Glutamate Decarboxylases in Nonneural Cells of Rat Testis and Oviduct: Differential Expression of GAD 65 and GAD 67

Γ-Aminobutyric acid (GABA) and its synthetic enzyme, glutamate decarboxylase (GAD), are not limited to the nervous system but are also found in nonneural tissues. The mammalian brain contains at least two forms of GAD (GAD 67 and GAD 65 ), which differ from each other in size, sequence, immunoreactivity, and their interaction with the cofactor pyridoxal 5′-phosphate (PLP). We used cDNAs and antibodies specific to GAD 65 and GAD 67 to study the molecular identity of GADs in peripheral tissues. We detected GAD and GAD mRNAs in rat oviduct and testis. In oviduct, the size of GAD, its response to PLP, its immunoreactivity, and its hybridization to specific RNA and DNA probes all indicate the specific expression of the GAD 65 gene. In contrast, rat testis expresses the GAD 67 gene. The GAD in these two reproductive tissues is not in neurons but in nonneural cells. The localization of brain GAD and GAD mRNAs in the mucosal epithelial cells of the oviduct and in spermatocytes and spermatids of the testis shows that GAD is not limited to neurons and that GABA may have functions other than neurotransmission.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66211/1/j.1471-4159.1992.tb09763.x.pd

Minor early embryonic chick hemoglobin M. Amino acid sequences of the epsilon and alpha D chains

Erythrocytes of the early chick embryo contain four hemoglobins, two major and two minor. In this paper, we present amino acid sequences for the beta-like and alpha-like chains of HbM, the least abundant of the four early chick hemoglobins. The complete amino acid sequence of the beta-like chain of HbM is identical with that of the epsilon chain of HbE, the other minor early embryonic hemoglobin in the domestic chicken. Analysis of the alpha-like chain of HbM (92 of 141 residues) reveals a globin sequence closely related to the minor adult alpha D chain. Comparison of our sequence data with the nucleotide sequence of the alpha D globin gene suggests that a single gene encodes both the embryonic and adult alpha D globin polypeptides. We discuss the structure, possible function, and evolution of the HbM globin chains

Complete amino acid sequence of the major early embryonic beta-like globin in chickens

The rho globin is the major beta-like chain found in 5-day-old chick embryos. In association with two unique early embryonic alpha-like globins, it forms the two major hemoglobins of early chick development. This paper presents the complete amino acid sequence of the rho globin. There are no amino acid differences between the rho chain and the adult chicken beta chain at known Bohr effect or organophosphate-binding positions, and there are only 19 differences altogether. The rho globin ought to be functionally equivalent to the adult chicken beta globin. Since the adult and embryonic chains are very similar in sequence, they may be products of a relatively recent gene duplication in the chicken beta globin gene family. The possibility of a gene correction event is discussed

Amino acid sequences of the epsilon and alpha E globins of HbE, a minor early embryonic hemoglobin of the chicken

We have determined amino acid sequences for the alpha-like and beta- like globin components of HbE, one of the two minor hemoglobins in early chick embryos. The complete primary structure of the epsilon chain differs at 18 positions from the adult chicken beta globin, but there are no changes in heme-binding residues, alpha 1 beta 2 contact positions, or allosteric regulatory sites. By amino acid sequence analysis, we have identified a new alpha-like globin that we have called alpha E. The alpha E globin chain differs from the major adult alpha A chain at 22 amino acid positions. This paper discusses the structural and implied functional characteristics of these globins and presents hypotheses regarding the possible role of minor embryonic hemoglobins

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

A flow platform for degradation-free CuAAC bioconjugation

We thank Vapourtec for the copper reactors, the EPSRC UK National Mass Spectrometry Facility at Swansea University for analyses, the University of Strathclyde for PhD studentship (M.Z.C.H.), the Leverhulme Trust for a postdoctoral fellowship (L.F.R.; grant no. RPG-2014-001), and the BBSRC for funding (grant nos. BB/R006857/1, BB/N016378/1).The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.Publisher PDFPeer reviewe

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection

Item does not contain fulltextBACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan

Cystic Fibrosis, Atopy, Asthma and ABPA

The role of atopy on cystic fibrosis (CF) progression remains unclear but evidence suggests that it may influence the appearance of co-morbid conditions such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA). Recognising asthma in patients with CF is not always easy but the identification of atopic markers favours the diagnosis. Physicians should be aware of this fact in order to achieve a better control of respiratory symptoms in patients with CF. Bronchial mucosa inflammation and abnormal mucus predispose to mould colonisation. These patients are at higher risk of allergic sensitisation, especially when atopic susceptibility is present. In the particular case of A. fumigatus, allergic sensitisation precedes ABPA development, which occurs in up to 10% of CF patients. Progression of lung function deterioration is most strikingly pronounced in patients with ABPA. Therefore, sensitisation with A. fumigatus should be regularly tested in patients with CF, especially those at higher risk. Recombinant allergens constitute an important advance in differentiating Aspergillus sensitisation from ABPA itself

Genome wide association study of Preserved Ratio Impaired Spirometry (PRISm)

Background: Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1 &lt;80% predicted, FEV1/FVC ≥0.70. PRISm is associated with respiratory symptoms and co-morbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated co-morbidities.Methods: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected SNPs reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait Linkage Disequilibrium score regression to estimate genome-wide genetic correlation between PRISM and pulmonary and extra-pulmonary traits. Phenome-wide association studies of top SNPs was performed. Results: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg = 0.62, p-value &lt;0.001) was observed, and genetic correlation with type II diabetes (rg = 0.12, p-value 0.007). PheWAS showed that 18 of 22 signals were associated with diabetic traits and 7 with blood pressure traits.Discussion: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals; rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B) have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extra-pulmonary co-morbidity.<br/