Characterization of the immunoglobulin lambda chain across diverse human populations.

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using six gold-standard assemblies of the IGL locus. Using IG-Cap and whole genome long-read sequencing data, we resolved the IGL locus in 238 individuals of diverse population origins. From these individuals, we identified 207 novel IGL alleles and resolved multiple large structural variations, including a large 60 KB deletion affecting 6 functional IGLV genes and population variable duplications in the IGL constant region. Additionally, we identified signatures of balancing and purifying selection in and around functional genes across the IGL locus including gene-specific patterns of heterozygosity and allelic richness. Finally, we found that IGLV alleles are enriched for nonsynonymous mutations resulting in disparate amino acid changes. Overall, this work revealed significant unexplored diversity in the IGL locus and provides an important set of genomic tools and resources to enable future functional studies, disease association studies, and targeted therapeutic development

WOLVES (\u3ci\u3eCanis lupus\u3c/i\u3e)

Two species of wolves occur in North America, gray wolves (Canis lupus) and red wolves (Canis rufus). During the 1800s, gray wolves ranged over the North American continent as far south as central Mexico. Gray wolves occupy boreal forests and forest/agricultural edge communities in Minnesota, northern Wisconsin, and northern Michigan. Mech (1970) reported that gray wolves prey mainly on large animals including white-tailed deer, mule deer, moose, caribou, elk, Dall sheep, bighorn sheep, and beaver. Gray wolves are highly social, often living in packs of two to eight or more individuals. The ability of wolves to kill cattle, sheep, poultry, and other livestock is well documented (Young and Goldman 1944, Carbyn 1983, Fritts et al. 1992)

WOLVES (\u3ci\u3eCanis lupus\u3c/i\u3e)

Two species of wolves occur in North America, gray wolves (Canis lupus) and red wolves (Canis rufus). During the 1800s, gray wolves ranged over the North American continent as far south as central Mexico. Gray wolves occupy boreal forests and forest/agricultural edge communities in Minnesota, northern Wisconsin, and northern Michigan. Mech (1970) reported that gray wolves prey mainly on large animals including white-tailed deer, mule deer, moose, caribou, elk, Dall sheep, bighorn sheep, and beaver. Gray wolves are highly social, often living in packs of two to eight or more individuals. The ability of wolves to kill cattle, sheep, poultry, and other livestock is well documented (Young and Goldman 1944, Carbyn 1983, Fritts et al. 1992)

M87, Globular Clusters, and Galactic Winds: Issues in Giant Galaxy Formation

New VRI photometry is presented for the globular clusters in the innermost 140'' of the M87 halo. The results are used to discuss several issues concerning the formation and evolution of globular cluster systems in supergiant ellipticals like M87. (1) we find no significant change in the globular cluster luminosity function (GCLF) with galactocentric radius, for cluster masses M < 10^5 solar masses, indicating that the main effects of dynamical evolution may be only on lower-mass clusters. (2) Within the core radius (1') of the globular cluster system, the metallicity distribution is uniform, but at larger radii the mean metallicity declines steadily as Z ~ r^-0.9. (3) The various options for explaining the existence of high specific frequency galaxies like M87 are evaluated, and scaling laws for the GCSs in these galaxies are given. Interpretations involving secondary evolution (formation of many globular clusters during mergers, intergalactic globular clusters, etc.) are unlikely to be the primary explanation for high-S_N galaxies. (4) We suggest that central-supergiant E galaxies may have formed in an exceptionally turbulent or high-density environment in which an early, powerful galactic wind drove out a high fraction of the protogalactic gas, thus artificially boosting the specificComment: 67 pages, 17 figures. To appear in Astronomical Journal, in press for May 1998. Preprints also available from W.Harris; send e-mail request to [email protected]

Remote sampling of biomarkers of inflammation with linked patient generated health data in patients with rheumatic diseases:an Ecological Momentary Assessment feasibility study

BACKGROUND: People with rheumatic diseases experience troublesome fluctuations in fatigue. Debated causes include pain, mood and inflammation. To determine the relationships between these potential causes, serial assessments are required but are methodologically challenging. This mobile health (mHealth) study explored the viability of using a smartphone app to collect patient-reported symptoms with contemporaneous Dried Blood Spot Sampling (DBSS) for inflammation. METHODS: Over 30 days, thirty-eight participants (12 RA, 13 OA, and 13 FM) used uMotif, a smartphone app, to report fatigue, pain and mood, on 5-point ordinal scales, twice daily. Daily DBSS, from which C-reactive Protein (CRP) values were extracted, were completed on days 1–7, 14 and 30. Participant engagement was determined based on frequency of data entry and ability to calculate within- and between-day symptom changes. DBSS feasibility and engagement was determined based on the proportion of samples returned and usable for extraction, and the number of days between which between-day changes in CRP which could be calculated (days 1–7). RESULTS: Fatigue was reported at least once on 1085/1140 days (95.2%). Approximately 65% of within- and between-day fatigue changes could be calculated. Rates were similar for pain and mood. A total of 287/342 (83.9%) DBSS, were returned, and all samples were viable for CRP extraction. Fatigue, pain and mood varied considerably, but clinically meaningful (≥ 5 mg/L) CRP changes were uncommon. CONCLUSIONS: Embedding DBSS in mHealth studies will enable researchers to obtain serial symptom assessments with matched biological samples. This provides exciting opportunities to address hitherto unanswerable questions, such as elucidating the mechanisms of fatigue fluctuations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05723-w

Changing the narrative in diagnosis and management of pain in the sacroiliac joint area

The sacroiliac joint (SIJ) is often considered to be involved when people present for care with low back pain where the sacroiliac joint (SIJ) is located. However, determining why the pain has arisen can be challenging, especially in the absence of a specific cause such as pregnancy, disease, or trauma, where the SIJ may be identified as a source of symptoms with the help of manual clinical tests. Nonspecific SIJ-related pain is commonly suggested to be causally associated with movement problems in the sacroiliac joint(s); a diagnosis traditionally derived from manual assessment of movements of the SIJ complex. Management choices often consist of patient education, manual treatment, and exercise. Although some elements of management are consistent with guidelines, this perspective argues that the assumptions on which these diagnoses and treatments are based are problematic, particularly if they reinforce unhelpful, pathoanatomical beliefs. This article reviews the evidence regarding the clinical detection and diagnosis of SIJ movement dysfunction. In particular, it questions the continued use of assessing movement dysfunction despite mounting evidence undermining the biological plausibility and subsequent treatment paradigms based on such diagnoses. Clinicians are encouraged to align their assessment methods and explanatory models to contemporary science to reduce the risk of their diagnoses and choice of intervention negatively affecting clinical outcome

Implementing a Loosely-Coupled Integrated Assessment Model in the Pegasus Workflow Management System

Integrated assessment models (IAMs) are commonly used to explore the interactions between different modeled components of socio-environmental systems (SES). Most IAMs are built in a tightly-coupled framework so that the complex interactions between the models can be efficiently implemented within the framework in a straightforward manner. However, tightly-coupled frameworks make it more difficult to change individual models within the IAM because of the high level of integration between the models. Prioritizing flexibility over computational efficiency, the IAM presented here is built using a loosely-coupled framework and implemented in the Pegasus Workflow Management System. The modular nature of loosely-coupled systems allows each component model within the IAM to be easily exchanged for another component model from the same domain assuming each provides the same input / output interface. This flexibility allows researchers to experiment with different models for each SES component and facilitates smoother upgrades between each version of the independently developed component models