Attention module incorporated transfer learning empowered deep learning-based models for classification of phenotypically similar tropical cattle breeds (Bos indicus).

Accurate breed identification in dairy cattle is essential for optimizing herd management and improving genetic standards. A smart method for correctly identifying phenotypically similar breeds can empower farmers to enhance herd productivity. A convolutional neural network (CNN) based model was developed for the identification of Sahiwal and Red Sindhi cows. To increase the classification accuracy, first, cows's pixels were segmented from the background using CNN model. Using this segmented image, a masked image was produced by retaining cows' pixels from the original image while eliminating the background. To improve the classification accuracy, models were trained on four different images of each cow: front view, side view, grayscale front view, and grayscale side view. The masked images of these views were fed to the multi-input CNN model which predicts the class of input images. The segmentation model achieved intersection-over-union (IoU) and F1-score values of 81.75% and 85.26%, respectively with an inference time of 296 ms. For the classification task, multiple variants of MobileNet and EfficientNet models were used as the backbone along with pre-trained weights. The MobileNet model achieved 80.0% accuracy for both breeds, while MobileNetV2 and MobileNetV3 reached 82.0% accuracy. CNN models with EfficientNet as backbones outperformed MobileNet models, with accuracy ranging from 84.0% to 86.0%. The F1-scores for these models were found to be above 83.0%, indicating effective breed classification with fewer false positives and negatives. Thus, the present study demonstrates that deep learning models can be used effectively to identify phenotypically similar-looking cattle breeds. To accurately identify zebu breeds, this study will reduce the dependence of farmers on experts.

Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases.

BACKGROUND: Autosomal dominant mutations in α-synuclein, TDP-43 and tau are thought to predispose to neurodegeneration by enhancing protein aggregation. While a subset of α-synuclein, TDP-43 and tau mutations has been shown to increase the structural propensity of these proteins toward self-association, rates of aggregation are also highly dependent on protein steady state concentrations, which are in large part regulated by their rates of lysosomal degradation. Previous studies have shown that lysosomal proteases operate precisely and not indiscriminately, cleaving their substrates at very specific linear amino acid sequences. With this knowledge, we hypothesized that certain coding mutations in α-synuclein, TDP-43 and tau may lead to increased protein steady state concentrations and eventual aggregation by an alternative mechanism, that is, through disrupting lysosomal protease cleavage recognition motifs and subsequently conferring protease resistance to these proteins. RESULTS: To test this possibility, we first generated comprehensive proteolysis maps containing all of the potential lysosomal protease cleavage sites for α-synuclein, TDP-43 and tau. In silico analyses of these maps indicated that certain mutations would diminish cathepsin cleavage, a prediction we confirmed utilizing in vitro protease assays. We then validated these findings in cell models and induced neurons, demonstrating that mutant forms of α-synuclein, TDP-43 and tau are degraded less efficiently than wild type despite being imported into lysosomes at similar rates. CONCLUSIONS: Together, this study provides evidence that pathogenic mutations in the N-terminal domain of α-synuclein (G51D, A53T), low complexity domain of TDP-43 (A315T, Q331K, M337V) and R1 and R2 domains of tau (K257T, N279K, S305N) directly impair their own lysosomal degradation, altering protein homeostasis and increasing cellular protein concentrations by extending the degradation half-lives of these proteins. These results also point to novel, shared, alternative mechanism by which different forms of neurodegeneration, including synucleinopathies, TDP-43 proteinopathies and tauopathies, may arise. Importantly, they also provide a roadmap for how the upregulation of particular lysosomal proteases could be targeted as potential therapeutics for human neurodegenerative disease.

Conformational and Solvation Dynamics of an Amyloidogenic Intrinsically Disordered Domain of a Melanosomal Protein.

The conformational plasticity of intrinsically disordered proteins (IDPs) allows them to adopt a range of conformational states that can be important for their biological functions. The driving force for the conformational preference of an IDP emanates from an intricate interplay between chain-chain and chain-solvent interactions. Using ultrafast femtosecond and picosecond time-resolved fluorescence measurements, we characterized the conformational and solvation dynamics around the N- and C-terminal segments of a disordered repeat domain of a melanosomal protein Pmel17 that forms functional amyloid responsible for melanin biosynthesis. Our time-resolved fluorescence anisotropy results revealed slight compaction and slower rotational dynamics around the amyloidogenic C-terminal segment when compared to the proline-rich N-terminal segment of the repeat domain. The compaction of the C-terminal region was also associated with the restrained mobility of hydration water as indicated by our solvation dynamics measurements. Our findings indicate that sequence-dependent chain-solvent interactions govern both the conformational and solvation dynamics that are crucial in directing the conversion of a highly dynamic IDP into an ordered amyloid assembly. Such an interplay of amino acid composition-dependent conformational and solvation dynamics might have important physicochemical consequences in specific water-protein, ion-protein, and protein-protein interactions involved in amyloid formation and phase transitions.

Terminal Capping of an Amyloidogenic Tau Fragment Modulates Its Fibrillation Propensity.

Aberrant protein folding leading to the formation of characteristic cross-ß-sheet-rich amyloid structures is well known for its association with a variety of debilitating human diseases. Often, depending upon amino acid composition, only a small segment of a large protein participates in amyloid formation and is in fact capable of self-assembling into amyloid, independent of the rest of the protein. Therefore, such peptide fragments serve as useful model systems for understanding the process of amyloid formation. An important factor that has often been overlooked while using peptides to mimic full-length protein is the charge on the termini of these peptides. Here, we show the influence of terminal charges on the aggregation of an amyloidogenic peptide from microtubule-associated protein Tau, implicated in Alzheimer's disease and tauopathies. We found that modification of terminal charges by capping the peptide at one or both of the termini drastically modulates the fibrillation of the hexapeptide sequence paired helical filament 6 (PHF6) from repeat 3 of Tau, both with and without heparin. Without heparin, the PHF6 peptide capped at both termini and PHF6 capped only at the N-terminus self-assembled to form amyloid fibrils. With heparin, all capping variants of PHF6, except for PHF6 with both termini free, formed typical amyloid fibrils. However, the rate and extent of aggregation both with and without heparin as well as the morphology of aggregates were found to be highly dependent on the terminal charges. Our molecular dynamics simulations on PHF6 capping variants corroborated our experiments and provided critical insights into the mechanism of PHF6 self-assembly. Overall, our results emphasize the importance of terminal modifications in fibrillation of small peptide fragments and provide significant insights into the aggregation of a small Tau fragment, which is considered essential for Tau filament assembly.

Discerning Dynamic Signatures of Membrane-Bound α-Synuclein Using Site-Specific Fluorescence Depolarization Kinetics.

α-Synuclein is an intrinsically disordered protein that adopts an α-helical structure upon binding to the negatively charged lipid membrane. Binding-induced conformational change of α-synuclein plays a crucial role in the regulation of synaptic plasticity. In this work, we utilized the fluorescence depolarization kinetics methodology to gain the site-specific dynamical insights into the membrane-bound α-synuclein. We took advantage of the nonoccurrence of Cys in α-synuclein and created single-Cys variants at different sites for us to be able to label it with a thiol-active fluorophore. Our fluorescence depolarization results reveal the presence of three dynamically distinct types of motions of α-synuclein on POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) small unilamellar vesicles (SUVs): (i) the (local) wobbling-in-cone motion of the fluorophore on the subnanosecond timescale, (ii) the backbone segmental mobility on the nanosecond timescale, and (iii) a slow depolarization component with a characteristic long rotational correlation time (∼60 ns) that is independent of the residue position. This characteristic timescale could potentially arise due to global tumbling of the protein-membrane complex, the global reorientation of only the protein within the membrane, and/or the translation diffusion of the protein on the curved membrane surface that could result in fluorescence depolarization due to the angular displacement of the transition dipole. In order to discern the molecular origin of the characteristic long rotational correlation time, we then carried our depolarization experiments varying the curvature of the membrane and varying the binding affinity by changing the lipid headgroup. These experiments revealed that the long rotational correlation time primarily arises due to the translational diffusion of α-synuclein on the curved membrane surface with a diffusion coefficient of ∼8.7 × 10-10 m2/s. The site-specific fluorescence depolarization methodology will find broad application in quantifying diffusion of a wide range of membrane-associated proteins involved in functions and diseases.

Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation.

Post-translational modifications (PTMs) on tau have long been recognized as affecting protein function and contributing to neurodegeneration. The explosion of information on potential and observed PTMs on tau provides an opportunity to better understand these modifications in the context of tau homeostasis, which becomes perturbed with aging and disease. Prevailing views regard tau as a protein that undergoes abnormal phosphorylation prior to its accumulation into the toxic aggregates implicated in Alzheimer's disease (AD) and other tauopathies. However, the phosphorylation of tau may, in fact, represent part of the normal but interrupted function and catabolism of the protein. In addition to phosphorylation, tau undergoes another forms of post-translational modification including (but not limited to), acetylation, ubiquitination, glycation, glycosylation, SUMOylation, methylation, oxidation, and nitration. A holistic appreciation of how these PTMs regulate tau during health and are potentially hijacked in disease remains elusive. Recent studies have reinforced the idea that PTMs play a critical role in tau localization, protein-protein interactions, maintenance of levels, and modifying aggregate structure. These studies also provide tantalizing clues into the possibility that neurons actively choose how tau is post-translationally modified, in potentially competitive and combinatorial ways, to achieve broad, cellular programs commensurate with the distinctive environmental conditions found during development, aging, stress, and disease. Here, we review tau PTMs and describe what is currently known about their functional impacts. In addition, we classify these PTMs from the perspectives of protein localization, electrostatics, and stability, which all contribute to normal tau function and homeostasis. Finally, we assess the potential impact of tau PTMs on tau solubility and aggregation. Tau occupies an undoubtedly important position in the biology of neurodegenerative diseases. This review aims to provide an integrated perspective of how post-translational modifications actively, purposefully, and dynamically remodel tau function, clearance, and aggregation. In doing so, we hope to enable a more comprehensive understanding of tau PTMs that will positively impact future studies.

Catalytic Prion-Like Cross-Talk between a Key Alzheimer's Disease Tau-Fragment R3 and the Type 2 Diabetes Peptide IAPP.

The aberrant association of proteins/peptides is implicated in the etiology and pathogenesis of a variety of human diseases. In general, the primary protein component responsible for the formation of aggregates is different in each case and is specific to a particular disease condition. However, there are instances where multiple protein aggregates have been found to coexist in the same or different tissue(s), thereby leading to mixed pathologies and exacerbation of disease symptoms. In this context, a strong link has been established between Alzheimer's disease (AD) and type 2 diabetes (T2D). However, the underlying molecular details still remain elusive. Here, we report the direct interaction of an AD-associated amyloidogenic cytotoxic fragment of Tau (R3:306-336) with islet amyloid polypeptide (IAPP) implicated in T2D. Using ion-mobility mass spectrometry (IM-MS) in conjunction with fluorescence spectroscopy, circular dichroism, and transmission electron microscopy, we have been able to provide critical mechanistic insights into these interactions. Our IM-MS data showed the formation of hetero-oligomers of R3 and IAPP. Additionally, using IM-MS, we found that the amyloidogenic extended beta hairpin conformation of IAPP is favored much more in the R3-IAPP mixture, when compared with IAPP alone. Furthermore, we found that the oligomerization of R3 occurs much faster in the presence of IAPP. We also observed a secondary nucleation step in our kinetics data for the R3-IAPP mixture. We believe that the secondary nucleation step is demonstrative of R3 aggregation which otherwise requires the presence of anionic cofactors. Our results provide the first experimental evidence for direct molecular interaction between Tau and IAPP and highlights the repercussion of possible "prion-like" cross-talk in the proliferation of diseases that are associated with different tissues/organs.

Femtosecond Hydration Map of Intrinsically Disordered α-Synuclein.

Protein hydration water plays a fundamentally important role in protein folding, binding, assembly, and function. Little is known about the hydration water in intrinsically disordered proteins that challenge the conventional sequence-structure-function paradigm. Here, by combining experiments and simulations, we show the existence of dynamical heterogeneity of hydration water in an intrinsically disordered presynaptic protein, namely α-synuclein, implicated in Parkinson's disease. We took advantage of nonoccurrence of cysteine in the sequence and incorporated a number of cysteine residues at the N-terminal segment, the central amyloidogenic nonamyloid-ß component (NAC) domain, and the C-terminal end of α-synuclein. We then labeled these cysteine variants using environment-sensitive thiol-active fluorophore and monitored the solvation dynamics using femtosecond time-resolved fluorescence. The site-specific femtosecond time-resolved experiments allowed us to construct the hydration map of α-synuclein. Our results show the presence of three dynamically distinct types of water: bulk, hydration, and confined water. The amyloidogenic NAC domain contains dynamically restrained water molecules that are strikingly different from the water molecules present in the other two domains. Atomistic molecular dynamics simulations revealed longer residence times for water molecules near the NAC domain and supported our experimental observations. Additionally, our simulations allowed us to decipher the molecular origin of the dynamical heterogeneity of water in α-synuclein. These simulations captured the quasi-bound water molecules within the NAC domain originating from a complex interplay between the local chain compaction and the sequence composition. Our findings from this synergistic experimental simulation approach suggest longer trapping of interfacial water molecules near the amyloidogenic hotspot that triggers the pathological conversion into amyloids via chain sequestration, chain desolvation, and entropic liberation of ordered water molecules.

Water Rearrangements upon Disorder-to-Order Amyloid Transition.

Water plays a critical role in governing the intricate balance between chain-chain and chain-solvent interactions during protein folding, misfolding, and aggregation. Previous studies have indicated the presence of different types of water in folded (globular) proteins. In this work, using femtosecond and picosecond time-resolved fluorescence measurements, we have characterized the solvation dynamics from ultrafast to ultraslow time scale both in the monomeric state and in the amyloid state of an intrinsically disordered protein, namely κ-casein. Monomeric κ-casein adopts a compact disordered state under physiological conditions and is capable of spontaneously aggregating into highly ordered ß-rich amyloid fibrils. Our results indicate that the mobility of "biological water" (type I) gets restrained as a result of conformational sequestration during amyloid formation. Additionally, a significant decrease in the bulk water component with a concomitant increase in the ultraslow component revealed the ordering of trapped interstitial water (type II) upon disorder-to-order amyloid transition. Our results provide an experimental underpinning of significant water rearrangements associated with both chain desolvation and water confinement upon amyloid formation.

Direct Observation of the Intrinsic Backbone Torsional Mobility of Disordered Proteins.

The fundamental backbone dynamics of unfolded proteins arising due to intrinsic ϕ-ψ dihedral angle fluctuations dictate the course of protein folding, binding, assembly, and function. These internal fluctuations are also critical for protein misfolding associated with a range of human diseases. However, direct observation and unambiguous assignment of this inherent dynamics in chemically denatured proteins is extremely challenging due to various experimental limitations. To directly map the backbone torsional mobility in the ϕ-ψ dihedral angle space, we used a model intrinsically disordered protein, namely, α-synuclein, that adopts an expanded state under native conditions. We took advantage of nonoccurrence of tryptophan in α-synuclein and created a number of single-tryptophan variants encompassing the entire polypeptide chain. We then utilized highly sensitive picosecond time-resolved fluorescence depolarization measurements that allowed us to discern the site-specific torsional relaxation at a low protein concentration under physiological conditions. For all the locations, the depolarization kinetics exhibited two well-separated rotational-correlation-time components. The shorter, subnanosecond component arises due to the local mobility of the indole side chain, whereas the longer rotational-correlation-time component (1.37 ± 0.15 ns), independent of global tumbling, represents a characteristic timescale for short-range conformational exchange in the ϕ-ψ dihedral space. This correlation time represents an intrinsic timescale for torsional relaxation and is independent of position, which is expected for an extended polypeptide chain having little or no propensity to form persistent structures. We were also able to capture this intrinsic timescale at the N-terminal unstructured domain of the prion protein. Our estimated timescale of the segmental mobility is similar to that of unfolded proteins studied by nuclear magnetic resonance in conjunction with molecular dynamics simulations. Our results have broader implications for a diverse range of functionally and pathologically important intrinsically disordered proteins and disordered regions.

Confined Water in Amyloid-Competent Oligomers of the Prion Protein.

Conformational switching of the prion protein into the abnormal form involves the formation of (obligatory) molten-oligomers that mature into ordered amyloid fibrils. The role of water in directing the course of amyloid formation remains poorly understood. Here, we show that the mobility of the water molecules within the on-pathway oligomers is highly retarded. The water relaxation time within the oligomers was estimated to be ≈1 ns which is about three orders of magnitude slower than the bulk water and resembles the characteristics of (trapped) nano-confined water. We propose that the coalescence of these obligatory oligomers containing trapped water is entropically favored because of the release of ordered water molecules in the bulk milieu and results in the sequestration of favorable inter-chain amyloid contacts via nucleated conformational conversion. The dynamic role of water in protein aggregation will have much broader implications in a variety of protein misfolding diseases.

Constipation and Outcomes of Cecostomy.

Constipation, defined as delay or difficulty in defecation, present for 2 or more weeks, is a common problem encountered by both primary and specialty medical providers. There are no randomized controlled trials on the use of antegrade enemas in the pediatric population. Most published papers are based on the experience at a particular center. The aim of this article is to describe the pathophysiology of constipation, review the contribution of colonic manometry to the diagnosis of constipation, summarize the advancements in the management of constipation through the use of antegrade enemas, and study the outcomes of cecostomy at different centers. This study is a comprehensive literature review generated by computerized search of literature, supplemented by review of monographs and textbooks in pathology, gastroenterology, and surgery. Literature search was performed using the publications from 1997 to 2012. The search included publications of all types presenting or reviewing data on cecostomy. The antegrade continence enema is a therapeutic option for defecation disorders when maximal conventional therapy is not successful. Symptoms of defecation disorders in children with different underlying etiologies improve significantly after a cecostomy is created. In addition, there is a benefit on the patients' physical activity, healthcare utilization, and general well-being. Based on the review of published literature it seems that antegrade enemas are a successful therapeutic option in children with severe constipation and/or fecal incontinence. With the advent of cecostomy buttons, patient compliance and the overall cosmetic appearance have improved.

Conformational Switching and Nanoscale Assembly of Human Prion Protein into Polymorphic Amyloids via Structurally Labile Oligomers.

Conformational switching of the prion protein (PrP) from an α-helical normal cellular form (PrP(C)) to an aggregation-prone and self-propagating ß-rich scrapie form (PrP(Sc)) underlies the molecular basis of pathogenesis in prion diseases. Anionic lipids play a critical role in the misfolding and conformational conversion of the membrane-anchored PrP into the amyloidogenic pathological form. In this work, we have used a diverse array of techniques to interrogate the early intermediates during amyloid formation from recombinant human PrP in the presence of a membrane mimetic anionic detergent such as sodium dodecyl sulfate. We have been able to detect and characterize two distinct types of interconvertible oligomers. Our results demonstrate that highly ordered large ß-oligomers represent benign off-pathway intermediates that lack the ability to mature into amyloid fibrils. On the contrary, structurally labile small oligomers are capable of switching to an ordered amyloid-state that exhibits profound toxicity to mammalian cells. Our fluorescence resonance energy transfer measurements revealed that the partially disordered PrP serves as precursors to small amyloid-competent oligomers. These on-pathway oligomers are eventually sequestered into higher order supramolecular assemblies that conformationally mature into polymorphic amyloids possessing varied nanoscale morphology as evident by the atomic force microscopy imaging. The nanoscale diversity of fibril architecture is attributed to the heterogeneous ensemble of early obligatory oligomers and offers a plausible explanation for the existence of multiple prion strains in vivo.

Appearance of annular ring-like intermediates during amyloid fibril formation from human serum albumin.

The self-assembly of proteins triggered by a conformational switch into highly ordered ß-sheet rich amyloid fibrils has captivated burgeoning interest in recent years due to the involvement of amyloids in a variety of human diseases and a diverse range of biological functions. Here, we have investigated the mechanism of fibrillogenesis of human serum albumin (HSA), an all-α-helical protein, using an array of biophysical tools that include steady-state as well as time-resolved fluorescence, circular dichroism and Raman spectroscopy in conjunction with atomic force microscopy (AFM). Investigations into the temporal evolution of nanoscale morphology using AFM revealed the presence of ring-like intermediates that subsequently transformed into worm-like fibrils presumably by a ring-opening mechanism. Additionally, a multitude of morphologically-diverse oligomers were observed on the pathway to amyloid formation. Kinetic analysis using multiple structural probes in-tandem indicated that HSA amyloid assembly is a concerted process encompassing a major structural change that is primarily mediated by hydrophobic interactions between thermally-induced disordered segments originating in various domains. A slower growth kinetics of aggregates suggested that the protein structural reorganization is a prerequisite for fibril formation. Moreover, time-dependent Raman spectroscopic studies of HSA aggregation provided key molecular insights into the conformational transitions occurring within the protein amide backbone and at the residue-specific level. Our data revealed the emergence of conformationally-diverse disulfides as a consequence of structural reorganization and sequestration of tyrosines into the hydrophobic amyloid core comprising antiparallel cross ß-sheets.

Ordered water within the collapsed globules of an amyloidogenic intrinsically disordered protein.

Intrinsically disordered proteins (IDPs) confront the traditional sequence-structure-function paradigm and are associated with important functions and amyloid disorders. Water molecules residing in the vicinity of the polypeptide chain play potentially important roles in directing the course of binding-induced folding and amyloid aggregation of IDP. Here we characterized the nature of water molecules entrapped within the collapsed globules of an amyloidogenic IDP, namely, κ-casein. These globules can undergo further compaction in the presence of an anionic detergent that is capable of diminishing the intrachain repulsion from the positively charged glutamine/asparagine-rich amyloidogenic N-terminal domain comprising 100 residues. Using time-resolved fluorescence spectroscopy, we estimated the longer component of the solvation time to be ∼1.4 ns, which is 3 orders of magnitude slower than that in bulk water and more than an order of magnitude slower than the "biological water" present at the protein surface. Profoundly restrained water within the collapsed IDP globules resembles the ordered water cluster found under nanoconfinement. We suggest that the association of these globules would result in the release of ordered water molecules into the bulk milieu causing an entropic gain that would eventually drive the formation of the key (obligatory) oligomeric intermediates on the pathway to amyloids via nucleation-dependent polymerization.

Patellar tendinopathy alters the distribution of lower extremity net joint moments during hopping.

The purpose of the current investigation was to test the hypothesis that subjects with patellar tendinopathy would demonstrate altered sagittal plane joint moment contributions during hopping tasks. Fourteen subjects (7 patellar tendinopathy, 7 controls) participated. Sagittal net joint moments of the lower extremity, total support moment, and joint contributions to the total support moment were calculated while subjects hopped continuously at a self-selected frequency and at 1.67 Hz. Significant differences were observed for contributions to the total support moment (p=.022). When averaged across hopping frequencies, subjects with patellar tendinopathy demonstrated greater hip contribution (p=.030) and lesser knee contribution (p=.006) compared with the control subjects. Shifting the workload away from the knee and toward the hip may result in a detrimental increase in hip demand and potentially harmful long-term effects on the articular cartilage of the hip.

Knee extensor dynamics in the volleyball approach jump: the influence of patellar tendinopathy.

STUDY DESIGN: Controlled laboratory study using a cross-sectional design. OBJECTIVES: To evaluate knee joint dynamics in elite volleyball players with and without a history of patellar tendinopathy, focusing on mechanical energy absorption and generation. We hypothesized that tendinopathy would be associated withreduced net joint work and net joint power. BACKGROUND: Patellar tendinopathy is a common, debilitating injury affecting competitive volleyball players. METHODS: Thirteen elite male players with and without a history of patellar tendinopathy (mean ± SD age, 27 ± 7 years) performed maximum-effort volleyball approach jumps. Sagittal plane knee joint kinematics, kinetics, and energetics were quantified in the lead limb, using data obtained from a force platform and an 8-camera motion analysis system. Vertical ground reaction forces and pelvis vertical velocity at takeoff were examined. Independent sample t tests were used to evaluate group differences (α = .05). RESULTS: The tendinopathy group, compared to controls, demonstrated significant reductions (approximately 30%) in net joint work and net joint power during the eccentric phase of the jump, with no differences in the concentric phase. Positive to-negative net joint work and net joint power ratios were significantly higher in the tendinopathy group, which had a net joint work ratio of 1.00 (95% CI: 0.77, 1.24) versus 0.76 (95% CI: 0.64, 0.88) for controls, and a net joint power ratio of 1.62 (95% CI: 1.15, 2.10) versus 1.00 (95% CI: 0.80, 1.21) for controls. There were no significant differences in net joint moment, angular velocity, or range of motion. Peak vertical ground reaction forces were lower for the tendinopathy group, while average vertical ground reaction forces and pelvis vertical velocity were similar. CONCLUSION: Patellar tendinopathy is associated with differences in sagittal plane mechanical energy absorption at the knee during maximum-effort volleyball approach jumps. Net joint work and net joint power may help define underlying mechanisms, adaptive effects, or rehabilitative strategies for individuals with patellar tendinopathy.

Tendinopathy alters mechanical and material properties of the Achilles tendon.

The purpose of this study was to investigate the in vivo material and mechanical properties of the human Achilles tendon in the presence of tendinopathy. Real-time ultrasound imaging and dynamometry were used to assess Achilles tendon stiffness, Young's modulus, stress, strain, and cross-sectional area (CSA) in 12 individuals with Achilles tendinopathy and 12 age- and gender-matched controls. The results of this study suggest that tendinopathy weakens the mechanical and material properties of the tendon. Tendinopathic tendons had greater CSA, lower tendon stiffness, and lower Young's modulus. These alterations in mechanical characteristics may put the Achilles tendon at a higher risk to sustain further injury and prolong the time to recovery. Results from this study may be used to design treatment strategies that specifically target these deficits, leading to faster and permanent recovery from tendinopathy.

Effect of eccentric exercise program for early tibialis posterior tendinopathy.

BACKGROUND: Morphology and vascularization of painful tibialis posterior (TP) tendons before and after an intervention targeting the degenerated tendon were examined. Functional status and pain level were also assessed. MATERIALS AND METHODS: A10-week twice daily, progressive eccentric tendon loading, calf stretching program with orthoses was implemented with ten, early stage TP tendinopathy subjects. TP tendons were imaged by grayscale and Doppler ultrasound at INITIAL and POST evaluations to assess the tendon's morphology and signs of neovascularization. The Foot Functional Index (FFI), Physical Activity Scale (PAS), 5-Minute Walk Test, and single heel raise (SHR) test were completed at INITIAL and POST evaluations. The Global Rating Scale (GRS) was completed at 6 months followup. One-way ANOVA was used to compare the FFI at INITIAL, POST, and 6-MONTH time points. Paired t-tests were used to compare means between the remaining variables. The level of significance was p = 0.05. RESULTS: There was a significant difference in FFI total, pain, and disability at the three time-points. Post-hoc paired t-tests revealed that the FFI scores were lower for the total score and pain and disability subcategories when comparing from INITIAL to POST and INITIAL to 6-MONTH evaluations (p < 0.05 for all). The number of SHR increased significantly on the involved side from INITIAL to POST evaluation (p = 0.041). The GRS demonstrated minimum clinically important differences for improvements in symptoms at 6-MONTH. Tendon morphology and vascularization remained abnormal following the intervention. CONCLUSION: A 10-week tendon specific eccentric program resulted in improvements in symptoms and function without changes in tendon morphology or neovascularization.