Geographical mapping and seroprevalence of Burkholderia pseudomallei amongst livestock species in Lao People’s Democratic Republic

The Gram-negative bacterium Burkholderia pseudomallei causes a severe infectious disease known as melioidosis in humans and animals. It is considered endemic in tropical countries, including Thailand, Lao PDR (Laos), and Northern Australia. B. pseudomallei is a saprophyte found in contaminated soil and surface water. Humans and animals can become infected via direct exposure to contaminated water or soil and inhalation of dust or water droplets. Despite the high morbidity and mortality rates of melioidosis, there is a lack of knowledge of its geographical distribution and seroprevalence, even within endemic countries, raising a significant public health concern. For a better understanding of melioidosis in livestock in Laos, both as an animal health concern and as an indicator of human risk, we collected serum samples from an abattoir monitoring program for B. pseudomallei antibody testing using the Indirect Haemagglutination Assay (IHA). Out of the 917 sera collected, major findings included the identification of a significant cluster (p = 0.041) in the southwest border region adjoining northeastern Thailand, in the province of Savannakhet in Laos. Sera collected in January 2020 had the highest B. pseudomallei seroprevalence (17.0%), and cattle had the highest seroprevalence (22.8%), followed by buffalo (19.7%) and swine (4.0%). The B. pseudomallei seroprevalence results among the common livestock species and the maps generated can assist with future monitoring, prevention, and detection of melioidosis in Laos

The Modified Shields Classification and 12 Families with Defined DSPP Mutations

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II

Advances in Proline Ligation

Application of native chemical ligation logic to the case of an N-terminal proline is described. Two approaches were studied. One involved incorporation of a 3<i>R-</i>substituted thiyl-proline derivative. Improved results were obtained from a 3<i>R</i>-substituted selenol function, incorporated in the context of an oxidized dimer

Ionic Mechanisms Underlying the Effects of Vasoactive Intestinal Polypeptide on Canine Atrial Myocardium

Background— Vasoactive intestinal polypeptide (VIP) is released from intracardiac neurons during vagal stimulation, ischemia, and heart failure, which are associated with increased vulnerability to atrial fibrillation. VIP shortens atrial effective refractory periods in dogs. Endogenous VIP contributes to vagally mediated acceleration of atrial electric remodeling. VIP is also shown to prolong the duration of acetylcholine-induced atrial fibrillation. However, the ionic mechanisms underlying VIP effects are largely unknown. Methods and Results— The effects of VIP on transmembrane ion channels were studied in canine atrial cardiomyocytes using patch-clamp techniques. VIP increased delayed rectifier K + current and L-type calcium current but decreased the transient outward K + current and sodium current. Optical mapping technique was used to assess effects of VIP on action potential durations (APDs) in isolated canine left atria. VIP shortened APD and slowed conduction velocity in a dose-dependent manner. Furthermore, VIP increased spatial heterogeneity of APD and conduction velocity, as assessed by the SDs of APD and conduction velocity, and atrial fibrillation inducibility. Conclusions— Through its diverse effects on ion channels, VIP shortens APD with increased APD spatial heterogeneity and decreases intra-atrial conduction velocity, which may play an important role in the pathogenesis of atrial arrhythmias in scenarios where VIP release is increased. </jats:sec

The Modified Shields Classification and 12 Families with Defined DSPP Mutations

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5&prime;-group that affects protein targeting and a 3&prime;-group that shifts translation into the &minus;1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T&gt;C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5&prime;-DSPP mutations, and 3&prime;-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5&prime;-Dspp or 3&prime;-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5&prime;-DSPP defects be diagnosed as DGI-III, while those with 3&prime;-DSPP defects be diagnosed as DGI-II

The Modified Shields Classification and 12 Families with Defined DSPP Mutations

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5 '-group that affects protein targeting and a 3 '-group that shifts translation into the -1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5 '-DSPP mutations, and 3 '-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5 '-Dspp or 3 '-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5 '-DSPP defects be diagnosed as DGI-III, while those with 3 '-DSPP defects be diagnosed as DGI-II

The Modified Shields Classification and 12 Families with Defined DSPP Mutations

Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T&gt;C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.</jats:p