A Leaf Point Documents Hunting with Spears in the Middle Paleolithic at Hohle Fels, Germany

During the 2020 season at Hohle Fels Cave in the Ach Valley of southwestern Germany the excavation team from the University of Tübingen recovered a bifacial leaf point in archaeological horizon (AH) X. This horizon is the fifth deepest of the Middle Paleolithic horizons at the site and is located roughly 120 cm beneath the base of the rich Aurignacian layers of the cave. The new leaf point, or Blattspitze in German, is the first artifact of its kind found in situ in the Swabian caves since Gustav Riek’s excavation at Haldenstein Cave near the source of the Lone River recovered two leaf points in excellent preservation in 1936. The new find allowed our team to conduct the first techno-functional study of a freshly recovered leaf point from the European Middle Paleolithic. This study demonstrates that the leaf point was hafted at the less pointy end of the artifact. The leaf point bears clear damage to the pointed end of the artifact that occurred during a hunting episode. A Neanderthal knapper further damaged the tool during an attempt to resharpen and rejuvenate the tool. This damage was likely the reason the knapper discarded the leaf point at Hohle Fels. This result and a re-examination of the two leaf points from Haldenstein Cave indicate that late Neanderthals used Blattspitzen for hunting large game. The current results do not explicitly prove that spears with hafted leaf points were always thrown or used as thrusting spears, and one can easily imagine scenarios in which a weapon of this kind could be used in both ways. Ideally, the ongoing excavation at Hohle Fels will recover more leaf points, which will give us the opportunity to document the technological variability of this kind of tool with regard to their manufacture, function and life history. We also view the current research at Hohle Fels as an excellent opportunity to gain a better and more strongly contextualized understanding of the technological system linking lithic, botanical and osseous technologies during this phase of the Middle Paleolithic. This paper also considers the place that hafted leaf points have within the broader evolutionary development of hunting and projectile technology.

Structural Effects of Disease-Related Mutations in Actin-Binding Period 3 of Tropomyosin

Tropomyosin (Tpm) is an actin-binding coiled-coil protein. In muscle, it regulates contractions in a troponin/Ca2+-dependent manner and controls the thin filament lengths at the pointed end. Due to its size and periodic structure, it is difficult to observe small local structural changes in the coiled coil caused by disease-related mutations. In this study, we designed 97-residue peptides, Tpm1.164–154 and Tpm3.1265–155, focusing on the actin-binding period 3 of two muscle isoforms. Using these peptides, we evaluated the effects of cardiomyopathy mutations: I92T and V95A in Tpm1.1, and congenital myopathy mutations R91P and R91C in Tpm3.12. We introduced a cysteine at the N-terminus of each fragment to promote the formation of the coiled-coil structure by disulfide bonds. Dimerization of the designed peptides was confirmed by gel electrophoresis in the presence and absence of dithiothreitol. Using circular dichroism, we showed that all mutations decreased coiled coil stability, with Tpm3.1265–155R91P and Tpm1.164–154I92T having the most drastic effects. Our experiments also indicated that adding the N-terminal cysteine increased coiled coil stability demonstrating that our design can serve as an effective tool in studying the coiled-coil fragments of various proteins.

Allostery and molecular stripping mechanism in profilin regulated actin filament growth

Profilin is an actin-sequestering protein and plays key role in regulating the polarized growth of actin filament. Binding of profilin to monomeric actin (G-actin) allows continuous elongation at the barbed end, but not the pointed end, of filament. How G-actin exchanges between the profilin-sequestered state and the filament state (F-actin) to support the barbed end elongation is not well understood. Here, we investigate the involved molecular mechanism by constructing a multi-basin energy landscape model and performing molecular simulations. We showed that the actin exchanging occurs by forming a ternary complex. The interactions arising from the barbed end binding drive the conformational change of the attached G-actin in the ternary complex from twist conformation to more flatten conformation without involving the change of nucleotide state, which in turn destabilizes the actin-profilin interface and promotes the profilin stripping event through allosteric coupling. We also showed that attachment of free profilin to the barbed end induces conformational change of the barbed end actin and facilitates its stripping from the filament. These results suggest a molecular stripping mechanism of the polarized actin filament growth dynamics controlled by the concentrations of the actin-profilin dimer and the free profilin, in which the allosteric feature of the monomeric actin plays crucial role.

The effect of varied types of steel fibers on the performance of self-compacting concrete modified with volcanic pumice powder

The aim of this work involves studying the impact of varied types of steel fibers (SF) on the performance of self-compacting concrete (SCC), containing volcanic pumice powder (VPP). In this study, five types of steel fiber, which had a hooked end with two lengths of (SF1) and (SF3), flat end of length (SF2), in addition to the pointed end of (SF4) and (SF5) by 1% of volume fraction, were used. In addition, hybrid steel fiber (a mixture of all the steel fiber types) by 0.2% of volume fraction of concrete volume was used. Moreover, VPP was utilized by 30% cement mass as a substitute material for producing SCC. The impact of steel fiber properties in the shape of SF on the fresh concrete properties as slump flow and segregation were investigated. In addition to their influence on the compressive strength, split tensile strength, flexural strength, toughness, porosity, water absorption, and bulk density were examined. The results showed that SF led to decreasing the SCC fresh properties. Utilizing SF, on the other hand, improved the SCC hardened properties, as well as the toughness indices.

Effect of malaria parasite shape on its alignment at erythrocyte membrane

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite's apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite's shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.

CUERPO EXTRAÑO PUNZANTE LOCALIZADO EN APÉNDICE CECAL, DE DOS MESES DE EVOLUCIÓN. EXTRACCIÓN POR COLONOSCOPIA - INFORME DE CASO.

Introduction Ingestion of foreign bodies implies a 35% risk of possible complications, which are associated with their type (blunt or sharp) and their size. Although in most of them, it is expected that they pass along the gastrointestinal tract without difficulty or complications, the management will depend on the characteristics of the swallowed object, time of evolution and symptoms of the patient. Case description We present the clinical case of a 58-year-old female patient with a recent gastric bypass surgical history, who accidentally ingested a piece of dental equipment two months earlier during a dental procedure, remaining asymptomatic until she came to our office. In radiographic controls for confirmation, location and evolution, the presence of a 2 cm sharp object was evidenced, apparently located in the cecal appendix, which does not progress distally. For the management, initial expectant management was proposed, which was completed with therapeutic colonoscopy for its extraction, the technique recommends that the sharp object should be grasped by the pointed end, distal to the wall, which reduces the risk of perforation related to the procedure or damage of the mucosa during extraction, the case is completed with successful resolution and without complications. Conclusion Less invasive therapeutic management such as colonoscopy should be considered first line in this type of case, when there are no signs or radiological findings of perforation or clinical instability, due to its low incidence of complications and a high success rate.

Erythroid differentiation in mouse erythroleukemia cells is driven via actin filament-tropomodulin3-tropomyosin networks

Erythroid differentiation (ED) is a complex cellular process entailing morphologically distinct maturation stages of erythroblasts during terminal differentiation. Studies of actin filament assembly and organization during terminal ED have revealed essential roles for the pointed-end actin filament capping proteins, tropomodulins (Tmod1 and Tmod3). Additionally, tropomyosin (Tpm) binding to Tmods is a key feature promoting Tmod-mediated actin filament capping. Global deletion of Tmod3 leads to embryonic lethality in mice with impaired ED. To test a cell autonomous function for Tmod3 and further decipher its biochemical function during ED, we generated a Tmod3 knockout in a mouse erythroleukemia cell line (Mel ds19). Tmod3 knockout cells appeared normal prior to ED, but showed defects during progression of ED, characterized by a marked failure to reduce cell and nuclear size, reduced viability and increased apoptosis. In Mel ds19 cells, both Tpms and actin were preferentially associated with the Triton-X 100 insoluble cytoskeleton during ED, indicating Tpm-coated actin filament assembly during ED. While loss of Tmod3 did not lead to a change in total actin levels, it led to a severe reduction in the proportion of Tpms and actin associated with the Triton-X 100 insoluble cytoskeleton during ED. We conclude that Tmod3-regulation of actin cytoskeleton assembly via Tpms is integral to morphological maturation and cell survival during normal erythroid terminal differentiation.

FEATURES OF THE CONFIGURATION OF LAKES IN THE SOUTH OF WESTERN SIBERIA IN CONNECTION WITH THE PROBLEM OF THE ORIGIN OF THE GRIVAS TOPOGRAPHY

In the south of Western Siberia, there are lakes of a specific shape - teardrop-shaped, with a convex rounded side facing northeast and a pointed end-to the southwest. They are found only in the distribution area of the definite grivas relief. There is a complete gradual transition from symmetrical "drops" through to varying degrees asymmetric to special forms-lakes - "retorts". The necks of the "retorts" are twisted counterclockwise. Asymmetrical lakes are tentatively interpreted as the result of vortex currents in the Grosswald continuous flow.

Effect of malaria parasite shape on its alignment at erythrocyte membrane

During the blood stage of malaria pathogenesis, parasites invade healthy red blood cells (RBC) to multiply inside the host and evade the immune response. When attached to RBC, the parasite first has to align its apex with the membrane for a successful invasion. Since the parasite's apex sits at the pointed end of an oval (egg-like) shape with a large local curvature, apical alignment is in general an energetically un-favorable process. Previously, using coarse-grained mesoscopic simulations, we have shown that optimal alignment time is achieved due to RBC membrane deformation and the stochastic nature of bond-based interactions between the parasite and RBC membrane (Hillringhaus et al., 2020). Here, we demonstrate that the parasite's shape has a prominent effect on the alignment process. The alignment times of spherical parasites for intermediate and large bond off-rates (or weak membrane-parasite interactions) are found to be close to those of an egg-like shape. However, for small bond off-rates (or strong adhesion and large membrane deformations), the alignment time for a spherical shape increases drastically. Parasite shapes with large aspect ratios such as oblate and long prolate ellipsoids are found to exhibit very long alignment times in comparison to the egg-like shape. At a stiffened RBC, spherical parasite aligns faster than any other investigated shapes. This study shows that the original egg-like shape performs not worse for parasite alignment than other considered shapes, but is more robust with respect to different adhesion interactions and RBC membrane rigidities.