Late Holocene erosion in NW Anatolia from sediments of Lake Manyas, Lake Ulubat and the southern shelf of the Marmara Sea, Turkey

This paper deals with modern and ancient sedimentation in fresh water lakes and the marine shelf of the southern Marmara region, NW Anatolia, Turkey. Most of the information has been obtained from monitoring of suspended load discharged into two lakes (Manyas and Ulubat) in the last 45 years and from 8-11 m thick lacustrine sediments, in addition to radiocarbon-dated shelf sediments. This allows a holistic approach to the drainage basin denudation over time. The results show that the sedimentation rates in the lakes were low 0. 22 cm.yr-1, from 4000-2000 yr BP and then they increased (0.29 cm.yr-1) up to sub-recent times and reached 0.44 cm.yr-1 in the last century. It is suggested that deforestation created high rates of sedimentation in the basins and/or strong denudation of the region during the Late Holocene. This study also shows that for shallow freshwater lakes the calculation of sedimentation rates must include fine particles lost by the outlets and coarse-grained bed load deposited on their shores. In addition, a high rate of sedimentation has been created by short, but repetitive intense depositions. During the last century particularly during the last 45 years the rate of sedimentation or denudation has increased dramatically in NW Turkey. The two World Wars and mismanagement of the land had important local effects by increasing deforestation and resulting in the present erosive conditions

Wind control on the accumulation of heavy metals in sediment of Lake Ulubat, Anatolia, Turkey

Freshwater Lake Ulubat (zmean = 1.5-2.0 m and Area = ~138 km2), NW Anatolia, Turkey was filled in by fine-to-medium-grain silts during the late Holocene. Deposition in Lake Ulubat has been 1.6 cm yr-1 for the last 50 years, but the sedimentation rate over the last ~1,600 years was lower (0.37 mm yr-1). The organic matter and carbonate contents of the infill show cyclic changes that reflect environmental fluctuations. The silt-dominated lithology and the vertically uniform heavy metal distributions are probably due to wind-controlled sedimentation in the lake. Heterogeneous mud, derived from a large, mountainous drainage basin, is deposited in the lake mostly during summer, June to October, when conditions are hot and calm. Winter months are stormier and sediments are re-suspended due to the shallow water depth and the effect of waves on the lake bottom. It is likely that re-suspended sediments, particularly fine-grained particles, together with the heavy metals, are transported out of the lake via the outlet, especially during periods of high lake level. This resuspension and removal process probably caused the lake sediments to become silt-dominated and depleted in heavy metals. The role of broad shallow lakes in sequestering sediments and heavy metals can be described more accurately when wind data are considered. Such information may also be helpful for land-use planning in downstream areas

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3−/− mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3−/− and LtapLp/+ mutants, Dvl3+/−;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant

Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain

Besides protein-coding mRNAs, eukaryotic transcriptomes include many long non-protein-coding RNAs (ncRNAs) of unknown function that are transcribed away from protein-coding loci. Here, we have identified 659 intergenic long ncRNAs whose genomic sequences individually exhibit evolutionary constraint, a hallmark of functionality. Of this set, those expressed in the brain are more frequently conserved and are significantly enriched with predicted RNA secondary structures. Furthermore, brain-expressed long ncRNAs are preferentially located adjacent to protein-coding genes that are (1) also expressed in the brain and (2) involved in transcriptional regulation or in nervous system development. This led us to the hypothesis that spatiotemporal co-expression of ncRNAs and nearby protein-coding genes represents a general phenomenon, a prediction that was confirmed subsequently by in situ hybridisation in developing and adult mouse brain. We provide the full set of constrained long ncRNAs as an important experimental resource and present, for the first time, substantive and predictive criteria for prioritising long ncRNA and mRNA transcript pairs when investigating their biological functions and contributions to development and disease

Effectiveness of Progressive and Resisted and Non-Progressive or Non-Resisted Exercise in Rotator Cuff Related Shoulder Pain: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Objective: Synthesize evidence regarding effectiveness of progressive and resisted or non-progressive and non-resisted exercise compared with placebo or no treatment, in rotator cuff related pain. Data sources: English articles, searched in Cochrane CENTRAL, MEDLINE, EMBASE and CINAHL databases up until May 19, 2020. Methods: Randomized controlled trials in people with rotator cuff related pain comparing either progressive and resisted exercise or non-progressive and non-resisted exercise, with placebo or no treatment were included. Data extracted independently by two authors. Risk of bias appraised with the Cochrane Collaboration tool. Results: Seven trials (468 participants) were included, four trials (271 participants) included progressive and resisted exercise and three trials (197 participants) included non-progressive or non-resisted exercise. There was uncertain clinical benefit for composite pain and function (15 point difference, 95% CI 9 to 21, 100-point scale) and pain outcomes at >6weeks to 6months with progressive and resisted exercise compared to placebo or no treatment (comparison 1). For non-progressive or non-resisted exercise there was no significant benefit for composite pain and function (4 point difference, 95% CI –2 to 9, 100-point scale) and pain outcomes at >6weeks to 6months compared to placebo or no treatment (comparison 2). Adverse events were seldom reported and mild. Conclusions: There is uncertain clinical benefit for all outcomes with progressive and resisted exercise and no significant benefit with non-progressive and non-resisted exercise, versus no treatment or placebo at >6weeks to 6months. Findings are low certainty and should be interpreted with cautio

Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development

Dishevelled (Dvl) proteins are important signaling components of both the canonical β-catenin/Wnt pathway, which controls cell proliferation and patterning, and the planar cell polarity (PCP) pathway, which coordinates cell polarity within a sheet of cells and also directs convergent extension cell (CE) movements that produce narrowing and elongation of the tissue. Three mammalian Dvl genes have been identified and the developmental roles of Dvl1 and Dvl2 were previously determined. Here, we identify the functions of Dvl3 in development and provide evidence of functional redundancy among the three murine Dvls. Dvl3−/− mice died perinatally with cardiac outflow tract abnormalities, including double outlet right ventricle and persistent truncus arteriosis. These mutants also displayed a misorientated stereocilia in the organ of Corti, a phenotype that was enhanced with the additional loss of a single allele of the PCP component Vangl2/Ltap (LtapLp/+). Although neurulation appeared normal in both Dvl3−/− and LtapLp/+ mutants, Dvl3+/−;LtapLp/+ combined mutants displayed incomplete neural tube closure. Importantly, we show that many of the roles of Dvl3 are also shared by Dvl1 and Dvl2. More severe phenotypes were observed in Dvl3 mutants with the deficiency of another Dvl, and increasing Dvl dosage genetically with Dvl transgenes demonstrated the ability of Dvls to compensate for each other to enable normal development. Interestingly, global canonical Wnt signaling appeared largely unaffected in the double Dvl mutants, suggesting that low Dvl levels are sufficient for functional canonical Wnt signals. In summary, we demonstrate that Dvl3 is required for cardiac outflow tract development and describe its importance in the PCP pathway during neurulation and cochlea development. Finally, we establish several developmental processes in which the three Dvls are functionally redundant

Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway

Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.Fundacao Ciencia e Tecnologia - IP; IBB/CBME, LA [PTDC/BIA-BCM/69912/2006, Pest-OE/EQB/LA0023/2013]; FCTinfo:eu-repo/semantics/publishedVersio