ACTH. The apparent K_m of the enzyme for H₂O₂ is not altered after dexamethasone treatment or after adrenalectomy. The increase in enzyme activity following adrenalectomy is not blocked by actinomycin D or by α-amanitin, but is prevented by puromycin or cycloheximide. After administration of dexamethasone, the iodide concentration process in the gastric mucosa is not affected, but the organification of iodide is significantly diminished.     

A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations.     

Structural insights into the interactions of xpt riboswitch with novel guanine analogues: a molecular dynamics simulation study

Ligand recognition in purine riboswitches is a complex process requiring different levels of conformational changes. Recent efforts in the area of purine riboswitch research have focused on ligand analogue binding studies. In the case of the guanine xanthine phosphoribosyl transferase (xpt) riboswitch, synthetic analogues that resemble guanine have the potential to tightly bind and subsequently influence the genetic expression of xpt mRNA in prokaryotes. We have carried out 25 ns Molecular Dynamics (MD) simulation studies of the aptamer domain of the xpt G-riboswitch in four different states: guanine riboswitch in free form, riboswitch bound with its cognate ligand guanine, and with two guanine analogues SJ1 and SJ2. Our work reveals novel interactions of SJ1 and SJ2 ligands with the binding core residues of the riboswitch. The ligands proposed in this work bind to the riboswitch with greater overall stability and lower root mean square deviations and fluctuations compared to guanine ligand. Reporter gene assay data demonstrate that the ligand analogues, upon binding to the RNA, lower the genetic expression of the guanine riboswitch. Our work has important implications for future ligand design and binding studies in the exciting field of riboswitches.     

Diosgenin as a Novel Alternative Therapy for Inhibition of Growth,Invasion, and Angiogenesis Abilities of Different Glioblastoma Cell Lines

Neurochemical Research - Fenugreek (Trigonella foenum-graecum) seeds and roots of wild yam (Dioscorea villosa) possess nutritional and medicinal properties and have been used for centuries in...