In vivo biosynthesis and turnover of 35S-labeled glomerular basement membrane

Renal glomerular basement membrane was labeled in vivo by the injection of tracer amounts of radioactive sulfate into normal adult rats. The biosynthesis and turnover of [³⁵S]glycosaminoglycans in purified basement membrane was determined from the specific activity of ³⁵S in pronase digests of basement membranes isolated 1–7 days after injection. Peak radioactive labeling occurred 24 h after injection following which the specific activity of basement membrane sulfate, expressed as cpm/μg uronic acid, progressively declined over the ensuing period of study. The biologic half-life of radioactive sulfate in basement membrane was estimated at about 7 days, which is within the range previously reported for [³⁵S]glycosaminoglycans in whole renal cortex. The findings indicate that ³⁵S-labeled components of glomerular basement membrane have a relatively rapid turnover.     

ERK/MAPK and PI3K/AKT signal channels simultaneously activated in nerve cell and axon after facial nerve injury

BackgroundThe in-vitro study indicated that ERK/MAPK and PI3K/AKT signal channels may play an important role in reparative regeneration process after peripheral nerve injury. But, relevant in-vivo study was infrequent. In particular, there has been no report on simultaneous activation of ERK/MAPK and PI3K/AKT signal channels in facial nerve cell and axon after facial nerve injury.ResultsThe expression of P-ERK enhanced in nerve cells at the injury side on the 1 d after the rat facial nerve was cut and kept on a higher level until 14 d, but decreased on 28 d. The expression of P-AKT enhanced in nerve cells at the injury side on 1 d after injury, and kept on a higher level until 28 d. The expression of P-ERK enhanced at the near and far sections of the injured axon on 1 d, then increased gradually and reached the maximum on 7 d, but decreased on 14 d, until down to the level before the injury on 28 d. The expression of P-AKT obviously enhanced in the injured axon on 1 d, especially in the axon of the rear section, but decreased in the axon of the rear section on 7 d, while the expression of axon in the far section increased to the maximum and kept on till 14 d. On 28 d, the expression of P-AKT decreased in both rear and far sections of the axon.ConclusionThe facial nerve simultaneously activated ERK/MAPK and PI3K/AKT signal channels in facial nerve cells and axons after the cut injury, but the expression levels of P-ERK and P-AKT varied as the function of the time. In particular, they were quite different in axon of the far section. It has been speculated that two signal channels might have different functions after nerve injury. However, their specific regulating effects should still be testified by further studies in regenerative process of peripheral nerve injury.     

Eimeria dispersa and Eimeria gallopavonis: Infectivity, Survival, and Development in Primary Chicken and Turkey Kidney Cell Cultures

SYNOPSIS. Eimeria dispersa (turkey strain) and Eimeria gallopavonis sporozoites were inoculated into primary cultures of chicken kidney (CK) and turkey kidney (TK) cells. Eimeria dispersa sporozoites were more infective in either cell type than those of E. gallopavonis : at 4 hr, the percentage of infection was 67-98 for E. dispersa but only 23-56 for E. gallopavonis . E. dispersa also survived better in culture: at 2 days, losses of E. dispersa in both cell types were only 4-19%, whereas losses of E. gallopavonis were 35-47% in TK cells and 60–95% in CK cells. However, E. gallopavonis developed further than E. dispersa . Location and increase in numbers of intracellular stages at 4 days indicated that E. dispersa proceeded through 2 schizogonic generations before development stopped.     

SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.     

Effect of biceps-to-triceps transfer on rotator cuff stress during upper limb weight-bearing lift in tetraplegia: A modeling and simulation analysis

Rotator cuff stress during upper limb weight-bearing lifts presumably contribute to rotator cuff disease, which is the most common cause of shoulder pain in individuals with tetraplegia. Elbow extension strength appears to be a key determinant of rotator cuff stress during upper limb weight-bearing lifts since individuals with paraplegia who generate greater elbow extensor moments experience lower rotator cuff stress relative to individuals with tetraplegia. Biceps-to-triceps transfer surgery can increase elbow extension strength in individuals with tetraplegia. The purpose of this study was to determine whether active elbow extension via biceps transfer decreases rotator cuff stress during weight-bearing lifts in individuals with tetraplegia. A forward dynamics computational framework was used to estimate muscle stress during the lift; stress was computed as muscle force divided by the peak isometric muscle force. We hypothesized that rotator cuff stresses would be lower in simulated lifting with biceps transfer relative to simulated lifting without biceps transfer. We found that limited elbow extension strength in individuals with tetraplegia, regardless of whether elbow strength is enabled via biceps transfer or is residual after spinal cord injury, results in muscle stresses exceeding 85% of the peak isometric muscle stress in the supraspinatus, infraspinatus, and teres minor. The rotator cuff stresses we estimated suggest that performance of weight-bearing activities should be minimized or assisted in order to reduce the risk for shoulder pain. Our results also indicate that biceps transfer is unlikely to decrease rotator cuff stress during weight-bearing lifts in individuals with tetraplegia.     

Pathologic tooth deformities in modern and fossil chondrichthians: a consequence of feeding-related injury

Deformed teeth are found as rare components of the dentitions of both modern and fossil chondrichthians. Tooth deformities occur as bent or twisted tooth crowns, missing or misshaped cusps, atypical protuberances, perforations, and abnormal root structures. Deformed tooth files consisting of unusually overlapped or small teeth, or teeth misaligned in the jaw also occur in modern forms, but deformed tooth files generally are not recognizable in fossils due to post-mortem dissociation of teeth and jaws. A survey of 200 modern lamniform and carcharhiniform sharks as well as literature sources indicate that such deformities are produced by feeding-related injury to the tooth-forming tissue of the jaws, particularly by impaction of chondrichthian and teleost fin and tail spines. Tooth counts for several late Cretaceous genera, based on material recovered from coastal plain sites from New Jersey to Alabama, suggest that the frequency of occurrence of deformed teeth in a species varies from about 0.015% in Squalicorax kaupi to about 0.36% in Paranomotodon sp. Tooth counts for modern lamniform and carcharhiniform sharks yield a comparable range in frequency of tooth deformities. Variation in frequency of tooth deformity may reflect interspecific differences in feeding behavior and dietary preferences. There is no suggestion in our data of any strong patterns of temporal variation in tooth deformity frequency, or of patterns ­reflecting chondrichthian phylogenetic history and evolution. Skeletal components of the probable prey of the Cretaceous species are preserved in the same horizons as the deformed teeth, and also are found within co-occurring chondrichthian coprolites.     

Effect of ischemia-reperfusion injury on the morphology of peroxisomes

We have previously demonstrated that ischemic injury changed the density of peroxisomes into two distinct peaks, one with a normal density (1.21 g/cm³; Peak I) and a second peak with a lighter density (1. 14 g/cm³; Peak II).We studied the peroxisomes from both peaks under the Electron microscope. Examination of peak I following ischemia showed loss of matrix proteins and damaged limiting membranes with leakage of DAB positive material in direct proportion to the duration of ischemia. Upon reperfusion of the ischemic liver Peak I showed more severe damage to the organelle. These observations clearly demonstrated that ischemia reperfusion injury causes structural damage to peroxisomes. Interestingly ultrastructural examination of Peak II following ischemia showed evidence of perisomal proliferation with budding of existing peroxisomes and the presence of micro peroxisomes (changes similar to those noted under conditions leading to perisomal proliferation). However, peak II following reperfusion showed only damaged organelle. These observations underline the importance of peroxisomes in the response of the cell to ischemia-reperfusion injury.     

H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity

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Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rheumatoid arthritis rats by regulating expression of CTGF

This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.