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Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3). Here we show that AN3-deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a -deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro. Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3) . Here we show that AN3 -deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a - deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro . Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways.

A case report is presented of a patient with acetabular protrusio 2 years following hemiresurfacing of the femoral head for osteonecrosis associated with sickle cell disease. Renewed interest in bone-preserving hip arthroplasty has led to increased use of hemiarthroplasty and femoral resurfacing in young patients with arthritis. In cases of osteonecrosis, especially that associated with sickle cell disease, awareness of this potential complication is important.

The aim of this study was to evaluate the effects of immobilization and mobilization on the functional and biomechanical recovery of injured Achilles tendons. Male Sprague-Dawley rats were allocated randomly into four groups: (a) sham operation, (b) division only (surgical transection of the Achilles tendon without immobilization), (c) "dummy" external fixation (division of the Achilles tendon and application of Kirschner wires), and (d) rigid external fixation (division of the Achilles tendon and immobilization with Kirschner wires connected by two triangular frames). All procedures were performed on the right lower limb; the left, uninjured, lower limb served as an internal control. Kirschner wires and external fixators were removed on day 12. Functional performance was determined from measurements of hind pawprints of rats walking preoperatively and on postoperative days 1, 3, 5, 7, 9, 11, 13, and 15. On day 15, the animals were killed and biomechanical evaluations were performed on both the injured and the uninjured Achilles tendon constructs. No functional or mechanical deficits were observed in the sham-operation group. Animals subjected to division of the Achilles tendon had an initial functional deficit that returned to near normal by day 15. The application of Kirschner wires was associated with an impairment of the functional performance of the rat as well as of the mechanical properties of the tendon-bone constructs. Immobilization by connection of the Kirschner wires to an external frame had an additional, highly significant (p < 0.001) detrimental effect on the functional and mechanical recovery of Achilles tendon-calcaneal complexes.

The pathogenesis and treatment of rupture of the Achilles tendon remain a source of controversy. This study presents the results of a biomechanical, functional, and morphological evaluation of a group of rats that had division and repair of the Achilles tendon. A total of 46 rats were used: 18 for biomechanical testing, 18 for functional evaluation, and 10 for histology. Morphological examination revealed an early inflammatory response with loose connective tissue formation that was replaced gradually by fibroblasts and a collagenous matrix. The functional evaluation (Achilles functional index [AFI]) was made from measurements of the hind pawprints of walking rats. Division and repair of the Achilles tendon produced a significant functional impairment (mean [+/- SEM] AFI = -87 +/- 8; p < 0.001), which gradually improved with healing time. The load to failure for the repaired tendons consistently improved with healing time, in a manner similar to the functional recovery. The average deformation (repair/control) varied considerably and was not related to healing time. The stiffness of the repaired tendons increased with healing time and was 60% of the corresponding control side by day 15. The major finding of this study was a strong correlation between the AFI and the failure load of the healing tendon-bone constructs (250-300 g group, r = 0.97, p < 0.001; 325-375 g group, r = 0.96, p < 0.001).

Controversy exists regarding the treatment of Achilles tendon ruptures. The aim of this study was to determine whether surgical repair of the rat Achilles tendon offered any biomechanical, functional, or morphological advantage over no repair. Thirty-two male Sprague-Dawley rats were randomly allocated into four groups: (1) sham operated (skin incision only), (2) no repair (complete division of the Achilles tendon and plantaris tendon without repair), (3) internal splint (plantaris left intact), and (4) Achilles repair (with a modified Kessler-type suture). Functional performance was determined from the measurements of hindpaw prints utilizing the Achilles Functional Index. On day 15, the animals were killed, and biochemical and histological evaluations were performed on both the injured and uninjured Achilles tendon constructs. All groups subjected to Achilles tendon division had a significant initial functional impairment that gradually improved so that by day 15 there were no functional or failure load impairments in any group. The injured tendons in all three groups subjected to Achilles tendon division had a 13-fold increase in the cross-sectional area and were less stiff and more deformable than uninjured and sham-operated tendons on day 15 (P < .001). The magnitude of the biomechanical and morphological changes at postoperative day 15 and the initial impairment and rate of functional recovery were similar for no repair, internal splint, and Achilles repair groups. In summary, this study demonstrates that surgical repair of the Achilles tendon in the rat does not offer any advantage over nonoperative management.

The literature regarding the management of spontaneous rupture of the Achilles tendon is controversial and confusing. The relative infrequency of the condition in any one center prohibits the completion of well-designed clinical studies. Many of the disputes could be addressed and innovations tested if an appropriate animal model were available. We present a method for evaluating Achilles tendon function from measurements of the prints, preserved in bromphenol-blue-impregnated photocopying paper, of the hindfeet of walking rats. The stimulus for this study was derived from de Medinaceli's method for assessing the functional condition of rat sciatic nerves (de Medinaceli L, Freed WJ, Wyatt RJ: An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 77:634-643, 1982). Four variables were measured from these walking tracks, and comparisons between the damaged (experimental) and intact (normal) side were converted to proportional deficits. The relative contribution of each parameter to the overall deficit was determined by multiple linear regression analysis, and the variables were weighted accordingly to obtain an "Achilles Functional Index" (AFI). A sham operation produced no functional deficit, whereas animals subjected to a 0.5-cm midsubstance Achilles tendon defect demonstrated a markedly impaired AFI. Animals with repaired transected Achilles tendons also demonstrated a significant, but less severely impaired AFI. The functional deficit in this repair group returned to control values by postoperative day 15, whereas animals with a defect remained impaired at day 15. Furthermore, an excellent correlation was found between the functional recovery and biomechanical properties (ultimate failure load) of the healing tendon (r = 0.94; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)