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The earliest South African hominids (humans and their ancestral kin) belong to the genera Australopithecus, Paranthropus, and Homo, with the oldest being a ca. 3.67 million-year-old nearly complete skeleton of Australopithecus (StW 573) from Sterkfontein Caves. This skeleton has provided, for the first time in almost a century of research, the full anatomy of an Australopithecus individual with indisputably associated skull and postcranial bones that give complete limb lengths. The three genera are also found in East Africa, but scholars have disagreed on the taxonomic assignment for some fossils owing to historical preconceptions. Here we focus on the South African representatives to help clarify these debates. The uncovering of the StW 573 skeleton in situ revealed significant clues concerning events that had affected it over time and demonstrated that the associated stalagmite flowstones cannot provide direct dating of the fossil, as they are infillings of voids caused by postdepositional collapse.

Nanoconfinement offers opportunities to tune physical properties of molecular entities by altering their assembled structures. This also applies to acene-based molecules with potentially rich π–π interactions. Unlike most of the previous cases with acene-based guests directly incorporated into hosts, we take a further step by oligomerizing a fluorescent anthryl monomer, 9-vinylanthracene, inside nanochannels of a metal–organic framework, which is a pillared three-dimensional kagome net of [Zn2(bdc)2(dabco)] (bdc2– = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane). The fluorescence emission of the guest can be significantly enhanced after oligomerization, which is likely due to the suppressed nonemissive interaction between the oligomerized molecules in the nanospace and the MOF wall. The case we have demonstrated for fluorescence enhancement via confined oligomerization provides inspiration for the design of luminescent composites and is encouraging for further exploration of molecules in a nanoconfined space.

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Sterkfontein is the most prolific single source of Australopithecus fossils, the vast majority of which were recovered from Member 4, a cave breccia now exposed by erosion and weathering at the landscape surface. A few other Australopithecus fossils, including the StW 573 skeleton, come from subterranean deposits [T. C. Partridge et al. , Science 300, 607–612 (2003); R. J. Clarke, K. Kuman, J. Hum. Evol. 134, 102634 (2019)]. Here, we report a cosmogenic nuclide isochron burial date of 3.41 ± 0.11 million years (My) within the lower middle part of Member 4, and simple burial dates of 3.49 ± 0.19 My in the upper middle part of Member 4 and 3.61 ± 0.09 My in Jacovec Cavern. Together with a previously published isochron burial date of 3.67 ± 0.16 My for StW 573 [D. E. Granger et al. , Nature 522, 85–88 (2015)], these results place nearly the entire Australopithecus assemblage at Sterkfontein in the mid-Pliocene, contemporaneous with Australopithecus afarensis in East Africa. Our ages for the fossil-bearing breccia in Member 4 are considerably older than the previous ages of ca. 2.1 to 2.6 My interpreted from flowstones associated with the same deposit. We show that these previously dated flowstones are stratigraphically intrusive within Member 4 and that they therefore underestimate the true age of the fossils.

The StW 573 skeleton of Australopithecus prometheus from Sterkfontein Member 2 is some 93% complete and thus by far the most complete member of that genus yet found. Firmly dated at 3.67 Ma, it is one of the earliest specimens of its genus. A crucial aspect of interpretation of locomotor behaviour from fossil remains is an understanding of the palaeoenvironment in which the individual lived and the manner in which it would have used it. While the value of this ecomorphological approach is largely accepted, it has not been widely used as a stable framework on which to build evolutionary biomechanical interpretations. Here, we collate the available evidence on StW 573’s anatomy in order, as far as currently possible, to reconstruct what might have been this individual’s realized and potential niche. We explore the concept of a common Australopithecus “bauplan” by comparing the morphology and ecological context of StW 573 to that of paenocontemporaneous australopiths including Australopithecus anamensis and KSD-VP-1/1 Australopithecus afarensis. Each was probably substantially arboreal and woodland-dwelling, relying substantially on arboreal resources. We use a hypothesis-driven approach, tested by: virtual experiments, in the case of extinct species; biomechanical analyses of the locomotor behaviour of living great ape species; and analogical experiments with human subjects. From these, we conclude that the habitual locomotor mode of all australopiths was upright bipedalism, whether on the ground or on branches. Some later australopiths such as Australopithecus sediba undoubtedly became more terrestrial, allowing sacrifice of arboreal stability in favour of manual dexterity. Indeed, modern humans retain arboreal climbing skills but have further sacrificed arboreal effectiveness for enhanced ability to sustain striding terrestrial bipedalism over much greater distances. We compare StW 573’s locomotor adaptations to those of living great apes and protohominins, and agree with those earlier observers who suggest that the common panin-hominin last common ancestor was postcranially more like Gorilla than Pan.

Functional morphology of the atlas reflects multiple aspects of an organism’s biology. More specifically, its shape indicates patterns of head mobility, while the size of its vascular foramina reflects blood flow to the brain. Anatomy and function of the early hominin atlas, and thus, its evolutionary history, are poorly documented because of a paucity of fossilized material. Meticulous excavation, cleaning and high-resolution micro-CT scanning of the StW 573 (‘Little Foot’) skull has revealed the most complete early hominin atlas yet found, having been cemented by breccia in its displaced and flipped over position on the cranial base anterolateral to the foramen magnum. Description and landmark-free morphometric analyses of the StW 573 atlas, along with other less complete hominin atlases from Sterkfontein (StW 679) and Hadar (AL 333-83), confirm the presence of an arboreal component in the positional repertoire of Australopithecus. Finally, assessment of the cross-sectional areas of the transverse foramina of the atlas and the left carotid canal in StW 573 further suggests there may have been lower metabolic costs for cerebral tissues in this hominin than have been attributed to extant humans and may support the idea that blood perfusion of these tissues increased over the course of hominin evolution.

Membrane protein structure and function are modulated via interactions with their lipid environment. This is particularly true for integral membrane pumps, the P-type ATPases. These ATPases play vital roles in cell physiology, where they are associated with the transport of cations and lipids, thereby generating and maintaining crucial (electro-)chemical potential gradients across the membrane. Several pumps (Na+, K+-ATPase, H+, K+-ATPase and the plasma membrane Ca2+-ATPase) which are located in the asymmetric animal plasma membrane have been found to possess polybasic (lysine-rich) domains on their cytoplasmic surfaces, which are thought to act as phosphatidylserine (PS) binding domains. In contrast, the sarcoplasmic reticulum Ca2+-ATPase, located within an intracellular organelle membrane, does not possess such a domain. Here we focus on the lysine-rich N-termini of the plasma-membrane-bound Na+, K+- and H+, K+-ATPases. Synthetic peptides corresponding to the N-termini of these proteins were found, via quartz crystal microbalance and circular dichroism measurements, to interact via an electrostatic interaction with PS-containing membranes, thereby undergoing an increase in helical or other secondary structure content. As well as influencing ion pumping activity, it is proposed that this interaction could provide a mechanism for sensing the lipid asymmetry of the plasma membrane, which changes drastically when a cell undergoes apoptosis, i.e. programmed cell death. Thus, polybasic regions of plasma membrane-bound ion pumps could potentially perform the function of a “death sensor”, signalling to a cell to reduce pumping activity and save energy.

The ca. 3.67 Ma adult skeleton known as ‘Little Foot’ (StW 573), recovered from Sterkfontein Member 2 breccia in the Silberberg Grotto, is remarkable for its morphology and completeness. Preservation of clavicles and scapulae, including essentially complete right-side elements, offers opportunities to assess morphological and functional aspects of a nearly complete Australopithecus pectoral girdle. Here we describe the StW 573 pectoral girdle and offer quantitative comparisons to those of extant hominoids and selected homininans. The StW 573 pectoral girdle combines features intermediate between those of humans and other apes: a long and curved clavicle, suggesting a relatively dorsally positioned scapula; an enlarged and uniquely proportioned supraspinous fossa; a relatively cranially oriented glenoid fossa; and ape-like reinforcement of the axillary margin by a stout ventral bar. StW 573 scapulae are as follows: smaller than those of some homininans (i.e., KSD-VP-1/1 and KNM-ER 47000A), larger than others (i.e., A.L. 288-1, Sts 7, and MH2), and most similar in size to another australopith from Sterkfontein, StW 431. Moreover, StW 573 and StW 431 exhibit similar structural features along their axillary margins and inferior angles. As the StW 573 pectoral girdle (e.g., scapular configuration) has a greater affinity to that of apes—Gorilla in particular—rather than modern humans, we suggest that the StW 573 morphological pattern appears to reflect adaptations to arboreal behaviors, especially those with the hand positioned above the head, more than human-like manipulatory capabilities. When compared with less complete pectoral girdles from middle/late Miocene apes and that of the penecontemporaneous KSD-VP-1/1 (Australopithecus afarensis), and mindful of consensus views on the adaptiveness of arboreal positional behaviors soliciting abducted glenohumeral joints in early Pliocene taxa, we propose that the StW 573 pectoral girdle is a reasonable model for hypothesizing pectoral girdle configuration of the crown hominin last common ancestor.

Cholesterol’s effects on Na+,K+-ATPase reconstituted in phospholipid vesicles have been extensively studied. However, previous studies have reported both cholesterol-mediated stimulation and inhibition of Na+,K+-ATPase activity. Here, using partial reaction kinetics determined via stopped-flow experiments, we studied cholesterol’s effect on Na+,K+-ATPase in a near-native environment in which purified membrane fragments were depleted of cholesterol with methyl-β-cyclodextrin (mβCD). The mβCD-treated Na+,K+-ATPase had significantly reduced overall activity and exhibited decreased observed rate constants for ATP phosphorylation (ENa+3 → E2P, i.e. phosphorylation by ATP and Na+ occlusion from the cytoplasm) and K+ deocclusion with subsequent intracellular Na+ binding (E2K+2 → E1Na+3). However, cholesterol depletion did not affect the observed rate constant for K+ occlusion by phosphorylated Na+,K+-ATPase on the extracellular face and subsequent dephosphorylation (E2P → E2K+2). Thus, partial reactions involving cation binding and release at the protein’s intracellular side were most dependent on cholesterol. Fluorescence measurements with the probe eosin indicated that cholesterol depletion stabilizes the unphosphorylated E2 state relative to E1, and the cholesterol depletion-induced slowing of ATP phosphorylation kinetics was consistent with partial conversion of Na+,K+-ATPase into the E2 state, requiring a slow E2 → E1 transition before the phosphorylation. Molecular dynamics simulations of Na+,K+-ATPase in membranes with 40 mol% cholesterol revealed cholesterol interaction sites that differ markedly among protein conformations. They further disclosed state-dependent effects on membrane shape, with the E2 state being likely disfavored in cholesterol-rich bilayers relative to the E1P state because of a greater hydrophobic mismatch. In summary, cholesterol extraction from membranes significantly decreases Na+,K+-ATPase steady-state activity. Australian Research Council, National Health and Medical Research Council (Australia)

The Early Pleistocene site of Swartkrans in South Africa's Cradle of Humankind World Heritage Site has been significant for our understanding of the evolution of both early Homo and Paranthropus, as well as the earliest archaeology of southern Africa. Previous attempts to improve a faunal age estimate of the earliest deposit, Member 1, had produced results obtained with uranium-lead dating (U-Pb) on flowstones and cosmogenic burial dating of quartz, which placed the entire member in the range of1.7/1.8 Ma and2.3 Ma. In 2014, two simple burial dates for the Lower Bank, the earliest unit within Member 1, narrowed its age to between ca. 1.8 Ma and 2.2 Ma. A new dating program using the isochron method for burial dating has established an absolute age of 2.22 ± 0.09 Ma for a large portion of the Lower Bank, which can now be identified as containing the earliest Oldowan stone tools and fossils of Paranthropus robustus in South Africa. This date agrees within one sigma with the U-Pb age of 2.25 ± 0.08 Ma previously published for the flowstone underlying the Lower Bank and confirms a relatively rapid rate of accumulation for a large portion of the talus.

Ionic liquids (ILs) have exhibited enormous potential as electrolytes, designer solvents and reaction media, as well as being surprisingly effective platforms for amphiphile self-assembly and for preserving structure of complex biomolecules. This has led to their exploration as media for long-term biopreservation and in biosensors, for which their viability depends on their ability to sustain both structure and function within complex, multicomponent nanoscale compartments and assemblies. Here we show that a tethered lipid bilayer can be assembled directly in a purely IL environment that retains its structure upon exchange between IL and aqueous buffer, and that the membrane transporter valinomycin can be incorporated so as to retain its functionality and cation selectivity. This paves the way for the development of long-lived, non-aqueous microreactors and sensor assemblies, and demonstrates the potential for complex proteins to retain functionality in non-aqueous, ionic liquid solvents.

The aim of this work was the synthesis of hybrid materials of iron (II)-based therapeutic systems via the sol-gel method. Increasing amounts of polyethylene glycol (PEG 6, 12, 24, 50 wt%) were added to SiO2/Fe20 wt% to modulate the release kinetics of the drug from the systems. Fourier-transform infrared (FTIR) spectroscopy was used to study the interactions between different components in the hybrid materials. The release kinetics in a simulated body fluid (SBF) were investigated, and the amount of Fe2+ released was detected via ultraviolet-visible spectroscopy (UV-Vis) after reaction with ortho-phenanthroline. Furthermore, biological characterization was carried out. The bioactivity of the synthesized hybrid materials was evaluated via the formation of a layer of hydroxyapatite on the surface of samples soaked in SBF using spectroscopy. Finally, the potential antibacterial properties of seven different materials against two different bacteria—E. coli and S. aureus—were investigated.

We describe late Pliocene and early Pleistocene hominin fossils from Sterkfontein Caves (South Africa), including two femoral specimens, as well as a partial tibia and a partial fibula. The fossils are likely assignable to Australopithecus africanus and/or Australopithecus prometheus and the morphology of each corroborates previous interpretations of Sterkfontein hominins as at least facultative bipeds. Significance: A recent series of papers by our research team describes the morphology of a hominin skeleton from Sterkfontein Caves (South Africa), nicknamed ‘Little Foot’. Based on its unique skull morphology, R.J. Clarke, the skeleton’s discoverer, places it in the species Australopithecus prometheus, as distinct from the better-known and co-occurring Australopithecus africanus. Here we describe additional hominin thigh and leg fossils from Sterkfontein that, when considered in a comparative context, support the hypothesis that there was significant (probably interspecific) variation in South African hominin postcranial morphology during the late Pliocene and early Pleistocene.

Funder: DST-NRF Centre of Excellence in Palaeosciences, Funder: Palaeontological Scientific Trust, Numerous aspects of early hominin biology remain debated or simply unknown. However, recent developments in high-resolution imaging techniques have opened new avenues in the field of paleoanthropology. More specifically, X-ray synchrotron-based analytical imaging techniques have the potential to provide crucial details on the ontogeny, physiology, biomechanics, and biological identity of fossil specimens. Here we present preliminary results of our X-ray synchrotron-based investigation of the skull of the 3.67-million-year-old Australopithecus specimen StW 573 (‘Little Foot’) at the I12 beamline of the Diamond Light Source (United Kingdom). Besides showing fine details of the enamel (i.e., hypoplasias) and cementum (i.e., incremental lines), as well as of the cranial bone microarchitecture (e.g., diploic channels), our synchrotron-based investigation reveals for the first time the 3D spatial organization of the Haversian systems in the mandibular symphysis of an early hominin.

International audience; Because of its exceptional degree of preservation and its geological age of ∼3.67 Ma, StW 573 makes an invaluable contribution to our understanding of early hominin evolution and paleobiology. The morphology of the bony labyrinth has the potential to provide information about extinct primate taxonomic diversity, phylogenetic relationships and locomotor behaviour. In this context, we virtually reconstruct and comparatively assess the bony labyrinth morphology in StW 573. As comparative material, we investigate 17 southern African hominin specimens from Sterkfontein, Swartkrans and Makapansgat (plus published data from two specimens from Kromdraai B), attributed to Australopithecus, early Homo or Paranthropus, as well as 10 extant human and 10 extant chimpanzee specimens. We apply a landmark-based geometric morphometric method for quantitatively assessing labyrinthine morphology. Morphology of the inner ear in StW 573 most closely resembles that of another Australopithecus individual from Sterkfontein, StW 578, recovered from the Jacovec Cavern. Within the limits of our sample, we observe a certain degree of morphological variation in the Australopithecus assemblage of Sterkfontein Member 4. Cochlear morphology in StW 573 is similar to that of other Australopithecus as well as to Paranthropus specimens included in this study, but it is substantially different from early Homo. Interestingly, the configuration of semicircular canals in Paranthropus specimens from Swartkrans differs from other fossil hominins, including StW 573. Given the role of the cochlea in the sensory-driven interactions with the surrounding environment, our results offer new perspectives for interpreting early hominin behaviour and ecology. Finally, our study provides additional evidence for discussing the phylogenetic polarity of labyrinthine traits in southern African hominins.

This chapter describes 12 tarsal bones from Sterkfontein, and compares them to those of extant hominoids and other fossil hominins, adding new analyses for some of the bones which have been studied previously. In general, the Sterkfontein calcanei and tali more closely resemble those attributed to Australopithecus sediba from nearby Malapa than to Australopithecus afarensis tarsals from Hadar, Ethiopia. Overall, the bones are similar to those of humans, but African ape-like characters indicating selection on adaptive use of arboreal substrates are persistent throughout the Sterkfontein tarsals, although more prevalent on some bones than on others. Planes of the navicular and first metatarsal facets on the medial cuneiform are relatively parallel, suggesting the hallux was not notably divergent from the metatarsus. However, the anteroposteriorly short intermediate and lateral cuneiforms suggest that the anterior tarsal row had not yet elongated as in modern humans, adversely affecting the foot’s ability to serve as a rigid lever. A large groove for the flexor hallucis longus muscle and large navicular tubercle may be related to strong grasping and climbing. Overall, the Sterkfontein tarsal elements show mixture of modern human-like and African ape-like features.

The plasma membrane phospholipid distribution of animal cells is markedly asymmetric. Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are concentrated in the inner leaflet, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are concentrated in the outer leaflet. This non-equilibrium situation is maintained by lipid pumps (flippases or floppases), which utilize energy in the form of ATP to translocate lipids from one leaflet to the other. Scramblases, which are activated when physiologically required, transport lipids in both directions across the membrane and can abolish lipid asymmetry. Lipid asymmetry also causes imbalances in the areas occupied by lipid in the two membrane leaflets, contributing to membrane curvature. The asymmetry of PS across the plasma membrane plays a crucial signalling role in numerous physiological processes. Exposure of PS on the external surface of blood platelets stimulates blood coagulation. PS exposure by other cells during apoptosis provides an "eat me" signal to surrounding macrophages. Many peripheral and integral membrane proteins have polybasic PS-binding domains on their cytoplasmic surfaces which either provide a membrane anchor or affect activity. These domains can also determine trafficking within the cell and control regulation via an electrostatic switch mechanism, as well as potentially acting as "death sensors" when cytoplasmic PS is transferred to the extracellular leaflet during apoptosis. Apart from these physiological roles, external PS exposure by microorganisms, viruses and cancer cells allows them to mimic the immunosuppressive anti-inflammatory action of apoptotic cells and proliferate, thus providing a strong medical motivation for future research in the field of lipid asymmetry in membranes.

OBJECTIVES We provide descriptions and functional interpretations of 11 >2.0 Ma hominin vertebral and upper limb fossils from Sterkfontein. MATERIALS AND METHODS We employed taphonomic methods to describe postmortem damage observed on the fossils. We used osteometric tools and measurements to generate quantitative descriptions, which were added to qualitative descriptions of the fossils. These observations were then interpreted using published data on the same skeletal elements from extant and extinct hominoid taxa. RESULTS Six of the fossils carry carnivore tooth marks. Two vertebrae show morphologies that are consistent with fully developed lordosis of the lumbar spine, but which are not completely consistent with bipedal loading of the same intensity and/or frequency as reflected in the lumbars of modern humans. A clavicle shows a combination of humanlike and apelike features, the latter of which would have endowed its hominin with good climbing abilities. When combined, analyses of fragmentary radius and ulna fossils yield more ambiguous results. DISCUSSION The new fossil collection presents a mix of bipedal and climbing features. It is unclear whether this mix indicates that all Sterkfontein hominins of >2.0 Ma were terrestrial bipeds who retained adaptations for climbing or whether the collection samples two differently adapted, coeval hominins, Australopithecus africanus and Australopithecus prometheus, both of which are represented at Sterkfontein by skull remains. Regardless, the significant frequency of tooth-marked fossils in the sample might indicate that predation was a selection pressure that maintained climbing adaptations in at least some Sterkfontein hominins of this period.

Clusters of positively-charged basic amino acid residues, particularly lysine, are known to promote the interaction of many peripheral membrane proteins with the cytoplasmic surface of the plasma membrane via electrostatic interactions. In this work, cholesterol's effects on the interaction between lysine residues and membranes have been studied. Using poly-L-lysine (PLL) and vesicles as models to mimic the interaction between lysine-rich protein domains and the plasma membrane, light scattering measurements indicated cholesterol enhanced the electrostatic interaction through indirectly affecting the negatively charged phospholipid dioleoylphosphatidylserine, DOPS. Addition of PLL to lipid vesicles containing DOPS showed an initial increase in static light scattering (SLS), attributed to binding of PLL to the vesicle surface, followed by a slower continuously declining SLS signal, which, from comparison with fluorescent dye leakage studies could be attributed to vesicle lysis. Although electrostatic interactions between PLL and the membrane were not necessary for penetration to occur, cholesterol promoted membrane disruption of negatively charged vesicles, possibly by increasing the electrostatic interactions between PLL and the membrane. In contrast, cholesterol lowered the susceptibility of uncharged vesicles (formed using dioleoylphosphatidylcholine, DOPC) to PLL penetration. This can be explained by the absence of electrostatic interactions and cholesterol's known ability to increase membrane thickness and mechanical strength. Thus, the ability of cationic peptides to penetrate membranes including cholesterol is likely to depend on the membrane's PS:PC ratio.

A fluorescence ratiometric method utilizing the probe eosin Y is presented for estimating the ATP binding site polarity of P-type ATPases in different conformational states. The method has been calibrated by measurements in a series of alcohols and tested using complexation of eosin Y with methyl-β-cyclodextrin. The results obtained with the Na+,K+-, H+,K+- and sarcoplasmic reticulum Ca2+-ATPases indicate that the ATP binding site, to which eosin is known to bind, is significantly more polar in the case of the Na+,K+- and H+,K+-ATPases compared to the Ca2+-ATPase. This result was found to be consistent with docking calculations of eosin with the E2 conformational state of the Na+,K+-ATPase and the Ca2+-ATPase. Fluorescence experiments showed that eosin binds significantly more strongly to the E1 conformation of the Na+,K+-ATPase than the E2 conformation, but in the case of the Ca2+-ATPase both fluorescence experiments and docking calculations showed no significant difference in binding affinity between the two conformations. This result could be due to the fact that, in contrast to the Na+,K+- and H+,K+-ATPases, the E2-E1 transition of the Ca2+-ATPase does not involve the movement of a lysine-rich N-terminal tail which may affect the overall enzyme conformation. Consistent with this hypothesis, the eosin affinity of the E1 conformation of the Na+,K+-ATPase was significantly reduced after N-terminal truncation. It is suggested that changes in conformational entropy of the N-terminal tail of the Na+, K+- and the H+,K+-ATPases during the E2-E1 transition could affect the thermodynamic stability of the E1 conformation and hence its ATP binding affinity.

Bacterial colonization and biofilm development on medical devices can lead to infection. Antimicrobial peptide-coated surfaces may prevent such infections. Melimine and Mel4 are chimeric cationic peptides showing broad-spectrum antimicrobial activity once attached to biomaterials and are highly biocompatible in animal models and have been tested in Phase I and II/III human clinical trials. These peptides were covalently attached to glass using an azidobenzoic acid linker. Peptide attachment was confirmed using X-ray photoelectron spectroscopy and amino acid analysis. Mel4 when bound to glass was able to adopt a more ordered structure in the presence of bacterial membrane mimetic lipids. The ability of surface bound peptides to neutralize endotoxin was measured along with their interactions with the bacterial cytoplasmic membrane which were analyzed using DiSC(3)-5 and Sytox green, Syto-9, and PI dyes with fluorescence microscopy. Leakage of ATP and nucleic acids from cells were determined by analyzing the surrounding fluid. Attachment of the peptides resulted in increases in the percentage of nitrogen by 3.0% and 2.4%, and amino acid concentrations to 0.237 nmole and 0.298 nmole per coverslip on melimine and Mel4 coated surfaces, respectively. The immobilized peptides bound lipopolysaccharide and disrupted the cytoplasmic membrane potential of Pseudomonas aeruginosa within 15 min. Membrane depolarization was associated with a reduction in bacterial viability by 82% and 63% for coatings melimine and Mel4, respectively (p < 0.001). Disruption of membrane potential was followed by leakage of ATP from melimine (1.5 ± 0.4 nM) or Mel4 (1.3 ± 0.2 nM) coated surfaces compared to uncoated glass after 2 h (p < 0.001). Sytox green influx started after 3 h incubation with either peptide. Melimine coatings yielded 59% and Mel4 gave 36% PI stained cells after 4 h. Release of the larger molecules (DNA/RNA) commenced after 4 h for melimine (1.8 ± 0.9 times more than control; p = 0.008) and after 6 h with Mel4 (2.1 ± 0.2 times more than control; p < 0.001). The mechanism of action of surface bound melimine and Mel4 was similar to that of the peptides in solution, however, their immobilization resulted in much slower (approximately 30 times) kinetics.

International audience; The Sterkfontein Caves is currently the world's richest Australopithecus-bearing site. Included in Sterkfontein's hominin assemblage is StW 573 (‘Little Foot’), a near-complete Australopithecus skeleton discovered in Member 2 in the Silberberg Grotto. Because of its importance to the fossil hominin record, the geological age of StW 573 has been the subject of significant debate. Three main hypotheses have been proposed regarding the formation and age of Member 2 and by association StW 573. The first proposes that Member 2 (as originally defined in the type section in the Silberberg Grotto) started to accumulate at around 2.58 Ma and that the unit is contained within the Silberberg Grotto. The second proposes that Member 2 started forming before 3.67 ± 0.16 Ma and that the deposit extends into the Milner Hall and close to the base of the cave system. The third proposes a ‘two-stage burial scenario’, in which some sediments and StW 573 represent a secondary and mixed-age accumulation reworked from a higher cave. The stratigraphic and sedimentological implications of these hypotheses are tested here through the application of a multiscale investigation of Member 2, with reference to the taphonomy of the StW 573 skeleton. The complete infilling sequence of Member 2 is described across all exposures of the deposit in the Silberberg Grotto and into the Milner Hall. Sediments are generally stratified and conformably deposited in a sequence of silty sands eroded from well-developed lateritic soils on the landscape surface. Voids, clasts and bioclasts are organized consistently across and through Member 2 conforming with the underlying deposit geometry, indicating gradual deposit accretion with no distinct collapse facies evident and only localized intra-unit postdepositional modification. The stratigraphy and sedimentology of Member 2 support a simple single-stage accumulation process of Member 2 and a primary association between the sediments of Member 2 and the StW 573 ‘Little Foot’ skeleton.

© 2019 American Chemical Society. ATP is a fundamental intracellular molecule and is thought to diffuse freely throughout the cytosol. Evidence obtained from nucleotide-sensing sarcolemmal ion channels and red blood cells, however, suggest that ATP is compartmentalized or buffered, especially beneath the sarcolemma, but no definitive mechanism for restricted diffusion or potential buffering system has been postulated. In this study, we provide evidence from alterations to membrane dipole potential, membrane conductance, changes in enthalpy of phospholipid phase transition, and from free energy calculations that ATP associates with phospholipid bilayers. Furthermore, all-atom molecular dynamics simulations show that ATP can form aggregates in the aqueous phase at high concentrations. ATP interaction with membranes provides a new model to understand the diffusion of ATP through the cell. Coupled with previous reports of diffusion restriction in the subsarcolemmal space, these findings support the existence of compartmentalized or buffered pools of ATP.

© 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. Protein structure and function are modulated via interactions with their environment, representing both the surrounding aqueous media and lipid membranes that have an active role in shaping the structural topology of membrane proteins. Compared to a decade ago, there is now an abundance of crystal structural data on membrane proteins, which together with their functional studies have enhanced our understanding of the salient features of lipid-protein interactions. It is now important to recognize that membrane proteins are regulated by both (1) general lipid-protein interactions, where the general physicochemical properties of the lipid environment affect the conformational flexibility of a membrane protein, and (2) by specific lipid-protein interactions, where lipid molecules directly interact via chemical interactions with specific lipid-binding sites located on the protein. However, due to local differences in membrane composition, thickness, and lipid packing, local membrane physical properties and hence the associated lipid-protein interactions also differ due to membrane location, even for the same protein. Such a phenomenon has been shown to be true for one family of integral membrane ion pumps, the P2-type adenosine triphosphatases (ATPases). Despite being highly homologous, individual members of this family have distinct structural and functional activity and are an excellent candidate to highlight how the local membrane physical properties and specific lipid-protein interactions play a vital role in facilitating the structural rearrangements of these proteins necessary for their activity. Hence in this review, we focus on both the general and specific lipid-protein interactions and will mostly discuss the structure-function relationships of the following P2-type ATPases, Na+,K+-ATPase (NKA), gastric H+,K+-ATPase (HKA), and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), in concurrence with their lipid environment.

The Na+,K+-ATPase is present in the plasma membrane of all animal cells. It plays a crucial role in maintaining the Na+ and K+ electrochemical potential gradients across the membrane, which are essential in numerous physiological processes, e.g., nerve, muscle, and kidney function. Its cellular activity must, therefore, be under tight metabolic control. Consideration of eosin fluorescence and stopped-flow kinetic data indicates that the enzyme's E2 conformation is stabilized by electrostatic interactions, most likely between the N-terminus of the protein's catalytic α-subunit and the adjacent membrane. The electrostatic interactions can be screened by increasing ionic strength, leading to a more evenly balanced equilibrium between the E1 and E2 conformations. This represents an ideal situation for effective regulation of the Na+,K+-ATPase's enzymatic activity, because protein modifications, which perturb this equilibrium in either direction, can then easily lead to activation or inhibition. The effect of ionic strength on the E1:E2 distribution and the enzyme's kinetics can be mathematically described by the Gouy-Chapman theory of the electrical double layer. Weakening of the electrostatic interactions and a shift toward E1 causes a significant increase in the rate of phosphorylation of the enzyme by ATP. Electrostatic stabilization of the Na+,K+-ATPase's E2 conformation, thus, could play an important role in regulating the enzyme's physiological catalytic turnover. published

Labial striations on the anterior teeth have been documented in numerous European pre-Neandertal and Neandertal fossils and serve as evidence for handedness. OH-65, dated at 1.8 mya, shows a concentration of oblique striations on, especially, the left I1 and right I1, I2 and C1, which signal that it was right-handed. From these patterns we contend that OH-65 was habitually using the right hand, over the left, in manipulating objects during some kind of oral processing. In living humans right-handedness is generally correlated with brain lateralization, although the strength of the association is questioned by some. We propose that as more specimens are found, right-handedness, as seen in living Homo, will most probably be typical of these early hominins.

The membrane dipole potential, ψ