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CRISPR-Cas systems defend prokaryotic cells from invasive DNA of viruses, plasmids and other mobile genetic elements. Here, we show using metagenomics, metatranscriptomics and single-cell genomics that CRISPR systems of widespread, uncultivated archaea can also target chromosomal DNA of archaeal episymbionts of the DPANN superphylum. Using meta-omics datasets from Crystal Geyser and Horonobe Underground Research Laboratory, we find that CRISPR spacers of the hosts Candidatus Altiarchaeum crystalense and Ca. A. horonobense, respectively, match putative essential genes in their episymbionts' genomes of the genus Ca. Huberiarchaeum and that some of these spacers are expressed in situ. Metabolic interaction modelling also reveals complementation between host-episymbiont systems, on the basis of which we propose that episymbionts are either parasitic or mutualistic depending on the genotype of the host. By expanding our analysis to 7,012 archaeal genomes, we suggest that CRISPR-Cas targeting of genomes associated with symbiotic archaea evolved independently in various archaeal lineages.

DPANN archaea have reduced metabolic capacities and are diverse and abundant in deep aquifer ecosystems, yet little is known about their interactions with other microorganisms that reside there. Here, we provide evidence for an archaeal host-symbiont association from a deep aquifer system at the Colorado Plateau (Utah, USA). The symbiont, Candidatus Huberiarchaeum crystalense, and its host, Ca. Altiarchaeum hamiconexum, show a highly significant co-occurrence pattern over 65 metagenome samples collected over six years. The physical association of the two organisms was confirmed with genome-informed fluorescence in situ hybridization depicting small cocci of Ca. H. crystalense attached to Ca. A. hamiconexum cells. Based on genomic information, Ca. H. crystalense potentially scavenges vitamins, sugars, nucleotides, and reduced redox-equivalents from its host and thus has a similar metabolism as Nanoarchaeum equitans. These results provide insight into host-symbiont interactions among members of two uncultivated archaeal phyla that thrive in a deep subsurface aquifer.

OBJECTIVE: To explore modifiable psychosocial factors, sleep-related variables, indices of central pain processing and patients' characteristics as potential prognostic factors for pain, shoulder function, and quality of life (QoL) 1 year after rotator cuff repair. DESIGN: This observational longitudinal study included 142 patients who were undergoing rotator cuff repair. All measures took place pre--rotator cuff repair (T0), and 12 weeks (T1) and 12 months (T2) after rotator cuff repair. METHODS: Mixed-effects linear regression modeled relationships between the Western Ontario Rotator Cuff Index (WORC, model A), the Subjective Shoulder Value (SSV, model B), and EuroQol's EQ-5D-5L for QoL (model C), and potential prognostic factors over time. Factors included psychosocial variables, sleep-related indices, and proxies of central pain processing. Patients' age, sex, and body mass index complemented the analyses. RESULTS: At follow-up (T2), data from 124 participants were available for analysis. Five prognostic factors were identified for the 1-year outcome. Better expectations for symptom reduction (P<.0001, -1.4 mm) and an increase in Douleur Neuropathique 4 score (P = .0481, -0.9 mm) affected the evolution of WORC over time (model A). An increase in injury perception subscale consequence (P = .0035, 0.04%) influenced the SSV trajectory (model B). In addition, when sleep quality (P = .0011, -0.13%) and sleep efficiency (P = .0002, 0.005%) improved, the EQ-5D-5L slope was affected (model C). CONCLUSION: Addressing cognitions, pain mechanisms and sleep behavior prior to rotator cuff repair can identify people who are at risk of a poor outcome after surgery. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor that is almost uniformly lethal in humans. Activating mutations of KRAS are found in >90% of human PDACs and are sufficient to promote acinar-to-ductal metaplasia (ADM) during tumor initiation. The roles of miRNAs in oncogenic Kras -induced ADM are incompletely understood. The Ptf1a Cre/+ LSL-Kras G12D/+ and Ptf1a Cre/+ LSL-Kras G12D/+ LSL-p53R172H/+ and caerulein-induced acute pancreatitis mice models were used. mir-802 was conditionally ablated in acinar cells to study the function of miR-802 in ADM. We show that miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras G12D -induced transformation. Genetic ablation of mir-802 cooperates with Kras G12D by promoting ADM formation. miR-802 deficiency results in de-repression of the miR-802 targets Arhgef12 , RhoA , and Sdc4 , activation of RhoA, and induction of the downstream RhoA effectors ROCK1, LIMK1, COFILIN1, and EZRIN, thereby increasing F-actin rearrangement. mir-802 ablation also activates SOX9, resulting in augmented levels of ductal and attenuated expression of acinar identity genes. Consistently with these findings, we show that this miR-802–RhoA–F-actin network is activated in biopsies of pancreatic cancer patients and correlates with poor survival. We show miR-802 suppresses pancreatic cancer initiation by repressing oncogenic Kras -induced ADM. The role of miR-802 in ADM fills the gap in our understanding of oncogenic Kras -induced F-actin reorganization, acinar reprogramming, and PDAC initiation. Modulation of the miR-802–RhoA–F-actin network may be a new strategy to interfere with pancreatic carcinogenesis. [Display omitted] Pancreatic acinar-enriched miR-802 is a negative regulator of acinar-to-ductal metaplasia during early pancreatitis and pancreatic carcinogenesis. [ABSTRACT FROM AUTHOR]

SYNOPSIS: There is an absence of high-quality evidence to support rehabilitation and return-to sport decisions following shoulder injuries in athletes. The Athlete Shoulder Consensus Group was convened to lead a consensus process that aimed to produce best-practice guidance for clinicians, athletes, and coaches for managing shoulder injuries in sport. We developed the consensus via a 2-round Delphi process (involving more than 40 content and methods experts) and an in-person meeting. This consensus statement provides guidance with respect to load and risk management, supporting athlete shoulder rehabilitation, and decision making during the return-to-sport process. This statement is designed to offer clinicians the flexibility to apply principle-based approaches to managing the return-to-sport process within a variety of sporting backgrounds. The principles and consensus of experts working across multiple sports may provide a template for developing additional sport-specific guidance in the future. [ABSTRACT FROM AUTHOR]