LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice

The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion. Here, we report that deleting Pinch1 in limb mesenchymal stem cells (MSCs) and Pinch2 globally (double knockout; dKO) in mice causes severe chondrodysplasia, while single mutant mice do not display marked defects. Pinch deletion decreases chondrocyte proliferation, accelerates cell differentiation and disrupts column formation. Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone (PZ) chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone (HZ) chondrocytes. Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes, reduces bone formation, and increases bone resorption, leading to low bone mass. In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes. Through its C-terminal region, Pinch1 interacts with Smad2/3 proteins. Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells (BMSCs). Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs. Interestingly, compared to those from single mutant mice, BMSCs from dKO mice express dramatically lower protein levels of β-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity. Finally, ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening. Collectively, our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms.

Now, Boys, You Must Do Your Duty

On the Seventeenth Corps sector the main effort was launched by John A. Logan’s division along the Jackson Road. John E. Smith’s brigade advanced in column formation and struck the 3rd Louisiana Redan. It deployed into line before reaching the redan and all of its regiments managed to lodge at the foot of the parapet. They found it impossible to scale the slope, however, and remained there for the rest of the day. John D. Stevenson’s brigade, to the south of Smith, advanced out of a protective ravine toward the Great Redoubt. Some regiments made it to the foot of the slope but could not enter the work while others, especially the 81st Illinois, got stuck part way to the fort and suffered heavy losses. Thomas Ransom’s brigade of John McArthur’s division, north of Logan, spent the morning and the early afternoon making contact with the rest of Blair’s division to the north so the combined force might launch a coordinated attack. Meanwhile, James B. McPherson’s other division, commanded by Isaac F. Quinby, advanced to the south of Logan to demonstrate against the Confederates but did not launch an attack.

Dismay and Bewilderment

The big Federal attack of May 22 began at 10 a.m. and the most striking part of it was the assault by Frank P. Blair’s division against the Stockade Redan. It was led by Hugh Ewing’s brigade, commanded by William T. Sherman’s foster brother and brother-in-law. The brigade, leading Fifteenth Corps action that day, advanced in column formation along Graveyard Road into the teeth of heavy Confederate rifle and artillery fire from one of the strongest forts on the Confederate line of earthworks. Led by 150 volunteers called the Forlorn Hope, the attack faltered. Only a handful of the members of the Forlorn Hope managed to get into the ditch and onto the outside slope of the parapet of the Stockade Redan and could go no farther. Many members of the 37th Ohio lost their will to continue after getting stuck inside a road cut only 100 yards from the redan and blocked up the line of approach of the regiments behind them. The rest of Ewing’s brigade left the exposed Graveyard Road and formed in a ravine to the south where it prepared to continue the advance later that day.

Static Survey as Geological Engineering Method Verification of DSM Column Formation

The state-of-the-art methods for verifying the correctness of ground improvement performed using the DSM (Deep Soil Mixing) technology are largely focused on the selection of adequate factors impacting the achievement of a correct compressive strength fc [MPa] of the column core, which ensures the transfer of stress from the designed structures to the subsoil. In view of the operation of each of the columns, it is equally significant to ensure that their bases are located in load-bearing soil at the entire area of the improvement, without the need to perform many costly subsoil surveys. Based on the complementary soil investigation results and parameters obtained during deep soil mixing from an automatic logger installed on the drilling machine, a method of comparing the rotary drive pressure (working pressure) PKDK [bar] and the cone resistance qc [MPa] of the CPTU static probe (Cone Penetration Test Unit with Pore Pressure Measurement) was developed along with the method to interpret the results in the context of the correctness of the ground improvement on the construction site analyzed in this paper.

Columnar-jointed bentonite below a Doleritic Sill, Tideswell Dale, Derbyshire, UK: formation during prograde contact metamorphism

Columnar-jointed tuffs (bentonites) are located below the Lower Carboniferous Tideswell Dale Sill, Derbyshire, in an abandoned quarry. There are three zones of prismatic joints, columnar joints (∼60 cm thick and mean column width of 4.1 cm) and massive, conchoidally fractured rock sequentially from the dolerite contact downwards. The rocks are very fine-grained (1–10 µm) and consist mainly of sanidine, interlayered illite/smectite, and hematite, with minor quartz, apatite, montmorillonite, anatase and detrital minerals. High K2O and Fe2O3, low Na2O and low MgO are interpreted as due to alteration of felsic volcanic ash. The bentonite was contact-metamorphosed by the sill to temperatures of c. 300 °C. The progression of fracture geometries, thermal considerations and application of theories of column formation indicate that columns formed downwards away from the sill, due to prograde contact metamorphism of the originally clay-rich bentonite. The formation of columnar fracture networks by shrinkage due to igneous heating may have implications for the effectiveness of bentonite as a barrier for disposal of high-level radioactive waste. Regional dimensions include documenting widespread felsic explosive volcanism and inferring a Triassic oxidation event from palaeomagnetic data.

Aerial attack strategies of bat-hunting hawks, and the dilution effect of swarming

Aggregation behaviors can often reduce predation risk, whether through dilution, confusion, or vigilance effects, but these effects are challenging to measure under natural conditions, involving strong interactions between the behaviors of predators and prey. Here we study aerial predation of massive swarms of Brazilian free-tailed bats Tadarida brasiliensis by Swainson’s hawks Buteo swainsoni, testing how the behavioral strategies of predator and prey influence catch success and predation risk. The hawks achieved high overall catch success, but they were no more successful against lone bats than against bats flying in column formation. There was therefore no evidence of any net vigilance or confusion effect, and hawks attacking the column benefitted from the opportunity to make several attempted grabs. Even so, the bats’ overall risk of predation was an order of magnitude higher when flying alone. Attacks on lone bats (∼10% of attacks) were greatly overrepresented relative to the proportion of bats classified as flying alone (∼0.2%), so dilution is both necessary and sufficient to explain the higher survival rates of bats flying in the column. From the hawks’ perspective, their odds of catching a bat more than trebled if the attack involved a stoop rather than level flight, or a rolling rather than pitching grab maneuver. These behavioral tactics were independently deployed in nearly three-quarters of all attacks. Hence, whereas the survival rate of a bat depends principally on whether it flies alone or in a group, the catch success of a hawk depends principally on how it maneuvers to attack.Lay summaryBats emerging by daylight from a massive desert roost are able to minimise their predation risk by maintaining tight column formation, because the hawks that attack them target stragglers disproportionately often. Whereas the predation risk of a bat therefore depends on how it maintains its position within the swarm, the catch success of a hawk depends on how it maneuvers to attack. Catch success is maximised by executing a stooping dive or a rolling grab.