Disruption of a Transcriptional Repressor by an Insertion Sequence Element Integration Leads to Activation of a Novel Silent Cellobiose Transporter in Lactococcus lactis MG1363.

Lactococcus lactis subsp. cremoris strains typically carry many dairy niche-specific adaptations. During adaptation to the milk environment these former plant strains have acquired various pseudogenes and insertion sequence elements indicative of ongoing genome decay and frequent transposition events in their genomes. Here we describe the reactivation of a silenced plant sugar utilization cluster in an L. lactis MG1363 derivative lacking the two main cellobiose transporters, PtcBA-CelB and PtcBAC, upon applying selection pressure to utilize cellobiose. A disruption of the transcriptional repressor gene llmg_1239 by an insertion sequence (IS) element allows expression of the otherwise silent novel cellobiose transporter Llmg_1244 and leads to growth of mutant strains on cellobiose. Llmg_1239 was labeled CclR, for cellobiose cluster repressor.IMPORTANCE Insertion sequences (ISs) play an important role in the evolution of lactococci and other bacteria. They facilitate DNA rearrangements and are responsible for creation of new genetic variants with selective advantages under certain environmental conditions. L. lactis MG1363 possesses 71 copies in a total of 11 different types of IS elements. This study describes yet another example of an IS-mediated adaptive evolution. An integration of IS981 or IS905 into a gene coding for a transcriptional repressor led to activation of the repressed gene cluster coding for a plant sugar utilization pathway. The expression of the gene cluster allowed assembly of a novel cellobiose-specific transporter and led to cell growth on cellobiose.

Photobiomodulation therapy in dogs undergoing TPLO after cranial cruciate ligament rupture shows promise but no statistically significant difference in a randomized trial.

OBJECTIVE: Effect of photobiomodulation therapy (PBMT) in patients with CCLR after TPLO surgery by measuring C-reactive protein (CRP), percentage weight bearing, lameness using a short form of a composite measure pain scale, evaluated by the clinician and owners, and surgical site infection. SAMPLE: 54 client-owned dogs with CCLR undergoing unilateral TPLO surgery were enrolled in this study between April 5, 2021, through April 10, 2022. METHODS: The study population was randomly assigned to either a treatment group receiving PMBT (24 dogs) or a control group (30 dogs). PMBT was performed on the treatment group immediately after induction, and 6 hours, 24 hours, 48 hours, and 8 weeks postoperatively. The control group received sham PMBT (device turned off) at the same time. Evaluation of CRP, CMPS-SF, evidence of SSI, and %WB were evaluated for all dogs 24 hours preoperatively, and then 24 hours, 48 hours, and 8 weeks postoperatively. Owners completed CMPS-SF and subjective evaluations weekly for 8 weeks postoperatively. RESULTS: No statistically significant differences were found between treatment groups when evaluating CRP, %WB, and CMPS-SF by the clinician and weekly evaluation of the CMPS-SF by owners. Although no statistically significant differences were found in patients developing surgical site infections between treatment groups, SSI was only observed in patients in the control group (5/30, 16.6%). Most were minor/superficial infections (4/30 13.3%), and a single dog (1/30, 3.3%) had a major/deep surgical site infection. CLINICAL RELEVANCE: Although with promising but not statistically significant differences between groups, surgical site infections may be reduced after PBMT application.

A Chemerin Peptide Analog Stimulates Tumor Growth in Two Xenograft Mouse Models of Human Colorectal Carcinoma.

BACKGROUND: Chemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation, and migration of CRC cell lines in vitro as well as in animal models. METHODS: In vitro, microscopic assays to study proliferation, as well as a scratch-wound assay for migration monitoring, were applied using the human CRC cell lines HCT116, HT29, and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by an ex-vivo analysis of vessel density and mitotic activity. RESULTS: While the proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signals of HCT116-luc and HT29-luc xenografts. CONCLUSIONS: The results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.

Comparison of complications following tibial tuberosity advancement and tibial plateau levelling osteotomy in very large and giant dogs 50 kg or more in body weight.

OBJECTIVES: To analyse and compare major complications in dogs ≥50 kg undergoing tibial tuberosity advancement (TTA) or tibial plateau levelling osteotomy (TPLO) for treatment of cranial cruciate ligament disease. METHODS: Medical records and radiographs of client-owned dogs (≥50 kg) treated for cranial cruciate ligament disease with either TTA or TPLO between January 2011 and November 2015 were reviewed. Ninety-one TTA cases and 54 TPLO cases met the study inclusion criteria. All complications within one year of surgery were recorded. Major complications were those requiring surgical revision or intervening medical therapy to resolve. Logistic regression analysis evaluated for associations with major complication occurrence. Major complications were statistically compared between TTA and TPLO treatment groups. RESULTS: Incidence of major complications following TTA and TPLO surgery were 19.8% and 27.8%, respectively. Surgical site infection (SSI) was the single most common major complication following both TTA (15.4%) and TPLO (25.9%) surgery. There were no significant differences between TTA and TPLO treatment regarding the rate of SSI, surgical revision, or overall occurrence of major complications. Postoperative antibiotic therapy significantly reduced the risk of a major complication in all dogs ≥50 kg (p = 0.015; OR: 0.201: 95%CI: 0.055-0.737). CLINICAL SIGNIFICANCE: Major complications occurred frequently following TTA and TPLO treatment of cranial cruciate ligament disease in dogs ≥50 kg. The increased chance for SSI should be considered and postoperative antibiotic therapy is recommended.