Limited Genetic Diversity Preceded Extinction of the Tasmanian Tiger

The Tasmanian tiger or thylacine was the largest carnivorous marsupial when Europeans first reached Australia. Sadly, the last known thylacine died in captivity in 1936. A recent analysis of the genome of the closely related and extant Tasmanian devil demonstrated limited genetic diversity between individuals. While a similar lack of diversity has been reported for the thylacine, this analysis was based on just two individuals. Here we report the sequencing of an additional 12 museum-archived specimens collected between 102 and 159 years ago. We examined a portion of the mitochondrial DNA hyper-variable control region and determined that all sequences were on average 99.5% identical at the nucleotide level. As a measure of accuracy we also sequenced mitochondrial DNA from a mother and two offspring. As expected, these samples were found to be 100% identical, validating our methods. We also used 454 sequencing to reconstruct 2.1 kilobases of the mitochondrial genome, which shared 99.91% identity with the two complete thylacine mitochondrial genomes published previously. Our thylacine genomic data also contained three highly divergent putative nuclear mitochondrial sequences, which grouped phylogenetically with the published thylacine mitochondrial homologs but contained 100-fold more polymorphisms than the conserved fragments. Together, our data suggest that the thylacine population in Tasmania had limited genetic diversity prior to its extinction, possibly as a result of their geographic isolation from mainland Australia approximately 10,000 years ago

CD34+ cell mobilization, blood graft composition, and posttransplant recovery in myeloma patients compared to non‐Hodgkinʼs lymphoma patients: results of the prospective multicenter GOA study

BACKGROUNDAutologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non‐Hodgkinʼs lymphoma (NHL).STUDY DESIGN AND METHODSIn this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome.RESULTSMultiple myeloma patients mobilized CD34+ cells more effectively (6.3 × 106/kg vs. 3.9 × 106/kg, p = 0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100 days) nonrelapse mortality (NRM; 6% vs. 0%, p = 0.003).CONCLUSIONSNon‐Hodgkinʼs lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.</p

Physical and land-cover variables influence ant functional groups and species diversity along elevational gradients

Of particular importance in shaping species assemblages is the spatial heterogeneity of the environment. The aim of our study was to investigate the influence of spatial heterogeneity and environmental complexity on the distribution of ant functional groups and species diversity along altitudinal gradients in a temperate ecosystem (Pyrenees Mountains). During three summers, we sampled 20 sites distributed across two Pyrenean valleys ranging in altitude from 1,009 to 2,339 m by using pitfall traps and hand collection. The environment around each sampling points was characterized by using both physical and land-cover variables. We then used a self-organizing map algorithm (SOM, neural network) to detect and characterize the relationship between the spatial distribution of ant functional groups, species diversity, and the variables measured. The use of SOM allowed us to reduce the apparent complexity of the environment to five clusters that highlighted two main gradients: an altitudinal gradient and a gradient of environmental closure. The composition of ant functional groups and species diversity changed along both of these gradients and was differently affected by environmental variables. The SOM also allowed us to validate the contours of most ant functional groups by highlighting the response of these groups to the environmental and land-cover variables

Interactions of the Apolipoprotein A5 Gene Polymorphisms and Alcohol Consumption on Serum Lipid Levels

Little is known about the interactions of apolipoprotein (Apo) A5 gene polymorphisms and alcohol consumption on serum lipid profiles. The present study was undertaken to detect the interactions of ApoA5-1131T>C, c.553G>T and c.457G>A polymorphisms and alcohol consumption on serum lipid levels.A total of 516 nondrinkers and 514 drinkers were randomly selected from our previous stratified randomized cluster samples. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. The levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P<0.05-0.001). The genotypic and allelic frequencies of three loci were not different between the two groups. The interactions between -1131T>C genotypes and alcohol consumption on ApoB levels (P<0.05) and the ApoA1/ApoB ratio (P<0.01), between c.553G>T genotypes and alcohol consumption on low-density lipoprotein cholesterol (LDL-C) levels (P<0.05) and the ApoA1/ApoB ratio (P<0.05), and between c.457G>A genotypes and alcohol consumption on TG levels (P<0.001) were detected by factorial regression analysis after controlling for potential confounders. Four haplotypes (T-G-G, C-G-G, T-A-G and C-G-T) had frequencies ranging from 0.06 to 0.87. Three haplotypes (C-G-G, T-A-G, and C-G-T) were significantly associated with serum lipid parameters. The -1131T>C genotypes were correlated with TG, and c.553G>T and c.457G>A genotypes were associated with HDL-C levels in nondrinkers (P<0.05 for all). For drinkers, the -1131T>C genotypes were correlated with TC, TG, LDL-C, ApoB levels and the ApoA1/ApoB ratio (P<0.01 for all); c.553G>T genotypes were correlated with TC, TG, HDL-C and LDL-C levels (P<0.05-0.01); and c.457G>A genotypes were associated with TG, LDL-C, ApoA1 and ApoB levels (P<0.05-0.01).The differences in some serum lipid parameters between the drinkers and nondrinkers might partly result from different interactions of the ApoA5 gene polymorphisms and alcohol consumption

Internal Transcribed Spacer 2 (nu ITS2 rRNA) Sequence-Structure Phylogenetics: Towards an Automated Reconstruction of the Green Algal Tree of Life

L). Some have advocated the use of the nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative to the traditional chloroplast markers. However, the ITS2 is broadly perceived to be insufficiently conserved or to be confounded by introgression or biparental inheritance patterns, precluding its broad use in phylogenetic reconstruction or as a DNA barcode. A growing body of evidence has shown that simultaneous analysis of nucleotide data with secondary structure information can overcome at least some of the limitations of ITS2. The goal of this investigation was to assess the feasibility of an automated, sequence-structure approach for analysis of IT2 data from a large sampling of phylum Chlorophyta.Sequences and secondary structures from 591 chlorophycean, 741 trebouxiophycean and 938 ulvophycean algae, all obtained from the ITS2 Database, were aligned using a sequence structure-specific scoring matrix. Phylogenetic relationships were reconstructed by Profile Neighbor-Joining coupled with a sequence structure-specific, general time reversible substitution model. Results from analyses of the ITS2 data were robust at multiple nodes and showed considerable congruence with results from published phylogenetic analyses.Our observations on the power of automated, sequence-structure analyses of ITS2 to reconstruct phylum-level phylogenies of the green algae validate this approach to assessing diversity for large sets of chlorophytan taxa. Moreover, our results indicate that objections to the use of ITS2 for DNA barcoding should be weighed against the utility of an automated, data analysis approach with demonstrated power to reconstruct evolutionary patterns for highly divergent lineages

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Autograft cellular composition and outcome in myeloma patients: Results of the prospective multicenter GOA study

Background Autologous stem cell transplantation (auto-SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known. Study design and methods Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto-SCT was evaluated. Results A higher graft CD34(+) cell content predicted faster platelet recovery after auto-SCT in both the short and long term. In patients with standard-risk cytogenetics, a higher graft CD34(+) count (>2.5 x 10/kg) was linked with shorter progression-free survival (PFS; 28 vs. 46 months, p = 0.04), but there was no difference in overall survival (OS) (p = 0.53). In a multivariate model, a higher graft CD34(+)CD133(+)CD38(-) (>0.065 x 10/kg, p = 0.009) and NK cell count (>2.5 x 10/kg, p = 0.026), lenalidomide maintenance and standard-risk cytogenetics predicted better PFS. In contrast, a higher CD34(+) count (>2.5 x 10/kg, p = 0.015) predicted worse PFS. A very low CD3(+) cell count ( Conclusions Autograft cellular composition may impact outcome in MM patients after auto-SCT. More studies are needed to define optimal graft composition.Peer reviewe