The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be determined.Heterotopicossification(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues.Hypoxia andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote HO.However,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to beelucidated.Here,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell fate.Usingsingle-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in MPCs.Zeugopod mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in vivo.ScRNA-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of HO.Importantly,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1αdeletion.From a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic metabolism.This suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC fate.These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression.Aberrant glycosylation has been intricately linked with immune escape and tumor growth.SEMA7A is a highly glycosylated protein with five glycosylated sites.The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear.Here,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane.Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition.Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death.Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy.Finally,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing.These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

Carotid-subclavian bypass and endovascular aortic repair of Kommerell’s diverticulum with aberrant left subclavian artery:A case report

BACKGROUND Kommerell’s diverticulum(KD)with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it(35%of case study).There are three types of aortic arch diverticulum.Even literature concerning the treatment options are limited.CASE SUMMARY We present a case report of a 50-year-old male with KD in the right aortic arch with aberrant left subclavian artery.We conducted a total endovascular repair procedure,which is innovative and will spread more light in the medical world.Our patient has no past medical history and is a non-smoker and non-alcoholic.Patient presented with shortness of breath,chest pain and dizziness for six months.Blood tests were done and computerized tomography(CT)angiogram of the chest confirmed the diagnosis,illustrating showed a 3.9 cm KD.On Day 1,the CT angiogram showed mild dilatation of the thoracic aorta,adjacent esophagus,trachea was compressed and displaced.Surgery was planned as the treatment modality.Carotid-Subclavian artery bypass and endovascular aortic repair was conducted.We used prolene 5-0 C1 sutures to precisely anastomose a 6-mm Dacron graft to the left subclavian artery.Haemostasis was secured and wounds were closed.Protamine was administered and patient was shifted to intensive care unit.Post-operative,patient responded favorably and was discharged.Regular follow-up is done.CONCLUSION The procedure we performed is novel.This will help the cardio-thoracic surgeons a better insight about the full procedures we conducted,thereby bringing more light and better treatment options in managing KD with aberrant subclavian artery.

Cryptic divergences and repeated hybridizations within the endangered “living fossil” dove tree(Davidia involucrata) revealed by whole genome resequencing

The identification and understanding of cryptic intraspecific evolutionary units(lineages) are crucial for planning effective conservation strategies aimed at preserving genetic diversity in endangered species.However, the factors driving the evolution and maintenance of these intraspecific lineages in most endangered species remain poorly understood. In this study, we conducted resequencing of 77 individuals from 22 natural populations of Davidia involucrata, a “living fossil” dove tree endemic to central and southwest China. Our analysis revealed the presence of three distinct local lineages within this endangered species, which emerged approximately 3.09 and 0.32 million years ago. These divergence events align well with the geographic and climatic oscillations that occurred across the distributional range.Additionally, we observed frequent hybridization events between the three lineages, resulting in the formation of hybrid populations in their adjacent as well as disjunct regions. These hybridizations likely arose from climate-driven population expansion and/or long-distance gene flow. Furthermore, we identified numerous environment-correlated gene variants across the total and many other genes that exhibited signals of positive evolution during the maintenance of two major local lineages. Our findings shed light on the highly dynamic evolution underlying the remarkably similar phenotype of this endangered species. Importantly, these results not only provide guidance for the development of conservation plans but also enhance our understanding of evolutionary past for this and other endangered species with similar histories.

Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems for Escherichia coli Nissle 1917

The probiotic bacterium Escherichia coli Nissle 1917(EcN)holds significant promise for use in clinical and biological industries.However,the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its benefits.In this study,we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and pMUT2.The non-essential elements were removed to create more stable derivatives pMUT1NR△and pMUT2HBC△.Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinaseⅢand the biosynthesis of ectoine.Compared to traditional antibiotic-dependent expression systems,our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

Mitogenomic phylogeny,biogeography,and cryptic divergence of the genus Silurus(Siluriformes:Siluridae)

The genus Silurus,an important group of catfish,exhibits heterogeneous distribution in Eurasian freshwater systems.This group includes economically important and endangered species,thereby attracting considerable scientific interest.Despite this interest,the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus.Herein,we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes(mitogenomes)from 13 morphological species to reconstruct the phylogenetic relationships,biogeographic history,and species diversity of Silurus.Our phylogenetic reconstructions identified eight clades,supported by both maximum-likelihood and Bayesian inference.Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units(MOTUs)in several taxa,including the Silurus asotus complex(four MOTUs)and Silurus microdorsalis(two MOTUs),suggesting that species diversity is underestimated in the genus.A reconstructed time-calibrated tree of Silurus species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago(Ma),with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma,and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma.Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula,with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma.Key factors such as the Eocene-Oligocene extinction event,onset and intensification of the monsoon system,and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus Silurus.

Multidimensional images and aberrations in STEM

Recent advances in scanning transmission electron microscopy(STEM)have led to increased development of multidimensional STEM imaging modalities and novel image reconstruction methods.This interest arises because the main electron lens in a modern transmission electron microscope usually has a diffraction-space information limit that is significantly better than the real-space resolution of the same lens.This state-of-affairs is sometimes shared by other scattering methods in modern physics and contributes to a broader excitement surrounding multidimensional techniques that scan a probe while recording diffraction-space images,such as ptychography and scanning nano-beam diffraction.However,the contrasting resolution in the two spaces raises the question as to what is limiting their effective performance.Here,we examine this paradox by considering the effects of aberrations in both image and diffraction planes,and likewise separate the contributions of pre-and post-sample aberrations.This consideration provides insight into aberration-measurement techniques and might also indicate improvements for super-resolution techniques.

Stimulated Raman scattering microscopy with phase-controlled light focusing and aberration correction for rapid and label-free, volumetric deep tissue imaging

We report a novel stimulated Raman scattering(SRS)microscopy technique featuring phase-controlled light focusing and aberration corrections for rapid,deep tissue 3D chemical imaging with subcellular resolution.To accomplish phasecontrolled SRS(PC-SRS),we utilize a single spatial light modulator to electronically tune the axial positioning of both the shortened-length Bessel pump and the focused Gaussian Stokes beams,enabling z-scanning-free optical sectioning in the sample.By incorporating Zernike polynomials into the phase patterns,we simultaneously correct the system aberrations at two separate wavelengths(~240 nm difference),achieving a~3-fold enhancement in signal-to-noise ratio over the uncorrected imaging system.PC-SRS provides>2-fold improvement in imaging depth in various samples(e.g.,polystyrene bead phantoms,porcine brain tissue)as well as achieves SRS 3D imaging speed of~13 Hz per volume for real-time monitoring of Brownian motion of polymer beads in water,superior to conventional point-scanning SRS 3D imaging.We further utilize PC-SRS to observe the metabolic activities of the entire tumor liver in living zebrafish in cellsilent region,unraveling the upregulated metabolism in liver tumor compared to normal liver.This work shows that PCSRS provides unprecedented insights into morpho-chemistry,metabolic and dynamic functioning of live cells and tissue in real-time at the subcellular level.

Fuzzy splicing in precursor-mRNA sequences: prediction of aberrant splice-junctions in viral DNA context

RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing cryptic splice-junctions, which would remain unrecognized by T-memory cells of higher organisms in vaccine trials. Such aberrant splice- junctions result from evolution-specific non-conser- vation of actual splice-junction sites due to mutations;as such, locations of splice-junctions in a test DNA sequence could only be imprecisely specified. Such impreciseness of splice-junction locations (or cryptic sites) in a sequence is evaluated in this study via “noisy” attributes (with associated stochastics) to the mutated subspace;and, relevant fuzzy considerations are invoked with membership attributes expressed in terms of a spatial signal-to-noise ratio (SSNR). That is, SSNR adopted as a membership function expresses the belongingness of a site-region to exon/intron subspaces. An illustrative example with actual (Dengue 1 viral) DNA data is furnished demonstrating the pursuit developed in predicting aberrant splice-junctions at cryptic sites in the test sequence.

Accumulation of aberrant DNA methylation during colorectal cancer development

Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.

Implications of the presence of an aberrant right hepatic artery in patients undergoing pancreaticoduodenectomy

AIM:To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy(PD)in patients with and without aberrant right hepatic artery(aRHA).METHODS:All patients undergoing PD between January 2008 and December 2012 were divided into two groups,one with aRHA and the other without.These groups were compared to identify differences in the intraoperative variables,the oncological clearance and the postoperative morbidity,mortality and hospital stay.RESULTS:A total of 225 patients underwent PD,of which 43(19.1%)patients were found to have eitheraccessory or replaced right hepatic arteries(aRHA group).The aRHA was preserved in 79%of the patients.There was no significant difference in the intraoperative blood loss but operative time was prolonged,reflecting the complexity of the procedure[420±44(240-540)min vs 480±45(300-600)min,P<0.05)].There were no differences in the incidence of postoperative complications(pancreatic leak,pancreatic fistula,delayed gastric emptying and mortality)and hospital stay.Oncological clearance in the form of positive resection margins[13(7.1%)vs 3(6.9%)]and lymph node yield were also similar in the two groups.CONCLUSION:An aRHA is found in approximately one fifth of patients undergoing PD.Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.

Management of aberrant bile duct during laparoscopic cholecystectomy

Objective: To investigate the incidence of aberrant bile duct and its management during laparoscopic cholecystectomy (LC). Methods: In 10 000 patients undergoing laparoscopic cholecystectomy from 1992 to July 2001, 3 had the involvement of the right accessory hepatic duct. In patient 1, the aberrant duct drained into the cystic duct was confirmed by open operation. In patient 2, the aberrant duct, which drained to the common bile duct (CBD), was injured and treated with suture and ligature under laparoscopy. In patient 3, the ab- errant duct, which also drained to the CBD, was confirmed and preserved. Results: All patients recovered well except patient 1 who had a transient elevation of ALT. No bile leak- age or other complication occurred. Conclusions: Only variation near the confluence and the entrance of the cystic duct into the bile duct is discovered during laparoscopic cholecystectomy. Right accessory hepatic duct is common and should be preserved during the operation. The accidentally injured small accessory hepatic duct can be treated with ligature without severe disturbance to liver func- tion.

Aberrant crypt focus and fragile histidine triad protein in sporadic colorectal carcinoma

AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.

Azoxymethane-induced rat aberrant crypt foci:Relevance in studying chemoprevention of colon cancer

The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

Aberrant DNA Methylation in Human Cancers

DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.

Neuron-to-vessel signaling is a required feature of aberrant stem cell commitment after soft tissue trauma

The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of interest. Here, we sought to define the regulatory relationship of peripheral nerves on vasculature in a severe extremity trauma model in mice, which results in aberrant cell fate and heterotopic ossification(HO). First, a high spatial degree of neurovascular congruency was observed to exist within extremity injury associated heterotopic ossification. Vascular and perivascular cells demonstrate characteristic responses to injury,as assessed by single cell RNA sequencing. This vascular response to injury was blunted in neurectomized mice, including a decrease in endothelial proliferation and type H vessel formation, and a downregulation of key transcriptional networks associated with angiogenesis. Independent mechanisms to chemically or genetically inhibit axonal ingrowth led to similar deficits in HO site angiogenesis, a reduction in type H vessels, and heterotopic bone formation. Finally, a combination of single cell transcriptomic approaches within the dorsal root ganglia identified key neural-derived angiogenic paracrine factors that may mediate neuron-to-vascular signaling in HO. These data provide further understanding of nerve-to-vessel crosstalk in traumatized soft tissues, which may reflect a key determinant of mesenchymal progenitor cell fate after injury.

Inhibition of aberrant Hif1αactivation delays intervertebral disc degeneration in adult mice

The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

Aberrant pyramidal tract in a patient with corona radiata infarct A diffusion tensor tractography study

The aberrant pyramidal tract refers to the collateral pathway of the pyramidal tract through the medial lemniscus in the brainstem. A 63-year-old male patient presented with severe paralysis of the left extremities due to a right corona radiata infarct. He was able to extend the affected fingers against resistance at 2 months after stroke onset. At 6 months after stroke onset, he was able to perform some fine motor activities, as well as to walk with a nearly normal gait. Functional MRI, which was performed at 6 months after onset, showed that the contralateral primary sensorimotor cortex was activated during affected （left） hand movements. Diffusion tensor tractography results showed that at 2 weeks after stroke onset, pyramidal tracts of the affected hemisphere originated from the primary motor cortex and descended along the known pathway of the pyramidal tract with an aberrant pyramidal tract, which was bypassed through the medial lemniscus from the midbrain to the lower pons. However, the pyramidal tract from midbrain to pons in the affected hemisphere could not be depicted by diffusion tensor tractography at 6 months after stroke onset; instead, only the aberrant pyramidal tract existed for the course of the disappeared pyramidal tract. Results from this study indicate that the main motor functions of the affected extremities appeared to be controlled via the aberrant pyramidal tract with degeneration of the pyramidal tract in the brainstem of the affected hemisphere.

Aberrant activation of latent transforming growth factor-β initiates the onset of temporomandibular joint osteoarthritis

There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.

Motor recovery via aberrant pyramidal tract in a patient with a cerebral peduncle infarct

The presence of the aberrant pyramidal tract has been demonstrated by several studies; however, little is known about its role in motor recovery in stroke patients. In the present study, we reported a 69-year-old right-handed female patient with an infarct in the mid to lateral portion of the left cerebra peduncle, who showed an aberrant pyramidal tract by diffusion tensor tractography. The patient presented with severe weakness of the right extremities at stroke onset. The patient showed progressive motor recovery as much as being able to extend the affected extremities against some resistance at 6 months after onset. At 20 months after stroke onset, motor function of the left extremities had recovered to a nearly normal state. Diffusion tensor tractography results showed that the PT was disrupted at the lower midbrain of the affected （left） hemisphere at 3 weeks after stroke onset and this disruption was not changed at 20 months. An aberrant pyramidal tract in the left hemisphere was also observed, which originated from the primary motor cortex and descended through the corona radiata, posterior limb of the internal capsule, thalamus, the medial lemniscus pathway from the midbrain to the pons, and then entered into the pyramidal tract area at the pontomedullary junction. Transcranial magnetic stimulation did not elicit motor evoked potential from the affected hand muscle at 3 weeks, but it elicited motor evoked potential with mildly delayed latency and low amplitude in the affected hand muscle at 20 months. The main motor functions of the affected extremities in this patient appeared to be recovered via this aberrant pyramidal tract.