Evaluation of Extracellular Matrix Remodeling in Full-thickness Skin Grafts in Mice.

Abdominal hernia is a protruding weakness in the abdominal wall. It affects abdominal strength and life quality and can lead to complications due to intestinal entrapment. Autologous full-thickness skin graft (FTSG) has recently become an alternative material for reinforcement in the surgical repair of large abdominal hernias instead of synthetic mesh. FTSG eventually integrates with the abdominal wall, but the long-term fate of the graft itself is not fully understood. This has implications as to how these grafts should be optimally used and handled intraoperatively. This study investigates the remodeling of FTSG in either the onlay or the intraperitoneal position 8 weeks after FTSG transplantation in an experimental mouse model. There was a significant presence of fibroblasts, indicated by vimentin and S100A4 staining, but there were significant variations among animals as to how much of the graft had been remodeled into dense connective tissue. This correlated significantly with the proportion of vimentin-positive cells in the dense connective tissue. We also found that collagen hybridizing peptide staining intensity, a marker of active remodeling, was significantly associated with the proportion of S100A4-positive cells in the dense connective tissue of the FTSG.

The Role of Exercise in Cancer-Related Sarcopenia and Sarcopenic Obesity.

One of the most common adverse effects of cancer and its therapeutic strategies is sarcopenia, a condition which is characterised by excess muscle wasting and muscle strength loss due to the disrupted muscle homeostasis. Moreover, cancer-related sarcopenia may be combined with the increased deposition of fat mass, a syndrome called cancer-associated sarcopenic obesity. Both clinical conditions have significant clinical importance and can predict disease progression and survival. A growing body of evidence supports the claim that physical exercise is a safe and effective complementary therapy for oncology patients which can limit the cancer- and its treatment-related muscle catabolism and promote the maintenance of muscle mass. Moreover, even after the onset of sarcopenia, exercise interventions can counterbalance the muscle mass loss and improve the clinical appearance and quality of life of cancer patients. The aim of this narrative review was to describe the various pathophysiological mechanisms, such as protein synthesis, mitochondrial function, inflammatory response, and the hypothalamic-pituitary-adrenal axis, which are regulated by exercise and contribute to the management of sarcopenia and sarcopenic obesity. Moreover, myokines, factors produced by and released from exercising muscles, are being discussed as they appear to play an important role in mediating the beneficial effects of exercise against sarcopenia.

Mitochondrial Dysfunction and Sarcopenic Obesity: The Role of Exercise.

Sarcopenic obesity (SO) constitutes the coexistence of skeletal muscle mass loss (sarcopenia) and excess adiposity (obesity). It is mainly considered as a condition in the elderly with health-threatening impacts ranging from frailty to mortality. Mitochondrial dysfunction consists one of the basic pathophysiological mechanisms leading to the development of SO and its consequences. Indirect indicators of mitochondrial function, such as VO2max and exercise capacity, have been demonstrated to be negatively affected in individuals with SO, while the positive effect of exercise on mitochondrial function has been widely proved; thus, in this review, we aimed at investigating the effects of endurance, resistance, and concurrent exercise training on indexes of mitochondrial dysfunction in SO patients. The results of the clinical trials evaluated reveal positive effects of chronic exercise on VO2max and physical capacity, as well as mitochondrial biogenesis and activity. It has been concluded that utilizing a systematic exercise training program that includes both aerobic and strength exercises can be an effective strategy for managing SO and promoting overall health in these patients.

DNA methylation changes and increased mRNA expression of coagulation proteins, factor V and thrombomodulin in Fuchs endothelial corneal dystrophy.

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a disease affecting the corneal endothelium (CE), associated with a cytosine-thymine-guanine repeat expansion at the CTG18.1 locus in the transcription factor 4 (TCF4) gene. It is unknown whether CTG18.1 expansions affect global methylation including TCF4 gene in CE or whether global CE methylation changes at advanced age. Using genome-wide DNA methylation array, we investigated methylation in CE from FECD patients with CTG18.1 expansions and studied the methylation in healthy CE at different ages. The most revealing DNA methylation findings were analyzed by gene expression and protein analysis. 3488 CpGs had significantly altered methylation pattern in FECD though no substantial changes were found in TCF4. The most hypermethylated site was in a predicted promoter of aquaporin 1 (AQP1) gene, and the most hypomethylated site was in a predicted promoter of coagulation factor V (F5 for gene, FV for protein). In FECD, AQP1 mRNA expression was variable, while F5 gene expression showed a ~ 23-fold increase. FV protein was present in both healthy and affected CE. Further gene expression analysis of coagulation factors interacting with FV revealed a ~ 34-fold increase of thrombomodulin (THBD). THBD protein was detected only in CE from FECD patients. Additionally, we observed an age-dependent hypomethylation in elderly healthy CE.Thus, tissue-specific genome-wide and gene-specific methylation changes associated with altered gene expression were discovered in FECD. TCF4 pathological methylation in FECD because of CTG18.1 expansion was ruled out.

Effect of Mechanical Loading of Senescent Myoblasts on Their Myogenic Lineage Progression and Survival.

BACKGROUND: During aging, muscle cell apoptosis increases and myogenesis gradually declines. The impaired myogenic and survival potential of the aged skeletal muscle can be ameliorated by its mechanical loading. However, the molecular responses of aged muscle cells to mechanical loading remain unclear. This study examined the effect of mechanical loading of aged, proliferating, and differentiated myoblasts on the gene expression and signaling responses associated with their myogenic lineage progression and survival. METHODS: Control and aged C2C12 cells were cultured on elastic membranes and underwent passive stretching for 12 h at a low frequency (0.25 Hz) and different elongations, varying the strain on days 0 and 10 of myoblast differentiation. Activation of ERK1/2 and Akt, and the expression of focal adhesion kinase (FAK) and key myogenic regulatory factors (MRFs), MyoD and Myogenin, were determined by immunoblotting of the cell lysates derived from stretched and non-stretched myoblasts. Changes in the expression levels of the MRFs, muscle growth, atrophy, and pro-apoptotic factors in response to mechanical loading of the aged and control cells were quantified by real-time qRT-PCR. RESULTS: Mechanical stretching applied on myoblasts resulted in the upregulation of FAK both in proliferating (day 0) and differentiated (day 10) cells, as well as in increased phosphorylation of ERK1/2 in both control and aged cells. Moreover, Akt activation and the expression of early differentiation factor MyoD increased significantly after stretching only in the control myoblasts, while the late differentiation factor Myogenin was upregulated in both the control and aged myoblasts. At the transcriptional level, mechanical loading of the proliferating myoblasts led to an increased expression of IGF-1 isoforms and MRFs, and to downregulation of muscle atrophy factors mainly in control cells, as well as in the upregulation of pro-apoptotic factors both in control and aged cells. In differentiated cells, mechanical loading resulted in an increased expression of the IGF-1Ea isoform and Myogenin, and in the downregulation of atrophy and pro-apoptotic factors in both the control and aged cells. CONCLUSIONS: This study revealed a diminished beneficial effect of mechanical loading on the myogenic and survival ability of the senescent muscle cells compared with the controls, with a low strain (2%) loading being most effective in upregulating myogenic/anabolic factors and downregulating atrophy and pro-apoptotic genes mainly in the aged myotubes.

Secretome from In Vitro Mechanically Loaded Myoblasts Induces Tenocyte Migration, Transition to a Fibroblastic Phenotype and Suppression of Collagen Production.

It is known that mechanical loading of muscles increases the strength of healing tendon tissue, but the mechanism involved remains elusive. We hypothesized that the secretome from myoblasts in co-culture with tenocytes affects tenocyte migration, cell phenotype, and collagen (Col) production and that the effect is dependent on different types of mechanical loading of myoblasts. To test this, we used an in vitro indirect transwell co-culture system. Myoblasts were mechanically loaded using the FlexCell® Tension system. Tenocyte cell migration, proliferation, apoptosis, collagen production, and several tenocyte markers were measured. The secretome from myoblasts decreased the Col I/III ratio and increased the expression of tenocyte specific markers as compared with tenocytes cultured alone. The secretome from statically loaded myoblasts significantly enhanced tenocyte migration and Col I/III ratio as compared with dynamic loading and controls. In addition, the secretome from statically loaded myoblasts induced tenocytes towards a myofibroblast-like phenotype. Taken together, these results demonstrate that the secretome from statically loaded myoblasts has a profound influence on tenocytes, affecting parameters that are related to the tendon healing process.

The Global Search for Liquid Water on Mars from Orbit: Current and Future Perspectives.

Due to its significance in astrobiology, assessing the amount and state of liquid water present on Mars today has become one of the drivers of its exploration. Subglacial water was identified by the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) aboard the European Space Agency spacecraft Mars Express through the analysis of echoes, coming from a depth of about 1.5 km, which were stronger than surface echoes. The cause of this anomalous characteristic is the high relative permittivity of water-bearing materials, resulting in a high reflection coefficient. A determining factor in the occurrence of such strong echoes is the low attenuation of the MARSIS radar pulse in cold water ice, the main constituent of the Martian polar caps. The present analysis clarifies that the conditions causing exceptionally strong subsurface echoes occur solely in the Martian polar caps, and that the detection of subsurface water under a predominantly rocky surface layer using radar sounding will require thorough electromagnetic modeling, complicated by the lack of knowledge of many subsurface physical parameters. Higher-frequency radar sounders such as SHARAD cannot penetrate deep enough to detect basal echoes over the thickest part of the polar caps. Alternative methods such as rover-borne Ground Penetrating Radar and time-domain electromagnetic sounding are not capable of providing global coverage. MARSIS observations over the Martian polar caps have been limited by the need to downlink data before on-board processing, but their number will increase in coming years. The Chinese mission to Mars that is to be launched in 2020, Tianwen-1, will carry a subsurface sounding radar operating at frequencies that are close to those of MARSIS, and the expected signal-to-noise ratio of subsurface detection will likely be sufficient for identifying anomalously bright subsurface reflectors. The search for subsurface water through radar sounding is thus far from being concluded.

Evaluating four-dimensional time-lapse electrical resistivity tomography for monitoring DNAPL source zone remediation.

Practical, non-invasive tools do not currently exist for mapping the remediation of dense non-aqueous phase liquids (DNAPLs). Electrical resistivity tomography (ERT) exhibits significant potential but has not yet become a practitioner's tool due to challenges in interpreting the survey results at real sites. This study explores the effectiveness of recently developed four-dimensional (4D, i.e., 3D space plus time) time-lapse surface ERT to monitor DNAPL source zone remediation. A laboratory experiment demonstrated the approach for mapping a changing NAPL distribution over time. A recently developed DNAPL-ERT numerical model was then employed to independently simulate the experiment, providing confidence that the DNAPL-ERT model is a reliable tool for simulating real systems. The numerical model was then used to evaluate the potential for this approach at the field scale. Four DNAPL source zones, exhibiting a range of complexity, were initially simulated, followed by modeled time-lapse ERT monitoring of complete DNAPL remediation by enhanced dissolution. 4D ERT inversion provided estimates of the regions of the source zone experiencing mass reduction with time. Results show that 4D time-lapse ERT has significant potential to map both the outline and the center of mass of the evolving treated portion of the source zone to within a few meters in each direction. In addition, the technique can provide a reasonable, albeit conservative, estimate of the DNAPL volume remediated with time: 25% underestimation in the upper 2m and up to 50% underestimation at late time between 2 and 4m depth. The technique is less reliable for identifying cleanup of DNAPL stringers outside the main DNAPL body. Overall, this study demonstrates that 4D time-lapse ERT has potential for mapping where and how quickly DNAPL mass changes in real time during site remediation.

Optical properties of photonic crystal heterostructure cavity lasers.

We design, fabricate, and test photonic crystal heterostructure cavity lasers in the InP material system. A heterostructure cavity is formed by interfacing two different photonic crystals such that a dispersion maximum of the inner lattice lies within the band gap of the surrounding lattice. Feedback to slow light modes of the central region results in a lower threshold and single mode operation. The use of a kagome lattice as the inner defect area increases the semiconductor volume as well as the modal overlap with the gain material. We use a simulation technique to verify experimentally observed single mode operation as well as to quantify the effects of the heterostructure cavity formation.

Two-dimensional integration of a vertical-cavity surface-emitting laser and photodetectors for position sensing.

Noncontact long-range position sensing is desirable for a number of applications. We have designed and fabricated a monolithically integrated vertical-cavity surface-emitting laser (VCSEL) and p-type/intrinsic/n-type (PIN) photodetectors for optical position sensing. Calculations using the reflection from a periodic metallic corrugation as a position gauge indicate resolution in the submicron regime. High device uniformity is obtained using novel fabrication techniques. We observe a threshold current of 0.52 mA for the VCSELs and a detector responsivity of 0.38 A/W at 840 nm. The optical cross talk between VCSELs and detectors is also quantified.