Tenascin (TN) is a high-molecular-mass oligomeric glycoprotein of the extracellular matrix (ECM) endowed with a programmed expression in embryonic life and a neo-expression in the interstitium of some malignancies. Using monoclonal antibodies (MAbs) which identify human tenascin, we have conducted an extensive immunohistochemical analysis of TN expression in normal fetal and adult human tissues as well as in a wide variety of human tumors. Results of this study demonstrate that TN (1) is detectable in embryonic and fetal tissues at least from the 10th week of gestation; (2) is present in the interstitium of a variety of adult tissues of different embryonic origin; (3) may be neo-expressed in the stroma of benign and malignant tumors; (4) has the ability to accumulate in a highly variable manner in the ECM of tumors of the same and of different histotypes.
Fibronectin (FN) polymorphism is caused by alternative splicing patterns in at least three regions (ED-A, ED-B and IIICS) of the primary transcript of a single gene. Using monoclonal antibodies, we previously demonstrated that transforming growth factor-/l (TGF-B) preferentially increases the accumulation of the FN isoforms containing the ED-A sequence in cultured normal human fibroblasts [Balza et al., (1988) FEBS Lett. 228, 42441. To determine the basis of this effect, we have examined through Sl nuclease analysis, the levels of ED-A-and ED-B-containing mRNAs in cultured normal human skin fibroblasts before and after TGF-j? treatment. These experiments have shown that TGF-#I increases the relative amount of m-RNA for ED-A-and ED-B-containing FN isoforms. These data demonstrate that a growth factor may regulate the splicing pattern of a pre-mRNA.Transforming growth factor-/I; Fibronectin isoform; Pre-mRNA splicing regulation
Background
Contemporary strategies for prehabilitation and rehabilitation associated with total knee arthroplasty (TKA) surgery have focused on improving joint range-of-motion and function with less emphasis on neuromuscular performance beneficially affecting joint stability. Furthermore, prehabilitation protocols have been found to be too long and generic-in-effect to be considered suitable for routine clinical practice.
Methods
A pragmatic exploratory controlled trial was designed to investigate the efficacy of a novel, acute prehabilitative neuromuscular exercise-conditioning (APNEC) in patients electing TKA. Adults electing unilateral TKA were assessed and randomly allocated to exercise-conditioning (APNEC, n = 15) and usual care (Control, n = 14) from a specialised orthopaedic hospital, in the United Kingdom. APNEC prescribed nine stressful exercise-conditioning sessions for the knee extensors of the surgery leg, accrued over one week (3 sessions·week−1; 36 exercise repetitions in total; machine, gravity-loaded) and directly compared with usual care (no exercise). Prescribed exercise stress ranged between 60%—100% of participant’s daily voluntary strength capacity, encompassing purposefully brief muscular activations (≤ 1.5 s). Baseline and follow-up indices of neuromuscular performance focusing on muscle activation capacity (electromechanical delay [EMD], rate of force development [RFD] and peak force [PF]) were measured ipsilaterally using dynamometry and concomitant surface electromyography (m. rectus femoris[RF] and m. vastus lateralis[VL]).
Results
Group mean ipsilateral knee extensor muscular activation capacity (EMDRF [F(3,57) = 53.5; p < 0.001]; EMDVL [F(3,57) = 50.0; p < 0.001]; RFD [F(3,57) = 10.5; p < 0.001]) and strength (PF [F(3,57) = 16.4; p < 0.001]) were significantly increased following APNEC (Cohen’s d, 0.5—1.8; 15% to 36% vs. baseline), but unchanged following no exercise control (per protocol, group by time interaction, factorial ANOVA, with repeated measures), with significant retention of gains at 1-week follow-up (p < 0.001).
Conclusions
The exploratory APNEC protocol elicited significant and clinically-relevant improvement and its retention in neuromuscular performance in patients awaiting TKA.
Trial registration
(date and number): clinicaltrial.gov: NCT03113032 (4/04/2017) and ISRCTN75779521 (3/5/2017).
Over the last decades, the combined effects of global climate changes and severe land use modifications have been exacerbating river hydrological alterations and habitat fragmentation in many Mediterranean rivers. This trend is predicted to intensify, with expected significant impacts on taxonomic and functional diversity of benthic communities in the next future. The present research aims at investigating the long-term combined effects of flow intermittency, climate and land use changes on benthic diatom communities, by analysing data collected over 11 years in Mediterranean streams of the NW-Italy. We demonstrated that the ongoing global changes and local environmental pressures determined a significant decline in diatom species diversity at both local and regional scales. More in detail, flow intermittency affected both diatom diversity and life history traits, with communities of intermittent reaches taxonomically and functionally different and less heterogeneous than assemblages characterizing perennial ones. Communities inhabiting intermittent sections showed high percentages of small, mainly stalked and pioneer taxa belonging to the low profile guild, highlighting the strong environmental pressure exerted by the hydrological alterations. Conversely taxa colonizing permanent reaches were bigger, belonging to the high profile guild and able to produce colonies, denoting environmental stability. The results we obtained could be ascribed to the long-term effects of drying in Mediterranean streams and, as first in the literature, we highlight that diatoms are able to provide long-terms responses to environmental changes caused by water stress, when hydrological disturbance is persistent.
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