Bartonweinreich0070

The clinicopathological phenotype of G2019S LRRK2-associated Parkinson's disease (L2PD) is similar to idiopathic Parkinson's disease (iPD), and G2019S LRRK2 nonmanifesting carriers (L2NMCs) are at increased risk for development of PD. With various therapeutic strategies in the clinical and preclinical pipeline, there is an urgent need to identify biomarkers that can aid early diagnosis and patient enrichment for ongoing and future LRRK2-targeted trials.

The objective of this work was to investigate differential protein and phospho-protein changes related to G2019S mutant LRRK2 in peripheral blood mononuclear cells from G2019S L2PD patients and G2019S L2NMCs, identify specific phospho-protein changes associated with the G2019S mutation and with disease status, and compare findings with patients with iPD.

We performed an unbiased phospho-proteomic study by isobaric label-based mass spectrometry using peripheral blood mononuclear cell group pools from a LRRK2 cohort from Spain encompassing patients with G2son and Movement Disorder Society.

We found a differential phospho-signature associated with LRRK2 G2019S for which, consistent with disease status, the phospho-profile from PD at-risk G2019S L2NMCs was more similar to healthy controls than patients with G2019S L2PD with the manifested disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Diagnosis of pituitary pars intermedia dysfunction (PPID) using the thyrotropin-releasing hormone (TRH) stimulation test requires blood collection 10minutes after TRH injection; it is unknown if small differences in timing affect test results.

To determine whether early or late sampling results in a significant (≥10%) difference in plasma adrenocorticotropic hormone (ACTH) concentration compared to standard 10-minute sampling.

Twenty-four healthy adult horses with unknown PPID status.

In this prospective study, subjects underwent a single TRH stimulation test, with blood collected exactly 9minutes (early), 10minutes (standard), and 11 minutes (late) after injection. ACTH was measured by chemiluminescent immunoassay. Two aliquots of the 10-minute plasma sample were analyzed separately to assess intra-assay variability. Data were reported descriptively and bias was calculated using Bland-Altman plots. Significance was set at P=.05.

Minor variability was observed between the paired 10-minute sample aliquots (range, 0%-6%; median 3%). Overall variability of early or late samples compared to the corresponding paired (average) 10-minute standard concentration ranged from 0% to 92% (median 10%). Seventy-five percent of horses (18/24) tested had at least 1 early or late reading that differed by ≥10% from its corresponding 10-minute standard concentration, and 21% of horses (5/24) would have a different interpretation of testing result with either early or late sampling. Incidence of ≥10% variability was independent of PPID status (P=.59).

Precise timing of sample collection is critical to ensure accurate assessment of PPID status given the observation of significant variability associated with minor alterations in timing of sample collection.

Precise timing of sample collection is critical to ensure accurate assessment of PPID status given the observation of significant variability associated with minor alterations in timing of sample collection.In January 2017, a Nile hippopotamus (Hippopotamus amphibious) was born approximately six weeks premature at the Cincinnati Zoo & Botanical Garden. Due to the calf's weakened condition and lack of interest from the dam, management at the zoo made the decision to hand-rear the calf. Limited published information was available on hand-rearing this species of hippopotamus (hippo). To devise a nutritionally appropriate recipe, milk samples were acquired from the dam on Days 1, 3, 8, and 9 postpartum, and assayed for sugar, protein, fat, mineral, and water content using standard methods validated for multiple species of mammals at the Smithsonian National Zoo's Nutrition Science Laboratory. The sugar content stayed relatively constant (mean = 4.5%; range 4.3%-4.7%). The fat consistently increased from 0.48% to 4.24% (mean = 2%). Excluding Day 9, the protein content gradually decreased from 9.56% to 6.39% (mean = 8%). The dry matter (DM) ranged from 14.38% to 16.72% (i.e., water content of 85.62%-83.28%), with the sum of the solids (sugar, protein, fat, and ash) averaging 98.5% of measured DM. Fat content was lower than expected but within the range of other artiodactyls. Between Days 1 and 8, the trend of decreasing protein and increasing fat was consistent with a change from colostrum to mature milk. The sharp increase in fat and protein with a decrease in sugar on Day 9 may indicate the beginning of the involution of the mammary gland due to lack of nursing stimulus. Utilizing this information, the Cincinnati Zoo was able to formulate a successful milk replacement recipe that allowed the calf to be raised through weaning to maturity.The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via O S2 →B2,5 →1 S5 and 3 S1 →3 H4 →1 C4 . For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S-glycoside and mannoimidazole indicate a 4 C1 →4 H5 /1 S5 →1 S5 mechanism. However, as observed with the GH125 family, S-glycosides may not act always as good mimics of GH's natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E5 →B2,5 /1 S5 →1 S5 pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C-disaccharides, whose biochemical applicability was still a chimera.The hydrozoan family Cladocorynidae inhabits tropical to temperate waters and comprises the two genera Pteroclava and Cladocoryne. Pteroclava lives in association with some octocorals and hydrozoans, whereas Cladocoryne is more generalist in terms of substrate choice. This work provides a thorough morpho-molecular reassessment of the Cladocorynidae by presenting the first well-supported phylogeny of the family based on the analyses of three mitochondrial and four nuclear markers. BMS-754807 Notably, the two nominal genera were confirmed to be monophyletic and both morphological and genetic data led to the formal description of a new genus exclusively associated with octocorals, Pseudozanclea gen. nov. Maggioni & Montano. Accordingly, the diagnosis of the family was updated. The ancestral state reconstruction of selected characters revealed that the symbiosis with octocorals likely appeared in the most recent common ancestor of Pteroclava and Pseudozanclea. Additionally, the presence of euryteles aggregation in the polyp stage and the exumbrellar nematocyst pouches with euryteles represent synapomorphies of all cladocorynid taxa and probably emerged in their most recent common ancestor. The analysis of several Pteroclava krempfi colonies from Indo-Pacific and Caribbean localities associated with several host octocorals revealed a high intra-specific genetic variability. Single- and multi-locus species delimitations resulted in three to five species hypotheses, but the statistical analysis of morphometric data showed only limited distinction among the clades of P. krempfi. However, P. krempfi clades showed differences in both host specificity, mostly at the octocoral family level, and geographic distribution, with one clade found exclusively in the Caribbean Sea and the others found in the Indo-Pacific."Candidatus Sulcia muelleri" (Sulcia) is a diverse lineage of intracellular nutritional endosymbiotic bacteria strictly associated with auchenorrhynchous hemipteran insects. Sulcia has undergone long-term codiversification with its insect hosts but the phylogeny of these endosymbionts, their relationships to other bacteria, and the extent of their occurrence within various groups of Auchenorrhyncha remain inadequately explored. Comprehensive phylogenetic analyses of Sulcia and related bacteria were performed to elucidate its position relative to other members of Phylum Bacteroidetes and the degree of congruence to the phylogeny of its auchenorrhynchous hosts. Maximum likelihood (ML) and maximum parsimony (MP) analyses of Flavobacteriales based on genomic data from 182 bacterial strains recover a monophyletic Sulcia within a larger clade of flavobacterial insect endosymbionts, closely related to Weeksellaceae. Molecular divergence time analysis of Sulcia dates the origin of Sulcia at approximately 339.95 millicontribute to resolution of contentious aspects of Auchenorrhyncha phylogeny.Phylogenetic graph structures used in empirical and theoretical analysis have expanded beyond trees to more general directed acyclic graphs including networks and forests. Several methods to reconcile multiple such graphs are presented and discussed here, extending existing consensus and supertree techniques to form a set of phylogenetic supergraph methods. These graphs can be used as the summary of analytical results, or as heuristic initial graphs for further phylogenetic analysis.The Asian potamid subfamily Potamiscinae is the most species-rich group of primary freshwater crabs in the world, and a large number of these (318 species in 52 genera) are found in China where they exhibit a remarkably high rate of endemism. However, the evolutionary history and phylogenetic relationships of this subfamily is still poorly understood and the hypothesis that the Chinese potamids originated in the Indochina Peninsula has yet to be tested using a modern phylogeographic reconstruction and molecular dating methods. Here we analyze the phylogenetic relationships and biogeographic history of the Chinese potamiscines based on whole mitogenomes of 72 species of Asian freshwater crabs representing 65% of the potamiscine genera found in China, including new mitogenome sequences for 57 species. The mitogenomic phylogeny generated four separate clades Southwest China (SWC), Indochina-Southwest China (ISWC), Central China (CC), and South China-adjacent Islands (SCI). Our results suggest that the Chinese potamiscine fauna most likely originated in Indochina during the Eocene. The establishment of the East Asian monsoon during the Eocene/Oligocene resulted in major climate changes that coincide with the local diversification of the CC and SCI clades. In addition, diversification of two other clades (ISWC and SWC) may have been driven by past large scale environmental changes taking place at that time such as increased local precipitation and expanding freshwater habitats associated with the uplifting of the Hengduan Mountains. In addition, our phylogenies did not support monophyly for six currently recognized potamiscine genera, highlighting the need for further taxonomic revisions of this fauna. The broad taxonomic sampling and well-supported molecular phylogenies used here allow for the updating of our understanding of the evolutionary origins and diversification of the potamiscine freshwater crabs in China.